COLD PROTECTING EERO EMOLLIENTS AND FROSTBITE LEHMUSKALLIO Department of Dermatology and Venereology, University of Oulu, and Oulu Regional Institute of Occupational Health

OULU 2001 EERO LEHMUSKALLIO

COLD PROTECTING EMOLLIENTS AND FROSTBITE

Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in Auditorium of National Defence College in Santahamina, Helsinki, on June 15th, 2001, at 12 noon.

OULUN YLIOPISTO, OULU 2001 Copyright © 2001 University of Oulu, 2001

Manuscript received 10 May 2001 Manuscript accepted 21 May 2001

Communicated by Docent Tuula Estlander Docent Merja Kousa

ISBN 951-42-5988-2 (URL: http://herkules.oulu.fi/isbn9514259882/)

ALSO AVAILABLE IN PRINTED FORMAT ISBN 951-42-5987-4 ISSN 0355-3221 (URL: http://herkules.oulu.fi/issn03553221/)

OULU UNIVERSITY PRESS OULU 2001 Lehmuskallio, Eero, Cold protecting emollients and frostbite Department of Dermatology and Venereology, University of Oulu, P.O.Box 5000, FIN-90014 University of Oulu, Finland, Oulu Regional Institute of Occupational Health, -, Aapistie 1, FIN- 90220 Oulu, Finland 2001 Oulu, Finland (Manuscript received 10 May 2001)

Abstract Frostbite of the face and ears is a common problem in cold winters. Application of an emollient on the face is a traditional way to prevent frostbite in Finland. The preliminary results of an epidemiological study on frostbite in Finnish conscripts unexpectedly showed that the use of cold protecting emollients increased the risk of facial frostbite. This finding motivated studies on the effects and use of cold protecting emollients. 830 male Finnish conscripts answered a questionnaire concerning the use of cold protecting emollients, subjective experience of using them in cold and cumulative incidence of frostbite in the ears and face. Risk factors of frostbite were investigated in a prospective epidemiological study including 913 Finnish conscripts needing medical attention for frostbite of the ears or face and their 2478 matched, uninjured controls. Thermal properties of four different emollients were studied in vitro with a skin model and in vivo in experimental cold exposures of test persons. Test emollient was applied on one half of the face, as the other half acted as control. The skin temperatures of the face-halves were compared symmetrically by thermistors and infrared thermography. Subjective sensation of thermal half- difference was also registered. 21% of the conscripts had used emollients in the cold, a majority with an experience of protection. 47% of the conscripts had had frostbite in the head (42% in the ears and 23% on the face). There was a statistically significant correlation between the use of emollients and the incidence of facial frostbite in both epidemiological studies. Applying protective emollients formed an independent risk factor for frostbite of the cheeks, nose and ear lobes (odds ratios 3.3-5.6). The thermal insulation of test emollients on the skin model was minimal. On living skin, the applied half was somewhat cooler in a majority of comparisons. However, white petrolatum gave often a subjective perception of a warming effect. False sensation of safety may form the principal cause for the increased risk of frostbite associated with the use of emollients. When the warning symptoms of cold are weak, necessary protective measures are not carried out.

Keywords: emollients, frostbite, ear, face, skin temperature, risk factors, cold injury Acknowledgements

This study was carried out during 1989-2001 at the Department of Dermatology, University of Oulu and at Oulu Regional Institute of Occupational Health. The Research Institute of Military Medicine of the Finnish Defence Forces has promoted my work by providing an opportunity to write some of the original articles as its employee. My thanks are due to Professor Aarne Oikarinen, M.D., Ph.D. and Professor Jaakko Karvonen, M.D., Ph.D. at the Department of Dermatology of Oulu University, to Lieutenant General, Professor Kimmo Koskenvuo, M.D., Ph.D. and to Brigade General, Docent Timo Sahi, M.D., Ph.D., former and present Surgeon Generals of the Finnish Defence Forces as well as to Professor Juhani Hassi, M.D., Ph.D., Chief of the Oulu Regional Institute of Occupational Health. Without their support and facilities this investigation would have been impossible. I am deeply grateful to my supervisor, Docent Matti Hannuksela, M.D., Ph.D., for his encouraging help and guidance through all the years of slow progress. Despite his many obligations he has always found time for a prompt response to my questions and need for advice. I thank the reviewers of my thesis, Docent Tuula Estlander, M.D., Ph.D. and Docent Merja Kousa, M.D., Ph.D. for their constructive criticism. I am indebted to my collaborators, Docent Hannu Anttonen, M.Sc., Ph.D. and Docent Hannu Rintamäki, M.Sc., Ph.D., both distinguished seniors in the field of cold research at the Oulu Regional Institute of Occupational Health and Harri Lindholm, M.D., Ora Friberg, M.D., Ph.D. and Professor Antti Viljanen, M.D., Ph.D. at the Institute of Military Medicine. Professor in statistics, Seppo Sarna, Ph.D. at the Department of Public Health, University of Helsinki, Kimmo Juopperi, M.Sc. at Oulu Regional Institute of Occupational Health and Vesa Jormanainen, M.D., M.Sc. at the Health Division of the Defence Staff, have given valuable help in the statistical analysis of individual studies. Mr Kari Kelho at the Research Institute of Military Medicine and my son-in-law Jussi Lehmuskallio, M.Sc. have prepared the figures used in this thesis and in the original reports. Carrie Leger, M.B.A., has revised the language of the manuscript. My mother Martta is primarily responsible for my inner urge for academic achievement, and my beloved wife Paula has taken care that this flame has never died, in spite of years of slow progress due to several other activities, most of them together with her. I thank them and our children Sari, Meri-Tuuli, Tero and Siru for their loving support during the years of this study. Sari, M.A., graduated at Towson University, USA, has revised the English language of all individual reports. This study has been financially supported by the Scientific Committee of National Defence in Finland and by funds of the Finnish Dermatological Association and of Professor Kimmo K. Mustakallio, who over 30 years ago employed me to the dermatological staff at his clinic. Definitions

Emollients general name for non-medicated moisturizing and softening creams and ointments Creams emulsions of different lipids (mineral or vegetable oils, synthetic lipids, paraffin, mineral greases, waxes, etc.) and water Creams can be divided into oil-in-water, water-in-oil and ambiphilic emulsions Ointments waterless lipids or mixtures of lipids (i.e. mineral or vegetable oils, par- affins, mineral greases, etc.)

List of abbreviations

Aarea ah absolute humidity BMDP software for statistic evaluation of epidemiological data BMR basal metabolic rate CI confidence interval CIVD cold induced vasodilation, “Lewis waves” CNS central nervous system E energy, work (J) e.g. exempli gratia = for example, for instance et al. et alia = and others etc. etcetera = and so on, and the like, and other things FIM Finnish mark (~ 0.17 euros) i.a. inter alia = among others, among other things i.e. id est = that is, it is IR infra-red mmass (g, kg) OR odds ratio Ppower (W) PhN Pharmaca Nordica rh relative humidity 2 Rct thermal resistance (insulation) (m K/W) RR relative risk SPSS software for statistical evaluation of epidemiological data t time (s, min, h) T temperature (K or oC ) Ta ambient air temperature TEWL transepidermal water loss v air velocity (m/s) Wexternal work (W) WCI wind chill index (effect) (W/m2)

List of units oC centigrade, degree Celsius cm centimeter (0.01 m) g gram (0.001 kg) h hour (60 min, 3 600 sec) Jjoule K kelvin, degree Kelvin kg kilogram l liter m meter min minute (60 s) ml milliliter (0.001 l) mm millimeter (0.001 m) s second Wwatt

Conversion coefficients

Power 1 W = 1 J/s = 3.6 kJ/h Energy, work 1 J = 1 Ws Evaporation energy of 1 g of H20 at 30°C = 2.419 kJ = 0.672 Wh Kelvin is the same as a centigrade, but starts from –273.15°C (0°C = 273.15 K)

List of original publications

This thesis is based on the following original articles, which are referred to in the text by their Roman numerals: I Lehmuskallio E (1999) Cold protecting ointments and frostbite. A questionnaire study of 830 conscripts in Finland. Acta Derm Venereol 79: 67-70. II Lehmuskallio E, Lindholm H, Koskenvuo K, Sarna S, Friberg O & Viljanen A (1995) Frostbite on the face and ears: epidemiological study of risk factors in Finnish conscripts. BMJ 311: 1661-1663. III Lehmuskallio E & Anttonen H (1999) Thermophysical effects of ointments in cold: an experimental study with a skin model. Acta Derm Venereol 79: 33-36. IV Lehmuskallio E, Rintamäki H & Anttonen H (2000) Thermal effects of emollients on facial skin in the cold. Acta Derm Venereol; 80: 203-207.

Contents

Abstract Acknowledgements Definitions List of abbreviations List of units Conversion coefficients List of original publications 1 Introduction ...... 19 2 Review of the literature ...... 22 2.1 Thermophysiology of man in the cold ...... 22 2.1.1 Thermal homeostasis ...... 22 2.1.1.1 Perception of temperature ...... 23 2.1.1.2 Heat production ...... 23 2.1.1.3 Heat transfer ...... 24 2.1.1.4 Thermoregulation ...... 25 2.1.2 The skin in the cold ...... 27 2.1.2.1 Thermal insulation of the skin ...... 27 2.1.2.2 Circulation and vascular responses in the skin ...... 28 2.1.2.3 Kinetics of water in the skin ...... 30 2.1.2.4 Perspiration ...... 31 2.1.3 The head in the cold ...... 32 2.2 Adverse effects of the cold ...... 34 2.2.1 Disadvantageous effects of the cold ...... 34 2.2.2 Discomfort, cold sensation, cold pain and numbness ...... 35 2.2.3 Cold-related skin problems ...... 36 2.2.4 Local cold injuries ...... 37 2.2.4.1 Non-freezing cold injuries ...... 37 2.2.4.2 Freezing cold injuries ...... 38 2.2.4.3 Grading of frostbite ...... 40 2.2.4.4 Incidence and locations of frostbite ...... 41 2.2.4.5 Sequelae of frostbite ...... 44 2.3 Risk factors of frostbite ...... 45 2.3.1 Climatic factors ...... 46 2.3.2 Factors in contact freezing ...... 46 2.3.3 Short-acting individual factors ...... 46 2.3.4 Long-acting and permanent individual factors ...... 47 2.4 Emollients and moisturizers ...... 48 2.4.1 Types of emollients and moisturizers ...... 48 2.4.2 Occlusive and moisturizing effects ...... 49 2.4.3 Barrier effects ...... 50 2.4.4 Thermal effects ...... 50 2.4.5 Other effects ...... 51 3 Purpose of the study ...... 52 4 Material and methods ...... 53 4.1 Subjects and respondents ...... 53 4.2 Questionnaires ...... 55 4.3 Test emollients and their application ...... 55 4.4 Instrumentation and equipment ...... 57 4.5 Statistical analyses ...... 58 5 Results ...... 60 5.1 Use of cold protecting emollients in Finland ...... 60 5.1.1 Questionnaire study (I) ...... 60 5.1.2 Epidemiological study (II) ...... 62 5.2 Incidence of frostbite in the ears and face and the principal risk factors 63 5.2.1 Incidence of frostbite in the ears and face ...... 63 5.2.1.1 Questionnaire study (I) ...... 63 5.2.1.2 Epidemiological study (II) ...... 64 5.2.2 The principal risk factors of frostbite in the ears and face ...... 65 5.2.2.1 Questionnaire study (I) ...... 65 5.2.2.2 Epidemiological study (II) ...... 66 5.3 Thermophysical effects of emollients in the cold ...... 67 5.3.1 Thermal insulation (III) ...... 67 5.3.2 Occlusive thermal effects (III) ...... 67 5.4 The effects of emollients on skin temperature in acute cold exposure and on the subjective thermal skin sensation ...... 68 5.4.1 Questionnaire study (I) ...... 68 5.4.2 Experimental study with test subjects (IV) ...... 68 6 Discussion ...... 72 6.1 Winter xerosis of the skin ...... 72 6.2 Frostbite in the ears and face ...... 74 6.3 Prevention of cold injuries ...... 76 6.3.1 Preventive behaviour ...... 76 6.3.2 Clothing and outfit ...... 77 6.3.3 Cold protecting emollients ...... 78 6.3.4 Pharmaceutical preparations ...... 80 6.3.5 Cold adaptation ...... 80 6.4 Use of cold protecting emollients as a risk factor for frostbite of the ears and face ...... 81 6.4.1 Strength of association ...... 81 6.4.2 The effect of the quality of emollients and timing of the application . . . . 83 6.4.3 Mechanisms of the disadvantageous effect of emollients in the cold . . . . 84 7 Conclusions ...... 86 8 References ...... 88 1 Introduction

Finland’s geographical location between 60° and 70° northern latitude, with the polar circle demarcating Finnish Lapland to its northern side, gives our country a position as one of the most northern inhabited countries in the world. However, its climate in winter is only subarctic, due to the nearness of the Atlantic Ocean and especially of the Gulf Stream bringing warm water from the Gulf of Mexico and equatorial Atlantic along the northwestern coast of Scandinavia. There is a significant climatic difference between Finland´s southern and northern regions (Fig. 1). Earlier, during the agricultural and forestry phase of Finland’s history, outdoor duties formed a significant part of daily work also in wintertime. At that time, the inhabitants were used to protecting themselves against the risk of cold injuries. Industrialization, urbanization and mild winters especially in southern Finland, where the majority of population lives nowadays, have lead to more infrequent exposure to low temperature and thus to worsening of the coping skills. As a sign of it, exceptionally hard winter caused a high increase in the incidence of frostbite in 1976 (Koskenvuo et al. 1977), 1985 and 1987 (Lindholm et al. 1993). At the beginning of this project we did not find any national or otherwise comprehensive statistics on the incidence of frostbite. The biggest statistics focused on casualties in war (Orr & Fainer 1952, Hanson & Goldman 1969, Craig 1984), incidence of frostbite in peace-time army manoeuvres (Fraps 1985, Taylor 1992, Lindholm et al. 1993, Candler & Ivey 1997, Linné 2000) or severe, civilian cold injuries needing hospital treatment for surgery (Ervasti 1962, Kyösola 1974, Boswick et al. 1979, Foray 1992). The incidence of superficial frostbite, that forms the majority of everyday cold injuries could not be found in hospital or outpatient registers, as mild frostbite quite seldom causes medical visits. The preliminary results of a large questionnaire study Finriski ’97 (Hassi et al. 1998) on cold-related health problems in Finland were published recently. In this particular study 22% of 2624 adults living in various parts of Finland reported exposure to the cold almost every day (4% daily) in winter, men more often than women. Outdoor recreation was the primary activity causing cold exposure. 64% of respondents stated to have had cold induced harmful effects (frostbite, skin symptoms, cold pain, aching or numbness) in wintertime. 20

Fig. 1. Geographical location and climatic areas of Finland. (Number of winter days with a mean temperature below 0°C during 30 years, Finnish Meteorological Institute.)

Conscious avoidance of unnecessary cold exposure and other protective behavioural measures are most important in the prevention of cold injury in risky weather conditions. Warm clothing gives usually sufficient protection in short-lasting everyday cold exposure. Special outfit, a facemask, ”commando skicap” and protective goggles or faceguard with helmet are necessary only in extreme cold exposure, e.g. when driving a snowmobile. The use of a facemask may be unpleasant for seeing and breathing and the mask gets easily wet from respiratory humidity. Application of an emollient on the face before going outdoors has been a traditional way of topical cold protection in Finland, especially when children go out for recreation or other winter activities. The frequency of the use of protective emollients in the cold has not been studied in Finland or anywhere else, to our knowledge. Some Nordic experts (Ingvar Holmér, Sweden and Axel Wannag, Norway, personal communications 1998) in the field of cold research have assumed that the use of protecting emollients has, at least earlier, been a tradition also in Sweden and Norway. In some armies the use of emollients (sometimes medicated) also in other locations than the face has been recommended to troops entering manoeuvres in cold environment (Dick 1989). 21

A prospective epidemiological study on 2054 Finnish conscripts with mostly mild cold injuries (Lindholm et al. 1993) and their non-injured controls, showed already in the preliminary analysis after first years of its 13 years duration that the use of protective emollients formed an unexpected, considerable risk factor for frostbite in the face and ears. When this association of emollient use and local cold injury was first noticed, literature searches were done to look for studies concerning the effect and use of emollients in the cold. No reports on their cold protectivity were found. This lack of previous reports motivated the current series of studies to evaluate the effects of protecting emollients in prevention of local cold injury. These studies were performed mainly at the Department of Dermatology, University of Oulu and at Oulu Regional Institute of Occupational Health. Both institutes have arctic medicine and effects of the cold on the human health and performance as one of their main areas of interest. 2 Review of the literature

2.1 Thermophysiology of man in the cold

Excellent books and reviews on human thermophysiology in the cold have been written by e.g. Burton & Edholm 1955, Ilmarinen 1987, Pandolf et al. 1988, Granberg 1991, Parsons 1993 and Hassi et al. 1996. The basic facts have been summarized also in textbooks of medical physiology (Guyton 1991, Ganong 1997) and dermatology (Arndt et al. 1996, Champion et al 1998), the two latter with a special emphasis on dermatological aspects.

2.1.1 Thermal homeostasis

Man is principally a subtropical homeothermic animal maintaining the core temperature of the brain and other inner organs at a constant level of +37.0 ± 2°C in varying environments and physical activities. Irreversible pathologic changes happen if the core temperature exceeds +43°C or underlies +24—25°C. The core temperature has a regular circadian fluctuation of 0.5—0.7°C, being at its lowest in the early morning and highest in the evening. In fertile females there is also a monthly rhythm, as the ovulation causes a jump of 0.3—0.5°C in the core temperature that lasts to the next menstruation. The temperature in different regions of the body varies as follows: rectum > head > trunk > average skin > hands > feet. This regional variation is most obvious in the cold. Thermal homeostasis is maintained by keeping the heat production and thermal loss continuously in balance. Man is physiologically especially well adjusted to respond to warm surroundings but several of his responses and actions can protect him also in cold environment. 23 2.1.1.1 Perception of temperature

The thermoregulatory centre of a man is situated in hypothalamus. It responds to changes in its own temperature and to the information sent by peripheral warm-sensitive, cold-sensitive and pain receptors mainly on the surface of the man (free nerve endings are situated about 200 µm below the skin surface in dermis), but also deeper in subcutis, muscles and inner organs. Their role in different temperature levels is shown in Fig. 2 (Chen 1997). The hypothalamic centre is much more sensitive to a drop in core temperature than to a similar change in skin temperature (Elias & Jackson 1996). Cold receptors are more prevalent than warmth receptors in the skin. Their density is highest in the face and upper body. Clothing increases the importance of cold receptors in facial skin and upper respiratory membranes, as most of the skin surface elsewhere is usually covered. Thermal receptors are most active during a change of temperature. The primary thermal sensation fades away by rapid neural adaptation, as is experienced when a person goes into a hot tub or outdoors in cold weather.

Fig. 2. The function of thermal receptors in different temperature levels. Frequencies of discharge by cold-pain, cold, warmth and heat-pain nerve fibers. (Guyton 1991.)

Man feels comfortable when the skin temperature is 31—34oC with no sweating or sensation of draft (e.g. when resting naked in a still room at 27—29oC ambient temperature). Decrease in skin and tissue temperature is regarded as an uncomfortable perception that is accentuated by shivering and turns to cold pain and numbness along with further cooling. Factors that affect the cold sensation are dealt with in more detail in chapter 2.2.2.

2.1.1.2 Heat production

Heat production is based on basal metabolic rate (BMR, on average 75—110W in an adult) and physical (muscular) work. The liver and other abdominal organs produce 50% 24 of BMR, the brain and central nervous system 15—20%, the heart and circulatory system 10% and resting muscles about 20—25%. Factors affecting the metabolic rate are presented in Table 1.

Table 1. Factors affecting the metabolic rate in a human being.

Factors Muscular exertion Environmental and body temperature Height, weight and surface area Sex and age Emotional state Ingestion of food Circulatory levels of metabolic hormones (e.g. thyroxin, epinephrine, norepinephrine)

Heat production can be increased (but not decreased), even up to 15—20 times BMR, by autonomic and conscious muscular activity (Table 2). Increase in body temperature itself (e.g. fever) raises the metabolic rate by 10—14%/°C (Ganong 1997).

Table 2. The effect of muscular activity on the metabolic rate in an adult man.

Muscular activity Total metabolic rate Rest 75—110W (=BMR) Increase of the muscular tonus 150—200W Shivering 200—500W Medium heavy work 400W Heavy work 600—800W Short-time extreme sports or work performance above 2 000W

The proportion of muscular work from the total heat production increases from 20— 25% at rest to 75—90% in heavy physical activity. The majority of muscle energy expenditure goes to the production of heat at all levels of physical activity. In extreme cold exposure the survival may depend on individual physical capacity. The body may gain thermal energy also from external sources, e.g. by conduction from high ambient temperature and by radiation from sun or hot objects such as a hot stove.

2.1.1.3 Heat transfer

Heat transfer (thermal loss or gain) takes place by radiation, convection, conduction and evaporation (Table 3) (Parsons 1993, Elias & Jackson 1996, Ganong 1997). Urination and fecal excretion may add 1% to the total heat loss. 25

Table 3. The modes and proportions of human heat loss at rest (Ta 20°C, no clothing, no wind). (The proportions apply only for these special circumstances.)

Mode Proportion (%) Dry loss Infra-red (IR) radiation 60 Conduction to objects or material (e.g. air) 10—15 Convection Wet loss Evaporation of water from the skin 20—27 – Transepidermal water loss (TEWL) – Perspiration Respiratory evaporation 1—2

A great majority of the total heat loss in the cold occurs through the skin. Heat is first transferred from the deep tissues to the skin surface by circulation and tissue conductance. The quantitative proportions between the modes of thermal loss from the skin differ according to the temperature, humidity and flow of ambient air in the vicinity to the skin and to the rate of physical activity, behaviour and clothing of a man. IR-radiation occurs from warm items towards the cooler items. The dry conduction to the air causes usually only a minority of heat loss, and adequate insulation (usually by clothing) diminishes its share even more. Warming up of the air adjacent to the skin induces by itself a small convection as the lighter air rises upwards. Wind or body motion has a major influence on both the dry and wet heat losses. They hasten both evaporation and convection from the bare skin by blowing away the warm and moistened ”mini-climate” from its surface. “Insensible perspiration”, i.e. transepidermal water loss (TEWL, about 400—500 g/day in an adult man at room temperature) forms a daily energy loss of about 970—1 210 kJ when evaporating completely. The perspiration may increase the water loss to 3—4 kg/h for short periods. This causes a thermal loss of about 7 300—9 700 kJ per hour, if all the sweat excreted is vaporized. The loss of humidity in expiratory air (about 200 g/day at rest) forms a daily energy loss of about 480 kJ. In cold environment and in heavy work the role of warming and humidification of respiratory air may rise up to 20—25% of total thermal loss, as the respiratory volume grows from 8—12 l/min to 50—60 l/min, and while the clothing restricts the evaporation from the skin. Heat loss can be both increased and decreased by the body´s autonomic reactions and the person´s intentional behaviour (see 2.1.2 and 6.3). In special circumstances, e.g. when a person is immersed in cold water, the speed and distribution of thermal loss modes change totally (Keatinge 1998).

2.1.1.4 Thermoregulation

Man can adjust to almost all factors that influence the core or surface temperature: the production of thermal energy (only upwards from the BMR) and the heat loss (both up- 26 and downwards) (Table 4). The thermoregulatory centre in the preoptic area and anterior hypothalamus controls the autonomic responses of the body by using information sent by peripheral thermoreceptors. Cortical areas of the brain adjust the conscious behaviour. Man copes physiologically best with temperate (20—30°C) and warm climate. The autonomic adjustment of core temperature in the cold is regulated principally by diminishing the thermal loss, especially by vasculatory changes in the skin and extremities. The core temperature can also be maintained constant by seeking shelter and by wearing warm clothing or by intentionally increasing the physical activity in the cold.

Table 4. Thermoregulatory mechanisms in the cold.

Type of response Specific response Rapid autonomic responses Circulatory reflexes in the skin and periphery of extremities Vasoconstriction (+ Lewis periodic vasodilatory reflex in periphery) Opening of arteriovenous shunts Increase of blood pressure Piloerection Increase in muscular tension Shivering Slow autonomic adaptation to cold Psychological adaptation (development of cold tolerance) Adaptation of central nervous system Cold acclimatization Rapid and slow behavioural Avoidance of unnecessary cold exposure responses to cold Protection by posture Protection by clothing and special outfit Conscious adjustment of physical activity Cold habituation by learning, experience and tradition Curling up in a protective “fetal” position

Circulatory reflexes and piloerection will be presented in detail in chapter 2.1.2. Unconscious increase of muscular tension in the cold grows the metabolic production of thermal energy by 50—100% of BMR. This becomes distinctly higher (3—5 times the resting values) when rhythmical shivering begins, and merges into subconscious and conscious movements (foot stamping, dancing up and down, clapping arms and hands, etc.) if the cooling continues. The production of thermal energy by shivering returns back to only 1.5 times the resting value, if the cold exposure lasts for hours. In long-lasting exposure to the cold, there is first a psychological adaptation that takes a few days and consists of lowering the discomfort and pain perception of coldness. This is later followed by small physiological changes of basal metabolic rate, circulation, endocrine excretion, functions of the central nervous system, muscular tension and shivering capacity leading to better cold tolerance. This can be achieved also by repeated local cold exposures of e.g. hands. (Ilmarinen 1987.) Comparisons of arctic races and other people exposed to long-lasting or repeated cold exposures with subjects living in warm climate have given controversial results concerning the physiological mechanisms of the cold tolerance observed (e.g. Bittel 1992). The most important adjusting mechanisms affecting cold adaptation occur in central nervous system. 70% of the adaptive changes have occurred already within 10 days. The 27 maximal acclimatization takes 30 days, and the change in individual responses disappears again in the same time schedule when the subject returns to warm surroundings. Rapid and slow behavioural responses to the cold are dealt with in chapter 6.3 concerning the prevention of frostbite.

2.1.2 The skin in the cold

The skin is the largest organ of man. Its area is on average 1.74 m2 in an adult man and it weighs about 4—5 kg. Its microscopical structure is three-layered (epidermis, dermis and subcutis) and includes vasculature, neural elements and appendices. Blood circulation in skin is about 450 ml/min (260 ml/min m2 of body surface area) at room temperature and represents 8.5% of total blood flow. This is 10 times as much as is needed to supply the nutritive needs of the skin, and indicates that the primary function of skin circulation concerns thermal balance, not nutrition. Skin blood flow may increase as much as 10-fold in maximal vasodilatation and decrease to almost a standstill level (30 ml/min) in extreme vasoconstriction. (Elias & Jackson 1996.) As an organ forming the surface of the human body, the skin has an essential role in the perception of environment (as a peripheral sensor of touch, pain, temperature, etc.). The skin is also an important effector in maintaining thermal and fluid homeostasis. In thermoregulation the skin carries out a major part of autonomic thermophysiological responses as the body adjusts the insulatory capacity of the skin. Over 90% of the total heat loss (radiation, conduction, convection and evaporation) occurs through or on the surface of the skin in normal conditions. The skin has a very limited role in warmth production.

2.1.2.1 Thermal insulation of the skin

Human skin, especially subcutis with its fat layer, has a passive thermal insulative function similar to the subcutaneous fat of arctic animals. The fat conducts distinctly less heat than tissues with a higher water content (Elias & Jackson 1996). Cold induces also piloerection on the skin that can be seen as “goose bumps or pimples”, when the muscles of pilosebaceous units raise the sparse hairs of man into a more upright position. The thermal benefit is gained by enhanced air-trapping and thermal insulation in fur-coated animals. In the almost hairless humans, this response has no significant thermal effect, and is only a rudimentary reminiscent from our more hairy past. Piloerection may be provoked also by emotional reactions. In its heat dissipatory role, skin generally becomes warm when the body needs to dissipate excessive heat, and turns cold, when the body must preserve heat, becoming thus significantly more insulative. This active role in regulation of thermal insulation by the skin is managed specially by vascular responses. 28 2.1.2.2 Circulation and vascular responses in the skin

The arrangement of the blood vessels in the skin is ideally designed to either dissipate or conserve heat. The vasculature of the skin forms several capillary nets; a superficial subpapillary plexus in the upper dermis with capillary loops supplying each papilla with an ascending arterial and descending venous limb, and deeper plexuses in the reticular dermis and subcutis, connected via communicating vessels with each other (Fig. 4). In addition, there are particular plexuses around hair follicles and eccrine sweat glands in the border of dermis and subcutis.

Fig. 3. The arrangement of blood vessels in the skin. (Benfeldt 1999.)

Besides capillaries, there are other vascular connections between the arterial and venous network in the skin. The subcutaneous plexuses are connected with adjustable arteriovenous anastomoses (AVAs) with feeding arteries. AVAs are especially abundant in the pads and nail beds of toes and fingers, but they are also present elsewhere, e.g. in the ears and in the nose (Midttun & Sejrsen 1996, Daanen 1997). They have a relatively large diameter, on average 35 µm (20—70 µm) as compared to capillaries (5—10 µm) and are richly supplied with nerve fibres (Grant & Bland 1931). When they open, large amounts of blood can pass. AVAs play an important role in thermoregulation. Activation of symphatetic nerves leads to active vasoconstriction, and decrease in symphatetic activity leads to passive vasodilatation. In a moderately warm environment the AVAs are open. In a slightly cold environment, the AVAs are almost closed. When the core temperature is decreasing in the cold, it soon becomes evident that parts of the body are not truly homeothermic. The surface of man and his peripheral extremities behave as poikilothermic. Strong vasoconstriction of superficial and acral vasculature store body heat by preventing warm blood from losing its thermal energy to the environment. This response to the cold is adjusted by autonomic nervous system and short-circuits the blood from arterioles to veins directing it back to the “core”. When the ambient temperature diminishes from +27—29°C to +20—22°C the skin of a naked man starts to show regional differences in skin temperature that can vary widely from one region to another. Already at room temperature 20—30% of the body mass (skin, 29 subcutaneous tissue and peripheral parts of extremities) will adopt a new role of ”bark” or ”shell” with less importance for the health of human being (Fig. 4). In extremely cold conditions man is physiologically ready to reject even 50% of its total mass by freezing. Lowering of the skin temperature diminishes the temperature gradient between the skin and the environment, which further decreases heat loss.

Fig. 4. The growing of ”bark or shell” area of lowered skin temperature in naked body at decreasing ambient temperatures from left to right. (Modified from figures by Jessen 1984, Ilmarinen 1987 and Lloyd 1994.)

The blood circulation in skin may diminish to below 1/10 of its normal magnitude by vasoconstriction in the cold. The insulative capacity (thermal resistance) of the vasodilated skin can increase 5 times higher (from 0.04 up to 0.2 m2 K/W) in maximal vasoconstriction (Gordon 1974). A part of this change comes from the loss of tissue´s water content and relative increase of fat concentration in vasoconstricted skin. The majority of the vasoconstrictive response occurs in extremities. Blood supplied to the arms and legs by large arteries can return either by superficial veins near the skin surface or by deep companion veins adjacent to the main arteries. Under cold conditions, most of the venous return from the arms and legs is carried in the deep veins conserving thus thermal energy also by countercurrent heat exchange. A specific rhythmical cold-induced vasodilation (CIVD, “hunting reflex of Lewis” or “Lewis waves”) of the vasculature protects especially the peripheral extremities from rapid and permanent damage by enhancing the total blood flow (Lewis 1930, Daanen 1997). After the skin temperature in hands and feet underlies +10°C the AVAs lose their vasoconstriction from time to time and increase the circulating blood in fingers and toes warming them up temporarily by even 5—10°C, which is then followed by a new vasoconstriction and cooling wave when the vessel walls have regained their reactivity to regulatory mechanisms. Waves follow each other in rhythm that varies individually. CIVD is strong in normothermic subjects but weak, retarded or absent in hypothermia (Daanen et al. 1997) and hyperthermia (Daanen & Ducharme 1999). In 30

African-Americans and female gender CIVD is much weaker or totally absent (Hanson & Goldman 1969, Ilmarinen 1987) and in people living regularly in Arctic it may be especially strong, although the data of different studies is partially controversial. People who have been working with hands in cold conditions for a long time may have both weak vasoconstrictory and vasodilatory reflexes of peripheral tissues (Ilmarinen 1987).

2.1.2.3 Kinetics of water in the skin

Skin is a large water reservoir that actively participates in the regulation of the fluid balance in the organism. Water enters the skin via capillaries by ultrafiltration caused by the difference between the hydrostatic blood pressure and the pressure in the interstitium. There is a continuous passive diffusion of water across the different skin layers outwards leading to thermal loss by evaporation of the insensible transepidermal water loss (TEWL) from the skin surface. Naked adult resting in windless cabin at 27—29°C has an average TEWL of about 9 g/m2h (~400—500 g/day) (Lamke et al. 1977). The rate of TEWL is regulated mainly by the skin barrier in the stratum corneum, by the humidity, velocity and temperature of ambient air (see also chapter 6.1 concerning winter xerosis of the skin) and by clothing, which adjusts the “mini-climate” on the skin surface. TEWL varies depending on the skin region, the temperature of the skin, shown both in vitro (Mathias et al. 1981) and in vivo (Lamke & Wedin 1971, Grice et al. 1971), age and pathological conditions of the skin (Lotte et al. 1987), as well as on emotional state of the subject. Inter-individual variation and time-dependent circadian rhythm may also be significant (Yosipovitch et al. 1998, Denda & Tsuchiya 2000). The structure and chemical composition of the lamellar skin barrier in the intercellular space of corneal cell layers are quite well known, as well as the mechanism of its repair after injuries. Ceramides, cholesterol and free fatty acids form the major lipid components between water layers. (Feingold & Elias 2000.) Adverse environmental exposures (chemical or physical) may cause disturbance in barrier function, increase TEWL and cause clinical symptoms: irritation, desquamation, loss of corneal elasticity and eventually, surface cracks. Repeated irritations may initiate an inflammatory cycle and lead to eczema. For the health and normal function of the skin the grade of the humidity in the corneal layer is of major importance. The water content of the normal skin decreases from about 70% in the dermis towards the outmost layer of stratum corneum being 30% by weight in the lower and only 15% in the upper corneal layers of a healthy skin, both considerably less hydrated than the viable epidermis (Schaefer & Redelmaier 1996, Fig. 6). The superficial layers of stratum corneum are less hygroscopic and less capable of holding water than its deeper portions (Tagami et al. 1982). Water content of stratum corneum depends on both the degradation products of the keratin and on the components of sweat and sebum (so called natural moisturizing factor) as well as on the intercellular lipids, the essential components of the lamellar skin barrier (Imokawa et al. 1989). 31

Fig. 5. Water content of skin layers in healthy skin. (SC=stratum corneum, GR=str. granulosum, SP=str. spinosum, B=str. basale.) (Schaefer & Redelmeier 1996.)

2.1.2.4 Perspiration

Perspiration by 1.6—4 million eccrine sweat glands in the border between subcutis and dermis is excreted through the excretory coil openings on the surface of the stratum corneum. The number of eccrine sweat glands is the highest (600—700/cm2) on the palms and soles in order to guarantee a tight grasp. The relatively high density of eccrine sweat glands in the head, upper body and upper extremities makes this area responsible for the majority of evaporative thermal loss in physical exertion. Eccrine sweating is under both nervous (mediated principally by symphatetic nervous system with acetylcholine, and to a lesser extent, epinephrine) and non-nervous control. The latter is mediated by changes in plasma electrolyte concentrations. (Elias & Jackson 1996.) The rate of vaporization of perspiration is dependent on the vapor pressure gradient, the amount of sweat secreted and on the temperature and humidity of the ambient air. In dry atmosphere most of the sweat from the uncovered skin is evaporated. During 32 muscular exertion in hot environment, sweat secretion may reach values as high as 3—4 kg/h (1—1.5 kg/h for extended periods). When the heat production by physical activity shifts the core temperature upwards from the thermal balance, the body excretes sweat also in cold environment. As clothing in the cold usually covers the surface of the body, the high humidity of microclimate inside clothing decreases the quantity of evaporation.

2.1.3 The head in the cold

The head forms 5% of the body weight and 7% of the surface area (about 0.12 m2 in 70-kg adult man). It uses 20% of the total body oxygen consumption and 15% of the circulating blood volume in resting man. Brain forms 40% of the mass of the head, and its thermal production (20 W) is quite constant and continuous. Additional thermal energy to the head comes from other organs of the body via blood vessels. The rate of circulation in the head depends only a little on the grade of physical performance. A stable temperature between 35.5—41.0°C is necessary for the undisturbed function of the brain. (Paso et al 1989.) The head differs from the extremities and trunk by having a very constant skin temperature at different ambient temperatures, even in the cold. This has led to the conclusion that the head (with the exception of ears) takes little part in the body´s vasoconstrictory reflexes in mild hypothermia (Burton 1934, Hertzman & Roth 1942, Froese & Burton 1957, Steegmann 1979). Only minimal vasoconstrictive changes were found in temperature alterations from normothermia (room temperature) towards mild hypothermia (bath in 21°C water). Facial evaporative heat loss rate did not change significantly between normo- and hypothermia, either (Rasch & Cabanac 1993). Low ambient temperature (+10°C) had no effect on the head tissue insulation of 0.06 m2K/W even though the finger tissue insulation increased simultaneously six-fold (Froese & Burton 1957). In hyperthermia (warm bath at 41°C), however, the blood flow in the facial skin increased 3 to 9 fold by active vasodilatation with only a minor change in skin temperature (due to increased evaporative thermal loss). This sequence of findings was explained by a theory that vasoconstriction seems to be the general vasomotor state in the facial skin already during normothermia (Rasch & Cabanac 1993), and therefore the vasoconstrictive response in the cold was almost absent. For this behaviour, the thermal resistance of head tissues is very constant in different ambient temperatures below room temperature. The relative lack of vasoconstrictive response in the cold keeps the facial skin temperature quite high compared with other regions of the body and leads to an increasing proportion of heat loss from the head as the ambient temperature declines (Ilmarinen 1987). The dry heat loss from the head is constantly about 45 W/m2 when the ambient temperature is between +20°C and –30°C. Bare-headed man loses through his head 5% from total body heat loss in thermal comfort, but a much higher proportion, up to 80% in heavy physical work in the cold, when the body elsewhere is covered by warm clothing and evaporative heat loss occurs mainly from the head and in respiration (Elias & Jackson 1996). The sweating capacity of the 33 head (ml/ surface area) differs regionally in the following order: forehead > cheeks > neck > chin corresponding with the density of sweat glands (Paso et al. 1989). Also the skin of the head has AVAs, most of them in the tip of the nose, as well as in the ear lobes (Bergersen 1993). The blood flow rate in the nose and ear lobes is almost equal to that in the finger pulp, and is almost twice as high as that in the toes. On the forehead there are only very few AVAs (Midttun & Sejrsen 1996). CIVD in the head was found to be most frequent in nose and cheeks, but its magnitude was small (only 1—2°C change in temperature) compared with toes and fingers (Steegmann 1979). Also ears participate in CIVD (Lewis 1930). The average skin temperature of the head is about 32—34°C at room temperature in whole body thermal balance. There are, however, quite distinctive differences of skin temperature between regions of the head in the cold when no garments are protecting it. The anatomy of superficial vasculature in the head affects the skin temperature significantly (Edwards & Burton 1960, Fig. 6). In ambient temperature of 0oC the increasing order of skin temperature in different locations of the uncovered head is as follows: rims of auricles < auricles < nose < chin < cheeks < forehead < neck < scalp (Edwards & Burton 1960, Steegmann 1979, Fig. 7). The coldest regions need most protection against adverse effects of the cold.

Fig. 6. The regional anatomy of superficial vasculature in the head. (Corel 6 software, 1995 by Corel Corp., checked with an anatomical picture in textbook by Hafferl 1957.) 34

Fig. 7. The coldest areas of the uncovered head at 0°C ambient temperature. (Modified from Edwards & Burton 1960 and Steegman 1979.)

Since the heat loss is dependent on the temperature gradient between the skin and the ambient air, the maximal heat loss will take place from the warmest areas, scalp, neck and forehead, if they are unprotected. These regions are, however, often hairy or covered and supplied with abundant circulation and therefore not prone to freeze in the cold. The hair gives some insulative protection to a hatless head warming up the scalp depending on the quantity, thickness and air content of hair. Also beard and moustache produce some insulation. Under the chin and in the neck the skin folds warm each other. Ears, nose and chin behave somewhat like acral parts of extremities with higher exposure to the cold and lower protection (larger skin area/ weight of tissue than elsewhere in the head) towards the ambient temperature. When a person is clothed, the collar and scarf protect the neck and somewhat also the chin and lower part of the earlobes. The scalp and auricles are often, but not always, protected with a hat or particular ear flaps. Skin blood flow in the face decreases with increasing age in different groups of male Eskimos, Finnish Skolt Lapps, Norwegian lumberjacks and indoor workers. The females seemed to have a lower facial skin circulation. (Wika 1981.)

2.2 Adverse effects of the cold

2.2.1 Disadvantageous effects of the cold

In the preliminary results of a large questionnaire study Finriski ’97 (Hassi et al. 1998) on cold-related health problems in Finland, 22% of 2624 adults living in various parts of Finland reported exposure to the cold almost every day (4% daily) in winter, men more often than women. People living in northern areas were more often exposed to the cold than those in southern regions were. Outdoor recreation was the primary activity causing cold exposure (in 88% of respondents), followed by going to and coming from work 35

(49%) and working outdoors (29%). Men had significantly more often than women did a job that exposed them to the cold. 64% of respondents stated to have had cold-induced harmful effects (frostbite, skin symptoms, cold pain, aching or numbness) in wintertime, 19% of them often. There was no significant difference between sexes. Women experienced the cold, however, more often as harmful on cheeks and nose, as men had more often discomfort from the cold in the auricles (Hassi et al. 1998). The adverse effects of the cold are summarized in Table 5.

Table 5. Adverse effects of the cold.

Signs and symptoms Thermal discomfort Cold sensation and cold pain Functional deterioration in tactile sensation (numbness, cold induced hyper- and paresthesia) other cognitive perceptions motor function (e.g. hand dexterity) physical performance and working capacity psychological performance (concentration, memory, innovativity) Initiation and aggravation of symptoms associated with prevalent systemic diseases including increased mortality related to cold stress asthma, angina pectoris, rheumatoid arthritis, Raynaud´s syndrome, etc. Cold related skin problems winter xerosis dryness and chapping of the face and lips hand dermatitis cold urticaria other (acrocyanosis, erythrocyanosis, etc.) Local cold injuries and their sequelae non-freezing injuries (perniosis=chilblains, immersion and trench foot) freezing injuries (frostbite) Hypothermia

2.2.2 Discomfort, cold sensation, cold pain and numbness

There are numerous investigations concerning the sensation of the cold by man (Franz & Iggo 1968, Crawshaw et al. 1975, Hensel 1981, Kreh et al. 1984, Enander 1986, Kaufman et al. 1987, Rintamäki & Hassi 1989, Havenith et al. 1992, Parsons 1993, Beise et al. 1998, Chen & Holmér 1998). Humans have no innate sense of temperature. Their response depends not only on physical (climatic) conditions and physiological state but also on individual factors, such as past experience, how subjects perceive the environment, how weather conditions differ from the norm (Kaufman et al. 1987), and 36 which region of the body is exposed to the cold (Stevens & Choo 1998). Discrepancies between physical data and subjective cold sensation are common. After repeated cold exposures, reduction in cold sensation, discomfort and pain have been found in several studies (e.g. Enander 1986), as well as diminishing of autonomic vascular responses to the cold. Several variables have been shown to influence the perception of the cold: the actual temperature (of ambient air or an object in contact with the skin), the material of the cold object, the skin region, area and pressure of the cold contact, the presence of skin protection, the speed of the temperature change, the core and skin temperatures of man, the psychological attitude and vigour of the test person, etc. The human body is unreliable as a temperature measuring instrument. (Parsons 1993.) Stevens and Choo 1998 analysed detection thresholds for cooling in 13 body regions in 60 adults. They found that the thermal sensitivity varied 100-fold over body surface, the extremities being least sensitive. The face (forehead) behaved differently from the other parts of the body by showing a much greater sensitivity to the cold by both autonomic response and cold sensation than other areas when exposed to local cooling (Crawshaw et al. 1975, Stevens & Choo 1998). The former authors speculated that the high sensitivity of the face to thermal stimuli may have evolved at a time of man´s past when the face was thinly furred compared with the other body areas and functioned, therefore, as the thermally responsive skin region of otherwise well insulated primitive mammals. With the use of clothing, man has recreated these conditions, re-establishing the relative importance of the face as a sensor in thermoregulation. A man feels his hands and feet to be cool at below 29°C skin temperature and cold at 25°C. This is sensed as discomfort and leads to cold pain at 14—18°C of skin temperature. Both the threshold and the quality of cold pain vary in man, the quality being frequently described as dull, aching or pulling. Nerve conduction velocity diminishes at below 25°C of skin temperature in both motor and sensory nerves. The mean blocking temperature of non-myelinated axons, +2.7°C, was significantly lower than that of myelinated axons, +7.2°C (Franz & Iggo 1968). Vasomotor and motor functions of nerves were blocked well before the sensation of touch. The approximate critical limit of finger skin temperature was +8 to +12°C for tactile sensitivity and higher for manual dexterity (Chen et al. 1994). Pain was not sensed any more, when facial skin temperature was below +8°C. When sensory nerves were completely blocked, the cold receptors did not warn of frostbite risk, anymore. However, a sharp freezing pain was sensed when contact frostbite caused a rapid crystallization of water in the supercooled superficial skin at –5 to –12°C in otherwise normothermic test subjects. (Wilson & Goldman 1970, Beise et al. 1998.)

2.2.3 Cold-related skin problems

Cold-related skin problems are usually divided into cold injuries (caused by physiological reactions to the cold) and diseases of abnormal sensitivity to cold. The former group includes frostnip and frostbite, conditions, which may affect anyone if the cold exposure is strong enough. These local cold injuries are presented in chapter 2.2.4. The latter group 37 consists of diseases like perniosis, cold urticaria, acrocyanosis, Raynaud’s phenomenon, cryoglobulinemia, etc., with a prerequisite of abnormal susceptibility to the cold. (Dover et al. 1996, Dowd 1998.) As these dermatoses of individual cold sensitivity are not in the scope of this report, most of them are not presented here. Non-freezing cold injuries are, however, described in chapter 2.2.4. The nature of winter xerosis of the skin is somewhat obscure. Chapping of the skin and lips is usually assessed as a consequence of air dryness during the cold season, but the possible role of the cold in its pathomechanism remains to be elucidated. This is discussed in chapter 6.1.

2.2.4 Local cold injuries

Several reviews on cold injuries have been published (e.g. Orr & Fainer 1952, Washburn 1962, Hanson & Goldman 1969, Koskenvuo 1976, Höflin 1979, Vaughn 1980, Steinman 1987, Hamlet 1987 and 1998, Fritz & Perrin 1989, Friberg 1993, Kappes et al. 1993, Mills et al. 1993, O´Malley et al. 1993, Tervahauta et al. 1993, Pulla et al. 1994, Dover et al. 1996, Friberg 1996, Granberg 1996, Hassi et al 1996, Koskenvuo et al. 1996, Kanzenbach & Dexter 1999, Berg et al. 1999, Hassi & Mäkinen 2000). Among U.S. Army and Army Air Force troops, there were over 90 000 cold injuries requiring medical treatment during World War II, and another 10 000 during the Korean war, accounting for 10% of all casualties experienced during these conflicts (U.S. Army Research Institute of Environmental Medicine 1992). Lesser degrees of cold cause pronounced changes in normal physiology. All enzymes and vital processes are depressed when the tissue temperature decreases. A strong cooling of superficial and acral tissues leads to a threat to the maintenance of cells and functions. Skin temperature may decrease to low figures, even under the freezing point of water leading to damage to the tissues. There are specific non-freezing, moist-cool injuries starting at temperatures even above 15°C. At lower tissue temperatures (below 0°C) the freezing of the skin liquids may start.

2.2.4.1 Non-freezing cold injuries

Perniosis consists of localized, erythematous, swollen, tender and itching inflammatory lesions (chilblains) of the subcutaneous tissue and dermis. Chilblains present often in acral extremities as an abnormal reaction to non-freezing cold temperature (at or below 16°C) in combination with a high humidity. Chilblains tend to start in the early part of the winter in children and women with acrocyanosis and/or erythrocyanosis. They occur usually in a bilateral, symmetrical distribution on the fingers and toes, heels, lower legs, thighs, nose and ears. Individual lesions are located between the joints and their course is typically self-limiting in about three weeks (perniosis acuta). However, chronic cases (perniosis chronica) are sometimes seen after repeated exposures to the cold, especially in the presence of arterial or systemic disease. 38

In the pathogenesis of perniosis, a persistent or repeated cold-induced vasoconstriction of large cutaneous arterioles and persistent dilatation of the smaller, more superficial vessels together with localized histamine release occur in persons often genetically susceptible to this disease. As the lesion progresses, pain and tenderness replace the itching, and the situation sometimes leads to blisters or ulcerations. Perniosis has been common in the temperate, humid climate of northwestern Europe but in northern Europe the higher standard of home heating has made it quite rare. Recurrence each winter for a few years is common but complete recovery is usual. Prophylaxis with warm housing and adequate clothing is more important than different modalities of treatment. (Dover et al. 1996, Dowd 1998.) Immersion foot (synonym trench foot) develops also already at non-freezing temperature (mostly at or below 10°C) after longstanding (>12 hours, usually several days) coldness, wind and damp, assisted by immobility, dependency on the limbs and constrictive clothing or footwear (Francis 1984, Hamlet 1998). The distribution of findings is usually symmetrical and limited by the level of original submersion or occlusion. In pre-hyperaemic stage the tissue is cold, blue and numb. On rewarming, a phase of hyperaemia may last up to three months; there is tingling pain, swelling, blisters, sometimes ulcers and superficial gangrene. The post-hyperaemic phase can last many years and vasoneuropathy produces post-injury sequelae, such as Raynaud´s syndrome, cold sensitivity, hypo- or hyperhidrosis, dry, scaly skin, paresthesia, leg spasms and persistent pain or other debilitating local symptoms, such as chronic ulceration. (Dover et al. 1996, Dowd 1998, Hamlet 1998.) This is a circulatory and neuralgic injury. Absorption and retention of water results in swelling, thickening and fragmentation of corneal layer. For many years it was accepted that immersion foot and trench foot were the result of ischemia and anoxia caused by vasospasm and stasis of venous flow. There is now a considerable body of evidence showing that the cold itself may have a damaging effect on the cells already at below 22—24°C tissue temperature (Dinep 1975). Severe endothelial damage in true capillaries and venous vessels has been shown in non-freezing cold injuries of test animals (Endrich et al. 1990).

2.2.4.2 Freezing cold injuries

The data on freezing temperature of skin and other tissues differs in many investigations. Some of the discrepancies are based on different methodology, some on measuring the temperature either on the skin surface or deeper in the tissue without specifying the site. Keatinge & Cannon 1960 found that the freezing temperature of skin is about –0.6°C. However, the actual freezing occurs mostly at lower tissue temperature between –5 and – 10°C or even colder (Danielsson 1996). This phenomenon is called supercooling (Wilson & Goldman 1970, Wilson et al. 1976). The freezing phenomenon (crystallization) usually stops the further cooling of the tissue and causes a measurable temporary jump from the supercooling temperature (e.g. Beise et al. 1998). 39

There was a linear relationship between the frequency of finger frostbite and its surface temperature. As the skin temperature of a finger fell from –4.8 to –7.8°C, the risk of frostbite increased from 5% to 95% (Danielsson 1996). Increasing the water concentration in stratum corneum led to a warmer freezing point both in vitro (Inoue et al. 1986) and in vivo (Keatinge & Cannon 1960, Molnar et al. 1973). The moistened skin supercooled to the average temperature of only –5.4°C (–3.3 — 6.9°C) before the crystallization started, when the dry skin could supercool to the average temperature of –10.9°C (–8.8 — 12.0°C) (Molnar et al. 1973). In an in vitro study using differential scanning calorimetry for evaluation of the hydration state in corneal layer, stratum corneum sheets (not the entire skin) with various levels of water content were cooled to –40°C and then heated to +20°C at a rate of 0.6°C/ min. The melting of the ice in the stratum corneum sheet was measured to occur at between –6°C and –17°C. Water binding amino acids and lipids formed the reason for the low melting temperature. If these components were removed, melting occurred at 0°C. Exogenic substitution of these components returned the capacity to bind water to the skin. (Imokawa et al. 1991.) Several reports have investigated or reviewed the pathomechanism of freezing cold injuries (e.g. Dinep 1975, Waris & Kyösola 1982, Marzella et al. 1989, Endrich et al. 1990, Mills et al. 1993, Junila et al. 1999, Berg et al. 1999). Two separate types of mechanisms can be differentiated. The rapid freezing process is activated usually by conductive heat loss in the development of contact frostbite, e.g. when touching, intentionally or accidentally, a cold object (e.g. metal), liquid (e.g. gasoline) or gas (e.g. evaporating liquid nitrogen) with bare skin. There is often neither significant general cold exposure nor enough time even for the rapid autonomic response of the vasculature, and the body temperature is usually quite normal. The local skin cools abruptly to a freezing temperature, the intracellular fluid of skin cells crystallizes and the cells die immediately. This mechanism of causing tissue necrosis by local contact freezing is utilized in medical cryotherapy of certain skin problems, e.g. warts and various tumours. In slow freezing mechanism, there is time for the rapid autonomic cold responses. The core temperature may be normal or decreased, but the skin and tissue temperatures on the site of the cold exposure and its surroundings are lowered. The vasculature shows usually maximal vasoconstriction. The cold causes extracellular crystallization of water that leads to increased concentration of salts in the remaining, non-crystallized fluid. The enhanced extracellular osmolarity leads to diffusion of intracellular liquid out of the cells into the extracellular compartment and to dehydration of cells. In addition, there are simultaneous endothelial changes, extravasation and hyperviscosity of blood and microvascular clotting leading to cessation of capillary flow, long-acting hypoxia and damage to the affected tissues. Cellular membranes become injured because of both local vascular damage and loss of liquid balance, and the situation leads to a slow death of cells. During thawing and reperfusion of frozen tissue, inflammatory mediators (vasodilative, histamine-like substances from degranulating mast cells, bradykinin, leukotrienes, metabolites of arachidonic acid and prostaglandins) and thrombotic agents (e.g. thromboxans) are freed. These result in inflammatory and immune responses that modulate vascular contraction and permeability, to platelet aggregation and recruitment and activation of leukocytes. There is reason to suspect that oxygen free-radical injury is also involved in the pathomechanism of frostbite. Cold shock (cooling at 4°C for 60 min) 40 induced the synthesis of stress proteins in human keratinocytes in situ and in cell cultures during the recovery period (Holland et al. 1993). Stress proteins could play a protective role if the epidermis was again presented with a low temperature challenge. During initial post-frostbite reactive vasodilatation, a lot of intravascular liquid diffused through the damaged endothelium into the extravascular compartment leading to microcirculatory problems and edema that was maximal during 2—6 hours after thawing (Mills et al 1993). Tromboxan and prostaglandins mediated paradoxical vasospasm that occurs in the borderline of the frozen area. The catecholamines released from degenerating adrenergic nerves increased the spasticity of the blood vessels during the critical 24-h after the injury (Waris & Kyösola 1982).

2.2.4.3 Grading of frostbite

When the frostbite is observed in the cold, the area of the injury can be seen and its depth palpated, both giving hints of the severity of injury, together with the history of its development. The exact grading of frostbite is, however, not possible when the injured is still in the cold. Only after thawing for several hours grades II and I may be separated from each other. The severity, extension and depth of grade III and IV tissue damage will be apparent after several days or even weeks (Orr & Fainer 1952, Washburn 1962). Grade I frostbite is sensed first in the cold as local tingling or pain that fades away and turns to numbness in the affected area. This phase looks like a whitish skin spot when compared with the normal-coloured surroundings where dermal circulation is still in function. After the numbness has begun, the injured rarely senses subjectively the further development of the frostbite. When people challenge the cold exposure in a group, it is important to observe one another´s face and ears from time to time to notice the early signs of danger. After returning to warm conditions, the affected area of grade I frostbite gets back its sense of touch and pain: it tingles, aches, turns reddish by reactive hyperaemia and inflammation and swells up somewhat in hours. The injured area gets back its earlier appearance in some days or a week, sometimes in conjunction with some chapping and desquamation of the skin. On rewarming of the frostbite, it is possible that no clinical signs of cold injury are seen after the tingling and reactive hyperemia. The lack of skin signs does not mean that the injury did not leave sequalae (Riddell 1984). Grade II frostbite affects the skin a little deeper causing similar symptoms and signs in the cold as grade I: local blanching with numbness after a period of tingling and pain. The affected area may feel somewhat harder than in grade I. After returning to warm surroundings, there is vesicle or bullous formation in 2—20 hours, often surrounded by a reddish, oedematous area of grade I frostbite. Sometimes the liquid in bullae takes a bloody colour as a sign of a deeper damage to the vasculature. The recovery takes usually about two weeks. Thick layers of skin (the roof of the bullae) often peel from the affected area. Some crusting may also occur. The new growth of pink skin is often very sensitive to touch during the recovery. Grade III deep frostbite causes a necrosis of the dermis or deeper tissues, sometimes including ligaments, tendons, muscles, nerves and bones. In cold, this damage to the deep 41 tissues cannot be seen with certainty. The skin colour is white or mottled and the consistency is very hard. The seriousness of the damage can be anticipated by the solidity of tissue, by the area affected and by the history of severe cold exposure. In warm surroundings, grade III injury causes a dry or moistened gangraena especially in peripheral parts of extremities and may need surgical operation after weeks of demarcation. Many authors use grade IV to specify very deep frostbite from grade III frostbite damaging (by definition) only the skin layers. For taxonomy, superficial frostbite includes grades I and II, and deep frostbite grades III and IV.

2.2.4.4 Incidence and locations of frostbite

The majority of epidemiological information concerning the incidence and locations of frostbite has been statistics of casualties in different armies from ancient wars to more recent conflicts. Cold injuries have conducted the destiny of many armies when the soldiers, often far from home, were unprepared for the harshness of unfamiliar climatic conditions (Orr & Fainer 1952, Hanson & Goldman 1969, Craig 1984, Paton 2000). Several papers handle with hospitalized cases of deep frostbite needing amputation (Korhonen 1940, Ervasti 1962, Kyösola 1974, Boswick et al. 1979, Nieminen & Suominen 1987). Cold injuries in special cold exposures: mountain climbing (Foray 1992), Antarctic or Arctic expeditions (Schissel et al. 1998, Cattermole 1999), peace-time army field manoeuvres (Taylor et al. 1989, Rosén et al. 1991, Taylor 1992, Lindholm et al. 1993, Candler & Ivey 1997) and reindeer herding (Ervasti et al. 1991) have also been presented in epidemiological reports. The information concerning frostbite of every-day civilian life has been scanty. However, in recent years especially a group at Oulu Regional Institute of Occupational Health has performed several extensive questionnaire studies in Finland. In a population study Finriski ´97, consisting of a randomized adult sample from a population register representing five different geographical areas of Finland, there was a special subgroup including 2 624 persons of both sexes (25—74 years old) for responding to questions concerning cold exposure, incidence of cold injuries and clothing in winter. Although so far only the basic numeric tables (without analysis of associations) have been published (Hassi et al. 1998) it was possible to calculate some incidence figures from this material. The incidence of cold-induced problems in this study during the last five years in different locations is presented in Table 6. 42

Table 6. The incidence of cold-induced problems (distinct adverse effect of the cold, i.e. frostbite, skin symptoms, cold pain, aching or numbness occurring after cold exposure) in different regions of the body. (Self reported five-year incidence of 2 624 adult respondents in Finriski ´97 study (Hassi et al. 1998).)

Location 5-year incidence (%) Upper extremities Fingers 4 Palms 16 Arms 6 Lower extremities Toes 46 Feet 23 Thighs 14 x Knees 12 x Ankles 9 Calves 6 Head Ears 25 xx Cheeks 22 x Nose 22 x Chin 14 x significant female preponderance, xx significant male preponderance

There are very few studies assessing the lifetime incidence of frostbite. In Finriski ’97 study, the lifetime cumulative incidence of grade II or deeper frostbite in any location was 11% on average, with a distinct difference between genders (14% in men, 7% in women) (Hassi et al. 1998). Somewhat higher cumulative incidence (22%) of grade II—IV frostbite was found among Finnish maritime personnel (Juopperi et al. 2000). In a questionary on 5 839 Finnish male conscripts, their lifetime incidence of frostbite at the average age of 20 years was estimated to be 44% (grade I 40%, more severe cases 12%) (Hassi et al. 1999). The geographical variation of lifetime cumulative frostbite incidence in this population was shown to follow climatic regions (41% among conscripts in the southern thermal zone, 43% in the middle zone and 61% in the coldest northern zone) (Juopperi et al. 1999). Among major epidemiological studies both on civilians and military personnel various numbers have been reported concerning the annual incidence of frostbite in any location. The lowest annual frostbite figures (0.4—2.3% of the examined material) were reported among Finnish conscripts (Lindholm et al. 1993, Ervasti et al. 1999) and US soldiers in Alaska (Sumner et al. 1974, Candler & Ivey 1997). Intermediate annual incidences (6.6— 10%) were found during British Antarctic Survey 1986—95 (Cattermole 1999) and among Finnish civilian adults (Hassi et al. 1998). Much higher annual incidences (13— 22% of the examined material) were observed among Finnish maritime personnel and reindeer herders, both exposed to severe cold in their professions (Ervasti et al. 1991, Juopperi et al. 2000). 43

Table 7 shows the proportion of frostbite in the head (ears and face) of all frostbite injuries in major epidemiological studies.

Table 7. Proportion of frostbite located in the head (ears or face) of all cold injuries in major epidemiological studies. (n = number of frostbite patients.)

Study Year n % Location Population Range (average) War-time military 0.5—6 casualties (3) Korhonen 1940 142 1.4 ears Finnish soldiers in winter war 1939—40 Orr & Fainer 1952 1 880 0.5 ears, face, US soldiers in Korean war knees 1950—51 Nechaev 2000 ~ 4 000 6 face and ears Russian soldiers in winter war 1939—40 Civilians needing 0—14 hospital care (5) Kyösola 1974 110 0 Helsinki, Finland Boswick Jr. et al. 1979 843 14 ears Chicago, USA Nieminen & 1987 33 6 ears Turku, Finland Suominen Urschel 1990 79 4 ears Edmonton, Canada Conway et al. 1998 327 4 face Alaska, USA Military personnel in 5—47 peace-time training (23) Sumner et al. 1974 292 28 ears US soldiers in Alaska 12.7 nose 6.5 other, incl. face Fraps 1985 858 7.5 ears German soldiers 2.5 face Taylor et al. 1989 74 14 face and ears US soldiers in Germany Rosén et al. 1991 49 6 ears Norwegian conscripts Taylor 1992 214 5 face and ears US soldiers in Germany Lindholm et al. 1993 2 054 44 face and ears Finnish conscripts Candler & Ivey 1997 272 23.9 ears US soldiers in Alaska 15.2 nose 8.1 other, incl. face Linné 2000 180 14 face Swedish conscripts Civilians in special cold 17—80 exposure (54) Ervasti et al. 1991 453 72 face and ears Finnish reindeer herders 388 80.4 face and ears – (during snowmobile riding) 131 52.7 – (during other tasks) Foray 1992 1 261 17 face and ears mountain climbers and skiers in the Alps Virokannas & Ant- 1993 443 72 face and ears Finnish reindeer herders tonen Cattermole 1999 58 47 face and ears British Antarctic Survey

The incidence of cold injury and distribution of frostbite grades and locations has depended significantly on the selection of patient material. It was evident that minor frostnip and superficial frostbite were underreported in the war reports, as these cold injuries were felt to be a trivial matter. In a majority of war statistics, at very cold ambient 44 temperature and in long-standing cold exposure, frostbite of the extremities has been preponderant over other locations, cold injuries of toes and feet occurring more often than frostbite in the fingers and hands. The superficial cold injuries were (self)reported in remarkable numbers only in questionnaire studies. In studies on reindeer herders in Finland, there was an exceptionally high proportion of facial frostbite (Ervasti et al. 1991, Virokannas & Anttonen 1993).

2.2.4.5 Sequelae of frostbite

Even a superficial frostbite may cause prolonged or permanent sequelae (Riddell 1984, Ervasti et al. 1993 a and b, Huh et al. 1996), which was not commonly understood in the past. The sequelae are attributed to a damage to the blood vessels and sympathetic nerves. Even grade I frostbite leaves usually a long lasting hypersensitive vasoconstrictory response to the cold in the affected area. This causes a significantly elevated risk for new cold injuries. Deep frostbite leads usually to a permanent handicap, scarring, mutilation, and signs of amputation or functional and cosmetic deficiencies with subjective complaints, especially in the extremities (Blair et al. 1957, Ervasti 1962, Taylor et al. 1989, Rosen et al. 1991, Ervasti et al. 1993 a and b, Ervasti et al. 2000). Blair et al. 1957, Hassi & Mäkinen 2000 have reviewed sequelae of local cold injuries and they are summarized in Table 8.

Table 8. Sequelae of frostbite.

Tissue Signs and symptoms Nerves, brain Decreased tactile sense (hypaesthesia and numbness) Hyperaesthesia Chronic pain Impairment of neurological cognitive and motor functions leading to functional disa- bility of especially hands Increased perspiration Blood vessels Cold sensitivity (hypersensitive vasoconstrictory response) leading to cold feet and hands plus increased risk of recurrence of frostbite Skin Abnormal skin colour changes Hyperhidrosis Skin atrophy and scarring Abnormal nails Teleangiectasia Tissue loss Squamous cell carcinoma in frostbite scar Muscles, bones, joints Growth disturbance after premature closing of epiphyseal lines in children Muscular atrophy Arthralgia Mutilation of terminal phalanxes Articular and juxta-articular punched-out defects in x-ray Osteoarthritic and arthrotic changes in joints Osteoporosis 45 2.3 Risk factors of frostbite

Predisposing and risk factors of frostbite have been reviewed by many authors (e.g. Orr & Fainer 1952, Sumner et al. 1974, Vaughn 1980, Urschel 1990, Rosén et al. 1991, Kappes et al. 1993, Lindholm et al. 1993, Conway et al. 1998, Hassi & Mäkinen 2000, Rintamäki 2000) and they are summarized in Table 9.

Table 9. Predisposing and risk factors of frostbite. Type of risk factors Specification of risk factors Climatic factors Low environmental temperature Convection (wind-chill) Duration of the cold exposure Humidity of the ambient air Rain, snow or other source of environmental moisture Immersion in cold water Hypoxia at high altitude (in mountain climbing, air crewmen)

Contact with cold objects or material Temperature and thermal conductivity of the cold object or material Duration, pressure and area of cold contact Individual factors Short-acting Fatique, exhaustion Anxiety, battle stress Immobilization and inactivity Wet or/and constricting clothing and boots Hypohydration, insufficient nutrition Hypothermia Smoking, tobacco chewing Alcohol or other intoxicating agents Intercurrent disease and medication Vasoconstrictive drugs Inappropriate clothing and behaviour Long-acting or permanent Previous cold injuries Hypersensitivity of hands and feet to cold Profusely sweating hands and feet Cold-induced white finger (Raynaud) syndrome Earlier exposure of hands to vibration Smoking habit Poor physical fitness Psychiatric disorders and ignorance Chronic cardiovascular and other debilitating somatic diseases Regular medication African-American or African race Advanced age, newborns, female gender, low body fat Homelessness, malnutrition, alcoholism, drug addiction Insufficient experience and training in the cold Unspecified individual sensitivity to the cold Profession or hobby with a severe or longstanding cold exposure 46 2.3.1 Climatic factors

Recreational activities were the most common risk situations leading to cold injuries (Foray 1992, Hassi et al. 1998), even in Antarctica (Cattermole 1999). Exposure to the ambient cold temperature is, of course, the most common and important reason for cold injuries. The bigger the difference of temperature between the body or its exposed part and the environment, the bigger is the thermal loss. Doubling the temperature difference doubles the heat flow rate out of the body. 95% of 2054 frostbite injuries suffered during military training occurred at temperatures below –15°C and the average temperature at the time of injury was –25°C (Lindholm et al. 1993). The duration of cold exposure is in direct relationship to the risk of cold injury. Wind-chill index (WCI) is a term indicating the importance of wind or other cause of air movement (convection) on the cooling of the bare skin (Siple & Passel 1945, Wilson & Goldman 1970, Kaufman & Bothe 1986, Dixon & Prior 1987, Anttonen et al. 1991, Danielsson 1996). Doubling the airspeed increases the heat flow from the unprotected skin by 50% and decreases total thermal insulation of clothing to a degree which depends on the air permeability of outerwear. In every-day cold exposure WCI applies only to the face and ears, as they are usually the only bare skin regions in the cold. Also the humidity of the ambient air and wet climate (rain, snow, wet terrain, etc.) enhance the risk of both non-freezing and freezing injuries by wetting the clothing and skin tissue. Hypoxia at high altitude forms a special risk factor for frostbite in mountain climbing and downhill skiing (Foray 1992, Ward 1993, Peacock 1998), as it did in World War II fighter planes.

2.3.2 Factors in contact freezing

Intentional or accidental skin contact (often by hands) with cold objects that conduct thermal energy (e.g. metals), cold or supercooled liquids or gases may decrease the skin temperature to its freezing point in a few seconds. This is quite a rare reason for frostbite of the head. Children sometimes suffer from rapid contact freezing during licking or touching a cold metallic object with mouth. Freezing “glues” the moist mucous membranes immediately to the metal, and children usually tear superficially their tongue and lips when trying to get out of this painful situation. Contact area, contact mass and pressure increase the frostbite risk in a mathematical ratio (Chen et al. 1994). Even a thin insulative layer between the skin and cold object diminishes significantly the risk of contact frostbite (Rintamäki et al. 2000). Individual predisposing factors did not affect the risk for contact frostbite in a questionnaire study on 5 243 Finnish conscripts (Ervasti et al. 1999).

2.3.3 Short-acting individual factors

Fatique, hypohydration (sometimes caused by cold diuresis), smoking, use of alcohol or other intoxicating agents, etc. enhance the risk of cold injury either by influencing the 47 circulation of blood in the skin and extremities, by diminishing the physical capacity to thermal production, or by leading to erroneous behaviour in the cold. Inadequate material preparedness for cold exposure and negligence of special device in high-risk situations increase the probability of cold injuries, too. 2/3 of US soldiers having a frostbite in Korean war were immobilized at the time of injury, often because of the actions of the enemy. Sometimes the frostbite happened also while the soldiers were sleeping, or riding in a vehicle. In these instances, the risk was explained both by low heat production, decreased blood circulation and diminished awareness of the risk. (Orr & Fainer 1952.) Lack of preventive measures (see prevention of cold injuries in 6.3) forms a major risk for frostbite. When clothing is inadequate, gets wet, is too tight or permeable to wind, the susceptibility to cold injury is enhanced. The face and sometimes the auricles are often the only uncovered skin areas that are exposed to cold. 16.4% of Finnish women and 12.3% of men did not use a hat at temperatures between 0oC and 10°C in winter. 2.6% of adults did not wera a hat in even colder weather, according to Finriski ’97 study. Especially young men in the southern towns of Finland take the obvious risk of auricular frostbite by neglecting the use of a hat in the cold (Lindholm et al. 1993, Hassi et al. 1998).

2.3.4 Long-acting and permanent individual factors

There are individual differences in how well a subject can adapt to coldness (Sumner et al. 1974). A fairly small positive change in the mean freezing temperature due to cold adaptation lowers the risk of freezing significantly. Individual cold tolerance depends on several factors (Sampson 1984, Urschel 1990, Kappes et al. 1993) (Table 10).

Table 10. Long-acting individual factors influencing on the risk of frostbite.

Factor Size and form of the body Thickness of the subcutaneous fat Age, gender, race Physical fitness and health Psychological and psychiatric factors Cerebral function State of nourishment Medication Smoking Prior cold injury Raynaud’s syndrome Prolonged or repeated use of vibrating tools 48

Children are in greater danger of cold injuries because of their large ratio of body surface area to mass. Tall adults are more likely to have problems because the relatively large surface area of extremities and cooling of blood in their long vasculature lead to an increased loss of heat. Body fat functions as an insulative layer and helps obese people to survive better in cold environment, although their usually lower physical capacity works in the opposite direction. African-Americans seem to get frostbite more easily than Caucasians in many epidemiological studies (Orr & Fainer 1952, Sumner et al. 1974, Taylor 1992, Candler & Ivey 1997). Advanced age, sickness and permanent disability, alcoholism, some medications (e.g. beta-blockers) and even female gender may cause trouble in the cold for the low capacity in heat production. Elderly people are at increased risk for hypothermia because of weakening of the vasoconstriction response (reviewed by Smolander 2000) and of the lower insulation (Budd et al. 1991). The effect of smoking on frostbite risk is unconfirmed; some studies indicate higher risk among smokers (Ilmarinen 1987), some do not (Orr & Fainer 1952, Lindholm et al. 1993). Prior cold injury was shown to be associated with a further cold injury in Korean war (Orr & Fainer 1952), in Scandinavian studies (Ervasti et al. 1999, Linné 2000) as well as in studies on expeditions in Alaska (Sumner et al. 1974) and Antarctica (Cattermole 1999). A past history of even a superficial frostbite predisposed to subsequent freezing injury (Riddell 1984). Local hyperreactivity to the cold caused an exaggerated vasoconstriction response for years. Skin temperature was shown to decrease more quickly and deeper in the skin region that had earlier been cold injured than in areas without previous frostbite (Ervasti et al. 1993a). The risk of a new frostbite was not limited to the previous site of cold injury in frostbite-prone individuals. Cold-induced white finger symptoms (Raynaud´s syndrome) and earlier exposure to vibration (after repeated and prolonged use of chain-saw or other vibrating tools) were noted to increase the risk of frostbite (Ervasti et al. 1991, Virokannas & Anttonen 1993, Ervasti et al. 1999).

2.4 Emollients and moisturizers

2.4.1 Types of emollients and moisturizers

Emollients (softeners) and moisturizers (moisteners) are commonly used names for non-medicated creams and ointments intended for the treatment of dry skin. There is no consensus regarding their definition. Emollients and moisturizers are not classified to belong to the group of pharmaceutical preparations (medicines). A name “cosmeceuticals” was suggested to this group for assessing their position as more medical than mere cosmetics have (Kligman 2000). However, no distinct separation can be made between medicines, “cosmeceuticals” and cosmetics by definition. In this paper, we use a term emollient as a common name for non-medicated emollients and moisturizers. Emollients can be divided into groups according to their lipid and water content and to their (somewhat theoretical) microscopic structure (Table 11). In addition to lipid and water components, emollients consist usually of other ingredients with special functions (Table 12). 49

Table 11. Types of emollients.

Type Gels Lotions Emulsion creams oil-in-water (o/w) emulsions water-in-oil (w/o) emulsions ambiphilic emulsions Waterless ointments vegetable/animal oils, fats or waxes mineral oils, fats or waxes macrogols

Table 12. The functional ingredients of emollients (in addition to lipid and water components).

Ingredient Water-binding chemicals = humectants (NMF®, polyols, urea, etc.) Lipids for replacing or supplementing corneal interstitium (ceramides, cholesterol, free fatty acids) Occlusives (e.g. dimeticone) Emulsifiers Preservatives and antioxidants *NMF = “natural moisturizing factor”: a mixture of humectants)

2.4.2 Occlusive and moisturizing effects

Most of the effects of emollients and moisturizers have been thought to be caused by their physical effects. However, there is growing evidence of chemical influence on the skin, too. Topically applied lipids, including petrolatum, have been recently found to penetrate the viable epidermis, to be metabolized, and to possibly modify endogenous epidermal lipids significantly (Fendler 2000). Intermingling of both physical and chemical mechanisms is probably common. This physico-chemical effect concerns also the bases or vehicles of topical pharmaceutical preparations and gives importance to their role in the therapy of skin problems. Water content of stratum corneum affects the sensation of comfort in the human skin. The water concentration of corneal layer increases with the use of occlusives. This mechanism forms an important part of the therapeutic effect of emollients in the treatment of dry, flaky skin. As a rule, the greasier ointments, e.g. petrolatum, have been considered to be more occlusive than emulsion creams with a relatively high water content (Kligman et al. 1982, Barry 1992), although there is some controversy in this matter. An occlusive 50 epicutaneous film or membrane prevents the evaporation of water from stratum corneum. The diffusing water (TEWL) is captured in the stratum corneum and in the occlusive emollient itself. The emollients may occlude also the perspirative humidity, in a limited scale. Some emollients include special humectants, water-binding chemicals, which may increase the water content of stratum corneum when absorbed into it. Glycerine and other substances, which inhibit the lipid phase transition from liquid to solid crystals under dry environmental conditions, may provide an alternate mechanism for a moisturizer or softener. (Fendler 2000.)

2.4.3 Barrier effects

In conjunction with emollients, the barrier name refers to two entirely different structures or functions: a) the natural diffusion barrier structure in the corneal layer of epidermis regulating the diffusion of water and chemicals both out- and inwards, and b) the barrier function executed by the emollients together with skin as “barrier creams” on the surface of the skin against environmental chemical hazards. Emollients may hasten or retard the recovery of the disturbed barrier function in diseased (e.g. in atopic dermatitis and psoriasis) or experimentally damaged skin (after barrier perturbation by tape stripping or lipid solvent treatment) (Fendler 2000). Petrolatum and lanolin accelerated the recovery of the skin´s normal barrier properties (Ghadially et al. 1992, Harris & Hoppe 2000). Emollients which include ceramides, cholesterol and free fatty acids in equimolar ratio had an advantageous effect on the rapidity of barrier repair (Halkier-Sörensen 2000), as well as ceramides alone (Imokawa 2000), although there are also discrepant results concerning the effect of one-lipid component therapy (Thornfeldt 2000). Emollients may decrease the absorption of toxic or allergic chemicals into the skin by forming a superficial, low penetration layer together with the stratum corneum. In the light of investigations during recent decades, the efficacy of barrier creams in prevention of occupational contact dermatitis by this mechanism is not considered to be very high (Kanerva 1988, Elsner 1997).

2.4.4 Thermal effects

It seems that the thermal effects of non-medicated creams and ointments have not been of interest to researchers. The use of emollients for skin protection in cold environment has been apparently restricted to small geographic areas with arctic or subarctic climate. Furthermore, the emollients are not used for skin problems concerning hot environment, to our knowledge, if sunburn is excluded. Theoretically, the lipid components of emollients may have a physical insulating effect as long as the emollient forms a lipid layer on the skin. When emollients are applied on the skin, a time period follows, when some of the lipids are absorbed into the superficial skin layers and some stay on the surface. If the emollient contains water at least a part of 51 it evaporates into the surrounding air causing a cooling effect. The water in some oil-in-water emulsion creams evaporates quite freely and rapidly (Blichmann et al. 1989). Some of the water may temporarily invade the corneal layer. The occlusivity of emollients and their water-binding characteristics may have a major impact on water cinetics in the skin and possess secondarily also some thermal effects. Same applies to the influence of emollients on the barrier function of stratum corneum.

2.4.5 Other effects

In addition to the repair of barrier function and hydration of the stratum corneum, emollients can modify the physical and chemical nature of the skin´s surface, making it smoother, softer, and more pliable. Emollients may also act as weak anti-inflammatory agents in therapy of mild eczema, such as atopic dermatitis and superficial injuries of the skin caused by e.g. environmental exposure, such as sunburn. This anti-inflammatory effect has been observed both in vasoconstriction tests and especially in clinical investigations of topical corticosteroid preparations. In these tests the emollient bases (vehicles) have often shown a weak but distinct therapeutic effect even when they were used as “negative” placebo-like control creams. In Finland, emollients are most commonly used for treating mild chronic eczema as steroid-sparing therapeutic agents. The mechanism of this anti-inflammatory effect has not been fully elucidated. Emollients may affect the structure of lipids in the stratum corneum. Warner & Boissy (2000) have reported preliminary data on the possibility that emollients may restore the ideal lamellar lipid structure of corneal layer. 3 Purpose of the study

This study project was designed to find answers to the following questions: 1. What is the incidence of frostbite in the head, which are its principal risk factors and does the use of protecting emollients play a role in the incidence of frostbite? (I, II) 2. What kind of thermophysical effects do emollients have in the cold and how efficient is their thermal insulation in dry, humid and wet conditions? (III) 3. How do the emollients influence the temperature of human skin in the cold? (IV) 4. How do people feel subjectively their thermal effect? (I, IV) 4 Material and methods

4.1 Subjects and respondents

In study I, 832 Finnish male conscripts (mean age 19.3, range 17—29 years) answered a questionnaire under supervision. These conscripts served in three garrisons from southern (Santahamina) and middle Finland (Kajaani) to Lapland (Sodankylä). At the time of the study, all healthy men in Finland were obliged to serve in the Defence Forces for 8—11 months. About 92% of the male age-group was medically qualified to start their military service. The respondents represented this population. All conscripts attending the first lessons in health education participated in the questionary. The answers of the respondents were estimated to represent the opinions of young civilian men of the same age. This is based on the fact that the conscripts had just started their military service and had not yet received any information from the military personnel concerning the use of protecting emollients in the cold or other issues in the questionnaire. Only two forms were filled out so inadequately that they were rejected from the study, thus leaving 830 approved forms. The subjects were divided into four groups by their home regions in the south-north axis of Finland (Fig. 8) to find out possible climatic differences in the incidence of frostbite or in the use of protecting emollients. 54

Fig. 8. The geographical home regions of 830 Finnish conscripts and corresponding climatic areas.

In study II, all 913 young male conscripts (mean age 19 years, range 17—29) with local frostbite of the head (533 in ears, 197 in the nose and 183 in other locations of the face) that needed medical attention during the period of late winter 1976 — spring 1989 filled out a questionnaire. These conscripts formed a subgroup of the research material in another study (Lindholm et al. 1993) with a total of 2054 frostbite injuries in various locations of the body. Information on weather, type of activity and other conditions at the time of injury, as well as the medical details were given by local medical officers or nurses. When possible, two conscripts who had not developed frostbite in the same circumstances as the injured, were randomly selected from the same squad to act as controls. Valid controls could not always be found as the injured man was sometimes alone when he was frostbitten. This happened often in frostbite injuries during vacation. The controls for all 2054 injured numbered 2478 and were handled as one group in statistical analysis. In study IV, the test group of 24 voluntary, healthy male test persons (mean age 26 years, range 19—48) consisted mainly of medical students at the University of Oulu, the researchers themselves and the technical assistants in this study. Test subjects did not have any clinically apparent skin problems on their face. A pause of at least 48 hours was required between tests with the same subject. The maximal number of tests per subject 55 was four and the average number of tests was two. Subjects that took part in tests with pharmaceuticals were not used in tests with emollients.

4.2 Questionnaires

In study I, the subjects were asked if they had personally used cold protective emollients, at which age period, and how many of them still used them currently (Appendix V). The subjective experiences concerning the effect of emollients on cold protection and on skin dryness were also registered. The frequency of ointment use by men, women and children in the families of respondents was also asked. The opinions of conscripts about the right timing of application and about the ideal water content of protective emollients were also registered. The habit of using protecting emollients was correlated with the respondents´ domestic climatic region, self-estimated previous cold exposure, subjective cold sensitivity, habit of smoking and lifetime cumulative incidence of frostbite in different regions of the head. The annual sales figures of sports ointments (in monetary value) in Finland 1990— 1999 were obtained from the Technochemical Infocenter in Finland (the numbers concerning years 1998—99 were added to this dissertation after the report I was published). In study II, there were two separate questionnaires (Appendices VI and VII). The first was answered by the injured conscript himself and his personal controls (noninjured companions). This form included questions of clothing, shoes, use of protective emollients, fatique, sensitivity to cold and excessive sweating of the extremities, smoking, earlier indoor work, etc. The other form collected information on weather, type of activity at the time of injury, as well as the detailed medical information on the frostbite. This questionnaire was filled out with the help of local medical personnel.

4.3 Test emollients and their application

The four emollients tested in studies III and IV (Table 13) were chosen to represent a wide scale of existing emollients in the Finnish market, although not all of them were claimed to act as cold protecting by their manufacturers. Emollient A (Aqualan L®) was an o/w cream with 65% water content and was the most popular multi-purpose, non-cosmetic moisturizer in Finland for the care of healthy and diseased skin. Emollient B (Neribase® in orange-coloured tube and package) was an w/o emulsion cream with 30% water content. As it was anticipated that the general public in Finland prefers the use of waterless, greasy emollients in cold protection, two of these were chosen for our studies. Ointment C (Ceridal® lipogel) was marketed in the beginning of our studies, among other things, as protecting the skin against the cold. This claim has since been omitted. The lipid content of C differs a lot from ointment D (100% white petrolatum) that was aimed to resemble the greasy ointments, which are most commonly used in Finland for cold protection. 56

Table 13. Properties of test emollients in studies III and IV.

Quality Water content (%) Lipid content Trademark/Manufacturer A. Emulsion cream o/w Vegetable oils ® 65 Aqualan L /Orion Pharma, Espoo B. Emulsion cream w/o White beeswax, liquid par- ® 30 Neribase /Leiras Co., affin, white petrolatum Turku C. Lipogel Long-chain hydrocarbons ® 0 Ceridal /Rhone-Poulenc Rorer A/S, Birkeröd D. White petrolatum 0 Vaselinum album Ph.N. Valkovaseliini (in Finnish)

In physics, the grade of thermal insulation is in direct mathematical ratio to the thickness of the insulative layer. The amount of application was chosen to be considerably thicker than in the ordinary topical therapy to find out even small thermal effects. In study III, the thickness of emollient layer (10g/0.0511 m2 = 196 g/m2) was on average over 10 times thicker than in ordinary application (9.9-24.2 g/m2, on average 16 g/m2) for the skin treatment (Schlagel & Sanborn 1964, Long et al. 1998). Another reason for the thick application in study III was that the skin model equipment was usually used for measuring of garments with distinctly higher thermal insulation than anticipated of the emollients. In study IV, the emollients and topical preparations were applied, for similar reasons, in about threefold thicker layer (approximately 50 g/m2) than in the average topical therapy. 46 acute cold exposure tests were carried out, 9-16 with each emollient. Right and left facial halves were used equally for application and control to avoid bias caused by possible asymmetry of the test conditions (Table 14).

Table 14. Number of face-half comparison tests in acute cold exposure (study IV).

Application right/left sum all Emollients 46 A7/613

A1 1/2 3 B5/49 C4/610 D6/511 All 23/23 No application -/- 6 6 Pharmaceuticals 7

Vasodilator2 2/1 3

Vasoconstrictor3 2/2 4 All tests 27/26 59 1 ”late” cold exposure after one hour from the application, 2 cold exposure started 4 min after the application, 3 cold exposure started 4 h after the first application or after repeated applications 57

One half of the face of test persons was applied with one of the test emollients at room temperature and the other half was left unapplied to act as control. Tests lasted 25-30 min starting usually 2 min after the application. Three cold exposures with o/w emulsion cream A were started after 1 hour had elapsed from the application to investigate the effect of evaporation of the water content on the skin temperature. The thermal effects of non-medicated test emollients were compared in vivo with topical vasodilative (nicotinate-containing), vasoconstrictive (clobetasol propionate or halcinonide-containing) pharmaceutical preparations and with the influence of facial asymmetry (no application on either face-half). The vasodilators were applied 4 min before entering the cold chamber, and the effect of vasoconstrictors was tested after 4 h of first application in one test and after repeated applications in three tests.

4.4 Instrumentation and equipment

In study III, the tests of thermal resistance by four emollients were performed with a plane skin model with sweating hot plate in a climatic box. This equipment was originally constructed at Oulu Regional Institute of Occupational Health for the routine measuring of thermal insulation by clothing material. Its properties have been presented in detail by Anttonen 1993. The skin model fulfils the demands of Finnish and international standards (SFS 5681 and ISO DIS 11092). These in vitro tests were conducted by keeping the temperature of the skin model constant at +20°C in a climatic box with –15°C ambient temperature. Both temperatures were continuously monitored. The first tests were done in dry conditions. Normal transepidermal water loss (TEWL) and perspiration were separately simulated in this device by controlling the input of water that ran through several channels under the semipermeable surface of the skin model. Test emollients were applied on a goretex laminate that was taped on the skin model. The amount of ointment with the laminate and its supporter were weighed before and after tests. The need of heating power to maintain the constant temperature of the skin model was measured continuously. It indicated the thermal resistance of emollients when the other parameters were kept constant. Tests were continued as long as needed to stabilize the power-need. One of the test series was conducted by first simulating perspiration, then abruptly stopping the water-input and changing into dry conditions. The equipment had not been used earlier for testing of emollients or other very thin materials. The maximal error of the apparatus in repeatability tests was <1 % in dry tests (as with waterless white petrolatum) and was estimated to be <10% in tests with emulsion creams and/or water input. In study IV, symmetrical skin temperatures were recorded continuously with thermistors (YSI 400 series) attached with tape symmetrically on the cheeks and forehead. An infra-red (IR) videocamera (Inframetrics 600) continuously registered the facial temperatures on a video recorder tape (Fig. 9). The use of IR thermography in clinical and experimental dermatology has been reviewed by Di Carlo 1995 and Anbar 1995 a) and b). 58

Fig. 9. The location of thermistors, infra-red (IR) areas and horizontal graphs in the measurement of facial skin temperature.

During IR-monitoring it was possible to “freeze” the picture at desired intervals in order to investigate the simultaneous skin temperatures on symmetrical locations in specific points or areas. It was also possible to draw temperature graphs from wanted horizontal levels to measure and visualize the temperature differences between face-halves. The temperatures were evaluated both as varying colours and in digital numbers. The subjective thermal sensations and their difference between facial halves were expressed verbally by test persons in the beginning, in the middle and at the end of each test period lasting 25—30 min each.

4.5 Statistical analyses

In study I, the statistical analysis was performed with SPSS software (SPSS 1986). The statistical significance of different associations was determined by using a χ2 -test. P-value under 0.05 was qualified as significant. Risk ratios (RR), the relative risk of the exposed group compared with the unexposed group, were calculated using Epi-Info software. 95% confidence intervals (CI) were given for each RR. In study II, BMDP software (BMDP 1988) was used for the statistical analysis. Univariate analysis was used to determine which variables had an effect. The proportions in injured and control groups were compared by using a χ2 -test. Thereafter, a logistic stepwise regression model was used to avoid unnecessary multiple colinearity. In the final analysis a fixed module was used, with calculation of the odds ratios to measure the degree of risk. All tests were two-sided, and all controls were handled as one group. 59

The statistical analysis in study IV was performed by summing up the face-half comparisons of different emollients and by calculating 95% CIs for all observed proportions based on an assumption that a thermoneutral effect gives a binomial distribution (a balance of warming and cooling effects) (Gardner & Altman 1989). The agreement of observed and expected distributions in proportion of cooling and warming effects of individual emollients was tested by using a χ2 -test. 5 Results

5.1 Use of cold protecting emollients in Finland

5.1.1 Questionnaire study (I)

A total of 173 out of 827 (21%) conscripts (in almost unselected male material, mean age 19 years) reported earlier personal experience of using cold protective emollients, 96% of them on the face and 4% on the ears (10% also elsewhere, mostly on the hands, feet and lips). Childhood was the principal age-period of use, and only one third of users reported to have continued their use after school age. At the time of the questionary, 97 out of 830 (12%) still used them seldom and 39 (5%) often or always when exposed to the cold (Table 15).

Table 15. The use of cold protecting emollients in Finland. (Proportions of the respondents in a questionnaire study on 830 male conscripts.)

Use Proportion Previous own use 21 Age when using Before school-age 50 1 At school age 62 1 After school age 31 1 Present own use 17 Regularly or often 5 Seldom 12 Use by family members 25 Women 18 Children 9 Men 3 1 = proportion of the emollient users 61

Some other family member (or several of them) than the respondent had used cold protecting emollients in 25% of the conscripts´ families (often in 8%, seldom in 17%). This occurred 10 times more often in families in which the conscript himself had also used protective emollients (p = 0.0001). Women had used them more often than children and men, in a mathematical ratio of 6 : 3 : 1. Use of protecting emollients by both conscripts and their family members was the most common in southern Finland (Fig. 10), conversely related to the anticipated climatic cold exposure. Even in one third of the families living in southern Finland some member had used cold protecting emollients compared with 8% of families in Lapland. The cumulative lifetime use of protecting emollients was 2.7 times more common among the conscripts and 4.1 times more common among their family members in southern Finland than in Lapland. This association of climatic domestic region with the use of cold protecting emollients was statistically highly significant (p < 0.0001).

60 Personal cumulative use Cumulative use by family members 50 Personal use at present

40 34.3 31.1 30 24.3 24.0 19.4

Use (%) 16.9 20 13.9 14.1 11.0 11.6 8.4 10 8.1 0 ABCD

Fig. 10. Use of cold protecting emollients by 830 Finnish conscripts and their families in 4 geographical home regions. (A—D, see Fig. 8.)

Self-assessed high or moderate exposure to the cold was statistically associated with the use of emollients (p = 0.02). Neither subjective cold sensitivity nor smoking was significantly correlated with the use of protective ointments. The ideas and expectations of respondents concerning the optimal water content of cold protective emollients were obscure. 47% of all respondents had no opinion about this issue, 36% preferred waterless ointments and 10% ointments with some or abundant water content. Also the opinions of optimal timing in application differed greatly. 42% presented no opinion, 33% preferred application less than 15 min and 24% a period longer than 15 minutes before cold exposure. Two commercial products (Nivea® and Vitalis®) formed an even couple as well in use as in familiarity. Of the 131 users who remembered the name of the emollient that they had used themselves for cold protection, 40% named Nivea®, an international imported product (Beiersdorf, Kungsbacka), and 38% Vitalis®, a domestic Finnish product (Valkoinen Risti, Helsinki). Of all respondents 443 remembered at least one product name of cold protecting emollients, 44% of them Nivea® and 37% Vitalis®. Both products are 62 greasy ointments, although named as cremés by their manufacturers. Their ingredients according to the package declarations in July 2000 (the compositions may have changed during our studies) are shown in Table 16.

Table 16. The ingredients of Nivea® and Vitalis® cremés.

Emollient Ingredients Nivea® cremé Aqua, paraffinum liquidum, cera microcristallina, glycerin, lanolin alcohol, paraffinum, cer- esin, magnesium sulfate, decyl oleate, octyldecanol, aluminium stearates, panthenol, citric acid, magnesium stearate, parfum. Vitalis® cremé Paraffinum liquidum, petrolatum, glycerin, paraffinum, cera alba, ceresin, sorbitol, lanolin, isopropylpalmitate, sorbitan palmitate, cetylpalmitate, zinc oxide, stearic acid, octyl methoxy- cinnamate, parfum, propylparaben, BHT, colorants.

The sales statistics of sports ointments during 1990s given by Technochemical Infocenter in Finland is shown in Table 17 and is compared with the sales of lip balms and sticks. The data concerning the years 1998—99 has been added after the report of study I. There is no consistent trend in the sales of sports ointments. The average annual number of consumer packages sold is estimated to be about 220 000—250 000. The use of lip balms and sticks has been significantly higher from the start of this observation period and has almost doubled its value during the decade.

Table 17. The sales of sports ointments and lip balms and sticks in Finland 1990—99 (thousands FIM). (Tecnochemical InfoCenter in Finland)

Therapeutic or 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 preventive product Sports ointments 2 537 2 385 2 303 2 351 2 247 2 205 2 257 2 360 2 525 2 321 Lip balms and sticks 12 503 12 080 12 807 11 877 12 376 13 854 15 954 16 974 17 857 20 025

5.1.2 Epidemiological study (II)

345 (17%) out of the whole sample of 2054 conscripts with frostbite in any location (a selected frostbite material) had used cold protecting ointments at the moment of cold injury. Of the 913 conscripts with frostbite of the ears or face, 143 (16%) had used protecting emollients. Most patients (98/109; 90%) with grade II frostbite of the head had used emollients. 63 5.2 Incidence of frostbite in the ears and face and the principal risk factors

5.2.1 Incidence of frostbite in the ears and face

5.2.1.1 Questionnaire study (I)

The self-reported, cumulative lifetime incidence of frostbite in the head (one or more cold injuries in the ears or face) is presented in Table 18. Already at the average age of 19 years, almost half (378) of 811 respondents had suffered from a frostbite in the ears or face. 83% of cold injuries in the ears were superficial grade I injuries, 14% of grade II and only 3% of grade III. 91% of the cases with facial frostbite were of grade I, 8% of grade II and only 1% of grade III indicating that the ears were more prone to deep frostbite than facial areas in this group.

Table 18. Self-reported cumulative incidence of frostbite in the head. (At least one frostbite in the mentioned location among 830 male conscripts.)

Location % of respondents Head 47 Ears 42 Face 22 Cheeks 15 Nose 14 Chin 5 Others 2.6

The climatic difference in cumulative lifetime incidence of ear frostbite showed a statistically significant increase from south to north (33—40—50—54% in climatic areas A-B-C-D, p-value 0.006) (Fig. 11). A small, but not statistically significant difference was also present in the cumulative incidence of facial frostbite (20—24—24—25%) from south to north. Sixty-six percent of ear frostbites and 70% of facial frostbites had occurred at school age (7—16 years in Finland). 64

60 All frostbites of the head 56.0 53.1 54.2 Frostbites on ears 50.2 50 Frostbites on the face 46.8 40 39.6 40.0 33.3

30 23.8 23.7 25.0 20 19.7

Incidence (%) 10 0 ABCD Fig. 11. Self-reported cumulative life-time incidence of (one or more) frostbite injuries in the head of 830 Finnish conscripts from 4 geographical home regions. (A—D, see Fig. 8.)

The incidence of ear frostbite was distinctly connected with the incidence of facial frostbite (p-value < 0.0001). Subjects with ear frostbite had had four times more often also a facial frostbite than conscripts without ear frostbite.

5.2.1.2 Epidemiological study (II)

The mean annual incidence of frostbite in the head (ears and/or face) was 1.8/1000 conscripts (95 % CI 1.3—2.3) during the study period. The annual incidence in this material of 913 cold injuries varied greatly (1—10/1000 conscripts) depending on the coldness of the temperature, being highest in the coldest winters. Severity grading of frostbite in this material is shown in Table 19. Only a minority (12%) of patients had grade II or III frostbite, the nose being most prone to more severe cold injuries. Grade III frostbite occurred only sporadically.

Table 19. The location and grading of 913 cases of frostbite in the head.

I II III Location n n (%) n (%) n (%) Ears 533 509 (95) 23 (4) 1 (0.2) Nose 197 142 (72) 54 (27) 1 (0.5) Other 183 150 (82) 32 (17) 1 (0.5) All 913 801 (88) 109 (12) 3 (0.3)

Frostbite of the ear lobes (58% of cold injuries in the head) was more than twice as common as frostbite of the nose (22%) and of other regions of the face, mostly the cheeks (20%). 65

The proportion of frostbite in the ears and face of all registered 2054 cold injuries in any location differed greatly (13—64%, 44% on average) between the years of the study, being significantly highest in the coldest winters. This proportion was surprisingly low (5%) during land manoeuvres. Only 196 (21%) of all 913 cases of frostbite in the ears and face had occurred in land manoeuvres. 468 (51%) occurred at garrison service (while marching, guarding, shooting, in sports performance, etc.). From 277 frostbite injuries (in the whole sample of 2054 cases of frostbite in any location) occurring on leave, 213 (77%) affected the head area.

5.2.2 The principal risk factors of frostbite in the ears and face

5.2.2.1 Questionnaire study (I)

38% of 830 conscripts assessed themselves subjectively as cold sensitive, more often in southern Finland (40%) than in Lapland (31%). Subjective cold sensitivity was associated with an increased incidence of facial frostbite (p = 0.02). The association of cold sensitivity with the incidence of ear frostbite was weaker. The correlations of evaluated risk factors to cold injuries are presented in Table 20. Smoking had an impact on the incidence of both ear and nasal frostbite (p < 0.03 in both locations) but not in other regions of the face. Self-reported high cold exposition was associated with an increased frequency of life-time cumulative frostbite on the nose (p < 0.05) but not in other locations of the face. Same persons were prone to both ear and facial frostbite (p < 0.0001).

Table 20. Correlation of possible risk factors with the cumulative incidence of frostbite in the head (percentage of risk holders among the frostbitten/not frostbitten + p-value of the difference).

Risk factor Frostbite in the head Ear frostbite Facial frostbite %p %p %p

Smoking 61/53 0.02x 61/53 0.03x 61/56 0.2

Cold sensitivity 42/35 0.05x 41/35 0.1 46/36 0.02x

Cold exposition 70/64 0.07 71/64 0.05x 32/33 0.6 Use of protective 24/17 x 22/18 0.2 28/18 xx emollients 0.03 0.003 x statistically significant, xx statistically highly significant

Conscripts with experience of using cold protective emollients had a significantly higher incidence of facial frosbite (Table 21) when compared with the non-users. (Some of the numbers have been corrected after the publishing of study I. This did not cause changes in the principal results.) 66

Table 21. Relative risk (RR) of the use of protecting emollients causing self-reported frostbite in the ears or face of 830 Finnish conscripts. (u = no. of users, n-u = no. of non-users, all = u + n-u. Small discrepancies in no. of all are caused by missing data in some questionnaires. n.s. = not significant.)

Location of frostbite u /n-u all RR 95% CI p-value Head 89/287 378 1.37 0.78—2.41 0.025 Ears 72/256 330 1.21 0.79—1.85 n.s. Face 50/130 182 1.55 1.30—1.85 0.003 Cheeks 37/ 83 121 1.67 1.44—1.93 0.001 Nose 26/ 84 111 1.19 1.14—1.24 n.s. Chin 14/ 26 40 2.00 1.76—2.28 0.015 Other 6/ 15 21 1.33 1.27—1.39 n.s.

5.2.2.2 Epidemiological study (II)

The independent risk factors in the prospective study on 913 frostbite injuries with noninjured controls are presented in Fig. 12. The protection to the auricles given by ear flaps was shown to be very important, as the most effective contemporary risk factor for ear frostbite was not wearing a hat with earflaps when exposed to cold injury. Neglect of using a scarf increased the risk of ear frostbite and frostbite on the cheeks and chin. Use of cold protective emollients formed a statistically significant risk factor for the occurrence of frostbite in all usual cold injury regions of the head.

Fig. 12. The independent risk factors of cold injuries in the face and ears of 913 Finnish conscripts (odds ratio ± standard error).

The application of emollients caused a consistent increase in risk for frostbite in the ears and nose also during terrain manoeuvres. Easily sweating feet, increased sensitivity 67 to cold in both hands and feet and former working indoors in civilian life were additional risk factors for frostbite in the head in land manoeuvres (Fig. 13).

Fig. 13. The independent risk factors of cold injuries in the face and ears of 196 Finnish conscripts during land manoeuvres (odds ratio ± standard error).

5.3 Thermophysical effects of emollients in the cold

5.3.1 Thermal insulation (III)

Thermal insulation (thermal resistance) of all four test ointments A, B, C and D was minimal (~ 0.001 m2K/W) even when applied thickly in dry conditions. This effect was hardly measurable with the skin model equipment in our use. In ten times thicker layer than used in the previous test, white petrolatum caused a thermal resistance of 0.014 m2K/W, about ten times more than the thinner layer. A thick layer of ointment D did not increase measurably the insulative property of suede boot leather. In dry conditions there were no detectable differences between the insulative effects of individual test ointments except during the first 40 min after the application when the o/w cream A lost most of its water content (originally 65%) by evaporation. This period caused a distinct cooling effect. Emulsion cream B with its 35% water content behaved quite differently and did not let its water to evaporate measurably during the dry test.

5.3.2 Occlusive thermal effects (III)

In humid tests, the small water input (simulating TEWL in the living skin) increased the thermal resistance of ointments B, C and D but not of cream A. The major reason for the difference was probably associated with the fact that cream A let the water pass easily 68 through it without trapping, as the other emollients increased their thickness by absorbing the input water (Table 22).

Table 22. The occlusive effect of test emollients in humid and wet tests. (Percentages are calculated from the total amount of input water.)

Emollient Low input of H20 High input of H20 E A t E A t % % min % % min None 91 6 180 89 8 80 A 136 –43 180 90 4 180 B 32 61 180 24 70 180 C 3 92 180 28 67 180 D 2 95 180 12 85 180

E = H2O evaporated, A = H2O absorbed, t = duration of test

In the beginning of wet tests simulating perspiration, the input water caused an increase in thermal resistance of cream B and ointments C and D up to the point, when the excess water had penetrated them and started thereafter to cool down the skin model by evaporation. In dynamic tests (first ”sweating”, then a drying phase) the thermal resistance of all emollients diminished somewhat during the high water input phase. In the transition phase to dry conditions, the thermal resistance increased distinctly by 20—26% and stayed quite steady during the dry phase.

5.4 The effects of emollients on skin temperature in acute cold exposure and on the subjective thermal skin sensation

5.4.1 Questionnaire study (I)

The perceived personal experience concerning the cold protectiveness of emollients in general was advantageous in 84% (clearly positive in 28%, and weakly advantageous in 56%) of 173 respondents having used protecting emollients. 69% of emollient users assessed that also the skin dryness in the cold was prevented or diminished.

5.4.2 Experimental study with test subjects (IV)

During the cold exposures, the skin temperature on cheeks and forehead diminished from 32—34°C to around 10°C, approaching the risk level of non-freezing cold injury. In comparisons between facial halves, the application of non-medicated test emollients caused a cooling effect on the facial skin significantly more often than a warming effect. This result was consistent in all modes of thermistor and IR-scanner measurements. The 69 effects of all four emollients were more often cooling than warming. However, inter-emollient differences were found, although they were not statistically significant in either modes of measurement. White petrolatum D caused less often a cooling effect than emulsion creams A and B. Lipogel C had an intermediate position in this respect (Table 23).

Table 23. Effects of emollients A—D on facial temperature (T) in cold. Comparisons of the applied half of the forehead and cheeks with the untreated half. Values ≥0.7°C were considered as thermal difference. Ta –15°C, wind 3 m/s against the face. Emollients were applied 2 min before the cold exposure, except in tests marked A* in which cold exposure was started 1 h after the application to let the water content of o/w emulsion cream A to evaporate first.

Method Emollient Cooling No effect Warming Observations n (%, 95% CI) n (%, 95% CI) n (%, 95% CI) n Thermistors T at 5, 10, 15, 20 and 25 min A96419 A* 2125 B121417 C64515 D94619 All 38 (51, 40—62) 16 (21, 12—30) 21 (28, 18—38) 75 Average T during period 13—23 min A75719 A* 2125 B121417 C82515 D85619 All 37 (49, 38—60) 14 (19, 10—28) 24 (32, 21—43) 75 Infra-red scanner Area T at 5, 10, 15, 20 and 25 min A12122 26 A* 3306 B79218 C98320 D7 11422 All 38 (41, 31—51) 43 (47, 37—57) 11 (12, 5—19) 92 Overall estimation at 5, 10, 15, 20 and 25 min (°C) A194326 A* 3126 B141318 C135220 D89522 All 57 (62, 52—72) 20 (22, 13—30) 15 (16, 8—23) 92 70

The effect of emollients on lowering the temperature was small (mean difference –0.6°C both on the forehead and on the cheeks in IR area registrations). The pharmacologically active vasodilative liniments caused an average half difference of +3.8°C on the forehead and +8.1oC on the cheeks (Fig. 14). As a rule, the temperature difference between face-halves was at its highest in the beginning of the cold exposition and it diminished towards the end of tests together with the lowering of the absolute skin temperature. The natural asymmetry of the face was shown to concern also the skin temperature. The average temperature difference between the unapplied face halves was 0.7°C (0—2.2°C) on the forehead and 0.8°C (0—2.2°C) on the cheeks in the IR area registrations.

Fig. 14. An example of a “frozen” IR-picture taken in a test, when a test subject had applied a vasodilative liniment on the left half of his face. The temperature difference (> 5°C) can be distinctly observed.

In contrast to the objective temperature findings, the effect of all test emollients was neutral on subjective thermal sensation when the results were summed up. In the analysis of individual emollients, white petrolatum D differed significantly from the other test emollients by causing a warming skin sensation much more often (in 15 out of 33 comparisons) than a cooling sensation (6/33). The other emollients caused mostly either a cooling (o/w cream A) or neutral (emollients B and C) effect on the subjective thermal sensation (Table 24). All test subjects without exceptions sensed distinctly the warming effect of vasodilators. 71

Table 24. The effect of individual test emollients A—D on the subjective sensation of facial skin temperature in the cold. Comparison of the applied and untreated face halves in the beginning, in the middle and at the end of cold exposure. Ta –15°C, wind 3 m/s against the face. Emollients were applied 2 min before cold exposure, except in tests marked A* in which cold exposure was started 1 h after the application to let the water content of cream A to evaporate first.

Cooling Neutral Warming Observations Emollientnnnn A1222539 A* 4 5 — 9 B515727 C716730 D 6 12 15 33 All347034138 6 Discussion

6.1 Winter xerosis of the skin

Coldness causes uncomfortable skin sensations, mild or more apparent skin problems and severe local tissue injuries. The pathomechanisms and manifestations of cold injuries may intermingle with each other and confuse both lay people, clinicians and scientists. A minority of respondents considered lip balms or sticks as cold protecting topical agents in study I, indicating difficulties in defining skin problems by lay people. This justifies the following question: which is the principal motive for using cold protecting emollients in the cold, the drying of the skin or the risk of frostbite? In cold, there is a gradient of temperature and of water content within and across the stratum corneum with the outer layers being colder and drier than the deeper layers. Convection on the skin surface transports the humidified and warmed air away increasing the gradients of temperature and humidity. Convection also gives an opportunity to the drying and cooling to proceed. When the temperature outdoors is below the freezing point, the ambient air indoors is usually dry as the heaters of central heated homes are working efficiently. The relative humidity (rh) of the ambient air is the ratio (expressed as a percentage) of the amount of water vapour compared to the amount necessary for its saturation at a given temperature. The absolute humidity (ah) indicates the mass of water vapour present in an unit volume of the atmosphere (measured as mg/l). Ah cannot rise to high figures in the cold, as the saturation of air with humidity occurs already at a low water content. The average ah during wintertime is distinctly lower than in summer. For a given ah, rh increases with lowering of temperature. Cooling of +20°C air with rh of 22% to 0°C increases the rh-value to 85% without changing the ah. Thus the coldness of ambient air diminishes the evaporation from the skin while the low humidity, often prevalent in cold weather, and convection (e.g. wind, transportation in open air) increases it. The sum effect depends on several factors and is not easy to predict. The function of the stratum corneum is to protect the underlying tissues from desiccation and from chemical and physical insults, including those caused by environmental temperature. Concentration of water in corneal layer plays a major role in regulating the flexibility and elasticity of the skin in vitro (Blank 1952). The corneum 73 tends to crack and flake, if its water content is diminished to less than 10%. The skin surface becomes rough, scaly and sensitive. This condition is more common during the winter months and is often referred to as skin chapping or winter xerosis. The signs of skin dryness are manifested mostly on lips, cheeks and backs of the hands and fingers. Barrier function of stratum corneum is usually disturbed and TEWL is increased in skin chapping. There is a physiological association between the water content of the skin and humidity of the ambient air. Rh-values < 35—40% may induce clinical symptoms and signs of skin dryness, especially in atopic dermatitis. Many atopic cases have a tendency to have more symptoms in winter (Eberlein-König et al. 1996). Rh was earlier assumed to be the major determinant to the skin chapping. However, the chapping of the skin occurred also when the air temperature was low outdoors, although rh was high (Gaul & Underwood 1951). Later investigators showed that the absolute humidity was more important than rh in inducing skin xerosis (Cooper et al. 1992, Uter et al. 1998). Exposure to prolonged low humidity (rh < 10% for two weeks) reduced the TEWL of hairless mice by 31%, increased the thickness of epidermis, number of cell layers and total lipids of stratum corneum without changes in lipid distribution. Barrier recovery after its intentional disturbance was accelerated by prolonged low humidity. These observations were estimated to represent a homeostatic response to protect the animal from excessive TEWL in a dry environment. (Denda et al. 1998 a.) When hairless mice were exposed to low humidity (rh = 10% for two days), this induced a hyperproliferative response to barrier disruption and increased markers of inflammation. These changes were attributable to changes in stratum corneum moisture content and became also evident as scaling occurred. Occlusive plastic membrane, petrolatum and nonocclusive humectant prevented these changes. (Denda et al. 1998 b.) Investigations on the pathomechanism of cold-induced xerosis in the human skin have shown that stratum corneum phospholipids, especially ceramides decrease during winter (Nieminen et al. 1967, Rawlings et al. 1993 and 1994, Conti et al. 1996). The levels of stratum corneum ceramide 1 linoleate and cholesterol were decreased by 40% in healthy test subjects in winter months, whereas fatty acid level declined only by 5% (Conti et al. 1996). Cooling of the skin blocked completely endogenous barrier recovery after its artificial disruption. Cold exposure had an inhibitory effect on the enzymes necessary for the new lipid synthesis and other metabolic processes, thereby preventing the formation and secretion of lamellar bodies needed for barrier repair. (Halkier-Sörensen 2000.) Cold (winter) induced stronger irritant skin reactions to propylene glycol (Hannuksela et al. 1975) and to sodium lauryl sulphate (Agner & Serup 1989) in epicutaneous testing, probably as a sign of general decrease of skin resistance to irritants in wintertime. Skin extensibility in vitro was significantly less at 4—5°C than at 18—22°C (Middleton & Allen 1974) due to a direct effect of temperature on the corneum. The ambient temperature was an independent determinant of the skin extensibility also at temperatures greater than 25°C (Middleton 1969). Several clinical investigations on winter xerosis have been performed. The flaking score of the faces of 55 female subjects was associated statistically with low temperature, absolute humidity of the ambient air and mean wind speed during a follow-up for over a year (Cooper et al. 1992). Cold exposure for three weeks was associated with a high prevalence of lip injury (1.1% severe, 52.3% moderate) in a material of 1422 subjects. 74

The relative risk caused by coldness and dryness of the ambient air could not be separated from each other. Actinic radiation was not a major risk factor. The use of lip protectants did not diminish the prevalence of lip injury. (Lewis et al. 1985.) A short exposure (3 h daily on 4—5 consecutive days) to severe cold caused visible alteration (roughness, fine fissures, desquamation), decreased surface lipids and enzymes in stratum corneum of the hands. The changes were reversed in 18—19 days after the cold exposure (Parish 1992, number of test subjects not defined). Winter months with low temperature and low absolute humidity were strongly associated with an increased prevalence of irritant hand dermatitis in 742 hairdressing apprentices (Uter et al. 1998). In the fish processing industry, cold masked a barrier defect in hands caused by continuous exposition to iced fish products, fish fluids and water during the working hours. The irritant dermatitis became evident only after warming up of the skin to normal temperature (Halkier-Sorensen et al. 1995). Whether the low temperature or even superficial cold injury is contributing to the development of winter xerosis has not been thoroughly investigated. Out of the usual xerotic locations, at least the cheeks are often exposed and vulnerable to the cold and wind. On the other hand, lips are not prone to freezing injuries thanks to their abundant circulation.

6.2 Frostbite in the ears and face

The proportion of frostbite in the head differed between 0% and 80% of all cold injuries in numerous studies on different populations (Korhonen 1940, Orr & Fainer 1952, Kyösola 1974, Sumner et al. 1974, Boswick Jr. et al. 1979, Fraps 1985, Nieminen & Suominen 1987, Taylor et al. 1989, Urschel 1990, Ervasti et al. 1991, Rosén et al. 1991, Taylor 1992, Foray 1992, Lindholm et al. 1993, Virokannas & Anttonen 1993, Candler & Ivey 1997, Conway et al. 1998, Cattermole 1999, Linné 2000, Nechaev 2000). The major determinant seems to be the selection of the observed subjects in respect to the special risk factors. In epidemiological studies concerning casualties of fighting armies in past wars, the cold injured consisted almost entirely of in-patients having either immersion foot or deep frostbite in extremities, rarely elsewhere (Korhonen 1940, Orr & Fainer 1952, Francis 1984). Superficial frostbite, like the majority of cold injuries in the ears and face, has been abundantly registered in health statistics only when it was specially asked by means of questionaries. The interest on these mild cases has increased during the last decades when the risk of disability and other sequelae associated also with superficial cold injuries was realized (Blair et al. 1957, Riddell 1984, Linné 2000). Large epidemiological questionaries have been made especially in Finland, both in the Defence Forces (Lindholm et al. 1993, Ervasti et al. 1999, Hassi et al. 1999, Juopperi et al. 1999), and among the civilian population (Hassi et al. 1998, Juopperi et al. 2000). In the questionnaire study I on Finnish conscripts, frostbite of the head had a cumulative lifetime incidence of almost half of the male population already at the age of 19 years. In study II, the mean annual incidence of frostbite of the head was 1.8 per 1 000 conscripts during military service, varying greatly with the hardness of the winters. 75

Frostbite of the head (n=913) formed 44% of all 2 054 cases of frostbite in any location, the majority of which had occurred in the acral parts of feet and hands (II). The highest incidence of cold injury in the head was found among Finnish reindeer herders in Lapland. The reason was evident; high risk was associated with cold local climate and high wind-chill index towards the head when driving snowmobile in their profession. (Ervasti et al. 1991, Virokannas & Anttonen 1993.) A great majority of frostbite injuries (83% in ears and 91% in the face) in study I were of grade I. Also during military service (study II), most cold injuries of the head were mild, grade I frostnips. Grade II frostbite with vesicles or bullae formed 5—15 % all cold injuries of the head being most common in the nose and ears. Only a few cases of grade III frostbite were reported in this material. The ears were the most frequent locations of frostbite in the head (cumulative incidence of ear frostbite 42%) followed by cheeks (15%), nose (14%) and chin (5%) (I). Although the circumstances during 8—11 months´ army service can differ a lot from the civilian life, the relative incidence between frostbite locations in study II was quite similar as in study I. During service, frostbite of the head affected primarily the ears (58% of all frostbite of the head), then the nose (22%) and other regions of the face, mostly the cheeks (20%). The incidence order of frostbite in different locations of the head in our studies (ears > nose > others) was in accordance with the cooling order of skin temperature (ears < nose < chin < cheeks < forehead) found in experimental cold exposures of bareheaded test persons (Edwards & Burton 1960, Steegmann 1979), if the protection to the chin given by appropriate clothing is regarded. There was a distinct correlation between ear and facial frostbite, both occurring in the same high-risk persons (I). In Finriski ´97 study, cold induced adverse effects (up to frostbite) had occurred during the last five years in 25% of adult respondents in ears, in 22% both in cheeks and nose, and in 14% in chin. During the previous year, grade I frostbite in the ears or face had occurred in 8.6% of respondents and deeper frostbite in 1.1%. (Hassi et al. 1998.) In an extensive questionary on 5 839 Finnish conscripts, lifetime cumulative incidence of frostbite in any location of the body was reported to be 44% at this young age. 65% of the frostbite injuries were reported to have occurred in other regions of the body than extremities, mostly in the face. (Hassi et al. 1999.) This gives a cumulative incidence of ≤ 29% for frostbite of the head, distinctly less than 47% in our study I. The cumulative incidence of frostbite in the ears increased significantly from southern Finland towards north (I). In other locations of the head, the trend of the climatic influence was similar, but not statistically significant. Juopperi et al. 1999 found among 2 866 Finnish conscripts a similar increase in the lifetime cumulative incidence of frostbite in any area of the body from southern (41%) to middle (43%) and further to northern Finland (61%). In Finriski ’97 study, there were similar geographical variations in the lifetime incidence of grade II or deeper frostbite in any location, as well in male face as in ears. Also during shorter observation periods, there was a preponderance of facial and ear frostbite in northern Finland. (Hassi et al. 1998.) Cold injury of the ears was somewhat more common in our studies (I and II) concerning exclusively young males than in Finriski ´97, in which adults of both genders were represented. The difference can probably be explained by differences in clothing, hairstyle and cold exposure between genders. About 10% of young men and less than 5% 76 of young women living in southern Finland reported that they did not use hats even when the temperature was colder than –10°C (Hassi et al. 1998). Evidently, shorter hair of men does not protect the ears as well as the female hairdo. Cold exposure was significantly more common in male than in female adult population. Men had a higher incidence of ear frostbite, while frostbite of the cheeks and nose occurred more often in the female gender in Finriski ´97 study. (Hassi et al. 1998.)

6.3 Prevention of cold injuries

Successful prevention of cold injuries consists of a combination of actions, such as avoiding thermal loss, regulating physical performance and maintaining adequate thermal insulation, as has been reviewed by Washburn 1962, Koskenvuo 1976, Vaughn 1980, Hamlet 1987, Fritz & Perrin 1989, Conway et al. 1998, Hamlet 2000 and Rintamäki 2000.

6.3.1 Preventive behaviour

Most people, even in arctic and subarctic countries, live in conditions where the risk of frostbite is not actual on every day of the winter. The risk of cold injury in the face or ears is a threat only in especially cold days or in otherwise exceptional circumstances. Usually there is no need for other regular protective measures besides warm clothing. However, especially after a period of mild winters cold days have taken unaccustomed citizens by surprise and caused a rapid rise in the incidence of cold injuries in Finnish Defence Forces (Koskenvuo et al. 1977, Lindholm et al. 1993) and among British civilians (Bishop et al. 1984) indicating that coping with the cold can fail. Thermal balance of the body is an important prerequisite for the prevention of local cold injuries. This is usually maintained both by adequate clothing, by adjusting physical activity and by avoiding exhaustion and perspiration that may wet the clothing and diminish its insulative properties. A local contact frostbite may, however, occur in full thermal balance of the body. Most important in the prevention of cold injury is that a subject recognizes (by experience, tradition or training and by utilizing meteorological data) when the climatic risk will be present, avoids the short acting individual factors predisposing to cold injury (chapter 2.3) when possible and knows how to protect himself. Smoking was a risk factor for ear frostbite in subjects of study I, but not in study II. Inconsistent results concerning the effect of smoking have been reported also earlier (Orr & Fainer 1952, Ilmarinen 1987). Long acting individual risk factors, easily sweating hands and feet, as well as increased subjective cold sensitivity in fingers and toes increased the incidence of frostbite in the nose and the latter also in the ears (II). Important behavioural measures include avoiding nonmandatory exposure to severe cold (staying indoors, looking for shelter, increasing clothing and physical performance, turning the bare and sensitive areas, such as the face, away from the wind, lighting a campfire, etc.). Transportation in an open vehicle was a risk factor for facial cold injury in 77 study II. Hot food and drink are recommended as external heat sources. They reduce also the risk of cold injury based on inadequate nourishment and dehydration. Working or training at constant pace helps in prevention of wetting the clothing and cooling during the resting pauses. Direct contact with cold terrain (snow, ice, etc.) or metallic objects should be avoided by insulative material, when possible. In military service, leaders are responsible for the prevention of cold injury among their troops. Susceptibility to cold injuries varies considerably between individuals. Newcomers, who have little or no cold-weather training and experience, often sustain cold injuries first. In manoeuvres and other special expeditions, a “buddy inspection” system should be instructed to encourage group members to observe each other for the early detection of threatening cold injuries. Proper training gives confidence in the ability to survive and perform the mission also during cold weather. Leaders must be alert for carelessness even in soldiers experienced in cold weather operations. Unit members who have previously experienced cold injuries should be identified and they should receive special training in cold-injury prevention. (US Army Research Institute of Environmental Medicine 1992, Tervahauta et al. 1993.) Chewing of a chewing gum was shown to increase the facial skin temperature in the cold (Hannu Rintamäki, personal information 1999), probably by local increase of circulation in the masticatory muscles.

6.3.2 Clothing and outfit

Appropriate clothing and special outfit, when needed, are important examples of avoidance of cold injury. The longer the cold exposure and the lower the temperature, the more essential is adequate clothing for the well-being. The experts appreciate dry, clean and non-compressing multilayer clothing adjustable for various levels of activities. Clothing has to be warm enough, but not too hot, to avoid sweating that wets the clothing from inside and weakens its thermal insulation. The superficial layer of clothing should allow the diffusion of water vapour outwards but prevent its penetration inwards. Wet clothing, socks and shoes should be changed into dry ones as soon as possible, even in the cold circumstances. Although the trunk and extremities are usually well covered with warm clothing, parts of the head are often left bare for convenience of breathing and seeing. Also the ears are often left uncovered, more usually for looks than for hearing. Face masks and protective glasses or goggles are used only in extreme cold exposure directed against the face. The radical difference of thermal loss from the head in varying performances and at rest sets great demands for the thermal properties of headgear (Table 25) and face covering garments (Table 26) in work and recreational activities in the cold. 78

Table 25. The optimal properties of headgear in the cold.

Property Thermal insulation Air permeability and ventilation Water vapour permeability (outwards) Resistance to water penetration (inwards) Adjustability according to rate of physical performance

Table 26. Face covering garments in the cold.

Location of the garment Garment On or in front of the face Face mask, balaclava Face gear/guard/visor Full-face helmet Safety glasses/goggles On the side or around the face Collars Scarf Hat Hood Earflaps (separate or as part of the hat)

Using a thin face mask lowered the freezing ambient air temperature by 10—20°C (Anttonen et al. 1991, Anttonen 1995). A hood with a wide opening kept up the facial temperature, especially in its lateral parts. Only the tip of the nose was not significantly protected. Since the hood did not disturb respiration and caused no significant accumulation of moisture from the expired air, it was superior to face mask in regard to user compliance. (Rintamäki et al. 1998, Rintamäki 2000.) A hat that protected the ears or separate earflaps was of outmost importance in prevention of ear cold injuries. Their neglect caused odds ratio of 18.5 in study II. Ear frostbite of conscripts occurred especially often on leave and very rarely during land manoeuvres. The difference was probably caused by the fact that in terrain all conscripts wore hats belonging to the army winter uniform. Hat protected the ears and other parts of the face quite well, in contrast to lighter clothing at the garrison service and especially on leaves when conscripts were often bareheaded and used their own civilian clothes. A scarf protected cheeks and also ears surprisingly well (study II), indicating a warming zone in its vicinity.

6.3.3 Cold protecting emollients

The results in study I confirmed the personal impression and experience that the use of cold protecting emollients in Finland has been relatively common. Self-reported present 79 use by conscripts (5% frequently and 12% seldom) was well compatible with the results of study II on the actual registered use by 17% of the injured at the time of frostbite. Emollients were used most often in early childhood and at school age and were probably applied on the face of children mostly by their mothers. The conscripts´ estimation of the use of protecting emollients by family members was, obviously, quite rough. Women were reported to use protecting emollients distinctly more often than male adults. More precise figures indicating the use by female gender should be investigated in a separate study. The ratio between the use by females, children and male adults was about 6 : 3 : 1 according to the information given by young male conscripts. These numbers suggested that the woman in the family was in a great majority the decision-maker for the use of cold protecting emollients. Some Nordic cold researchers from Sweden (Ingvar Holmér) and Norway (Axel Wannag) have told in personal interviews 1998 that people in these Scandinavian countries have also used cold protecting ointments, especially “in old days”. They did not have the knowledge, however, to estimate the magnitude of the present use. A few cold experts from USA (Murray Hamlet 1999, Andrew Young 2000, personal communications) have supposed that this habit is not common in USA or Canada. It was somewhat surpirising that people living in southern Finland, with less actual climatic exposure to the cold, use protective ointments distinctly more often than in northern Finland. This difference is probably explained by both psychological and perceptional factors. The scanty experience and low habituation to the cold in the mostly mild winter climate in southern parts of the country leave the inhabitants often without psychological cold tolerance and adaptation of skin perception. The random really cold days lead to a subjective need for protective measures. This is in contrast to the more regular cold exposure in northern Finland leading to cold tolerance. Subjective cold sensitivity, although more prevalent among ointment users, did not rise statistically to a significant correlation in study I with the use of protective ointments (p = 0.08). The standard of living in northern Finland is somewhat lower than in southern parts and may form a small relative hindrance for buying ”skin creams”, the use of which is often assessed as waste of money and time by northern men. ”It is not a real man who can not tolerate the cold”. Nivea® and Vitalis® cremés, both greasy emollients, were by far the most popular cold protecting emollients marketed and consumed in Finland. The annual sales figures of these sports ointments had no clear tendency either to increase or to decrease during the 1990s, although some winter recreational activities, especially snow boarding, have become more popular. It is possible that the release of the preliminary results of our studies in mass media ten years ago has already had a restrictive influence on the use of cold protecting emollients. This is true at least in the Finnish Defence Forces where the new information has been transformed into official recommendations and a decision not to manufacture and distribute a cold protecting ointment by the Military Pharmacy, anymore. Several of the respondents in study I named also lip balms as cold protective emollients. This indicates that people do not distinctly distinguish the topical protection against frostbite and the prevention of cold-induced skin xerosis from each other. A majority of the conscripts, who had personally used cold protecting emollients, assessed 80 their effect clearly or weakly advantageous both as cold protective agents (84%) and as skin moisturizers (69%). Dryness of the skin has been shown to be a quite subjective perception. In healthy persons a number of irrational, subjective factors was shown to play a role in the use of moisturizers, not the clinical or objectively measured dryness of the skin. Female preponderance in subjective complaints of skin dryness was significant, although objective parameters showed similar distribution of skin dryness between both genders. (Jemec & Serup 1992.) The sensation of skin temperature was also shown to be subjective and irrespective of objective results in study IV, especially when white petrolatum was applied on the skin. Thus, a psychological component plays probably a part also in the use of cold protecting ointments. The effect of gender on the subjective skin sensation of temperature has not been studied, to our knowledge. All the test subjects in our study IV were men.

6.3.4 Pharmaceutical preparations

Theoretically, local cold injuries could be prevented by using topical (e.g. nicotinic and salicylic acid derivatives, nitro-glycerine) or systemic vasodilators (e.g. nifedipine, papaverin, reserpine) that increase the blood circulation in risk areas. However, these pharmaceutical agents diminish or prevent the natural vascular cold responses and increase the heat loss and thus the risk of hypothermia. Whether the sum effect of medication is advantageous or injurious, depends on the timing, severity and type of the cold exposure. Dick 1989 recommended the topical use of a mixture of methylsalicylate and nicotinic acid ester for soldiers with a tendency to excessive skin reactions in the cold, particularly to be used on the face and ears. He did not, however, present any scientific data to justify his recommendation. Our data with vasodilator liniments (study IV) showed a consistent warming effect, maximally by 4—8°C. As this influence diminished remarkably already during the test period of 25—30 min, it is not likely to function successively in natural cold exposures lasting for hours. Free radical scavengers (rutin, hydergine, DMSO, glycerol), anti-prostaglandin and anti-thrombotic agents (thromboxane inhibitors, dextran i.v.) and anti-inflammatory agents have been suggested for the therapy of frostbite. In the review of Mills et al. 1993 on the pathomechanism of cold injuries and on the possibilities of prevention and therapy no confirmed evidence was presented of the preventive efficacy by pharmaceutical agents.

6.3.5 Cold adaptation

Working indoors as a civilian was shown to be a risk factor for cold injury during land manoeuvres. This indicates that local and general cold adaptation may increase cold tolerance and prevent both local frostbite and general hypothermia. On the other hand, cold sensitive individuals may have intentionally chosen an indoor job to avoid cold exposure. Local adaptation of extremities, e.g. in hands, has been studied in arctic native 81 people and cold-exposed professional workers. The positive impact is characterized by warmer local skin temperature, less pain, greater manual dexterity, higher blood flow and earlier CIVD (Bittel 1998). Heat loss through ”fisherman´s hands” is high but manual performance is good. Metabolic, insulative, hypothermic and insulative hypothermic modes of cold adaptation have been described in studies on natives in their natural cold environment (acclimatization) or test subjects in laboratory circumstances (acclimation) (Bittel 1998). The term “cold habituation” includes the reduction of negative (physiological and behavioural) responses to the cold and diminished perception of the cold after repeated cold stimulation. The cultural cold adaptation that includes the local tradition transferred to children by parental guidance to use accurate clothing and other preventive measures is, of course, an important part of cold adaptation, too. In military the knowledge is forwarded by education and training of leaders and troops, although such schooling can never completely compensate self-obtained, life-time experience. The physiological cold adaptation develops to its maximum in about four weeks. Although the benefits of intended physiological cold adaptation are debatable and the data is conflicting, it has been reported that the annual incidence of frostbite in the people in their second year in the Antarctic was only 29%, compared with 74% in the first year of newcomers (Massey 1959).

6.4 Use of cold protecting emollients as a risk factor for frostbite of the ears and face

6.4.1 Strength of association

In the epidemiological questionnaire study I on 830 conscripts, the temporal association between various risk factors and occurrence of frostbite was not evaluated. The evidence of possible causal association between the use of emollients and frostbite was, therefore, very indirect as it was assessed from the general connection of frostbite incidence in the head with the habit to use (sometimes or often) emollients in prevention of cold injury. A strong cold exposure or an actual personal cold sensitivity might both lead to the increased risk of frostbite and to a subjective need for using protective ointments. A traditional “knowledge” of their advantages probably strengthens this idea in one´s mind. Both subjective cold sensitivity and a high or moderate cold exposure were, indeed, associated in study I with a significantly higher frequency of frostbite in almost all locations of the head and with the more common use of protecting emollients. This latter association between cold sensitivity and use of protecting emollients was not, however, statistically significant. In the epidemiological study II of 913 frostbite cases in the head having occurred during the military service, the risk factors evaluated were influencing simultaneously with the occurrence of frostbite. The use of protecting emollients was calculated to be statistically independent of other risk factors. The controlled structure of this study, the great number of probands and controls, and the high risk values found accentuate the 82 significance and value of the results in this investigation leading to a high probability of a causal relationship between the use of emollients and frostbite. As the data of both epidemiological studies was unexpected and contradictory to traditional knowledge, there was a good reason to reconsider, re-evaluate and retest the new observations. Two further studies (III and IV) were carried out in order to confirm or disprove the findings in the prior studies and to clarify, if possible, the mechanisms of the thermal effects of emollients. In our series of studies, both the thermophysical tests in vitro (III) and the face-half comparison study on the living facial skin in vivo (IV), the latter combining both the physical and physiological effects of emollients, led to compatible results with the epidemiological studies. The thermal insulation of test ointments in vitro (study III) was shown to be very small in dry circumstances. The evaporation of water content from o/w cream A led to a “negative insulation”, it increased thermal loss for about half an hour. Water-input made the evaluation of thermal effects more complicated. The concentration of water and other individual characteristics in emollients affected the grade of the thermal resistance, which did not rise into high level in any condition. While the cooling effect of emollients was not evident in every in vivo test on facial skin (study IV), the majority of objective comparisons with all test emollients and with both methods of temperature measurements showed a significant preponderance of cooling effect, even when the subjective skin sensation suggested otherwise in some tests. In the cold, the superficial skin layers are cooler than the deeper layers. This applies probably also to the emollient layers on the skin. The measurement of skin temperature may give theoretically different results depending on which layer the measurement is carried out or how deep in the skin the sensors are. IR-thermography gave values from the surface of the skin or the emollient layer. This could cause a bias giving lower temperatures to the emollient half than to the nonapplied half. Our data in study III showed, however, that the thermal insulative effect of even a thick emollient layer was insignificant. This means that the temperature gradient between the surfaces of the skin and emollient is probably very small. On the other hand, the thermistors in study IV were attached on the skin surface before and under the application. They measured thus the temperature of the skin surface on both halves of the face. The temperatures on the applied and nontreated facial halves were thus registered by two methods: one measuring the temperature on the surface of the skin on both sides, the other measuring the temperature in the emollient surface on the applied half and in the skin surface on the untreated half. The absolute temperature values of IR -thermography were not lower than temperatures measured with thermistors. As both methods gave consistent results in the thermal comparison of facial halves, the possibility of methodological bias in this respect was considered minimal. A person senses the state of his nerve-endings that act as cold receptors. These are situated about 200 µm below the skin surface and fire nerve impulses depending both on ”static” ambient temperature and also on rate of change in temperature. (Parsons 1993.) The slightly different levels of skin temperature measurements and skin thermal perception may have had some influence on the discrepancy between objective data and subjective sensation. 83 6.4.2 The effect of the quality of emollients and timing of the application

Four different test emollients were chosen into this series of studies to represent a wide variety of creams and ointments, with an emphasis on waterless ointments. The resources did not make it possible to widen the spectrum with more emollients. In vitro tests (study III) were performed using a skin model that, when estimated afterwards, was quite rough for measuring so minimal thermal effects as the emollients possessed, even in 10-times thicker application than in normal topical therapy. Inter-emollient differences could not be found in dry tests, except during the time period when emulsion cream A lost its own water content by evaporation. The difference in the water evaporation and diffusion characteristics between emulsion creams A and B was of unexpected magnitude and warned against generalization of thermophysical behaviour of emollients according simply to their water content. Cream B kept its water content in dry tests when cream A lost it rapidly by evaporation. When the water input was simulating TEWL, the behaviour of test emollients diverged again. O/w cream A lost the input water quite easily letting it diffuse through the emollient and evaporate from its surface together with its own water content. W/o cream B and the waterless ointments occluded the input humidity and absorbed it into them thus increasing their thermal insulation a little. When the water input into the skin model was simulating perspiration, it caused spilling-over of water and cooling of the skin model with all test emollients after a period of saturation with humidity. The traditional avoidance of emulsion creams in cold protection seems to be somewhat justified by our data. The evaporation of the own water content from emulsion cream A in study III caused a cooling effect for about half an hour. The cooling effect of both emulsion creams was more obvious compared to waterless ointments in cold exposure comparisons in vivo (IV) at least for 25—30 min after their application. The cooling effect of cream A diminished only a little in tests when it was applied as early as one hour before the cold exposure. This gave enough time for the evaporation of cream A´s water content to end. The timing of the physical or physiological effects of emollients on the skin is not precisely known, whether applied once or repeatedly on consecutive days. From clinical and scientific experience the moisturizing and smoothing effects of one application could be estimated to last for hours rather than days (Blichmann et al. 1989, Loden & Lindberg 1990), but much longer efficacy has also been observed. The therapeutic effect of repeated applications (2—3 weeks) of petrolatum on skin xerosis lasted longer, for one to three weeks, after cessation of treatment (Kligman 1978). An oil-in-water emulsion lotion and glycerol had a protracted moisturizing effect lasting at least 7 days after cessation of one-week (lotion) or three-day (glycerol) treatment (Serup et al. 1989). This difference of efficacy duration can be explained by a hypothesis that one application influences mainly physically as a temporary inert occlusion and repeated applications lead to a penetration of lipids into the intercellular structures of stratum corneum and have a more prolonged, pharmacological type of influence (Ghadially et al. 1992). The timing of thermal effects and of the interaction of emollients with the skin is difficult to predict. At the moment, there is no certainty on how many hours before a cold exposure the moisturizing emollients should be applied to be certain of their safety in respect to the risk of cold injury. 84 6.4.3 Mechanisms of the disadvantageous effect of emollients in the cold

The mechanism of the observed disadvantageous effect of cold protecting emollients stays unconfirmed and debatable. The slightly lower skin temperature on the site of the application may have a contributing effect on the skin freezing, as well as many other factors (Fig. 15).

Fig. 15. Schematic summary of the evidence correlating the use of cold protecting emollients with frostbite of the face and ears. Estimation of the strength of significance in epidemiological data and importance of possible mechanisms involved is indicated by the width of the arrows.

Preventive and protective behaviour has a major influence on the risk of frostbite. The human body has been shown to be unreliable as a temperature-measuring instrument. The facial skin perception of protection, when using greasy emollients (study IV), leads inevitably to a false sensation of safety and to neglect of effective preventive efforts. The mixing of lipid components of emollients with intercellular lipids of epidermis and their invasion even deeper in the skin may change the thermal perception of cold receptors. It is interesting that the use of lip protectants was also shown to be associated with a little higher incidence of lip injuries in the cold, although the effect did not rise to the level of statistical significance (Lewis et al. 1985). This result indicates that the lip protectants are ineffective, if not disadvantageous, against cold-induced lip injuries. The observations of Jemec & Serup 1992 concerning the erroneous perception of skin dryness leading to subjective need for using moisturizers, show an additional dimension in the incapability of a human being to sense correctly the state of his or her skin. 85

Other mechanisms may also be involved either as major or minor contributing factors. Moisturizing of the corneal layer by the occlusive effect of emollients is one possible mechanism, as wetting of the skin has been shown to raise the freezing temperature both in vivo (Keatinge & Cannon 1960, Molnar et al. 1973) and in vitro (Inoue et al. 1986). There is a possibility that emulgators in some compositions of emollients increase TEWL and evaporation of water and cool down the skin surface. There may still be other factors, such as actual cold sensitivity and severity of cold exposure, that may lead to both increased risk of frostbite and to use of ”protective” ointments, causing a possible fundamental bias in estimation of the risk of emollients. High or moderate exposure to the cold was associated with the use of emollients (study I). Statistical evidence of the use of emollients as an independent risk factor for frostbite and its high odds ratios in study II, together with low significance of cold sensitivity in this respect, indicate against this possibility. In study I, the association of subjective cold sensitivity with the use of protective emollients was not statistically significant. Our hypothesis is that a mixture of false skin perception, erroneous trust based partly on tradition and the lack of expected protecting effects by the greasy emollients form the main basis of the injurious influence of cold protecting emollients on the facial skin in the cold. 7 Conclusions

Especially mild frostbite of the bare areas of the head, ears and face, was common in Finland, having occurred in almost half of the young men already at the age of 19 years. Ears were more prone to cold injury than other locations of the head. Frostbite of the nose and cheeks occurred with equal frequency with each other, as the chin and other parts of the face stayed below these three locations in the frostbite incidence. Cold exposure was, of course, the main cause of cold injuries. Neglect to use protective clothing in the cold, especially a hat with earflaps and scarf, formed a very significant risk factor for frostbite of the ears. Applying a protective ointment on the face and (more rarely) on ears formed a considerable independent risk factor for both facial and ear frostbite. This unexpected association was found both in our epidemiological study (II) concerning simultaneous occurrence of ointment use and frostbite and in a more general level in the questionnaire study (I) in which the temporal connection was not evaluated. The frequency of using cold protective emollients was quite high. On average 21% of conscripts had used them by the age of 19 years in Finland. Women and children seemed to use them much more often than adult men. The more the citizens were habituated with the cold exposure of local climate, the less they seemed to use protective ointments. The subjective experience of a great majority of users indicated a protecting effect both on local cold injury and drying of the facial skin in the cold. In thermophysical studies of four different emollients in dry conditions in vitro, the thermal insulation of test creams and ointments, in thick applications, was insignificant even after the water content of an oil-in-water cream had evaporated. This evaporation caused an extra cooling effect on the surface of the skin model. The thermal insulation given by emollients in this study was at best minimal and in some conditions their total thermal effect was cooling. The effect of different ointments on the facial skin temperature in vivo was quite small, mostly a little cooling and sometimes not clearly discernible from the temperature difference caused by normal asymmetry of the face. Subjective thermal sensation of test 87 subjects was, however, warming in majority of tests with the greasy white petrolatum, but neutral or cooling with other tested emollients. It is probable that one of the main reasons for the increased risk of frostbite, associated with the use of protective emollients in the cold, was not their actual, quite small lowering effect on the skin temperature, but indirectly their effect on facial thermal sensation. White petrolatum gave a skin perception of warmth, leading to a false sensation of safety in the cold, without having the presumed protective effect. This skin perception, observed both in the questionnaire study (I) and in the experimental cold chamber study (IV), forms probably the ground for the traditional habit of using thick greasy ointments and may lead to a neglect of efficient preventive and protective measures. It is also likely that people with cold-sensitive skin use emollients more often than people who have cold-resistant skin. It is possible that the increase of water content of skin under occlusive ointments may promote freezing. On the other hand, at least some oil-in-water creams cool the skin by evaporation of their water content after their application. In this respect the subjective perception of users has led to a correct traditional conclusion to avoid applying creams with high water content in the cold. The increased risk of local cold injury indicates that the traditional use of protective emollients can not be recommended. This data wakes up also questions of the possible dangers connected with the application of cosmetic moisturizers on the face when going out and exposing the bare facial skin to an actual risk for frostbite. 8 References

Agner T & Serup J (1989) Seasonal variation of skin resistance to irritants. Br J Dermatol 121: 323— 328. Anbar M (1995 a) Dynamic area telethermometry and its clinical applictions. SPIE 2473: 312—322. Anbar M (1995 b) Multiplewavelength infrared cameras and their biomedical applications. SPIE 2473: 323—331. Anttonen H, Virokannas H & Paso R (1991) Effect of temperature, wind and behaviour on frostbite. Arch Complex Environ Studies 3: 31—35. Anttonen H (1993) Construction and testing a sweating hot plate for evaluation of textile materials. Acta Univ Oul C 70, Oulu. Anttonen H (1995) Taisteluasu M91:n käyttöalueet ja suojaavuus eri tilanteissa. Kirjassa: Anttonen H & Vuori E (toim) Sotilasvaatetus ja sen kehittäminen. Pääesikunnan materiaalihallinto-osasto ja Oulun aluetyöterveyslaitos. Puolustusvoimien koulutus- ja kehittämiskeskus. Ykkös-Offset Oy, Vaasa. Ss. 93—103. Arndt KA, LeBoit PE, Robinson JK & Wintoub BU (eds) (1996) Cutaneous Medicine and Surgery, an Integrated Program in Dermatology. WB Saunders Co., Philadelphia. Barry RW (1992) Enhancement of drug absorption through human skin. In: Champion RH & Pye RJ (eds) Recent Advances in Dermatology, No. 9. Churchill Livingstone Inc., Singapore, p 185— 198. Benfeldt E (1999) In vivo microdialysis for the investigation of drug levels in the dermis and the effect of barrier perturbation on cutaneous drug penetration. Thesis. Acta Derm Venereol, Suppl. 206. Beise RD, Carstens E & Kohllöffel LUE (1998) Psychophysical study of stinging pain evoked by brief freezing of superficial skin and ensuing short-lasting changes in sensations of cool and cold pain. Pain 74: 275—286. Berg A, Aas P & Lund T (1999) Lokale frostskader. Tidsskr Nor Laegeforen 119: 382—385. Bishop HM, Collin J, Wood RFM & Morris PJ (1984) Frostbite in Oxfordshire: the impact of a severe winter on an unprepared civilian population. Injury 15: 379—380. Bittel JHM (1992) The different types of general cold adaptation in man. Int J Sports Med 13: 172— 176. Bittel JHM (1998) Cold adaptation – its relevance for long term exposure. In: Holmér I & Koklane K (eds) Problems with cold work. Arbete och hälsa 18: 147—151. National Institute for Working Life, Solna. Blair JR, Schatzki R & Orr KD (1957) Sequelae to cold injury in one hundred patients. Follow-up study four years after occurrence of cold injury. JAMA 163: 1203—1208. 89

Blank IH (1952) Factors which influence the water content of the stratum corneum. J Invest Dermatol 18: 433—440. Blichmann CW, Serup J & Winther A (1989) Effects of single application of moisturizer: evaporation of emulsion water, skin surface temperature, electrical conductance, electrical capacitance and skin surface (emulsion) lipids. Acta Derm Venereol 69: 327—330. BMDP Manual (1988). BMDP Statistical Software Inc., Los Angeles. Boswick Jr JA, Thompson JD & Jonas RA (1979) The epidemiology of cold injuries. Surg Gyn Obst 149: 326—332. Budd GM, Brotherhood JR, Hendrie AL & Jeffery SE (1991) Effects of fitness, fatness, and age on men´s responses to whole body cooling in air. J Appl Physiol 71: 2387—2393. Burton AC (1934) The application of the theory of heat flow to the study of energy metabolim. J Nutrition 7: 497—533. Burton AC & Edholm OG (1955) Man in a cold environment. Edward Arnold Publishers, London. Candler WH & Ivey H (1997) Cold weather injuries among US soldiers in Alaska: a five-year review. Mil Med 162: 788—791. Cattermole TJ (1999) The epidemiology of cold injury in Antarctica. Aviat Space and Environ Med 70: 135—140. Champion RH, Burton JL, Burns DX & Breatnach SM (eds) (1998) Rook/Wilkinson/Ebling Textbook of Dermatology, 6th ed. Blackwell Science, Oxford. Chen F (1997) Thermal responses of the hand to convective and contact cold – with and without gloves. Dissertation. Arbete och hälsa, 1997:3. National Institute for Working Life, Solna. Chen F, Nilsson H & Holmér I (1994) Finger cooling by contact with cold aluminium surfaces – effects of pressure, mass and whole body thermal balance. Eur J Appl Physiol 69: 55—60. Chen F & Holmér I (1998) Subjective sensation during local cold exposure. In: Holmér I & Kuklane K (eds) Problems with cold work. Arbete och hälsa 18: 240—242. National Institute for Working Life, Solna. Conti A, Rogers J, Verdejo P, Harding CR & Rawlings AV (1996) Seasonal influence on stratum corneum ceramide 1 fatty acids and the influence of topical essential fatty acids. Int J Cosm Sc 18: 1—12. Conway GA, Husberg BJ & Lincoln JM (1998) Cold as a risk factor in working life in the circumpolar regions. In: Holmér I & Kuklane K (eds) Problems with cold work. Arbete och hälsa 18: 1—10. National Institute for Working Life, Solna. Cooper MD, Jardine H & Ferguson J (1992) Seasonal influence on the occurrence of dry flaking facial skin. In: Marks R & Plewig G (eds) The environmental threat to the skin. Martin Dunitz, London, p 159—164. Craig RP (1984) Military cold injury during the war in the Falkland Islands 1982: an evaluation of possible risk factors. J Roy Arm Med Corps 136: 89—96. Crawshaw LI, Nadel ER, Stolwijk JAJ & Stamford BA (1975) Effect of local cooling on sweating rate and cold sensation. Pflugers Arch 354: 19—27. Daanen HAM (1997) Central and peripheral control of finger blood flow in the cold. Thesis. Vrije University. Daanen HAM, Van de Linde FJG, Romet T & Ducharme MB (1997) The effect of body temperature on the hunting response of the middle finger skin temperature. Eur J Appl Physiol 76: 538—543. Daanen HAM & Ducharme MB (1999) Finger cold-induced vasodilatation during mild hypothermia, hyperthermia and at thermoneutrality. Aviat Space Environ Med 70: 1206—1210. Danielsson U (1996) Windchill and the risk of tissue freezing. J Am Physiol Soc 81: 2666—2673. Denda M, Sato J, Masuda Y, Tsuchiya T, Koyama J, Kuramoto M, Elias PM & Feingold KR (1998 a) Exposure to a dry environment enhances epidermal permeality barrier function. J Invest Dermatol 111: 858—863. 90

Denda M, Sato J, Tsuchiya T, Elias PM & Feingold KR (1998 b) Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses. J Invest Dermatol 111: 873—878. Denda M & Tsuchiya T (2000) Barrier recovery rate varies time-dependently in human skin. Br J Dermatol 142: 881—884. Di Carlo A (1995) Thermography and the possibilities for its applications in clinical and experimental dermatology. Clin in Dermatol 13: 329—336. Dick HJ (1989) Prevention of cold injury on exercises with the allied military force (land) in north Norway. Medical Corps International 4: 41—47. Dinep M (1975) Cold injury: a review of current theories and their application to treatment. Connecticut Medicine 39: 8—10. Dixon JC & Prior MJ (1987) Wind-chill indices – a review. The Meteorological Magazine 116: 1— 17. Dover JS, Dowd PM & Tonnesen MG (1996) Cutaneous effects of heat and cold. In: Arndt KA, LeBoit PE, Robinson JK & Wintoub BU (eds) Cutaneous Medicine and Surgery, an Integrated Program in Dermatology. WB Saunders Co., Philadelphia, p 823—835. Dowd PM (1998) Reactions to cold. In: Champion RH, Burton JL, Burns DX & Breatnach SM (eds) Rook/Wilkinson/Ebling Textbook of Dermatology. 6th ed. Blackwell Science, Oxford, p 957— 968. Eberlein-König B, Spiegl A & Przybilla B (1996) Change of skin roughness due to lowering air humidity in a climate chamber. Acta Derm Venereol 76: 447—449. Edwards M & Burton AC (1960) Temperature distribution over the human head, especially in the cold. J Appl Physiol 15: 209—211. Elias PM & Jackson SM (1996) What does normal skin do? In: Arndt KA, LeBoit PE, Robinson JK & Wintroub BU (eds) Cutaneous Medicine and Surgery, an Integrated Program in Dermatology. WB Saunders Co., Philadelphia, p 46—57. Elsner P (1997) Efficacy assessment of preventive creams. Where do we stand in 1997 (abstract)? In: Kanerva L & Turtiainen P (eds) Proceedings of the fifth international congress on occupational dermatoses. The Nordic Institute for Advanced Training in Occupational Health (NIVA), Helsinki, p 47—50. Enander A (1986) Sensory reactions and performance in moderate cold. Thesis. Arbete och hälsa 1986: 32. National Institute for Working Life, Solna. Endrich B, Hammersen F & Messmer K (1990) Microvascular ultrastructure in non-freezing cold injuries. Res Exp Med 190: 365—379. Ervasti E (1962) Frostbites of the extremities and their sequelae: a clinical study. Acta Chir Scand Suppl 299: 1—69. Ervasti O, Virokannas H & Hassi J (1991) Frostbite in reindeer herders. Arct Med Res 50: Suppl 6: 89—93. Ervasti O, Virokannas H, Hassi J, Pramila S, Linna T, Tolonen U & Manelius J (1993 a) Sormipalel- tumien jälkiseuraukset. Raportti 1993/2 A, Maanpuolustuksen tieteellinen neuvottelukunta (MA- TINE), Helsinki. Ervasti O, Hassi J & Manelius J (1993 b) Paleltuma aiheuttaa myöhäismuutoksia luustossa ja nivelis- sä. Duodecim 109: 60—63. Ervasti O, Juopperi K, Hassi J, Rintamäki H, Latvala J, Linna T & Pihlajaniemi R (1999) Paleltumat varusmiespalveluksen aikana pohjoisella maanpuolustusalueella saapumiserissä 2/95 ja 1/96. Tut- kimusraportti osana rahoittajaraporttia: Hassi J, Juopperi K, Ervasti O, Latvala J, Rintamäki H, Pihlajaniemi R & Linna T: Paleltumaherkkyyden arviointi. Työterveyslaitos, Oulu. Ervasti O, Hassi J, Rintamäki H, Virokannas H, Kettunen P, Pramila S, Linna T, Tolonen U & Manelius J (2000) Sequelae of moderate finger frostbite as assessed by subjective sensations, clinical signs, and thermophysiological responses. Int J Circumpolar Health 59: 137—145. 91

Feingold KR & Elias PM (2000) The environmental interface: regulation of permeability barrier homeostasis. In: Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 45—58. Fendler EJ (2000) Physico-chemical considerations. In Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 175—182. Foray J (1992) Mountain frostbite. Sports Med 13: 193—196. Francis TJR (1984) Non freezing cold injury: a historical review. J Roy Nav Med Serv 70: 134—139. Franz DN & Iggo A (1968) Conduction failure in myelinated and non-myelinated axons at low temperatures. J Physiol 199: 319—345. Fraps P (1985) Kälteschäden während der Ubungen des Heeres im I. Quartal 1985. Wehrmed Mschr Heft 11: 469—479. Friberg O (1993) Kylmän aiheuttamat vammat. Kirjassa: Koskenvuo K (toim) Kenttälääkintä, ensi- hoidon perusteet. Pääesikunnan terveydenhuolto-osasto, Hämeenlinna, ss. 373—380. Friberg O (1996) Toiminta kylmissä oloissa. Kylmävammat. Kirjassa: Koskenvuo K (toim) Sotilasterveydenhuolto, 3. p. Pääesikunnan terveydenhuolto-osasto, Hämeenlinna, ss. 287—297. Fritz RL & Perrin DH (1989) Cold exposure injuries: prevention and treatment. Clin Sports Med 8: 111—128. Froese G & Burton AC (1957) Heat losses from the human head. J Appl Physiol 10: 235—241. Ganong WF (1997) Review of Medical Physiology. 18th ed., Appleton & Lange, Stamford, Connecticut. Gardner MJ & Altman DG (1989) Statistics with confidence: confidence intervals and statistical guidelines. BMJ, London. Gaul LE & Underwood GB (1951) Clinical aspects of dry skin. J Invest Dermatol 18: 9—12. Ghadially R, Halkier-Sörensen L & Elias PM (1992) Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol 26: 387—396. Gordon RG (1974) The response of a human temperature regulatory system model in the cold. Thesis. University of California, Santa Barbara. Granberg P-O (1991) Human physiology under cold exposure. Arct Med Res 50: Suppl. 6: 623—627. Granberg P-O (1996) Lokala kylskador. Arbete och hälsa 5: 85—90. National Institute for Working Life, Solna. Grant RT & Bland EF (1931) Obervation on arteriovenous anastomoses in human skin and in bird´s foot with special reference to the reaction to cold. Heart 15: 385—411. Grice K, Sattar H, Sharrat M & Baker H (1971) Skin temperature and transepidermal water loss. J Invest Dermatol 57: 108—110. Guyton AC (1991) Textbook of Medical Physiology, 8th ed. WB Saunders Co., Philadelphia. Hafferl A (1957) Lehrbuch der Topografischen Anatomie. 2nd ed. Springer-Verlag, Berlin-Göttingen-Heidelberg. Halkier-Sörensen L, Menon GK, Elias PM & Thestrup-Pedersen K (1995) Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish processing industry. Br J Dermatol 132: 391—401. Halkier-Sörensen L (2000) Efficacy of skin care products and different mixtures of lipids on barrier function. In: Gabard et al. (eds) Dermatopharmacology of topical preparations – a product-development oriented approach. Springer-Verlag, Berlin, Heidelberg, p 329—363. Hamlet MP (1987) An overview of medically related problems in the cold environment. Mil Med 152: 393—396. Hamlet MP (1998) Peripheral cold injury. In: Holmér I & Kuklane K (eds) Problems with cold work. Arbete och hälsa 18: 127—131. National Institute for Working Life, Solna. Hamlet MP (2000) Prevention and treatment of cold injury. Int J Circumpolar Health 59: 108—113. Hannuksela M, Pirilä V & Salo OP (1975) Skin reactions to propylene glycol. Contact Dermatitis 1: 112—116. 92

Hanson HJ & Goldman RF (1969) Cold injury in man: a review of its etiology and discussion of its prediction. Mil Med 134: 1307—1316. Harris I & Hoppe U (2000) Lanolins. In: Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 259—267. Hassi J, Rintamäki H & Koskenvuo K (1996) Toiminta kylmissä oloissa. Fysiologia. Kirjassa: Kos- kenvuo K (toim) Sotilasterveydenhuolto, 3. p. Pääesikunnan terveydenhuolto-osasto, Hämeenlin- na, ss. 280—286. Hassi J, Juopperi K, Remes J, Rintamäki H, Näyhä S, Ervasti O, Jousilahti P & Vartiainen E (1998) FINRISKI ´97. Kylmäaltistusalaotos. Tutkimus suomalaisten kylmäaltistuksesta, -haitoista ja kyl- mältä suojautumisen tavoista. Tutkimuksen toteutus ja perustaulukot. Raportti 4, Oulun aluetyö- terveyslaitos, Oulu. Hassi J, Ervasti O, Juopperi K, Rintamäki H, Latvala J, Pihlajaniemi R & Linna H (1999) Paleltumien elinaikainen ilmaantuvuus ja niiden riippuvuus yksilötekijöistä. Tutkimusraportti osana rahoitta- jaraporttia: Hassi J, Juopperi K, Ervasti O, Latvala J, Rintamäki H, Pihlajaniemi R & Linna T: Pa- leltumaherkkyyden arviointi. Työterveyslaitos, Oulu. Hassi J & Mäkinen TM (2000) Frostbite: occurrence, risk factors and consequences. Int J Circumpolar Health 59: 92—98. Havenith G, van de Linde EJG & Heus R (1992) Pain, thermal sensation and cooling rates of hands while touching cold materials. Eur J Appl Physiol 65: 43—51. Hensel H (1981) Thermoreception and temperature regulation. Monographs of the Physiological Society No. 38. Academic Press Inc., London. Hertzman AB & Roth LW (1942) The absence of vasoconstrictor reflexes in the forehead circulation. Effects of cold. Am J Physiol 136: 692—697. Holland DB, Roberts SG, Wood EJ & Cunliffe WJ (1993) Cold shock induces the synthesis of stress proteins in human keratinocytes. J Invest Dermatol 101: 196—199. Huh J, Wright R & Gregory N (1996) Localized facial teleangiectasias following frostbite injury. Cutis 57: 97—98. Höflin FG (1979) Kälteschäden. Therapeutische Umschau 36: 16—20. Ilmarinen R (1987) Kylmän fysiologiset vaikutukset ihmiseen. Kirjassa: Ilmarinen R (toim) Ihminen kylmässä. Työympäristötutkimuksen aikakauskirja 87:4. Työ ja ihminen, Työterveyslaitos, Hel- sinki. Kirja- ja offsetpaino Purhonen Oy, ss. 277—319. Imokawa G, Akasaki S, Minematsu Y & Kawai M (1989) Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin. Arch Derm Res 281: 45—51. Imokawa G, Kuno H & Kawai M (1991) Stratum corneum lipids serve as a bound-water modulator. J Invest Dermatol 96: 845—851. Imokawa G (2000) Skin moisturizers: development and clinical use of ceramides. In: Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 269—298. Inoue T, Tsuji K, Okamoto K & Toda K (1986) Differential scanning calorimetric studies on the melting behaviour of water in stratum corneum. J Invest Dermatol 86: 689—693. ISO DIS 11092 (1993). Textiles – Determination of physiological properties – Measurement of thermal and water vapour resistance under steady state conditions. International Organization for Standardization, Geneva. Jemec GBE & Serup J (1992) Scaling, dry skin and gender. A bioengineering study of dry skin. Acta Derm Venereol Suppl 177: 26—28. Jessen K (1984) Akcidentel hypotermi – principper for behandling af universelle og lokale tilstande. Nord Med 99:72—75. Junila J, Kaarela O & Waris T (1999) The formation of the demarcation line at experimental frostbite. Int J Circumpolar Health 58: 44—51. 93

Juopperi K, Hassi J, Ervasti O, Rintamäki H, Latvala J, Pihlajaniemi R & Linna T (1999) Paleltumien elinaikainen ilmaantuvuus ja niiden riippuvuus kylmäaltistuksesta. Tutkimusraportti osana rahoit- tajaraporttia: Hassi J, Juopperi K, Ervasti O, Latvala J, Rintamäki H, Pihlajaniemi R & Linna T: Paleltumaherkkyyden arviointi. Työterveyslaitos, Oulu. Juopperi K, Remes J, Raatikka V-P, Hassi J, Risikko T & Toivonen L (2000) Merenkulkulaitoksessa kylmätyötä tekevien kylmälle altistuminen ja kylmästä aiheutuvat oireet ja vauriot. Raportti 8. Oulun aluetyöterveyslaitos, Oulu. Kanerva L (1988) Suojavoiteet. Kirjassa: Jolanki R, Tammela E, Estlander T, Jaakkola J, Kanerva L, Lähteenmäki M-T, Riihimäki V & Örn M: Käsien suojaus. Työterveyslaitos ja työsuojeluhallitus, Helsinki, ss. 116—118. Kappes B, Mills W & O´Malley J (1993) Psychological and psychophysiological factors in prevention and treatment of cold injuries. Alaska Med 35: 131—140. Kanzenbach TL & Dexter WW (1999) Cold injuries: protecting your patients from the dangers of hypothermia and frostbite. Postgrad Med 105: 72—78. Kaufman WC & Bothe DJ (1986) Wind chill reconsidered, Siple revisited. Aviat Space Environ Med 57: 23—26. Kaufman WC, Laatsch WG & Rhyner CR (1987) A different approach to wind chill. Aviat Space Environ Med 58: 1188—1191. Keatinge WR & Cannon B (1960) Freezing-point of human skin. Lancet 1:11—14. Keatinge WR (1998) Hazards of cold immersion. In: Holmér I & Kuklane K (eds) Problems with cold work. Arbete och Hälsa 18: 120—123. National Institute for Working Life, Solna. Kligman AM (1978) Regression method for assessing the efficacy of moisturizers. Cosm Toil 93: 27—35. Kligman AM, Lavker RM, Grove GL & Studemayer TJ (1982) Some aspects of dry skin and its treatment. In: Kligman AM & Leyden JJ (eds) Safety and efficacy of topical drugs and cosmetics. Grune & Stratton, Inc., New York, p 221—238. Kligman A (2000) Dry skin and moisturizers, introduction. In: Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 3—9. Korhonen A (1940) Sodanaikaisista paleltumavammoista. Duodecim 56: 128—135. Koskenvuo K (1976) Paleltumien torjunta. Sotilaslääket AikakL 51: 59—62. Koskenvuo K, Karvonen M & Korvenkontio M (1977) Varusmiesten alkutalven 1976 paleltumat. So- tilaslääket AikakL 52: 9—13. Koskenvuo K, Tervahauta R, Hassi J, Friberg O, Lindholm H, Anttonen H, Lehmuskallio E & Vuori E (1996) Toiminta kylmissä oloissa. Toimintakyvyn säilyttäminen maastossa pakkasella. Kirjas- sa: Koskenvuo K (toim) Sotilasterveydenhuolto 3. p. Pääesikunnan terveydenhuolto-osasto, Hä- meenlinna, ss. 297—310. Kreh A, Anton F, Gilly H & Handwerker HO (1984) Vascular reactions correlated with pain due to cold. Exp Neurol 85: 533—546. Kyösola K (1974) Clinical experiences in the management of cold injuries: a study of 110 cases. J Trauma 14: 32—36. Lamke LO & Wedin B (1971) Water evaporation from normal skin under different environmental conditions. Acta Derm Venereol 51: 111—119. Lamke LO, Nilsson GE & Reitner HL (1977) Insensible perspiration from the skin under standardized environmental conditions. Scand J Lab Invest 37: 325—331. Lewis T (1930) Observations upon the reactions of the vessels of the human skin to cold. Heart 15: 177—208. Lewis DM, Schulman JD & Carpenter WM (1985) The prevalence of lip injury during U.S – Army cold-weather exercises. Mil Med 150: 87—90. Lindholm H, Koskenvuo K, Sarna S & Friberg O (1993) Varusmiesten paleltumat vuosina 1976— 1989. Raportti A 1993/1. Maanpuolustuksen tieteellinen neuvottelukunta (MATINE), Helsinki. 94

Linné A (2000) A method for detection of previous cold injuries (abstract). In: Jormanainen V & Lohi O (eds) Proceedings of XXXIII Congress on Military Medicine. Defence Staff of Finnish Defence Forces, Vantaa, p 35. Lloyd EL (1994) Temperature and performance I: cold. ABC of sports medicine. BMJ 309: 531— 534. Lodén M & Lindberg M (1990) The influence of a single application of different moisturizers on the skin capacitance. Acta Derm Venereol 71: 79—82. Long CC, Mills CM & Finlay AY (1998) A practical quide to topical therapy in children. Br J Dermatol 138: 293—296. Lotte CA, Wilson DR & Maibach HI (1987) In vitro relationship between transepidermal water loss and percutaneous penetration of some organic compounds in man: effect of anatomical site. Arch Dermatol Res 279: 351—356. Marzella L, Jesudass RR, Manson PN, Myers RAM & Bulkley GB (1989) Morphologic characterization of acute injury to vascular endothelium of skin after frostbite. Plastic and Reconstructive Surgery 83: 67—75. Massey PMO (1959) Finger numbness and temperature in Antarctica. J Appl Physiol 14: 616—620. Mathias CG, Wilson DM & Maibach HI (1981) Transepidermal water loss as a function of skin surface temperature. J Invest Dermatol 77: 219—220. Middleton JD (1969) The effect of temperature on extensibility of isolated corneum and its relation to skin chapping. Br J Dermatol 81: 717. Middleton JD & Allen BM (1974) The influence of temperature and humidity on stratum corneum and its relation to skin chapping. J Soc Cosmet Chem 24: 239—243. Midttun M & Sejrsen P (1996) Blood flow rate in arteriovenous anastomoses and capillaries in thumb, first toe, ear lobe, and nose. Clin Physiol 16: 275—289. Mills WJ, O´Malley J & Kappes B (1993) Cold and freezing: a historical chronology of laboratory investigation and clinical experience. Alaska Med 35: 89—116. Molnar GW, Hughes AL, Wilson O & Goldman RF (1973) Effect of skin wetting on finger cooling and freezing. J Appl Physiol 35: 205—207. Nechaev A (2000) Cold trauma in Russian soldiers in winter war of 1939—1940 (abstract). In: Jormanainen V & Lohi O (eds) Proceedings of XXXIII Congress on Military Medicine. Defence Staff of Finnish Defence Forces, Vantaa, p 10. Nieminen S & Suominen E (1987) Paleltumavammat. Suomen Lääkärilehti 42: 613—616. Nieminen E, Leikola E, Koljonen M, Kiistala U & Mustakallio KK (1967) Quantitative analysis of epidermal lipids by thin layer chromatography with special reference to seasonal and age variation. Acta Derm Venereol 47: 327—338. O´Malley J, Mills W, Kappes B & Sullivan S (1993) Frostbite: general and specific treatment. The Alaskan method. Alaska Med 35; Appendix. Orr KD & Fainer DC (1952) Cold injuries in Korea during 1950—51. Medicine 31: 171—220. Parish WE (1992) Chemical irritation and predisposing environmental stress (cold wind and hard water). In: Marks R & Plewig G (eds) The environmental threat to the skin. Martin Dunitz, London, p 185—193. Parsons KC (1993) Human thermal environments. The effects of hot, moderate and cold environments on human health, comfort and performance. The principles and the practice. Taylor & Francis, London. Paso R, Anttonen H & Rintamäki H (1989) Pään kylmäkäyttäytymisen ennustemalli. Tutkimusra- portti, Oulun aluetyöterveyslaitos, Oulu. Paton BC (2000) A history of frostbite treatment. Int J Circumpolar Health 59: 99—107. Peacock AJ (1998) Oxygen at high altitude. BMJ 317: 1063—1066. Pulla RJ, Pickard RJ & Carnett TS (1994) Frostbite: an overview with case presentations. J Foot Ankle Surg 33: 53—63. 95

Rasch W & Cabanac M (1993) Vasomotor response of the human face: laser-Doppler measurements during mild hypo- and hyperthermia. Acta Physiol Scand 147: 431—436. Rawlings AV, Mayo AM, Rogers J & Scott IR (1993) Aging and the seasonal influence on stratum corneum lipid levels. J Invest Dermatol 101: 483. Rawlings AV, Watkinson A, Rogers J, Mayo A-M, Hope J & Scott IR (1994) Abnormalities in stratum corneum structure, lipid composition, and desmosome degradation in soap-induced winter xerosis. J Soc Cosmet Chem 45: 203—220. Riddell DI (1984) Is frostnip important? J Roy Nav Med Serv 70: 140—142. Rintamäki H & Hassi J (1989) Foot temperature and thermal sensation in the foot in the naked and clothed man. In: Mercer JB (ed) Thermal physiology. Elsevier Science Publishers B.V., p 173— 176. Rintamäki H, Mäkinen T & Gavhed D (1998) Effect of a wide hood on facial skin temperature in cold and wind. In: Holmér I & Kuklane K (eds) Problems with cold work. Arbete och hälsa 18: 58— 59. National Institute for Working Life, Solna. Rintamäki H, Rissanen S & Hassi J (2000) Factors affecting the cooling of fingers with contact on small metal object (abstract). In: Jormanainen V & Lohi O (eds) Proceedings of the XXXIII International Congress on Military Medicine. Defence Staff of Finnish Defence Forces, Vantaa, p 26. Rintamäki H (2000) Predisposing factors and prevention of frostbite. Int J Circumpolar Health 59: 114—121. Rosén L, Eltvik L, Arvesen A & Stranden E (1991) Local cold injuries sustained during military service in the Norwegian army. Arct Med Res 50: 159—165. Sampson JB (1984) Anxiety as a factor in the incidence of combat cold injury: a review. Mil Med 149: 89—91. Schaefer H & Redelmaier TE (1996) Skin barrier, principles of percutaneous absorption. S Karger AG, Basel. Schissel DJ, Barney DL & Keller R (1998) Cold weather injuries in arctic environment. Mil Med 163: 568—571. Schlagel CA & Sanborn EC (1964) The weights of topical preparations required for total and partial body inunction. J Invest Dermatol 42: 253—256. Serup J, Winther A & Blichmann CW (1989) Effects of repeated application of a moisturizer. Acta Derm Venereol 69: 457—459. SFS 5681 (1991) Textiles, physiological properties. Determination of thermal isolation, water vapour resistance and the combined effect of heat and moisture. Skin model method. Finnish Federation of Standardization. Siple PA & Passel CF (1945) Measurements of dry atmospheric cooling in subfreezing temperatures. Proc American Philos Soc 89: 177—199. Smolander J (2000) Ageing and performance in the cold (abstract). In: Hassi J, Holmér I & Rintamäki H (eds) Health and performance in the cold – workshop. Cold work action program. Investigation A3, Oulu Regional Institute of Occupational Health, Oulu. SPSS-X User´s Guid (1986), 2nd ed., McGraw-Hill and SPSS Inc., New York. Steegmann AT Jr (1979) Human facial temperatures in natural and laboratory cold. Aviat Space Environ Med 50: 227—232. Steinman A (1987) Adverse effects of heat and cold on military operations: history and current solutions. Mil Med 152: 389—392. Stevens JC & Choo KK (1998) Temperature sensitivity of the body surface over the life span. Somatosens Mot Res 15: 13—28. Sumner DS, Criblez TL & Doolittle WH (1974) Host factors in human frostbite. Mil Med 139: 454— 461. 96

Tagami H, Kanamary Y, Inoue K, Suehisa S, Inoue F, Iwatsuki K, Yoshikuni K & Yamada M (1982) Water-sorption-desorption test of the skin in vivo for functional assessment of the stratum corneum. J Invest Dermatol 78: 425—428. Taylor MS, Kulungowski MA & Hamelink JK (1989) Frostbite injuries during winter maneuvers: a long-term disability. Mil Med 154: 411—412. Taylor MS (1992) Cold weather injuries during peacetime military training. Mil Med 157: 602—604. Tervahauta R, Hassi J, Anttonen H, Vuori E & Lehmuskallio E (1993) Toimintakyvyn turvaaminen kenttäoloissa; kylmät olosuhteet. Kirjassa: Koskenvuo K (toim) Kenttälääkintä, ensihoidon perusteet. Pääesikunnan terveydenhuolto-osasto, Karisto Oy, Hämeenlinna, ss. 461—470. Thornfeldt C (2000) Critical and optimal molar ratios of key lipids. In: Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 337—347. Urschel JD (1990) Frostbite: predisposing factors and predictors of poor outcome. J Traum 30: 340— 342. U.S. Army Research Institute of Environmental Medicine (1992) Sustaining health and performance in the cold: environmental medicine guidance for cold weather operations. Natick, Massachusetts 01760—5007. Uter W, Gefeller O & Schwanitz HJ (1998) An epidemiological study of the influence of season (cold and dry air) on the occurrence of irritant skin changes of the hands. Br J Dermatol 138: 266—272. Ward M (1993) The first ascent of Mount Everest. BMJ 306: 1455—1458. Waris T & Kyösola K (1982) Cold injury of the rat skin. Scand J Plast Reconstr Surg 16: 1—9. Warner RR & Boissy YL (2000) Effect of moisturizing products on the structure of lipids in the outer stratum corneum of humans. In: Lodén M & Maibach HI (eds) Dry skin and moisturizers – chemistry and function. CRC Press, New York, p 349—369. Washburn B (1962) Frostbite, what it is – how to prevent it – emergency treatment. NEJM 266: 974— 989. Vaughn PB (1980) Local cold injury – menace to military operations: a review. Mil Med 145: 305— 311. Virokannas H, Hassi J, Anttonen H & Järvenpää I (1984) Symptoms and health hazards associated with the use of snowmobiles by reindeer herders. Arct Med Res 38: 20—26. Virokannas H & Anttonen H (1993) Risk of frostbite in vibration-induced white finger cases. Arct Med Res 52: 69—72. Wika M (1981) A comparative study of skin blood flow capacity in the face in ethnic groups subject to differential cold exposure, as measured by 133/54/ Xenon clearance technique. Arct Med Res, Report 28. Wilson O & Goldman R (1970) Role of air temperature and wind in the time necessary for a finger to freeze. J Appl Physiol 29: 658—664. Wilson O, Goldman RF & Molnar GW (1976) Freezing temperature of finger skin. J Appl Physiol 41: 551—558. Yosipovitch G, Xiong GL, Haus E, Sackett-Lundeen L, Ashkenazi I & Maibach HI (1998) Time-dependent variation of the skin barrier function in humans: transepidermal water loss, stratum corneum hydration, skin surface pH, and skin temperature. J Invest Dermatol 110: 20— 23.