BRITISH -MEDICAL JOURNAL VOLUME 285 7 AUGUST 1982 397 Br Med J (Clin Res Ed): first published as 10.1136/bmj.285.6339.397 on 7 August 1982. Downloaded from CLINICAL RESEARCH

Prediction of haemorrhagic diathesis in thrombocytopenia by mean platelet volume

A ELDOR, M AVITZOUR, R OR, R HANNA, S PENCHAS

Abstract Introduction The Coulter counter, model S Plus, provides a platelet Severe thrombocytopenia is usually associated with the develop- count and a mean platelet volume in all routine specimens ment of haemorrhagic diathesis, though not all patients with ofblood for cell count. The value of mean platelet volume severe thrombocytopenia develop a bleeding tendency.1 2 Platelet in the prediction of the haemostatic potential ofthrombo- number alone may therefore be an insufficient predictor of cytopenic patients was investigated in 175 patients with bleeding tendency in a particular patient. Several investigators haematological disorders who underwent 1473 blood have suggested that platelet size also affects the haemostatic counts over five months. Eighty-four haemorrhagic potential of some patients because the function of platelets episodes were detected, most in thrombocytopenic depends on their size under normal conditions and, particularly, patients. The mean platelet volume of patients with in thrombocytopenic states.' 15 Using in-vitro adhesion and haemorrhagic tendency was significantly lower (5-52 ± SD aggregation studies3-9 and in-vivo tests and observations such

017 fl) than that of patients without these tendencies as bleeding time and bleeding episodes in patients'0-12 it was http://www.bmj.com/ (7-87 ± SD 1-75 fl) (p <0 001). In cases of severe thrombo- evident that large platelets were haemostatically more active than cytopenia (<20x 109/l platelets) haemorrhagic episodes small platelets and functioned more efficiently in the prevention were frequent; however, the frequency of bleeding was of haemorrhagic tendency.' 12 It has been suggested that platelet considerably lower in cases in which the mean platelet size as well as number must be considered when predicting volume was higher than a suggested cut-off point of haemostatic potential in thrombocytopenic states.2 6-4 fl. Discriminant analysis selected mean platelet Until recently, platelet sizing was an elaborate and tedious volume as more important than platelet count for procedure performed in only a few laboratories equipped with

prediction of haemorrhagic state in severe thrombo- special expensive instruments. The introduction of the Coulter on 2 October 2021 by guest. Protected copyright. cytopenia. counter, model S Plus, has made it possible to determine In view of the useful discrimination that mean platelet platelet size from any routine specimen of blood for cell count.'3 volume provides between thrombocytopenic patients Platelet size as measured by this Coulter counter is expressed as who bleed and those who do not bleed, it may serve as a the mean platelet volume. We examined the mean platelet guide to predict the danger of haemorrhage and the need volume of all patients treated by the department of haematology for prophylactic platelet transfusion. from January to May 1981. We examined the association between the number and the size of the platelets with the appearance of a haemorrhagic diathesis. Patients taking anticoagulants or anti- aggregating agents and those with abnormal results of coagulation tests or congenital haemorrhagic disorders were excluded from this study. The results indicated that the platelet size, expressed Department of Haematology, Hadassah University Hospital, as mean platelet volume, is a valuable variable for the prediction Jerusalem, Israel 91120 of haemorrhagic diathesis in thrombocytopenic patients. A ELDOR, MD, senior lecturer R OR, MD, house officer R HANNA, medical laboratory technician Department of Social Medicine, Hebrew University-Hadassah Materials and methods School of Public Health and Community Medicine, Jerusalem, All patients under the care of the department of haematology either Israel 91120 in the day care unit or as inpatients were considered for the study. M AVITZOUR, BSC, statistician senior lecturer in medicine Blood samples-Samples were obtained daily from these patients and S PENCHAS, MD, MSC, were collected into dipotassium EDTA in a concentration of 1 mg/ml. 398 BRITISH MEDICAL JOURNAL VOLUME 285 7 AUGUST 1982

All samples were processed in the Coulter counter model S Plus TABLE II-Mean platelet volume and platelet count in different patient groups. Br Med J (Clin Res Ed): first published as 10.1136/bmj.285.6339.397 on 7 August 1982. Downloaded from within one hour of venesection. The patients were checked daily for Results are means±SD signs of haemorrhagic diathesis: those patients exhibiting any positive signs of bleeding underwent routine coagulation studies, which Mean platelet Mean platelet No of No of included determination of partial thromboplastin time, prothrombin Group count x 109/l volume fl patients tests time, thrombin time,14 and fibrinogen degradation products (Thrombo- 1 12 4±6 5* 6-6±1-83t 31 152 2 52-2±43-5 7-9±2-4 60 362 Wellcotest, Wellcome Research Laboratories, Beckenham, England). 3 235 2 ±180 3 7 8 ±5-5 141 836 Patients with congenital haemorrhagic disorders or found to have 4 622-1 ±196-5 8 06±4 2 22 114 abnormalities in these coagulation tests were excluded from the study. 5 255-3 ±76-7 8-48±1 0 200 200 Patients treated with or anticoagulant drugs anti-aggregating agents *Results adjusted to cluster sampling. were also excluded. A total of 175 patients (98 male, 77 female; age tDifference between group 1 and each of the other groups was significant (p < 0-001) range 8-93 years) were included. Patients receiving platelet trans- by Student's t test. fusions were excluded from the study for 14 days- after the last transfusion. Only one blood sample was taken during any episode of bleeding and only one examination of blood allowed for each patient daily (usually in the morning). Punch cards were prepared for each examination; they included the results of the various haematological 20 solIo o 00 o 000 o 0000 00 tests printed by the Coulter counter as well as the identifying number, 1 00000000 00 175 0 00 0 00 sex, and age of the patient, a code for the diagnosis of his disease, and * ol 00 0 0 000 00 0 a code for the existence and type of haemorrhage-purpura, ecchy- 0o0 15 * _ I0 oocoo mosis, and so on. Blood counts were also performed on normal subjects @0. 0 000 0 0 00 0 0 _125 * *0 -Io 00 0o0 0 and served as references. ema 0 00 0 0 0

Quality control for the Coulter counter, model S Plus, was estab- 10 . 0-0 -"*sm so 0 -o0 lished to the instructions of the manufacturer. A 0 daily according daily *o " *0 lb 7.5 *00 @5 0 calibration was performed using the 4C Plus normal haematology , 0000 00 reference control Electronics Northwell @00 0@0 (Coulter Ltd, Drive, England). a- The results for white blood red blood and * 0 0 0 cells, cells, haemoglobin, 25 *0 With hoemorrhoge * mean corpuscular volume were comparable to the results obtained Without hoemorrhoge 0 from the Coulter counter model S, while platelet counts correlated 0 well with phase microscopy counts. 4 5 6 7 8 9 10 11 12 Statistical analysis of the data-Punched cards were processed in a Mean platelet volume (fl) Cyber Control Data Co (USA) computer, model 172, and analysed in 179. The Statistical Mean platelet volume in patients with severe thrombocytopenia: a Cyber computer, model Package for Social association with platelet number and with haemorrhagic diathesis Sciences, version No 8, was used for analysis of the data.15 The (Scattergram constructed by the Cyber computer). following statistical tests were used: Student's t test, discriminant analysis, and sensitivity and specificity indices.'6 The data was referred to as cluster sampling. Each patient represents a cluster of cell counts. Intraclass correlations, in each subgroup of platelet numbers considerably lower than that of the other groups, and the difference were used to compute variances for cluster sampling.'7 The t tests was statistically significant (p < 0-001). The figure shows the associa- were computed using those variances. Discriminant analysis was tion between mean platelet volume and platelet time among severely performed only on those patients with severe thrombocytopenia, in thrombocytopenic patients (group 1). which intraclass correlations for both mean platelet volume and platelet Bleeding episodes-Eighty-four bleeding episodes were observed in number were low (0 18 and-0 19, respectively), hence we analysed our 28 patients. Most haemorrhages were associated with severe thrombo- sample as a simple random sample. cytopenia (group 1) since no other abnormalities were detected by the screening coagulation tests. One patient in group 3 had two haemor- rhagic episodes that could not be attributed to any other coagulation abnormality. The most frequent types of bleeding were purpura (45%)

Results and mucosal haemorrhages (33%), which occurred mainly in the http://www.bmj.com/ Table I gives the list of different diseases diagnosed in the 175 mouth. Other types of haemorrhage included: ecchymosis (11%), patients who completed the study, the number of cases in each vaginal bleeding (4%), haematuria (2%), epistaxis (4%), and wound and the number cell counts A of 1473 bleeding (1%). No severe haemorrhages were observed in these category, of performed. total because received immediate cell counts were performed, ranging from one to 66 tests per patient. patients they platelet transfusions. The results of the cell counts were classified according to platelet To further evaluate whether platelet size plays a part in the patho- number: those with less than 20 x 109/l platelets were classified as genesis of haemorrhagic diathesis, the results of the blood tests in each showing severe thrombocytopenia (group 1), those with 20-100 x 109/1 group were divided into two subgroups: those of patients with and platelets as showing moderate thrombocytopenia (group 2), those with those of patients without haemorrhagic diathesis (table III). The all on 2 October 2021 by guest. Protected copyright. 100-500 x 109/1 platelets as having a normal count (group 3), and those mean platelet volume of patients from all groups who exhibited a with above 500 x 109/l platelets as showing thrombocytosis (group 4). bleeding tendency was significantly lower (5-52 ±07 fl) than the mean For comparison, 200 cell counts were performed on normal volunteers platelet volume of patients without a bleeding tendency (7 87 ±1-7 fl, were and as p <0-0001). In groups 1 and 2 there were significant differences in and the results analysed separately designated group 5. volume between Mean platelet volume-Table II summarises the mean platelet mean platelet those patients with and those without a volume of all groups. The mean platelet volume of group 1 was bleeding tendency. Most of the bleeding episodes were observed in patients from group 1. The mean platelet count in patients with a bleeding tendency was also considerably lower than in those with no bleeding tendency (table III): this difference was statistically signifi- cant in group 1. Hence, the results were further divided according to platelet number into two additional subgroups la and lb. Group la TABLE i-Diagnoses, number of patients, and number of cell counts consisted of patients with platelet count less than 10 x 109/1, and group No of No of lb of patients with platelet count 10-20 x 109/1. In group la there Disease patients cell counts was no significant difference in mean platelet number between those Acute myeloid leukaemia .23 330 with and those without bleeding episodes whereas the mean platelet Acute lymphatic leukaemia .14 71 volume was significantly lower among those with bleeding episodes. Chronic lymphatic leukaemia 12 123 Chronic myeloid leukaemia .15 177 In group lb, though mean platelet number was significantly lower Hodgkin's lymphoma .16 66 among patients with bleeding tendency, the difference was not so Non-Hodgkin's lymphoma .30 250 Aplastic anaemia 8 153 great as to allow for clinical discrimination between those with and Idiopathic thrombocytopenic purpura 4 20 those without bleeding episodes. The mean platelet volume in this Multiple myeloma.12 77 in Polycythemia vera .5 18 group was also significantly lower those with a bleeding tendency Myelofibrosis .3 24 than in those without. Seventeen patients in group 1 who had at least Iron-deficiency anaemia 6 27 Other .27 137 one cell count associated with a bleeding episode and one count without a bleeding episode were further analysed. In each patient, BRITISH MEDICAL JOURNAL VOLUME 285 7 AUGUST 1982 399

TABLE. III-Platelet count and mean platelet volume in specimens from patients with and without bleeding tendency. Results are means± SD Br Med J (Clin Res Ed): first published as 10.1136/bmj.285.6339.397 on 7 August 1982. Downloaded from

Patients without bleeding tendency Patients with bleeding tendency Group Platelet count Platelet volume No of No of Platelet count Platelet volume No of No of ( x 109/1) (fl) cases counts ( x 109/1) (fl) cases counts 1 14 68±4-2* 7 40 ±1 3 28 88 9 25±4 lt 5 46 ±05t 19 64 2 52 35 ±43-4 9 04 ±2-28 57 343 49 78±21 5 5-68±1 23t 8 18 3 235 4 ±180 3 7 8 4 5 5 140 834 (134 0 ±21 2) (6 3 ±0 1) 1 2 4 622-1±1965 806±4-2 22 114 0 0 Total 247 1379 28 84 la 7 92+2 2 6-3±2-2 7 12 6-93±2-3 5 40±0 35t 13 42 lb 15 75 ±3-1 7 50 ±1-2 28 76 13 68±2 6t 5 55 ±0 6t 13 22

Due to fluctuations in platelet counts, some patients may appear in more than one group. *Results adjusted to cluster sampling."' tSignificantly (p < 0 001) different from the results in cases without bleeding tendency.

two counts matched for platelet number were selected. The platelet platelet volume as more important than platelet count in counts were similar in 10 of the 17 pairs, and in the others the predicting the patient's haemostatic potential in severe thrombo- difference was not larger than 7 x 109/l platelets. The mean platelet cytopenia. volume of the patients' platelets during a bleeding episode was Life-threatening haemorrhages due to thrombocytopenia compared with that when no bleeding was detected, using a paired t test, appear mostly in with and the results showed a significant decrease of the mean platelet patients a platelet count of less than volume when a haemorrhagic tendency was observed (p < 0 0001). 20 x 109/1. In this study analysis of mean platelet volume To find the mean platelet volume that discriminates between those discriminated between those patients with and without bleeding, with a tendency to bleeding and those without in the severe thrombo- both when the platelet was extremely low (less than 10 x 109/1) cytopenic group (group 1), a scattergram of mean platelet volume v and when it was between 10 x 109/1 and 20 x 109/1. Our data platelet number was constructed (figure). All the tests performed on indicate that a volume of 6-4 fl is a suitable cut-off point as an patients with bleeding episodes were marked and it may be seen that indicator of haemorrhage in this patient population. most of them had mean platelet volume of less than 6 4 fl. The The observation that large platelets are haemostatically strength of the association between mean platelet volume and bleeding superior to small platelets is not new. Many studies have was measured by the specificity and sensitivity at low volume (under indicated that large platelets are metabolically and functionally 6-4 fl). As an indicator of bleeding, specificity was 9466% and sensitivity was 93% for the total population. more active than small platelets. Large platelets have been Linear discriminant analysis was used to distinguish between those found to contain more glycogen, adenine nucleotides, ortho- patients with and without bleeding tendency in group 1. Erythrocyte phosphate, reduced glutathione, NADH, and NADPH, and count, packed cell volume, leucocyte count, platelet count, and platelet show greater rate of protein, carbohydrate and lipid metabolism volume were chosen as potential discriminating variables. This and contained more platelet factor III activity.'-4 20-23 Large procedure selected only two of the five variables as significant dis- platelets were also found to aggregate better on the addition of criminators: platelet volume first and platelet number second. The adenosine diphosphate, epinephrine, thrombin, and collagen.4-6 intraclass correlation of the two variables in group 1 was low (0 18 and In normal heterogenous platelet populations the large platelets 0 19, respectively), hence this group could be referred to as a random formed aggregates on the addition of low concentrations of sample. The two variables produced a canonical correlation of 0 714 and a Wilkes's X of 0 489 with z2= 106 49. The percentage of the adenosine diphosphate, while the small platelets remained cases that were correctly classified by the discriminant function was unreactive.7 Large platelets also showed greater adhesiveness to 84 1 for those without bleeding episodes (specificity) and 93 8 for those glass beads and collagen.8 9 Clinical observations indicated also with bleeding episodes (sensitivity). the haemostatic superiority of large platelets.9-11 Harker and http://www.bmj.com/ Slichter and Schulman et al found that bleeding time in patients with thrombocytopenia and increased number of large platelets Discussion was shorter than that expected for patients with low platelet count.'0 11 Two studies have investigated the clinical usefulness of mean It was also found that in patients recovering from thrombo- platelet volume as measured by the Coulter counter, model S cytopenia caused by chemotherapy, bleeding time shortened to Plus.'8 19 Giles analysed the data of 5000 unselected blood normal before the platelet count rose appreciably.'0 In these specimens and found a wide range of mean platelet volume in patients platelet size was not estimated and therefore could not on 2 October 2021 by guest. Protected copyright. various haematological disorders."8 Nelson and Kehl analysed be correlated with the shortened bleeding time. Still, other the cell counts of87 unselected inpatients with thrombocytopenia investigators have shown that platelet size increases in conditions and found differences in mean platelet volume between patients associated with active thrombopoiesis.24 27 Nelson and Kehl, with marrow failure and patients with thrombocytopenia who used the Coulter counter, model S Plus, to measure mean resulting from loss or consumption of the platelets.19 The platelet volume, showed that patients with thrombocytopenia correlation between the clinical state of the patients or the resulting from loss or consumption had higher mean platelet appearance of haemorrhagic diathesis and mean platelet volume volume than patients with bone marrow failure.' 9 The shortening was not examined in these studies. We investigated whether mean of bleeding time in patients with active thrombopoiesiscould platelet volume, as measured by the Coulter counter S Plus, reflect an increase in the number of large platelets. The patient provides an additional variable that may help predict the risk of population that we studied included mainly patients with various haemorrhagic diathesis, particularly in thrombocytopenic haematological malignancies. In these patients, platelet size and patients. number could vary according to degree of marrow suppression The study was performed on a selected patient population- (induced by the disease or the treatment) or marrow recovery. that is, those treated by the department of haematology over The figure shows that among the patients with severe thrombo- five months-chosen because of the high incidence of thrombo- cytopenia, there was- a good correlation between platelet number cytopenia caused by disease or treatment. The results of this and platelet size. This group included mainly patients with study clearly indicate that in severe thrombocytopenia mean leukaemia and lymphoma and a few with aplastic anaemia. The platelet volume is the most important variable that discriminates parallel rise of both platelet count and size probably reflected an between those patients with and those without haemorrhagic active thrombopoiesis. diathesis. Discriminant analysis of the data selected mean One of the major problems in treating severe thrombocyto- 400 BRITISH MEDICAL JOURNAL VOLUME 285 7 AUGUST 1982 penic patients is to decide when to give platelet transfusions to 11 Shulman NR, Watkins SP Jr, Itscovitz SB, Students AB. Evidence that Br Med J (Clin Res Ed): first published as 10.1136/bmj.285.6339.397 on 7 August 1982. Downloaded from It is common practice to give the spleen retains the youngest and hemostatically most effective plate- prevent dangerous haemorrhages. lets. Trans Assoc Am Physicians 1969;81:302-7. transfusions only to those thrombocytopenic patients who 12 Johnson CJ, Abildgaard CF, Schulman I. Functional studies of young exhibit a bleeding tendency. When dealing with patients with versus old platelets in a patient with chronic thrombocytopenia. Blood platelet counts of less than 20 x 109/1 who do not show overt 1971 ;37:163-71. bleeding tendency, however, the decision whether to give plate- 13 Rowan RM, Fraser C, Gay JH, McDonald GA. The Coulter Counter Model S Plus-the shape of things to come. Clinical and Laboratory let transfusions is difficult even for the experienced haematologist. Haematology 1979;1:29-40. In view of the useful discrimination that mean platelet volume 14 Dacie JV, Lewis SM. Practical haematology. 5th ed. Edinburgh: Churchill provides between those patients who bleed and those who do Livingstone, 1975. not, it may serve as a guideline to predict the danger of haemor- 15 Nie NH, Hadlai Hull C, Jenkins JG, Steinbrenner K, Bent DH. Statistical package for the social sciences. 2nd ed. New York: McGraw-Hill, 1978. rhage and the need for prophylactic platelet transfusion. 16 Fleiss JL. Statistical methods for rates and proportions. New York: John Wiley and Sons, 1973:3-5. AE was supported by a grant from the A Jurzykowski Foundation, 17 Hubert M, Blalock JR. Social statistics. 2nd ed. New York: McGraw-Hill, New York, USA. SP is supported by the Fund for the Advancement 1980:37-375,569. of Humanity. We thank Professor E A Rachmilewitz and Professor 18 Giles C. The platelet count and mean platelet volume. Br Jf Haematol J H Abramson for their help. 1981 ;48:31-7. 19 Nelson RB III, Kehl D. Electronically determined platelet indices in thrombocytopenic patients. Cancer 1981 ;48 :954-6. References 20 Steiner M, Boldini M. Protein synthesis in aging blood platelets. Blood 1969 ;33 :628-33. Karpatkin S, Garg SK. The megathrombocyte as an index of platelet 21 Friedhoff A, Miller JC, Karpatkin S. Heterogeneity of human platelets. production. Br J Haematol 1974 ;26 :207-1 1. VII. Platelet monoamine oxidase activity in normals and patients with 2 Hirsh J. Platelet age: its relationship to platelet size function and meta- autoimmune thrombocytopenic purpura and reactive thrombocytosis: bolism. Br J Haematol 1972;23:209-14. its relationship to platelet protein density. Blood 1978;51 :317-23. 3Karpatkin S, Charmatz A. Heterogeneity of human platelets. I. Metabolic 22 Leone G, Agostini A, DeCrescenzo A, Bizzi B. Platelet heterogeneity: and kinetic evidence suggestive of young and old platelets. J Clin Invest relationship between buoyant density, size, lipid peroxidation and 1969 ;48:1073-82. platelet age. ScandJ, Haematol 1979 ;23 :204-10. 4 Karpatkin S. Heterogeneity of human platelets. II. Functional evidence 23 Ginsburg AD, Aster RH. Changes associated with platelet aging. Thromb suggestive of young and old platelets.7 Clin Invest 1969;48:1083-7. Diath Haemorrh 1972 ;27 :407-12. 6Karpatkin S. Heterogeneity of human platelets. VI. Correlation of platelet 24 Garg SK, Amorosi EL, Karpatkin S. Use of the megathrombocyte as an function with platelet volume. Blood 1978;51 :307-16. index of megakaryocyte number. N EnglJ3 Med 1971 ;284:11-7. 6 Mannucci PM, Sharp MV. Platelet volume and shape in relation to 25 Amorosi E, Garg SK, Karpatkin S. Heterogeneity of human platelets. IV. aggregation and adhesion. Br J7 Haematol 1967 ;13 :604-17. Identification of a young platelet population with [75Se] selenomethio- 7Haver VM, Geor ARL. Functional fractionation of platelets. Jf Lab Clin nine. BrJ Haematol 1971 ;21 :227-32. Med 1981 ;97:187-204. 26 Weinhaub AH, Karpatkin S. Heterogeneity of rabbit platelets. II. Use of Kraytman M. Platelet size in thrombocytopenias and thrombocytosis of the megathrombocyte to demonstrate a thrombopoietic stimulus. J Lab various origin. Blood 1973;41 :587-98. Clin Med 1974;83:896-901. 9 Hirsh J, Glynn MF, Mustard JF. The effect of platelet age on platelet 27 Minter FM, Ingram M. Platelet volume: density relationships in normal adherence to collagen. J Clin Invest 1968;47:466-73. and acutely bled dogs. BrJ3 Haematol 1971 ;20:55-68. 10 Harker LA, Slichter SJ. The bleeding time as a screening test for evalua- tion of platelet function. N EnglJ3 Med 1972 ;287:155-9. (Accepted 20 May 1982)

ONE HUNDRED YEARS AGO The following is the report of bronchitis rather severely for about a fortnight. In the spring, nearly http://www.bmj.com/ Mr W H Neale, the medical officer to the Eira Expedition. "In everyone was affected with snow-blindness in a mild form. The eyes drawing up a report on the health of the men engaged in the above ran with water, and in many cases were much inflamed, with severe expedition, I am happy to say that a few words only are necessary to shooting pains over the frontal regions. As a rule, no case had to stay give an account of any illness which occurred during the fourteen indoors more than forty-eight hours; no one sustained any permanent months we were absent from England. On August 21st, 1881, twenty- injury to their sight. Unfortunately, we had two invalids during the five men were thrown on Cape Flora, with scarcely meat enough for whole winter, and I regret to say they are still on my hands. Both cases two months. A house was built of stones and turf, and covered with got worse during the winter, owing to the cold, and not from the food sails. Ventilation was easily secured, our only door being a piece of we lived on. One invalid was the mate, who sustained a wound on the canvas, hung at the inner end of the porch. Several holes were cut in right forearm in July 1881. He never mentioned it to anybody for some on 2 October 2021 by guest. Protected copyright. the roof, through which old provision-tins were put; a lid was fitted time, and seldom redressed the wound, until eczema (to which he was to each tin, so that the ventilators could be shut when it snowed predisposed) set in; then he came and asked to have it dressed. Our heavily, or the frost was too severe to keep them open. Our food for other invalid was the second mate, who had a bad lip before we left ten months was procured by hunting, and consisted of walrus, bears, Peterhead; it never showed signs of healing; when the frost set in, it and looms. The meat was cut up into small pieces and boiled for about gradually became worse. Considering the manner in which we lived, three hours. We had three meals a day, and about twelve pounds of the almost inactive state in which we were compelled to pass the vegetables were divided among the three meals every day. Every day winter, and the healthy condition of everyone when we were rescued, from October to May 1st, each man had a quarter of a pound of flour it ought to be a great source of encouragement to following expeditions made into a 'dough-boy' for dinner. Whenever it was possible, the to winter in Franz Josef Land, and to live on the meat of the country." blood was saved when a bear was shot; a pint of it put into the dinner- (British Medical Journal, 1882.) pan made the soup beautifully rich. The effect of living on the meat of the country was (I am certain), that there was not the slightest symptom of scurvy among us. When the daylight returned, instead of everyone looking pale and anaemic, it was a surprise to all old wintering hands ONE HUNDRED YEARS AGO Ladies' dresses.-An exhibition to see everyone with rosy cheeks. No limejuice was saved, but one-fifth of ladies' hygienic wearing apparel, including specimens of Greek gill of rum per man was served out every day from October 1st to dresses, divided skirts, tennis dresses, aesthetic dresses, and many May 1st. I must for the present defer expressing any opinion as to the other costumes, sanitary boots, stockings, petticoats, bodices, corsets, relative value of lime-juice or rum in the prevention of scurvy. No and underclothing, will be opened, under the auspices of the National severe cases of frostbite occurred, and cases of sickness were rare. Health Society, at the Cavendish Rooms, 51, Mortimer Street, Several cases of minor surgery came under my care, and, as a rule, the Regent Street, on Tuesday, March 21st, 2 till 5, and will remain open smallest wound took a long time to heal. One man had bronchitis till Saturday of the same week. The price of admission will be one followed by pleurisy, which kept him in bed three weeks; another had shilling. (British Medical3Journal, 1882.)