perforation. Any ulcers visible from the serosal surface but 9 Mandcl BK, Mani V. Colonic involvement in salmonellosis. Lan et 1976;i:887-8. 10 Pascall CR, Stearn EJ, Mosley JG. Salmonella hadar peritoniltis. BrMed.7 1980;280:26. unperforated should be oversewn. 11 Tauiner WA, Collins PG, Fah\ AM. Spontaneotus perforation of the coloti in salmonlella enterocolitis. IrJ Med Sci 1980;149:37. Gastroenteritis resulting from the various serotypes of 12 Gill KP, Feelev TM, Keanie FBV. T'oxic megacolon and perforationi caused by salmonclla. S enteritidis is becoming increasingly common and may Br Surg 1989;76:796. 13 Boyd JF. Colonic involvement in salmonellosis. Lancit 1976;i:1415. be extremely severe. The presentation varies but usually 14 Kurtx JB. Leg abscesses caused by Salmonella heidelberg. Lancet 1976;i:20(0-1. includes abdominal cramps, pain, and diarrhoea that may be 5 Christie AB. 'I'rcatment of typhoid carriers with ampicillin. Br Medj 1964;i: 1609. BMJ: first published as 10.1136/bmj.300.6724.553 on 3 March 1990. Downloaded from bloody. This picture may be confused with that of ulcerative colitis.9 Diagnosis may sometimes be difficult: salmonella enteritis and ulcerative colitis are both common and their sigmoidoscopic appearances are similar. If the colitis is treated with corticosteroids then simultaneous systemic anti- Raynaud's syndrome biotic cover is essential.' The micro-organisms invade focal areas of the small Thymoxamine, , and ACE inhibitors and large bowel,9 and occasionally the colitis progresses to perforation. This has been reported after are among the effective treatments now infection with many different species, including S hadar,'° available S typhimurium," and S newport.' We recently encountered perforation and faecal peritonitis in a patient infected in the Raynaud's phenomenon was described over 100 years ago, recent outbreak of S kegougou. A high index of suspicion is but we still do not understand the pathogenesis of the ab- necessary during an outbreak of salmonella enteritis; if normally prolonged (sometimes painful) episodic peripheral perforation of the colon does occur prompt colectomy is in response to cold or emotional stimuli. The essential for a favourable outcome.'I controversy has yet to be settled between the hyperactivity of Extraintestinal focal lesions with salmonella are often the sympathetic nervous system described by Raynaud' and associated with other chronic . The focal lesions may Lewis's local fault.2 manifest themselves long after an episode of enteritis or the The clinical classification into primary and secondary original bowel infection may have been silent. S enteritidis Raynaud's syndrome and phenomenon is also unsatisfactory. has a predilection for blood vessels. Possibly, intravascular Patients who have Raynaud's phenomenon but are otherwise salmonellas localise at sites of atheromatous ulceration and fit may commonly be shown to have one or more autoanti- may cause of major vessels or may colonise bodies present in low titre. Some of these patients will later vascular grafts.'9 In addition they may damage the venous develop one of the connective tissue .34 system, causing septic ,'4 iliac throm- So what do we know? Patients with Raynaud's syndrome bosis, or pulmonary . These focal lesions have a may be shown to have increased sensitivity or density of the tendency to chronicity and may mimic tuberculosis, particu- peripheral c1 adrenoceptors, or both, in both the vessel walls3 larly in osteomyelitis of a vertebra or paravertebral abscess. and the platelet membranes.6 Other factors implicated in Circulating S typhi is trapped by the liver and excreted in the the disease are abnormal platelet adhesiveness,7 increased bile. Acute cholecystitis as a complication of typhoid has whole blood and reduced red cell deform- become rare since the advent ofantibiotics, but it may develop plasma viscosity,-'0

ability," reduced activity of the fibrinolytic system,'2 '3 an http://www.bmj.com/ in a normal gall bladder and may proceed to perforation and imbalance in the cyclo-oxygenase products of arachidonic biliary peritonitis. acid - thromboxane (TXA2) and (PGI2)-and Finally, the general surgeon may be asking for help in the hypersensitivity of serotonin (5-HT2) receptors.'4 Whether management of patients who are chronic typhoid carriers. any or all of these are crucial in the pathogenesis or are simply The typhoid carrier passes organisms in the faeces, presum- epiphenomena remains to be determined. Attempts to correct ably derived from a focus of infection in the gall bladder or these abnormalities have been reflected in numerous thera- biliary tract. Chronic typhoid cholecystitis is symptomless. peutic approaches to the disease. Despite the high proportion The most notorious carrier was Mary Mallon, who was the of women affected the contribution of oestrogen and other on 30 September 2021 by guest. Protected copyright. source of an outbreak affecting 1300 people in New York in female sex hormones remains vague and poorly defined.'* A 1903. Although prolonged administration of ampicillin in possible exception may be those patients whose symptoms high dosage has been successful in eliminating carriage of in S even in patients with gall stones and non-functioning begin at or near the menopause, whom hormone replace- typhi ment treatment may be beneficial. ` gall bladders,'5 cholecystectomy is regarded as the most In the clinical setting primary Raynaud's syndrome is effective way of permanently curing the carriers-provided common. 16 The average general practitioner may expect to see there is no associated infection in the biliary or urinary tract. one or two new cases a year. Fortunately it is also usually J G MOSLEY benign and compatible with an entirely normal lifespan Consultant General and Vascular Surgeon (unpublished data). The prognosis of secondary Raynaud's A K CHAUDHURI syndrome is that ofthe underlying disease and depends on the Consultant Microbiologist severity with which target organs are affected.3 Leigh Infirmarv, As the common stimulus is cold, either local or general, Leigh, advice not to smoke and to keep warm remains the corner- Lancashire WN7 I HS stone of management. Smoking a cigarette may produce a fall in temperature of2°C or 3°C in the fingertips ofnormal people 1 Keenani JP, Hadley SP. The surgical maniagemcnt of pcrforations in childreni. Br] Surg in a comfortable ambient temperature. Patients may be 1984;71:928-9. 2 Dunkerley GE. Perforation of'the ileum in enteric fever. BrMledj 1946;ii:454-7. helped to keep warm with appliances ranging from chemically 3 Dickson JAS, Cole GJ. Perforation of the terminal ileum. Br_7 Surg 1964;51:893-7. activated handwarmers to electrically heated gloves, foot 4 Gibney EJ. Typhoid perforation. Brj7Surg 1989;76:887-9. 5 Angorn IB, Pillarv SP, Hegarty MM, Baker LWd. I'yphoid perforationi of the ileum. S Afr Aledj warmers, and hand and ear muffs. Further information 1975;49:781-5 concerning these may be obtained from the Raynaud's 6 Chouhan MK, Pandu SK. Typhoid enteric perforation. Brj Surg 1982;69:173-5. 7 Archampong EO. Operative treatment of tvphoid perf'oration of the bowel. Br Med J 1969;iii: Association (112 Crewe Road, Alsagar, Cheshire ST7 2JA; tel 273-6. 0270 872 8 Dronfield MW, Fletcher J, Langman MJS. Coincident salmonella inf'ections anld ulcerative colitis. 776). BrMedj 1974;i:99-100. About one third of patients also have attacks in response to

BAM1 VXiLrME 300 3 MARCII 1990 553 emotional stress, though the pattern of response in primary and cause generalised vasodilatation. These are acute effects and secondary disease may be different." Advice concerning and stop shortly after treatment is stopped. As circulatory avoidance of such stress may also be given. Patients in this (headache and dizziness) and gut (vomiting and diarrhoea) category may respond to behavioural therapy or may benefit side effects are frequent and may be severe their use has from conditioning (placing the affected hands and feet for a been confined to patients with severe secondary Raynaud's time in warm surroundings during general body cooling)- syndrome with much reduced resting perfusion complicated BMJ: first published as 10.1136/bmj.300.6724.553 on 3 March 1990. Downloaded from treatment requiring considerable time and motivation.'9 20 by digital ulceration and to patients with frank More simply, placing the hands in warm water for five who are undergoing digital surgery in the hope of enhancing minutes twice daily is said to increase resting peripheral postoperative wound healing. In patients with severe second- perfusion and reduce the reactivity to cold.2' ary syndrome with reduced perfusion and digital ulceration, The ineffectiveness ofcervical sympathectomy and plasma- regimens have varied with the prostanoid used. The stable pheresis has condemned these measures to interesting his- carbacycline analogue iloprost has been given for six to torical footnotes. The attacks may be so frequent, or so eight hours on three consecutive days at a rate starting with painful, or last so long that drug treatment may be offered in 0-5 ng/kg/min and increasing incrementally at 15 minute an attempt to enhance peripheral perfusion and reduce the intervals by 0 5 ng to a maximum of 2 ng/kg/min. Side effects response to cold, especially during the winter. Despite the may preclude this high dosage, but it has been shown to several drugs said to antagonise or correct one or more of the increase digital blood flow above the baseline for many weeks. pathogenic factors outlined above few have been assessed in Digital lesions have healed quickly and there has been a well controlled trials over many weeks rather than a few days. corresponding maintained clinical improvement.241' 49 No Studies of this kind have been reported with some calcium explanation for this prolonged beneficial effect has emerged- channel antagonists, mainly '2 24; the c( adreno- for it cannot be attributed to the acute effects, reduced platelet ceptor antagonist, thymoxamine2; the fibrinolytic activity stickiness and vasodilatation, which disappear almost as soon enhancing agent, stanazolol-"which should be used only in as the infusion is stopped. advanced cases when other methods have failed26"; and for Though the optimal dosage of prostanoids has not been El2 2 and prostacyclin (prostaglandin I),293" determined, patients with severe symptoms who are refrac- and its stable carbacyclin analogue, iloprost.24 3 tory to oral treatment may be treated with repeated infusions. The prostanoids are available only for intravenous infusion, Prostanoids have been available for 10 years but only one limiting their use to hospitals, though inpatient management transdermal preparation has become available. This is effec- is not usually necessary. tive in both adults404' and children,42 but unaccountably it was How do these drugs compare? Nifedipine reduces the withdrawn by the manufacturers. Other transdermal and oral severity and frequency of attacks in most patients and often preparations are awaited with interest. produces obvious peripheral skin vasodilatation in healthy In primary and less severe secondary Raynaud's syndrome and hypertensive people, but in our experience it does not other therapeutic approaches may be possible. Clearly the enhance peripheral perfusion in the affected hands and feet of effect of inhibition of the angiotensin converting enzyme patients with secondary Raynaud's syndrome.2124 Clearly its requires investigation in patients without renal impairment. benefits must be due to other mechanisms that enhance tissue Several new angiotensin converting enzyme inhibitors have oxidation.13 Side effects at conventional doses occur in about become available and others are being developed. Already, one third ofpatients: they are those side effects expected with however, captopril has been shown to be beneficial in patients http://www.bmj.com/ generalised peripheral vasodilatation-headache, , with primary Raynaud's syndrome at a dosage that did not dizziness, and, more rarely, peripheral oedema. Potentially lower . Nor at this dose were there any other more serious side effects such as hepatitis or the nephrotic undesirable side effects -such as neutropenia or a reduction syndrome are rare.94 Pain in the eyes and blurred vision may in renal function -as had been observed previously in some be due to increased ocular blood flow.9 The incidence of side patients when high doses were used.41 Another drug said to be effects may be reduced by starting with a small dose-say, effective but requiring further investigation is the serotonin

5 mg twice or three times daily - and increasing incrementally (5-HT2) receptor antagonist, (which is not yet on 30 September 2021 by guest. Protected copyright. until an effective dose is achieved that is free of side effects. available for general use in Britain)," with which improve- Thymoxamine acts by competitive antagonism at aL adreno- ment in digital perfusion may be modest.4" The ceptors and is known to block in some beneficial effect of transdermal glyceryl trinitrate may be vascular beds - for example, the skin -while maintaining difficult to determine because of the large placebo effect overall vascular resistance.16 3 The explanation for this associated with substances applied to the affected part by the selective effect may be the unique 10:1 ratio of (al to a2 patient.46 47 adrenoceptor activity.25 Three randomised control studies Fish oil dietary supplements-rich in the long chain w-3- have shown that in patients with Raynaud's syndrome polyunsaturated fatty acids, eicosapentaenoic acid and deco- (mostly primary) thymoxamine not only gives subjective saphexaenoic acid, have several actions that might benefit relief of symptoms but also abolishes the prolonged vaso- patients with .41 Not the least of these may be constriction after a cold stimulus as shown by measurement of the redirection of prostanoid formation to prostaglandin I3, blood velocity and skin temperatures by Doppler ultrasono- which retains its vasodilatory and platelet anti-aggregatory graphy (P M Dewland et al, first international congress of effects, and to thromboxane A3, which is biologically inert.49 50 clinical pharmacology and therapeutics, London 1980).25 38 At Fish oil supplements have recently been claimed to improve doses of 40 and 80 mg four times a day thymoxamine had no cold tolerance and delay the onset of vasospasm in patients effect on blood pressure and side effects were rare. In view of with primary but not secondary Raynaud's syndrome, a the low incidence of side effects thymoxamine is at present the finding that requires confirmation.9' Evening primrose oil, drug of choice in patients with primary Raynaud's syndrome available over the counter, also contains eicosapentaenoic who continue to get attacks of Raynaud's phenomenon acid. despite giving up smoking and protecting themselves from The recent advances made in our knowledge ofgeneral and cold. local 2 control mechanisms in the peripheral vasculature The prostanoids and their more stable analogues have two have raised hopes for increased understanding of episodic well documented activities: they reduce platelet adhesiveness peripheral vasospasm, in particular the response to cold

554 BMJ VOLUME 300 3 MARCH 1990 stimuli in health'- and disease.4 Meanwhile, we should aim at 38 Avlward A, Bater PA, D)avies DE1> Dewland PM, Lewis PA, Maddock J. Long term monitoring of effects of thNvmoxamine hydrochloride tablets in the management of- patients with Rasnaud's providing patients with as clear an understanding of their disease. Curr.Med ResOpin 1982;8:158-70. 39 Yardumtiai 1)A, Isenberg 1)A, Rustin AM, et al. StuccessfuLl treatment of Raynaud's syndrome with disease as possible and using the drugs available with iloprost, a chemically stable prostacyclin aitalogue. Br] Riheumatol 1988;27:220-6. circumspection, remembering that treatment is likely to be 40 Belch JJF, iNadlok R, Shaw B, Ieiberman P, Forbes CD, 'T'urrock RD. Doublc blind trial of' CL1 15,347, a transdermallv absorbed E2 attalogue. in treatment of Raynaud's pheniomcnon. lifelong. Decisions should be made with, rather than for, the Lancet 1985;i:1180-3. 41 patient, making it possible to share disappointment at failure C(ooke ED, Bowcock SA, Vatkinis GJ, ec al. CL 115347. An analogue of prostaglandin E2. BMJ: first published as 10.1136/bmj.300.6724.553 on 3 March 1990. Downloaded from Peripheral circulatory ef'fects of single ascending doses administcred transdermall in niormal and pleasure when treatment is effective. subjects anid patients with Raynauid's phenomenon. Angtology 1985;36:867-71. E D COOKE 42 Dutiger DB, D)illon MJ, D)aman-W'illems C, Cooke ED, Bowcock SA. 'I'reatment of childhood Ravnaud's disease by transdermal prostglandin E2 analogue. Lancet 1985;ii:50. Director, 43 Rustin M\IHA, Almond NE, Beacham JA, et al. TFhe effect of captopril on cutaneous blood flow in Thermographic and Blood Flow Unit, patients with primary Raynaud's phenomenon. Brj Dermnatol 1987;117:751-8. Department of Medical Electronics, 44 Roald OK, Seems E. Treatment of Raynaid's phenomenon with ketanserin in paticlits with connective tissue disorders. BrMed.7 1984;289:577-9. St Bartholomew's Hospital, 45 Seibold JR, 'I'erresino CA. Selective anitagonism of S.-serotonergic receptors relieves but does inot London EC1A 7BE prevetit cold induced vasoconstriction in primary RavnauLd's phenomenon. 7 Rheumatill A N NICOLALI)ES 1986;13:337-40. Director, 46 Nakir AM, Schapira D, Scharf Y. D)ouble-blind randomised trial for nitroderm TSS in the treatment of Raytnaud's phenomenon. Icsr] M1ed Sci 1986;22: 139-42. Irvine Laboratory for Cardiovascular 47 Anonyimous. NSAID's. A gimmick or a godsend? [Editorial] Lancet 1989;ii:779. Investigation and Research, 48 Rice R. Fish oils -their significance to hutman health. 7R SocMed 1988;81:499-501. Academic Surgical Unit, 49 Fishcr S, Weber PC. Thromboxane A; 'rXA) is formed in human platelets after dietary St Mary's Hospital Medical School, eictsopceltatioic acid (20:5V'A'i. Bilochem Bizophvs Res Commun 1983;116:1091-9. 50 Fisher S, Weber PC. Prostaglandin 1, is formed in vivio in man after dietary eicosopenitanoic acid. London W2 I NY Nature 1984;307: 165-8. 51 Di Giacomo RA, Kremer JlA, Shah DM. Fish-oil dietary supplemeitation in patients with Raynaud's phenomicon: a double-blind, coiitrolled, prospective trial. Am J Med 1989;86: 158-64. 1 Ravnatid Al. Oki local asphkxisc and stnimetrical gangrene of' the extremitjes and nezu researches in the nature and treatmtent of 'local acsphytxita oftlh' esxtremitttes. Seiected monographs, lVol 121. London: 52 Singer HA, Peach MJ. Endothertiatc-dependettt relaxation of rabbit aorta. 1. Relaxation stimtilated Svdenham Stocietv, 1888. bv T Barlow). by arachidonic acid. 7 PharrnaclFExp Ther 1983;226:790-801. (,Translated 53 Flavalian NA, 2 Lewis T. Experiments relating to the pcripheral mechanisms involved in spasmodic arrest of the Vanhoutte PJM. Thermosensitivitv of cutaneous and deep . Phlebologv circulationi in the finigers. A variety of Raynaucd's diseasc. lIeart 1929;15:7-101. 1988;3(suppl 1 ):41-5. 3 Black CMl. Connective tisstie disorders: scleroderina. Br] Hosp Med 1979;22:28-37. 54 Cooke ED, Ward C. Vicious circles in rcflex sympathetic dystrophy; a hypothesis.,7R Soc Mled (in 4 'T'an EM, Chem EKC, Sullivani KF, Rtibin RL. Antinuclear antibodies (ANAs): diagnostically press). specific immune matters and cluLcs towards the understanding of specific autoimmunity. Cliii Imniuntol Inimiunotpaithol 1988;47:121-41. 5 Frecdman RR, Sabharwal SC, D)esair N, Wenig P, Mlayes M4. Increased alpha-adrenergic respoiis ivecss in ididopathic Raynnaud's disease. Rheumtz 1989;32:61-5. 6 Keetiati EJ, Porter JAi. Alpha-two adrenergic receptors in platelets from patients with Ravnauid's ssndrome. Surger-c 1983;94:204-9. 7 Kahalch MIB, Osborn 1, Le Rov EC. Elevated levels of circulatory platelet aggregates and beta- Care for the infirm elderly thromboglobulin in . Ann Intern Aled 1982;96:610-3. 8 (icile KB, Dormandy JA. Abnormal blood viscosity in Ravnaud's phenomenon. Lancet 1976;i: 1317-8. A 9 MicGrath MIA, Peek R, Penny R. Blood hyperviscositv with reduccd skin blood flow its widening gap between the poor and the scleroderma. Ann Rheum Dis 1977:36:569-74. 10 Blunt RJ, George AS, Hurlow RA, Strachan CJL, StuLart J. Hyperviscosity and thrombotic changes better off in idiopathic and secondary Ravnaud's Syndrome. Br IlIaematol 1980;45:657-1. 11 Dodds AJ, O'Reily MjIIG, Yates CJlI, Cotton LT, Flute PT, Dormandy JA. Haemorrheological response to plasma exchange in RavnatLid's svndrome. Br Mledj 1979;ii: 1 186-7. 12 Cunliffe WJ, \Ienoi IS. Blood fibriiiol\-tic activity in discases of small blood vessels and thc eff'ect o' The 1990s seem likely to be a worrying decade for the elderly low molecular wcight dcxtran. Rr7 D)erntatol 1969;81:220-5. in Britain-all of whom are uneasily aware that at some time 13 Browsc NL, Gray I., Jarret PE, MIorland M,1. Blood and vein-wall fibrinolytic activity itn hcalth anld vascular disease. Br lIedj 1977;i:478-8 1. they may need residential care. The publication of the white 14 Halpcrni A, KLitum PH, Shettel HE, et al. Ravnatid's phenomenon atid serotonin. Angttiologs' paper Caringfor People on 14 November 19891 put an end to 1960;11: 15 1-67. http://www.bmj.com/ 15 Terregino CA, Setbold JR. Influencc ol thc menistrual cycle on RaInauLd's phcniomenon and cold the speculation about whether and how the government tolcrancc in ntormal wonien. Alngiolog 1985;36:88-95. would respond to the Griffiths report on community care.2 It 16 Heslop J, Coqgon D, Acheson ED. The prevalence ot intermittent digital ischaemia (Ra\naud's phenomenon,l in general practice. ] R Ctl/l G'ei Pract 1983;33:85-9. also completed another part of the jigsaw of radical reorgan- 17 Bennett R, Blueston R, Holt PJL, Bvwaters EGL. Survival in scleroderma. A-In Rheum Dis 1971;30:581-8. isation of health and social services provision that began with 18 Freedman RR, lanni P. Role of cold and emotional stress in Ravnaud's disease and scleroderma. Promoting Better Health3 and Workingfor Patients.4 The latest Br Mledj 1983;287:1499-502. 19 Jobe JB, Sampson JB, Roberts l)E, ei al. Induced as treatment for Ravnaud's disease. white paper has provoked less controversy than its predeces- Antn Intern Mled 1982;87:706-9. sors, but it falls short of the Griffiths report's recommenda- 20 Jobe JB, Batham VIP, Roberts )E, ettiil. Induced vasodilation as a home treatmelit for Ravnaud's disease. J Rheuriatotl 1985;12:953-6. tions, and it spells out new arrangements for financing and on 30 September 2021 by guest. Protected copyright. 21 Goodfield MIJD, Rowell NR. Hanid warming as a treatment for Raynaud's phenomenon iii systemic providing services for elderly sclerosis. Br] Derinatol 1988;119:643-6. people that require close 22 Smith Cl), \IcKentr\ R. (,ntrollcd trial ofiliifedipiic in the treatment of Raynaud's phcnomenoII. analysis. LatIcet 1982;ii:1299-301. 23 Thomas RHI\I, Radeiuakcr Al, (irimcs SI, ei al. Nifedipine in the treatment of Raynaud's The white paper cites the 100-fold increase in public phenomenon in paticnts with systcnic sclerosis. Brj Derniatol 1987;117:237-41. subsidy of residential and nursing home care over the past 24 Rademaker M, Cooke ED, Alinoiid NE, et a!. Comparison of intrasenious itifusions of iloprost anid oral nifedipine in treatment of Rayntaud's plietiomenon in patients with systemic sclerosis: a 10 years as evidence of the government's investment in double blind randomised study. BrMied] 1989;298:561-4. community care. But it also acknowledges the criticism by the 25 Grigg MIJ, Nicolaides AN, Papadakis K, V'olfe JHN. Thc efficacy of thymoxamine in primary Raynaud's phenomenon. Europeantournal of I 'asular Surgetr 1989;3:309-13. Audit Commission' and Griffiths that existing social security 26 Jarrett P'ENM, Morland Mi, Browse NL. Ireatment of Ravioaud's phenomenon by fibrinolytic ceihancement. BrMfed7 1978;ii:523-5 policies have created "perverse incentives" towards institu- 27 Martin MNIFR, Dowd PM\, Ring EFR, et a!. I'rostaglandin El infusion for sascular insufficiency in tional care. In the new proposals a unified budget covering the progressive systemic sclerosis. AInn Rheum Dis 198 1;40:350-4. costs 28 Kyle V, Parr G, Salisbury R, et al. Prostaglandin EI, vasospastic disease and thermography. Annt of "social care" will be introduced and managed by local Rheutn D)is 1985;44:73-8. authorities. It will be available for either domiciliary or 29 Dowd PM, Martin MFR, Cooke ED, et al. Treatment of Raynaud's phenomcnon by intravenous inmusion of prostacyclin l'CPI, BrjDerinatol 1982;106:81-9. residential care according to individual need. People in 30 Belch JJF, Newman 1i, lDruirv SK, it al. Ititermittetit epoprostenol (prostacyclin) itifusion in residential care will be entitled to claim income support or patients with Raynatid's svndrorne. L.aticet 1983;i:313-5. 31 Rademaker M, Thomas RHMI, Provuost Ci, et al. Prolonged increase in digital blood flow following housing benefit on a means tested basis, as they would in their iloprost infusion in patienits with systemic sclerosis. Postgrad Med] 1987;63:617-20. own homes, but they will be required to most of that 32 McHugh NJ, Csuka A, Wa\tson H, cial. Inftus.on of iloprost, a prcostacvclin analogue, for treatmcnt pay of Raynaud's phenomenon in systemic sclerosis. Antn Rheum Dis 1988:47:43-7. income to the local authority that is funding their care. Social 33 Aldoori R, Campbell 'B1, D)ieppe PA. Nifedipine in the trcatmnent of Raynaud's svndrome. Cardiovase Rets 1986;20:466-7(1. services departments will be given the responsibility for 34 Sorkin EM, Clissold SP, Brogden RN. Nifedipine: a rcview of its pharmacodynamic anid assessing the social care needs of dependent people and for pharmaceutic properties and its therapeutic efficacy itn ischaemic heart disease, hypertenision and related cardiovascular disorders. I)rgs 1985;30:182-274. planning and purchasing packages of care. They will be 35 Coulton D1)i\. Eye paiii with tiufedipine and disturbance of taste with captopril: a mutually expected to collaborate closely with health and other agencies, controlled study showing a method of post marketing survcillance. BrAlMed7 1988;296:1086-8. 36 Birmingham AT, Szolcsanvid J. Competitive blockage of adrenergic receptors and histamine to set up a system of quality control, and to reduce the part receptors by thymoxamine. ] I'harnt Pharmnacol 1965;17:449-58. they play as direct providers. The government expects local 37 Myers KA, Hobbs IT, Irvitne WT. Haemodynamic action of thvmoxamiie in occlusive pcriphcral arterial disease. CardzttOasc Res 1968;2:360-6. authorities to make "maximum use" of independent sector

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