ROYAL ACADEMY OF MEDICINE IN IRELAND Proceedings of meeting of Section of Medicine, held at University College, Cork, 10th-11th November, 1978. COELIAC DISEASE PRESENTING LATE IN LIFE C. M. Hyland. Department of Geriatrics, Regional Hospital, Cork. Four elderly women aged 70 to 81 presented with malabsorption syndrome. Three lived alone, one with an elderly brother and all had failed to cope and had difficulties in mobility. All were house-bound for at least a year before their admission to hospital. Two patients had bone pain, 2 had diarrhoea and all had proximal muscle weakness. Two patients had steatorrhoea and all the patients had abnormal jejunal biopsies, 2 with sub-total villous atrophy and 2 with partial villous atrophy. All had low xylose absorption as measured by blood xylose levels. The alkaline phosphatase was raised in all patients, the serum calcium was low and bone biopsies in 2 out of 3 patients confirmed osteomalacia. Anaemia was not a prominent feature, the haemoglobin being between 11.7 grams and 13 grams/ dl. All had a low red cell folate level but the B,~ levels were normal in all patients. None of the patients had a gastrectomy in the past, there was no evidence of pancreatic disease and barium follow-through showed no evidence of small intestinal diverticulosis. All the patients had normal renal function. The cause of the malabsorption syndromes is probably multifactorial but closely resembles coeliac disease. All the patients responded well to a gluten free diet with folic acid, calciferol and calcium supplements. Folowing treatment, all the patients were able to be discharged home again and have remained well at follow-up. BEHCET'S SYNDROME--A CASE WITH MUSCLE INVOLVEMENT Eileen Murphy and J. B. Ferriss. Department of Medicine, St. Finbarr's Hospital and University College, Cork. A 28 year old army private presented with a 3 year history of persistent aphthous ulceration, recurrent attacks of genital ulceration and arthritis involving the knee and ankle joints. He also experienced episodes of conjunctivitis, diarrhoea, generalised folliculitis and intermittent pyrexia. He had not been abroad. A diagnosis of Beh(;et's syndrome was based on the criteria of Mason and Barnes (Ann. Rheum. Dis. 28, 95, 1969). The patient experienced 2 episodes, of bilateral tender calf swelling with weakness, lasting a few weeks each time. Muscle biopsy revealed a deep-seated muscle abscess with degeneration of the surrounding muscle fibres. To our know63

ledge, muscle abscess has not been previously described in Behcet's syndrome. He subsequently developed swelling of the face, neck and arms and superior vena cava thrombosis was confirmed by venography. Results of other investigations included a hypochromic microcytic anaemia with normal iron stores, a persistently elevated ESR (100-140 mm / h ) , a moderately impaired creatinine clearance, microscopic haematuria, raised serum fibrinogen, negative anti-nuclear and rheumatoid factors, normal serum complement and a negative VDRL. He had HLA A2 A10 B6 tissue type. After an initial period of heparinisation the patient was commenced on plasminogen activators (phenformin hydrochloride and ethyloestrenol). There has been good symptomatic improvement, but there is still considerable thrombus in his superior vena cava. SECONDARY HYPERPARATHYROIDISM D. J. O'Sullivan, C. T. Doyle, M. J. Hickey and R. A. McEneaney. St. Finbarr's Hospital and University College, Cork. A 26 year old women had presented 5 months before with mild joint pains of 6 months duration. She had one uneventful pregnancy, a vague history of unconfirmed anaemia in the past with no other previous symptoms or hospital admissions. The only clinical abnormalities were short stature and bilateral genu valgum in a thin young woman. Blood counts were persistently normal but skeletal x-rays showed features suggestive both of hyperparathyroidism and osteomalacia with multiple islets of dense bone in the skull very like those found in Paget's disease. She was persistently normocalcaemic, normocalcuric and hypophasphataemic. Renal function was normal. She denied any bowel symptoms and contrast x-ray of the jejunum showed normal appearances. Bone biopsy showed marked osteitis fibrosa of hyperparathyroidism apparently associated with osteomalocia. Serum parathormone levels were persistently elevated. The diagnosis at this stage was of secondary hyperparathyroidism and osteomalacia with no obvious cause for either condition. A single blood count (one of many) late in the investigation of the patient showed a mild macrocytic anaemia and this lead to the finding of a low serum folate and a jejunal biopsy typical of coeliac disease with a totally flat surface and a densely cellular lamina propria.

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Response to a gluten free diet, oral calcium and folic acid, has in the first month been dramatic in weight gain, a new sense of wellbeing and a very marked improvement in the radiological appearances of the bones. While it is recognised that coeliac disease may be asymptomatic in adults, the complete absence of bowel symptoms throughout life with persistently normal haematological findings for so long in the presence of such gross bony change must be very unusual. A number of the radiological findings in the case were also quite atypical and their resolution with what could be described as little more than minimal treatment for a short time was dramatic. WILSON'S DISEASE B. M. Daly and M. T. N. Callaghan. Department of Neurology, St. Finbarr's Hospital, Cork. Wilson's disease is an inborn error of copper metabolism. Copper is deposited in increasing amounts in different tissues, thus giving rise to varying presenting symptoms. This results in diagnostic difficulties. Seventy-five per cent of all patients present with neurological or neuro-psychiatric disorders. This is we!l illustrated by the following 2 cases : Case One: A 23 year old female presented with aphonia and a 4-year history of deteriorating psychiatric state. This deterioration and the development of Parkinsonian features was, attributed to phenothiazines. In addition to her neurological disease, she had multiple spider naevi and Kayser-Fleisher rings. Case Two : A 16 year old schoolgirl was diagnosed as a hysterical conversion state. It was noted also that she had Parkinsonian features with generalised pigmentation, azur lanulae, dystonic movements and Kayser-Fleisher rings. There was considerable delay in the diagnosis of both these, girls. In each case, the difficulties were confounded by pheno~hiazine therapy. Case 1 has made an excellent recovery. The second case has remained unchanged. A case for routine ceruloplasmin estimation could be made in all psychiatric patients under 30 years. WELL'S SYNDROME D. J. Murnaghan. Department of Medicine, St. Finbarr's Hospital and University College, Cork. Two patients who recently contracted severe leptospirosis were presented. The bilirubin peaked at 610 and 846 nmol/I with return to normal by 47 and 60 days respectively. Both required dialysis (peritoneal) for acute renal failure which persisted for 26 and 42 days. The second patient was completely anuric for 20 days, was extremely ill for a long period and had evidence of myocarditis. The first patient required pericardiocentesis for pericardia1 tamponade. Both showed

evidence of disseminated intravascular coagula, tion on admission. Salient features with emphasis on hepatic and renal manifestations were discussed. Earlier series reported a 16% mortality in jaundiced patients: those with acute renal failure either died or recovered within 3 weeks. More seriously ill patients are now surviving and some long-term sequelae can be expected. The second pat!ent has residual renal impairment. The main manifestations of Well's syndrome appear to have a toxic pathogenesis but there has been complete failure to isolate toxins that would explain the observed changes. Release of endotoxins would account for many of the features of this syndrome. FAMILIAL DIABETES Robert McEneaney and D. J. O'Sullivan. Department of Medicine, St. Finbarr's Hospital and University College, Cork. The classification of diabetes has been revised into two main categories Type I and Type II. Type I is further subclassified Type IA and lB. All Type I diabetics are. insulin dependent. Type IA manifest islet and other cell autoimmunity. Type IB manifest islet cell damage caused by infection. Type II are non-insulin dependent and have a different genetic basis. We studied a family in which the father and 5 children are, diabetic. The paternal HLA typing was AIB8/A9B40 and maternal ASB8/A2B12 (normal G.T.T.). All 4 females (ages 18, 17, 15, 13) are frankly diabetic. The eldest 3 are insulin dependent and share the same genotype A9B40/A3B8. The t3 year old genotype is AIB8/A3B8 and will probably be insulin dependent soon. The 16 year old male is AIBB/A2B12. He has impaired GTT but is not insulin dependent. The 12 year old male is AlIB22/A3B8 and has a normal GTT. Islet cell antibodies were negative on all family members. Cudworth et al (1976) showed an increase relative risk of developing diabetes with the following antigens AI (1.6%), A2 (1.38%), B8 (2.63%, B18 (2.26%), B15 (1.85%, B40 (1.3%). Also there is a significantly decreased relative risk with all (0.3%) and B7 (0.41%) antigens. The relative risk increases even further when 2 high risk antigens occur in combination BBB40 (6.87%), B8B15 (5.03%). The 4 female diabetics all have high risk B antigen combinations. The male with the impaired GTT inherited the high risk AIB8 from his father. The paternal haptotype of the youngest boy was not investigated for social reasons. Environmental factors together with these HLA associations would account for the strikingly high incidence of diabetes in this family.

ROYAL ACADEMY OF MEDICINE IN IRELAND ARE THE RENAL ACTIONS OF ADH MODIFIED BY ENDOGENOUS PROSTAGLANDINS IN MAN ? W. J. Hall and M. Shinkwin* (Wellcome Medical Scholar). Department of Physiology, University College, Cork. Since prostaglandins are found in high concentrations in the medulla of the kidney a role for prostaglandins in. the regulation of water movement across the medullary collecting tubule is particularly attractive. An in vivo, role by endogenous prostaglandins in the modulation of ADH action on the kidney has been reported in dogs (Anderson et al, J. Clin. Invest. 56, 420-426, 1975). The primary purpose of this study was to determine the effects of aspirin, an inhibitor of prostaglandin biosynthesis in human kidney (Hamberg, Biochem. Biophys. Res. Commun. 49 (3), 720-726, 1973), on the renal response, in man to water loading and to infused ADH. In aspirin-treated subjects the onset of the diuresis after a water load was delayed, in the 15-25 min collection period after the water load, urine output was 3.37 4- 0.72 ml/min (n = 8), whereas in the same subjects, treated with tspirin, urine output in this period was only 1.77_+0.31 ml/min (P<0.05). Urine output in aspirin-treated subjects did not reach the output levels of the same subjects without aspirin until the 45-55 min collection period after the water load. In aspirin-treated subjects undergoing water diuresis, intravenous bolus injections of ADH, 2 or 5 mU, caused significant increases in Uo~m in a water loaded subject, treated with aspirin from 82_+8 to 755+127 mOsm/kg H=O' wherea,s in the same subject, without aspirin, the ADH infusion increased Uo~m from 45 _+ 2 to only 374 4- 112 mOsm/kg H=O. The findings are consistent with the hypothesis based on studies in animals, that endogenous prostaglandins attenuate the effects of ADH on the kidney. ENDOGENOUS FAECAL CALCIUM M. J. Whelton and B. Mee. Departments of Medicine and Physics, St. Finbarr's Hospital, Cork. Bone thinning is a metabolic complication which arises in some patients with chronic liver diseasel o steomalacia, osteoporosis or a combination of the 2 may occur. Parenteral vitamin D corrects

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malabsorption of calcium in these patients. Despite, this, the progression of bone disease may not be arrested. Excessive losses of calcium as endogenous faecal calcium (E.F.C.) might explain this paradox. Fifteen patients with chronic liver disease were studied using an intravenous Ca ~7 technique. E.F.C. was expressed as mg/kg/24 hours. The mean excretion of calcium or E.F.C. did not differ between liver disease and controls. Two patients did have high losses (in excess, of 12 m g / k g / 2 4 hours). Loss of calcium as E.F.C. is not an overall feature of liver disease. In individual patients, however, it may be quite significant and may well be a factor in some patients with progressive bone disease.

THE THERAPEUTIC RANGE OF PHENYTOIN : A REAPPRAISAL N. Feeiy, B. Duggan, J. Seldrup, M. O'Callaghan, N. C,allaghan. Departments of Neurology and Biochemistry, St. Finbarr's Hospital, Cork and The Mathematical Analysis Section, C:iba-Geigy, Macclesfield, Cheshire. The serum levels of phenytoin were compared with seizure control in a: prospective study of 31 patients with a wide variety of seizures of varying severity. Twenty-two patients were followed up for a period of 15 months and 9 for an average period of 6 months. Nine patients became seizure free. (excellent control) and a greater than 50% reduction in seizure frequency occurred in 13 patients (good control). Less than 50% reduction in seizure frequency occurred in 9 patients (poor control). An excellent or good response was associated with mean levels within the therapeutic range in 9 patients, and with subtherapeutic levels in 13 patients. Only 2 patients with poor control reached mean levels within the therapeutic range. Patients, with both mild, moderate and severe seizures responded at levels which were both sub-therapeutic and within the therapeutic range. The results suggest that the therapeutic range is not valid, as patients responded to a wide range of serum levels.