Showing papers in "QJM: An International Journal of Medicine in 1983"

Cryptogenic organizing pneumonitis.

Abstract: Eight patients with histological intra-alveolar organization, but no evidence of an infective or other aetiological agent, are reported. They characteristically presented with a short history of severe dyspnoea, cough, malaise, weight loss, bilateral radiographic shadowing and a raised ESR. There was a dramatic response clinically and radiologically to prednisolone but relapse occurred quickly as the dose was reduced. Control was re-established with an increased dose of prednisolone. In order to avoid confusion with post-infective organizing pneumonia the term cryptogenic organizing pneumonitis is suggested.

Prognostic Factors Predicting the Outcome of Sarcoidosis: An Analysis of 818 Patients

Abstract: SUMMARY A computerised, retrospective study of 818 patients with sarcoidosis was analysed to study the prognosis of each individual manifestation of the disease. The good prognosis of erythema nodosum, acute arthritis and bilateral hilar lymphadenopathy was confirmed, though 16 per cent of patients presenting with erythema nodosum pursued a chronic course. Cor pulmonale and nephrocalcinosis reflected the poorest prognosis while lupus pemio and sarcoidosis of the mucosa of the upper respiratory tract rarely resolved. Bone sarcoidosis also implied chronicity but in four of 31 patients there was no clinical evidence of disease activity two years after the initial diagnosis, although naturally the bone radiograph was still abnormal. Hepatomegaly carried a worse prognosis than splenomegaly, or indeed, than the finding of pulmonary mottling without hilar glands - a stage three chest radiograph.

Clinical features of fifteen patients with the hypereosinophilic syndrome.

Abstract: Fifteen patients with the hypereosinophilic syndrome were studied during a period of 6·5 years. The mean age at onset was 36 years. Two were female. The commonest presenting symptoms were nocturnal sweating with or without severe coughing attacks, symptoms of cardiovascular disease, anorexia and weight loss, neurological and gastrointestinal symptoms and itching with or without skin lesions. The mean blood eosinophil counts at presentation were 20·1 × 109/1. Eight patients had previous allergic or parasitic disease which could have predisposed them to the development of hypereosinophilia. Eight patients had raised serum immunoglobulin levels: IgM in five, IgE in four and IgG in one. Five of nine patients had raised serum eosinophil cationic protein levels. Episodes of clinical relapse occurred with increased white blood counts and were treated with prednisolone and cytotoxic drugs. Thrombotic and embolic complications developed in 10 patients, despite treatment with anticoagulants and inhibitors of platelet function, and were the cause of death in three. Two patients with severe endomyocardial fibrosis responded well to cardiac surgery, and a third required emergency mitral valve replacement. The 12 surviving patients have lived 0·8–11·5 years (mean 4·4), since the onset of their illness. It is concluded that the hypereosinophilic syndrome has distinctive features with an episodic course. The principal complications affect the cardiovascular system, especially endomyocardial fibrosis and thromboembolic occlusion of large and small blood vessels in many organs. Although treatment is usually effective in overcoming relapses, the underlying disease process appears to be unaffected. Despite this, patients can have prolonged periods of remission and may survive for many years.

The Natural History of Radiation-induced Proctosigmoiditis: An Analysis of 88 Patients

Abstract: The records of 88 patients with radiation-induced proctosigmoidosis seen over an eight year period were reviewed. Eighty-four (95 per cent) had been irradiated for a gynaecological malignancy. The peak incidence of bleeding occurred after a latent period of nine months from the time of irradiation. Twenty-five subjects (28 per cent) had associated injury to the urinary tract. A wide spectrum of radiological abnormalities found on barium enema is described. Twenty-four patients (27 per cent) underwent operations for radiation-induced injury to the colon and urinary tract. Operations on the bowel were attended by a high complication rate (79%). A clinical classification based on bowel symptoms is presented. Those whose only symptom was low grade rectal bleeding ( Group I ) had the most favourable outcome and of these, 35 per cent stopped bleeding spontaneously by six months. Patients who required frequent transfusions ( Group II ) had an increasing mortality rate with the passage of time. Patients whose predominant symptoms were pain and bowel dysfunction ( Group III ) had the highest death rate but some did well after an operative procedure.

Clinical diagnosis of the acute stroke syndrome.

Abstract: To assist physicians without easy access to CT scanning facilities, a scoring system was devised to aid the clinical diagnosis of acute stroke. A consecutive series of 192 patients under 76 years was studied prospectively from admission. The clinical features of 174 (91 per cent) of these patients were compared with their subsequent CT scan or autopsy diagnosis. The scoring system derived from this analysis determines the relative likelihood of infarction or haemorrhage from quantitative assessment of eight clinical variables. Clinical diagnosis with this method was more accurate than the diagnosis made by the patients' physicians. Lumbar puncture performed in 72 patients added little to the accuracy of diagnosis. Nine patients were found to have mass lesions, of whom only one presented with a clear history. Convulsions and neurological deficits which were prolonged or discontinuous in evolution occurred more frequently in patients with mass lesions than in those with vascular lesions.

Wegener's granulomatosis: observations on 18 patients with severe renal disease.

Abstract: Eighteen patients with Wegener's granulomatosis with renal involvement have been studied. Their course before treatment has indicated how the disease may progress and has provided a framework for diagnosis based on clinical and radiological features combined with available histology. The need for such diagnostic criteria is emphasised by the fact that a firm histopathological diagnosis could only be made in nine patients. A strong association between Wegener's granulomatosis and previous suppurative or tuberculous respiratory infection has been noted as well as between intercurrent infection and relapse. Evidence that immune complexes play a pathogenetic role has come from the association between active disease and circulating immune complexes. The observation of a reversible abnormality of splenic clearance of altered red cells suggests that immune complex handling by the spleen is defective. Treatment of these patients has shown a surprising degree of reversibility in many manifestations, especially renal failure. Remissions occurring spontaneously or induced by steroids alone are temporary and steroids, if used alone, may adversely affect outcome. While confirming the central role of cyclophosphamide in the induction of remission, this study has indicated that its combination with steroids and/or plasma exchange may be valuable in initial control of fulminating disease. The fact that seven patients died during induction (as well as a further four in the succeeding five years) reflects the advanced disease at presentation and the infective problems associated with immunosuppressive therapy. This highlights the need for earlier diagnosis.

Drug Associated Acute Interstitial Nephritis: Clinical and Pathological Features and the Response to High Dose Steroid Therapy

Abstract: Nine episodes of drug associated acute interstitial nephritis, in seven patients, were treated between 1972 and 1980. The drugs implicated were cotrimoxazole (three times), ampicillin, Magnapen (amplcillin and flucloxacillin), penicillin, gentamicin, paracetamol and ben-drofluazide. The time from exposure to the onset of symptoms ranged from one to 30 days. Presentation was with acute renal failure, which was non-oliguric in five cases, accompanied by rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristic interstitial infiltrate comprising substantial numbers of lymphocytes and plasma cells, with a variable number of neutrophils, eosinophils and histiocytes. Immunofluorescence was negative in all four cases studied in the acute phase, and showed scattered deposits of IgG, IgM, IgA and C3 on the tubular basement membrane in one patient during recovery. Significant proteinuria and an abnormal urine deposit were present in all cases, and seven of nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisolone and in all there was a response with a diuresis or spontaneous fall in serum creatinine within 72 hrs, and recovery of virtually normal renal function. Of two cases who did not initially receive steroids, one improved more slowly and one developed chronic renal impairment.

Ulcerative Colitis and Persistent Liver Dysfunction

Abstract: Six hundred and eighty-one patients with ulcerative colitis who attend the outpatient clinic in Oxford have been screened for the presence of persistently abnormal liver function tests. Of the 21 patients (3.0 per cent) found with abnormal liver function 17 (2.4 per cent) were shown by cholangiography to have primary sclerosing cholangitis. The liver biopsies from those patients demonstrated a wide range of histological features and were diagnostic of primary sclerosing cholangitis in only 50 per cent of the patients. When persistently abnormal liver function tests are demonstrated in patients with ulcerative colitis it is likely that primary sclerosing cholangitis will be present (81 per cent of patients in this study), and in order to make a reliable diagnosis it is necessary to perform cholangiography in addition to liver biopsy. A close association with primary sclerosing cholangitis and histocompatibility antigens HLA B8 and DR3 is also reported.

Immunopathological studies of polyarteritis nodosa and Wegener's granulomatosis: a report of 43 patients with 51 renal biopsies.

Abstract: Although it is generally considered that vasculitis of the polyarteritis nodosa (PAN) group and Wegener's granulomatosis (WG) is immune complex (IC) mediated, there are no simultaneous data on circulating IC, complement levels and deposits of Ig and complement in the kidney. Therefore we have performed a retrospective study of 43 patients suffering from PAN and WG. Ig glomerular deposits were uncommon and scanty, except in two patients with WG; C3 deposits were detected in 12 patients, whereas fibrinogen was constantly found when lesions were recent and active. Similar data were obtained for the renal vessel walls. Contrasting with these results, rheumatoid factors and cryoglobulins, suggestive of the presence of circulating IC, were detected respectively in nine of 39 and seven of 37 patients, and IC‘activity’ assessed by the Raji cell assay and the C1q binding assay was found respectively in six of 17 and nine of 10 patients before treatment, and in none of 10 and five of seven patients in remission. Haemolytic complement activity and complement components were never decreased, but the C3d breakdown product of C3 was elevated in all the eight patients studied before treatment. Signs of persistent hepatitis B virus (HBV). infection were detected in five of 25 patients of the PAN group, whereas three of eight patients with WG had only anti-HBV antibodies. Furthermore, cytomegalovirus (CMV) could be isolated from the blood in a case of WG before the treatment was started. Persistent interferonaemia was detected in one of five patients. These results suggest either that renal deposition of CIC is transient, the paucity of Ig deposits being due to rapid clearance of IC by phagocytic cells; or alternatively that vascular and glomerular lesions are not caused by CIC, as in some cases of experimental vasculitis induced by infectious agents.

Gastrointestinal manifestations of systemic vasculitis.

Abstract: Systemic vasculitis is known to affect the gastrointestinal tract but the nature of the complication is poorly characterized. Out of 65 patients with systemic vasculitis, the majority of whom had renal disease, the intestine was found to be affected in 18. These comprised four of eight patients with polyarteritis nodosa, nine of seventeen with microscopic polyarteritis, four of thirty-six with Wegener's granulomatosis and one of four with Churg-Strauss syndrome. The features included abdominal pain (85 per cent), diarrhoea (50 per cent), gut haemorrhage (44 per cent) and abnormal liver function tests (50 per cent). Manifestations of gastrointestinal disease were evident at presentation in half the patients and led to a fetal outcome in five. Ileus, mucosal abnormalities, perforation and slow transit were evident radiographically, and selective visceral angiography showed aneurysms or organ infarcts in five patients. Histological assessment of gut biopsies (chiefly rectal) revealed non-specific inflammation or ulceration in nine patients and intramucosal haemorrhage in two. Focal areas of necrosis and ulceration in colonoscopic biopsies were highly suggestive of vasculitis whereas arteritis was only found in one full thickness biopsy. Hence the diagnosis of gastrointestinal complications depends largely on clinical evidence. In patients who survived, the gastrointestinal features remitted as the systemic illness improved following treatment with steroids, cyclophosphamide or plasma exchange.

Chronic or fatal Q-fever infection: a review of 16 patients seen in North-East Scotland (1967-80).

Abstract: Sixteen patients with serologically proven Q-fever infection are reviewed. Fifteen had significantly raised antibody titres to both phase I and phase II Coxiella burneti antigens, indicating persistent or chronic infection. One patient, a premature infant who died, had raised phase II titres only, but is included together with the mother who had chronic Q-fever and was the presumed source of infection. Chronic Q-fever infection has previously been regarded as virtually synonymous with Q-fever endocarditis, but only seven of the patients in this survey had evidence of valvular endocarditis. In those who did, the infection had arisen on prosthetic valves or those affected by rheumatic or syphilitic heart disease. One patient had inexorably progressive destruction of an infected congenitally bicuspid aortic valve. Eight patients had infections associated with extra-valvular sites and several of these associations have not been previously described. These include extreme prematurity with perinatal death, possibly following transplacental infection, the sudden infant death syndrome (SIDS), multiple lower limb emboli from endocarditis of an abdominal aortic dacron graft, and colonization of ventricular endocardium following left ventricular myotomy/sub-aortic diaphragm resection. The current concept that chronic Q-fever is invariably associated with endocarditis is therefore untenable and the indications for phase I antibody screening should be extended to include patients other than those under investigation for ‘culture-negative’ endocarditis, for example those with unusual osteomyelitis of vertebrae.

The Heart Disease of Friedreich's Ataxia: a Clinical and Electrocardiographic Study of 115 Patients, with an Analysis of Serial Electrocardiographic Changes in 30 Cases

Abstract: One hundred and fifteen patients with carefully defined Friedreich's ataxia were assessed clinically and electrocardiographically for evidence of heart disease. Cardiac symptoms, of which dyspnoea and palpitations were the most frequent, occurred in less than 30 per cent. Abnormalities on clinical examination were present in a similar proportion; harsh systolic murmurs, ventricular hypertrophy and added heart sounds were the commonest of these. Cardiac failure and persistent arrhythmias were rare and occurred late in the evolution of the neurological disease. Two patients presented with heart disease before developing neurological symptoms. Cardiac signs and symptoms were uncommon in patients without electrocardiographic abnormalities. About two-thirds of the cases had definitely abnormal ECG recordings. The characteristic finding was of widespread T-wave inversion with ventricular hypertrophy. Serial ECGs, recorded over periods of up to 32 years, were available in 30 cases and showed that abnormalities may develop in patients with Friedreich's ataxia at any time up until 20 years after the onset of neurological symptoms. In four patients initial ECG abnormalities had either improved or disappeared subsequently.

Osteomalacia in patients with Chronic Renal Failure Before Dialysis or Transplantation

Abstract: The case records of 327 patients who underwent bone biopsy in late or terminal renal failure, before any form of dialysis or transplantation, were examined for clues to the aetiology of renal osteomalacia and its manifestations. Fifty four per cent of the biopsies showed pure osteitis fibrosa, 34 per cent osteomalacia with osteitis fibrosa and 12 per cent showed neither abnormality. Osteomalacia was strongly associated with chronic pyelonephritis and obstructive uropathy as primary renal disease. In two matched groups of 100 each, and within the major primary diseases, it was associated with acidosis, hypocalcaemia and normophosphataemia (as opposed to hyperphosphataemia). There was no association with known length or uraemia and only a weak and inconsistent relationship with severity of uraemia. In the few patients studied, there was no relationship between osteomalacia and serum 25-hydroxycholecalciferol level. In contrast to the state of patients treated by haemodialysis, osteomalacia in this undialysed group was manifested by a higher level of serum alkaline phosphatase than pure osteitis fibrosa, serum iPTH did not differ between the groups, there was no predominance of symptoms in one group, other than proximal myopathy which had a weak association with osteomalacia, and Looser zones were more common than complete fractures. Our study shows that osteomalacia has different manifestations, and probably different causes, before and after the start of haemodialysis. These two stages of renal failure should be clearly distinguished in reports of renal bone disease.

Cardiovascular features of 11 patients with eosinophilic endomyocardial disease.

Abstract: This report describes the clinical features, cardiac investigations and treatment of eleven patients with biventricular eosinophilic endomyocardial disease, who were followed up for a mean of 3.2 years. Three patients died. Five patients presented with heart disease and hypereosinophilia. Six other patients presented with hypereosinophilia and developed cardiac disease later. Histological studies showed early acute necrotic lesions in five patients, later thrombotic lesions in one and late fibrotic lesions in three patients. Endomyocardial biopsy was the method of choice for diagnosing early acute necrotic and thrombotic lesions. Late fibrotic lesions were best shown by amplitude processed 2D echocardiography and angiocardiography. Episodes of heart failure responded well to treatment with prednisolone which appeared to inhibit progression of heart disease in two patients. Three patients with severe ventricular disease and valvular regurgitation responded well to surgical treatment. This longitudinal study has shown that eosinophilic endomyocardial disease can now be investigated and treated effectively at each stage from early sub-clinical lesions to late incapacitating endomyocardial fibrosis.

Calcium metabolism and hyperparathyroidism after renal transplantation.

Abstract: Plasma calcium and albumin levels were measured serially in 100 patients for two years following successful renal transplantation. Mean plasma calcium increased during the first six months after grafting, in large part attributable to an increase in plasma albumin. The variance around the mean plasma calcium did not increase suggesting that mechanisms responsible for hypercalcaemia were common to the majority of patients. 36 per cent of patients developed hypercalcaemia within two years of grafting but the incidence fell to 11 per cent when more rigorous criteria for hypercalcaemia were used. The mechanisms maintaining plasma calcium were studied in 29 of the patients, nine of whom were hypercalcaemic and 20 of whom were normocalcaemic. Before transplantation, mean plasma calcium and phosphate levels were higher, the prevalence of subperiosteal erosions and extraskeletal calcification radiographically was greater, and the duration of haemodialysis treatment was longer in the hypercalcaemic patients than in the normocalcaemic recipients. At assessment after transplantation, hypercalcaemic patients had lower levels of plasma phosphate, higher plasma levels of alkaline phosphatase and parathyroid hormone, and higher hydroxyproline excretion. Renal function and 47Ca absorption were similar in the two groups. The major cause for apparent hypercalcaemia in transplanted patients appeared to be an increase in plasma albumin. In patients with true hypercalcaemia the major cause was pre-existing hyperparathyroidism where hypercalcaemia was mediated by increased renal tubular reabsorption of calcium.

Cushing's Disease Treated by Total Adrenalectomy: Long-term Observations of 43 Patients

Abstract: Forty-three patients were treated by total adrenalectomy for pituitary-dependent Cushing’s disease. The median period of observation was 10 years (range one to 20 years). Thirty-eight patients (88 per cent) had rapid and lasting remissions. Of the 38 in remission, 21 became pigmented but without pituitary enlargement, 11 became pigmented with evidence of further pituitary expansion (Nelson‘s syndrome) and six neither became pigmented nor showed pituitary expansion. Pituitary expansion was associated with high plasma ACTH values, and treatment of pituitary tumours by surgery or radiotherapy gave poor results. However, when compared with alternative methods of treatment, total adrenalectomy for Cushing’s disease is still satisfactory for many patients, despite advances in pituitary surgery, and has advantages over ‘medical adrenalectomy9 with drugs.

Continuous ambulatory peritoneal dialysis: three years' experience.

Abstract: We review the experience of the Renal Unit at Newcastle upon Tyne over the three years 1979-1981, during which 122 patients with chronic renal failure were treated by continuous ambulatory peritoneal dialysis (CAPD). Advantages of the technique included wide acceptability to a cross-section of patients reaching the renal unit, including the elderly and diabetics. Patients who experienced both techniques preferred CAPD to haemodialysis because of the greater freedom and sense of well-being. Patient survival was 94 per cent at two years and rehabilitation was as good as could be expected for the age and primary medical complications of the patients. Control of plasma potassium and phosphate was easier than with haemodialysis. Renal osteodystrophy responded well to a combination of CAPD and alfacalcidol therapy over the two year period for which we have performed serial bone biopsies. Serum aluminium was slightly raised as a result of consumption of phosphate binders and presumed uptake from dialysis fluid but no aluminium related disease has yet been encountered. Anaemia was partly corrected by CAPD with haemoglobin rising to about 10 g/dl on average. CAPD was less costly than home haemodialysis over the first three years and has been adopted as our standard treatment for patients who can expect an early transplant. Disadvantages were persisting problems with peritonitis which still occurred at an incidence of one attack per 39 patient weeks over the last two years, and an actuarial success rate for the technique of only 63 per cent at two years. Twenty patients developed hernias. Weight gain was common and occasionally gross. There was a significant rise in serum cholesterol. The arrival of CAPD has allowed us to increase the intake to our renal failure programme by 50 per cent. However, continued expansion of the technique demands advances in prevention of peritonitis, adequate facilities for admission and particularly an expanding hospital haemodialysis programme to accept the less successful patients from CAPD.

Alcoholic liver disease in Scotland and northeastern England: presenting features in 510 patients.

Abstract: A study of 510 patients in Scotland and northeastern England with hlstological evidence of alcohol-induced liver disease showed no difference in the age of presentation between males and females. Single men and widowed females were particularly susceptible to alcoholic liver disease. The social class distribution was similar to the population in general. Women were more reluctant to volunteer a history of alcoholism than men, they had a higher incidence of previous psychiatric illness (usually due to alcohol abuse) and they developed liver disease at lower consumption thresholds of alcohol than men. Patients under 40 years of age were more likely to have alcoholic fatty liver and less likely to have active cirrhosis than those over 40. Most often, the presenting symptoms were non-specific and tended to be related to the gastrointestinal system, particularly in women. Five per cent of patients were asymptomatic and 14% came to hospital for conditions other than alcoholic liver disease. Important clues to asymptomatic alcoholic liver disease included hepatomegaly, clubbing of the fingers and abnormal liver function tests. Gastro-oesophageal varices accounted for 40% of instances of haemorrhage and the mortality from upper gastrointestinal bleeding was 17%. Anaemia was the most common haematological abnormality. Alcoholic hepatitis was observed more frequently in the Glasgow area then elsewhere.

Complement-mediated leucoembolization: A mechanism of tissue damage during extracorporeal perfusions, myocardial infarction and in shock. A review

Abstract: The complement (C) system evolved as a beneficial antimicrobial system. However, when activated during extracorporeal perfusion as with haemodialysis or cardiopulmonary bypass modest pulmonary dysfunction associated with granulocyte aggregation and embolization can occur. When C activation is massive and prolonged, as with severe sepsis, trauma, or acute pancreatitis, severe pulmonary damage which is recognized as shock lung, or adult respiratory distress syndrome, may occur. Since ulcerating atherosclerotic plaques can also activate C, a mechanism by which myocardial infarcts may extend during the first few hours after infarction is also implied. Therapeutic ramifications of these conclusions are evident. Thus, high doses of corticosteroids or of nonsteroidal anti-inflammatory agents such as ibuprofen share the ability to prevent aggregation and embolization of stimulated granulocytes to patent vessels downstream and also inhibit their production of toxic oxygen radicals. These properties suggest the use of these agents in myocardial infarction and shock states, particularly shock lung, and appropriate clinical trials are awaited with interest.

Low Plasma 25-Hydroxyvitamin D and Serum Calcium Levels in Institutionalized Epileptic Subjects: Associated Risk Factors, Consequences and Response to Treatment with Vitamin D

Abstract: In a survey of 108 subjects with a history of epilepsy in a hospital for the mentally handicapped, administration of both phenobarbitone and phenytoin was associated with low serum calcium and plasma 25-hydroxyvitamin D (25-(OH)D) levels in female subjects only. Intake of phenytoin (as mg/kg body weight) in female subjects exceeded that in males by 22 per cent, whilst the intake of phenobarbitone was 37 per cent higher. The doses of phenobarbitone and phenytoin were each inversely related to plasma 25-(OH)D concentration, but anticonvulsant drug dosage did not correlate with the magnitude of the decline of plasma 25-(OH)D concentration in winter (November-February). No influence of sodium valproate was detected on serum calcium or on plasma 25-(OH)D levels. Limited exposure to ultraviolet irradiation (UVR) or oral administration of vitamin D restored plasma 25-(OH)D to normal levels and healed osteomalacia in a subject with tuberous sclerosis. In this subject, fit frequency declined in response to UVR and to a lesser extent in response to oral vitamin D, despite the attainment of similar levels of serum calcium and of plasma 25-(OH)D. Serum calcium levels in the other 108 subjects were lower in those experiencing the most frequent fits, but serum calcium could not be restored to levels found in subjects not receiving anticonvulsant drugs unless supraphysiological doses of vitamin D were given. Vitamin D deficiency in the epileptic population receiving drugs was assessed by the response of alkaline phosphatase to vitamin D administration. A consistent fall of serum alkaline phosphatase was found only if the initial level exceeded 175 per cent of the normal value established by reference to a population not receiving phenobarbitone or phenytoin. By this criterion five out of 45 subjects (11 per cent), aged nine to 36 years were vitamin D deficient.

Familial Benign Hypercalcaemia: STUDY OF A LARGE FAMILY

Abstract: Twenty-seven hypercalcaemic subjects were identified in three generations of a family. There were no clinical complications of chronic hypercalcaemia, but five had had parathyroid surgery which was unsuccessful in four. Twenty of the twenty-seven subjects were compared with twenty-four normocalcaemic controls from the same family and the findings were also compared with those from forty patients with surgically proven primary hyperparathyroidism. The relation between the serum and urinary calcium levels was studied by means of an oral calcium loading test. The ratio of calcium clearance to creatinine clearance was normal in this family (but elevated in the patients with primary hyperparathyroidism) and the concentration of parathyroid hormone was normal, as was the total urinary excretion of cyclic AMP. Thus, there was no evidence of either suppressed or increased parathyroid activity in this familial condition. Basal urinary calcium excretion was normal under steady-state conditions indicating that the hypercalcaemia could not be attributed to either increased bone resorption or increased calcium absorption from the gut. In accordance with this, the serum levels of 1,25-dihydroxycholecalciferol were normal. The hypercalcaemia in this condition can be accounted for in full by an increase in renal tubular reabsorption of calcium, and thus differs from that of primary hyperparathyroidism in which there is increased production of calcium from gut and/or bone as well as an increase in renal tubular reabsorption of calcium. Although the serum phosphate and renal tubular reabsorption of phosphate were both low in patients with familial benign hypercalcaemia, they were not as low as in patients with the same degree of hypercalcaemia due to primary hyperparathyroidism. The changes in phosphate transport in familial benign hypercalcaemia could be explained as a secondary effect of the increased filtered load of calcium in the kidney. The tendency towards hypermagnesaemia in our patients, which contrasts with a tendency towards hypomagnesaemia in primary hyperparathyroidism, could also be explained as a secondary effect of the abnormality of renal tubular reabsorption of calcium. Increased renal tubular calcium reabsorption and persistent normal functioning of the parathyroid glands in the face of hypercalcaemia remain the sole definite abnormalities of the syndrome.

Late Onset Systemic Lupus Erythematosus and Lupus-like Disease in Patients With Apparent Idiopathic Glomerulonephritis

Abstract: We report 17 patients who presented with either apparent idiopathic glomerulonephritis (16 patients) or post-streptococcal glomerulonephritis (one patient). Doubts arose about the nature of these patients' disease, either because their initial renal histology was suggestive of systemic lupus erythematosus (SLE) in the absence of its clinical or serological features, or because they developed with time the clinical or serological features of SLE. Three patients had a positive antinuclear antibody (ANA) test at the onset of their illness, but normal levels of serum binding of double-stranded DNA (dsDNAB). In another four patients the dsDNAB was slightly raised but with a negative ANA. On renal biopsy the predominant appearance was membranous glomerulonephritis (GN) in 10, subendothelial mesangiocapillary GN (MCGN) in three, and focal segmental glomerulosclerosis in two; one patient each had a focal proliferative GN and a diffuse endocapillary GN. On 1 micron renal sections stained with toluidine blue, 10 patients had immune deposits at multiple sites within the glomeruli. Over a period of one to 14 years, six patients developed extrarenal features suggestive of SLE, nine a positive ANA, and 12 increased serum levels of dsDNAB. Five patients became hypocomplementaemic. Cryoglobulins were isolated from the sera of 10 out of 12 patients; seven contained DNA. Separated cryoglobulin IgG from eight patients showed antibody activity directed against both ss and dsDNA in four, and against dsDNA only in three. On the basis of the clinical, histological and serological observation during follow-up five patients were reclassified as definite SLE, four as probable SLE and two as possible SLE. Rarely, SLE may present with nephritis as the sole disease manifestation, antedating other clinical features and even immunological markers of the disease by years. In addition, some patients with a glomerulonephritis may show clinical and immunological, or histological features of SLE, but do not fit accepted definitions of the disease.

Haemostatic abnormalities in systemic lupus erythematosus.

Abstract: Coagulation studies were performed in 112 consecutive patients with systemic lupus srythematosus (SLE). Abnormalities occured in 64 of 112 (57 percent) Patients. Eighteen Patients (16 per cent) had thrimboeytopnia, 19(16.9 percent) had circulating anticoagulants and 24 had decresed anthithrombin III levels. Abnormalities of fibrinogen were found in 28 patients (23 per cent), and abnormalitiesof platelet factor 3 and 4, indicating in vivo platelet activation occured in seven patients. In 25 patients two detected in any of the 50 healthy volunteers who served as controls. Only one patients with thrombocytopenila had patechine. None of the other patients, even those with multiple defects bled significantly, but several patients had vasculitis and/or phlebitis. There was no correlation between disease activity of SLE and the presence of haemostatic abnormalities, nor was there an assoclation between thease abnormalities and specific clinical haemotologic manifeastations.

Rapidly progressive glomerulonephritis with extensive glomerular crescent formation.

Abstract: Thirty-nine patients with severe crescentic glomerulonephritis and rapidly progressive renal failure were reviewed. Nineteen patients had a focal necrotizing glomerulonephritis, they usually presented with signs of multi-system disease, and eight had histologically-proven microscopic polyarteritis. A second group of 20 patients presented with an acute nephritic syndrome, often with nephrotic features, and had only minor prodromal symptoms. Renal biopsy material showed various forms of proliferative glomerulonephritis in addition to crescents. The most important prognostic feature at admission was renal function: only four of 21 patients who required dialysis recovered any renal function. The prognosis was worse for those with necrotizing glomerulonephritis, of whom two-thirds had oliguria on admission. All patients who were not oliguric, and some with oliguria, were treated with high doses of corticosteroids, usually accompanied by azathioprine and anticoagulants. Seventeen of 18 patients who were not oliguric initially retained or regained renal function, although three subsequently went into renal failure, and three others died of non-renal causes. At the most recent review, 25 of the 39 patients were either dead (16 patients) on dialysis or transplanted (nine patients). Ten were alive with diminished renal function, one had normal renal function but persisting proteinuria, and three were well. Prompt treatment may have contributed to these favourable results in a very severe disease.

Study of lupus nephritis: its classification and the significance of subendothelial deposits

Abstract: This study describes the clinical and pathological characteristics of 74 patients with lupus nephritis classified according to renal biopsy findings using light, electron and immunofluorescent microscopy, and further, assesses the significance of subendothelial deposits in evaluating disease activity. In membranous lupus nephritis (14 cases), many cases showed normal renal function even with the nephrotic syndrome, although five cases had little or no urinary abnormalities. Glomerular cellular proliferation was very mild and subepithelial deposits with a few mesangial deposits were the main pathological alterations. Mesangial proliferative lupus nephritis (17 cases) clinically had very mild renal disease. Renal biopsies in this group revealed mesangial deposits with slight cellular proliferation. Although clinical features of mild diffuse proliferative lupus nephritis (16 cases) were similar to those of mesangial lupus nephritis, glomerular loop deposits were seen in addition to mesangial deposits. In moderate diffuse proliferative lupus nephritis (17 cases), renal function was slightly decreased, moderate proteinuria with haematuria were found, and C3 level was low. Renal biopsies showed active proliferative changes, and subendothelial deposits were frequently seen. In severe diffuse proliferative lupus nephritis (10 cases), the duration from onset of SLE to renal biopsy was short. Impairment of renal function, and nephrotic syndrome with haematuria and hypocomplementemia were frequent. Only three patients survived in this group. Renal biopsies demonstrated highly active proliferative and necrotizing changes, and electron microscopy showed massive subendothelial and mesangial deposits accompanied by subepithelial and intramembranous deposits. The amount of subendothelial deposits correlated with those of mesangial deposits and subepithelial deposits in the cases with diffuse proliferative lupus nephritis. Urinary protein loss and histologic activity showed statistically significant correlations with the amount of subendothelial deposits, but C3 levels and creatinine clearance revealed negative correlations with those deposits.

Mitral Valve Prolapse: An Assessment of Clinical Features, Associated Conditions and Prognosis

Abstract: One hundred and eighty-two patients (100 females, 82 males) with mitral valve prolapse (MVP) confirmed by echocardiography are described. Their ages range from 12 to 87 years (mean 48 years). The symptoms of breathlessness, pain in the chest and palpitations were analysed. They were associated with left ventricular failure, co-existing ischaemic heart disease and arrhythmias in some, but in a proportion the symptoms were thought to be due to psychoneurosis. Seventy-two patients (40 per cent) were referred because of complications of MVP. In 67 patients (37 per cent) the condition was discovered by chance and in 43 patients (24 per cent) neurotic symptoms had led to referral to hospital. A systolic click was heard in 117 patients (54 per cent); 41 patients (23 per cent) had a late systolic murmur and 30 patients (16 per cent) had a pansystolic murmur. The incidence of murmurs rose with increasing age, and pansystolic murmurs were more frequent in males. Thirty-two patients (18 per cent) had neither a click nor a murmur. Twenty-four patients (13 per cent) had associated supraventricular tachycardia and 22 (12 per cent) atrial fibrillation. Twelve patients (7 per cent) had severe mitral incompetence and eight (4 per cent) developed bacterial endocarditis. Only three patients had symptoms suggesting cerebral ischaemia. Twelve patients (7 per cent) had associated aortic incompetence. Twenty-two patients had had an inguinal hernia, the incidence in males over 50 being 26 per cent. Twenty-six patients (14 per cent) had non-specific T wave changes in the electrocardiogram. Echocardiography showed that 112 patients (62 per cent) had mid-systolic buckling of the posterior leaflet and 70 patients (38 per cent) had holosystolic prolapse. In view of the high incidence of complications it is felt that the long-term prognosis not as good as has been generally believed.

Endocrine Abnormalities in Idiopathic Haemochromatosis

Abstract: Anterior pituitary functions and sex steroid levels were measured in 12 patients with idiopathic haemochromatosis (eight males, four postmenopausal females) and age-matched controls, 12 with diabetes mellitus and five with hepatic cirrhosis. In idiopathic haemochromatosis gonadotrophin deficiency was present in seven of 12 patients including six of seven patients who had clinical evidence of hypogonadism. Basal prolactin levels were significantly lower in the patients with idiopathic haemochromatosis compared with either of the control groups (p less than 0.02). Nine patients with idiopathic haemochromatosis exhibited subnormal prolactin responses to thyrotrophin releasing hormone. Thyroid and adrenocortical functions were normal in all patients with idiopathic haemochromatosis. Testosterone values were subnormal in five of eight males with idiopathic haemochromatosis; females with idiopathic haemochromatosis had significantly lower testosterone values compared with the diabetic females (p less than 0.05). Oestradiol values in both sexes and sex hormone binding globulin values in the males were not significantly different in patients with idiopathic haemochromatosis compared with the controls. Sex hormone binding globulin levels were significantly higher in females with idiopathic haemochromatosis compared with either diabetic or cirrhotic females (p less than 0.05). Impairment of anterior pituitary function occurs in idiopathic haemochromatosis but is selective; gonadotrophin and prolactin deficiencies are common. Clinical hypogonadism is usually hypogonadotrophic in origin.

Early-Onset Chronic Renal Failure as a Complication of Acute Intermittent Porphyria

Abstract: In a retrospective survey of patients who have had a proven attack of acute intermittent porphyria (AIP) in the West of Scotland a highly significant association (p less than 0.001) was observed between AIP and the development of early-onset chronic renal failure. Six patients with AIP and chronic renal failure arising in early middle-age are described. As no other cause could be attributed to the renal failure three possible causal links between these two conditions were considered, namely, enhanced susceptibility to analgesic nephropathy, porphyria-induced hypertension, and nephrotoxic effects of porphyrins and their precursors. We suggest that porphyria-induced hypertension is the most important factor in causing early-onset chronic renal failure in acute intermittent porphyria.

A Study on the Effects of Severe Repetitive Exercise on Serum Myoglobin, Creatine Kinase, Transaminases and Lactate Dehydrogenase

Abstract: Two groups of young men taking part in a 24-day training course involving increasingly severe exercise were studied. Serum myoglobin, creatine kinase, creatine kinase-MB, transaminases, lactate dehydrogenase, urea, creatinine, calcium and uric acid were estimated at intervals. During the first few days, increases in myoglobin and muscle enzymes correlated with the severity of the preceding exercise. Increases in myoglobin and muscle enzymes after the final most severe exercising were less than with the initial exercising, demonstrating the effect of physical training. The changes in myoglobin and the muscle enzymes correlated closely. Elevated myoglobin levels persisted for over 24 hours. There was no consistent correlation between changes in myoglobin and uric acid, both of which have been considered responsible for the renal failure which may occur with rhabdomyolysis.