Showing papers in "Postgraduate Medical Journal in 1986"

Serum uric acid, serum glucose and diabetes: relationships in a population study.

Abstract: The relationships between serum uric acid, serum glucose and diabetes have been examined in a survey of 7735 middle-aged men drawn at random from general practices in 24 British towns. There was a positive relationship between serum glucose and serum uric acid concentrations up to about 8.0 mmol/l; at higher levels of glucose, serum uric acid decreased. Uric acid levels were significantly reduced in insulin-dependent diabetics and in those on oral hypoglycaemics and also in 'non-diabetics' with casual glucose levels greater than 10 mmol/l. Both uric acid and glucose concentrations were positively related to body mass index; only uric acid was positively related to alcohol intake. Men on antihypertensive treatment had raised levels of uric acid (significant) and glucose (non-significant). The positive relationship between serum uric acid and serum glucose could not be explained by associations with body mass index, alcohol intake, age, social class, gout or treatment for hypertension. It probably reflects the biochemical interaction between serum glucose and purine metabolism, with increased excretion of uric acid during hyperglycaemia and glycosuria.

Anticardiolipin antibodies--clinical associations.

Abstract: Attention was first drawn to the presence of an anticoagulant in patients with systemic lupus erythematosus (SLE) by Conley & Hartmann (1952) who described two patients with haemorrhagic disorders and prolonged prothrombin and whole blood clotting times. This anticoagulant appeared to act at the level of the prothrombin converter complex of the clotting cascade and prolonged all phospholipid dependent coagulation tests activated partial thromboplastin time (APTT), the Russell viper venom test (RVVT) and, less often, the prothrombin time. The thrombin time is usually normal. It became evident over the years that this 'lupus anticoagulant' was not particularly associated with bleeding but, paradoxically, with thrombosis (Mueh et al., 1982). A more sensitive and reliable technique of solid phase radioimmunoassay for the detection of antibodies to cardiolipin (a-CL) was devised by Harris et al. (1983a). Subsequent studies have shown a close relationship between these antibodies and the 'lupus anticoagulant', both members of a 'family' of antibodies to phospholipid, an integral part of the clotting cascade. However, phospholipids are also present in cell walls of endothelial cells, platelets and even neuronal cells and the actions of the antibodies against these phospholipids have been thought to be important in the pathogenesis of some of their clinical effects. Approximately 30% of patients with the 'lupus anticoagulant' or antibodies to cardiolipin will have a false positive test for syphilis. The VDRL test is usually of low titre (1:4-1:8) in these patients (Harris et al., 1985a). The mechanism of action of these antibodies remains obscure. Carreras et al. (1982) postulated that they may facilitate coagulation by preventing the release of arachidonic acid from blood vessel endothelium. Prostacyclin production is thereby reduced and platelet aggregation may occur. Inhibition of prekallikrein (Fletcher Factor) and the resulting impairment of fibrin clearance as a mechanism was suggested by Angles-Cano et al. (1979) and this mechanism has been demonstrated in several patients by Sanfellipo & Drayna (1983) and Elias & Eldor (1984). Comp et al. (1983) have described IgG from two patients with tht lupus anticoagulant that inhibited the function of human thrombomodulin, the endothelial co-factor in the activation of protein C by thrombin. Thus the feedback inhibition of coagulation by activated protein C is prevented. This has recently been verified by other workers (Cario et al., 1986). There is also a clear association with thrombocytopenia and Harris et al. (1985a) suggest that anticardiolipin antibodies may play a direct role in mediating platelet destruction. It has been postulated that lupus anticoagulants damage platelets and increase their adhesiveness initiating thrombosis (Editorial, 1984). It has been shown that a-CL antibodies may be of the IgG, IgM or IgA subclass. Harris et al. (1986) have recently demonstrated the importance of the actual levels of a-CL antibodies in predicting thrombosis, recurrent fetal loss or thrombocytopenia and this seems to hold true particularly for the IgG subclass, while a group of patients with drug-induced 'lupus anticoagulant' activity recently analysed were found to have predominantly IgM elevations which appeared to be unassociated with any of the thrombotic clinical complications (Gharavi et al., 1986). Investigations by Dr G.R.V. Hughes and his associates from 1983 onwards at the Hammersmith Hospital and the Rayne Institute of St. Thomas' Hospital, have led the way to further detecting and delineating the character of the antiphospholipid antibodies, their clinical associations and the efficacy ofvarious therapies in the prevention ofthe associated clinical complications. Since then, two International Conferences have been held in London with investigators from many countries participating and it has become clear that not only has the original finding of an association with thrombosis been confirmed but that the clinical associations of antiphospholipid antibodies now extend far beyond the original concept and that there is significant 'spill-over' to non-lupus patients and indeed to the general population.

Record linkage study of hypokalaemia in hospitalized patients.

Abstract: Retrospective analysis of biochemical data from 58,167 hospital inpatients revealed that 21% developed hypokalaemia during hospitalization-in 5.2% the serum potassium was less than 3.0 mmol/l. Subsequent evaluation showed a positive correlation between hypokalaemia and both female sex and hospital mortality. Patients with leukaemia and lymphoid tumours, especially when receiving antibiotic or cytotoxic therapy, and patients with gastro-intestinal malignancy were amongst those most frequently experiencing hypokalaemia. There was no significant association with cardiovascular disease. Drug and intravenous fluid administration accounted for the hypokalaemia in 56% of patients. While drug-related hypokalaemia was most commonly seen with diuretics, it was also apparent following use of steroids, insulin and haematinics.

Pathology of hypertrophic cardiomyopathy.

Abstract: This communication will concentrate on the morphological recognition and diagnosis ofthis condition. The classical change at macroscopic examination of the heart is asymmetric hypertrophy of the interventricular septum, the maximal bulge occurring at various sites (Olsen, 1972). A few years ago doubt was cast upon the reliability of this change due to its occurrence in normal as well as congenitally abnormal hearts (Bulkley et al., 1977). There is no doubt that if the asymmetry of the septum is of sufficient severity, for example a ratio between the maximal bulge and the free left ventricular wall exceeding two, a diagnosis can be made on macroscopic examination alone (Olsen, 1971). Not infrequently, the changes may not be as severe or may even be absent, a symmetric form being recognized with increasing frequency. Recourse to histological examination then becomes mandatory. Microscopical changes include: severe hypertrophy, disarray, the fibres often displaying a whorled arrangement, bizarre shaped nuclei often surrounded by a clear zone and varying degrees of cellular interstitial fibrosis (Van Noorden et al., 1971). Some overlap between the changes occurring in hypertrophy due to known causes and that occurring in hypertrophic cardiomyopathy exist and several years ago the histological HOCM index was developed, assessing the various morphological features semi-quantitatively (Van Noorden et al., 1971). More recently, controversy has arisen as to whether disarray of myocardial fibres is pathognomonic of the condition or at least highly characteristic. It has been shown that if disorganisation of myocardial fibres is wide-spread involving 5% or more of the septum, that this represents a specific histological marker of this disease (Maron & Roberts, 1979). It is, however, unwise to single out one feature and only ifthe other characteristic changes are considered in combination with dis-

Levodopa withdrawal syndrome identical to neuroleptic malignant syndrome.

Abstract: A 60 year old woman with idiopathic Parkinson's disease had been prescribed thioridazine for schizophrenia. Five months after this was stopped, Sinemet also considered of dubious therapeutic value, was withdrawn. One week later she developed features of the neuroleptic malignant syndrome (NMS) accompanied by myoglobinuric renal failure. Post-mortem examination confirmed Lewy body degeneration in the substantia nigra. It is proposed that NMS may be caused by levodopa withdrawal in Parkinson's disease, and that it is withdrawal of dopaminergic drive that causes the syndrome.

The prognostic value of blood glucose and glycosylated haemoglobin estimation in patients with stroke.

Abstract: In a prospective study of 109 patients admitted to hospital with a provisional diagnosis of acute stroke, 87 were found to have acute hemiplegic stroke lasting more than 24 hours, and did not have any other co-existing life-threatening disorder. In 81 of these patients, blood glucose and glycosylated haemoglobin (HbA1) were measured at the time of admission. Thirteen of these 81 patients (16%) were hyperglycaemic--in 5 cases, normal HbA1 was found in conjunction with hyperglycaemia suggesting that this represented a 'stress' response. There was no significant difference in age or in blood glucose level between those who died as a result of stroke and those who survived. However, hyperglycaemia with normal HbA1 was demonstrated in 4 of 26 patients who died compared to only one of 55 survivors (P less than 0.02), and all 3 patients with blood glucose greater than 10 mmol/l in conjunction with normal HbA1 died as a result of stroke. Biochemical evidence of 'stress' hyperglycaemia in patients with acute stroke suggests a poor prognosis.

Asymmetric apical hypertrophy: ten years experience.

Abstract: This paper reports 10 years experience of 31 patients with asymmetric apical hypertrophy, in whom left ventricular hypertrophy involved the apex exclusively and giant T wave inversion in the left precordial leads was the characteristic finding. This type of hypertrophic cardiomyopathy was observed predominantly in men over 40 years of age. Family history was negative and patients usually had no complaints. Left ventricular hypertrophy was evident by physical examination as in other forms of hypertrophic cardiomyopathy, but a systolic murmur was faint or absent and the second heart sound was frequently split. Electrocardiographic signs may fluctuate, and occasionally progression or regression occurs. Echocardiography including the two-dimensional method was essential for the diagnosis and left ventriculography was helpful for confirmation. To date complications have been infrequent and the prognosis seems good. The relation of asymmetric apical hypertrophy to other forms of hypertrophic cardiomyopathy is under investigation.

Tuberculosis and renal transplantation--observations from an endemic area of tuberculosis.

Abstract: Ninety-five renal transplant recipients from an endemic area of tuberculosis were investigated to find out the prevalence and course of tuberculosis in pre- and post-transplant periods. Eleven patients had tuberculosis in the pre-transplant period - pulmonary (2), pleural (2), miliary (1), abdominal (2), lymph node (5) and pericardial (1). They were transplanted after antituberculous therapy of 3 to 6 months with satisfactory results. The anti-tuberculous treatment was usually continued for 2 years. Only one of the above 11 patients had evidence of tuberculosis in the post-transplant period. Nine patients developed tuberculosis for the first time in the post-transplant period - pulmonary (4), pleural (1), miliary (1), lymph node (4) and pericardial (1). There was no mortality due to tuberculosis. Thorough search for tuberculosis is mandatory both during pre-transplant assessment and post-transplant follow-up in areas of endemic tuberculosis.

Colitis caused by non-steroidal anti-inflammatory drugs.

Abstract: Four cases of acute proctocolitis associated with non-steroidal anti-inflammatory drug therapy are presented. The drugs implicated were flufenamic acid, mefenamic acid, naproxen and ibuprofen. After resolution of symptoms and signs of proctocolitis three of the four patients were subsequently rechallenged with the implicated drug: in each there was a rapid relapse.

Lymphoma of the colon and rectum.

Abstract: Lymphomatous involvement of the colon and rectum may occur either as a localized entity or as a manifestation of generalized lymphoma. It is important to distinguish between primary and secondary colorectal lymphoma as the natural history and management of the two conditions differs significantly. Colorectal lymphoma is a rare condition although several major series have been published as well as many case reports. A review of the literature is, however, complicated by a number of factors: (1) The distinction between primary and secondary involvement is not always clearly made and several different staging classifications have been used. (2) Colorectal lymphoma is sometimes not separated from other gastrointestinal lymphomas. (3) Comparison between different histological classifications is difficult, particularly as some of the major series were published over twenty years ago. (4) Childhood cases are included by some authors and excluded by others. (5) The exact site of origin of ileocaecal masses is difficult to determine. (6) Referral patterns differ between institutions. (7) Geographical factors may be important. (8) All the series reported are retrospective making the contribution of surgery, radiotherapy or chemotherapy difficult to assess. (9) Some individual cases have been reported more than once. This review therefore concentrates on the major series reported since 1960 in which sufficient information regarding these factors has been given to allow conclusions to be drawn.

Non-steroidal anti-inflammatory agents and the gastrointestinal tract.

Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have had a bad press recently. The proliferation of these widely used agents has attracted the derogatory appellation 'me too'. Some, such as benoxaprofen, zomepirac, indoprofen and a controlled delivery indomethacin formulation ('Osmosin'), have been withdrawn because of concern about adverse drug effects including gastrointestinal bleeding (benoxaprofen) (Editorial, 1982) and bowel perforation ('Osmosin') (Day, 1983). Concern has been expressed for as long as NSAIDs have been available and there is little doubt that acute administration of many of them causes gastric erosions in animals and provokes microscopic bleeding in man. What remains controversial is whether there is a causative link between NSAID ingestion and peptic ulceration or important upper gastrointestinal haemorrhage. During the last two decades admissions to hospital and mortality rates for peptic ulcer have fallen in the UK (Coggon et al., 1981). This is mostly accounted for by changes among the young with little change in the mortality rate for women over 75 years of age. Aspirin consumption and smoking have declined and this may be a partial explanation of the overall trend but the elderly are major users of other NSAIDs and this might explain the differential ulcer mortality rate between old and young. However, the situation is complex. The elderly often have other diseases and take other drugs, more prescriptions are issued for NSAIDs to those under 65 years ofage than those over 65 and the number of prescriptions written has been steadily increasing in all age groups. There is therefore a need to question our fundamental assumptions about NSAIDs.

Diclofenac-induced hepatotoxicity

Abstract: Two patients developed clinical, biochemical and histopathological signs of a liver hypersensitivity reaction following treatment with diclofenac. Hepatic side effects of this drug are very rare. The relevant literature is reviewed.

The morphological progression of viral myocarditis.

Abstract: In an attempt to document the morphological progression from acute idiopathic myocarditis to end-stage dilated cardiomyopathy we studied 20 patients with a diagnosis of myocarditis who had had serial endomyocardial biopsies performed with intervals of 1 month to 2 years and whose ages varied from 6 months to 62 years. Fifteen of these patients were treated with immunosuppressive drugs for myocarditis. Ten out of 15 treated patients stabilized clinically. In the remaining 5 cases there was worsening congestive heart failure and 1 patient underwent cardiac transplantation. Of the 5 patients who did not receive immunosuppression, 2 stabilized spontaneously, and 3 developed heart failure, 2 of whom subsequently had cardiac transplants. Whether the patients received immunosuppression or not, in all cases, the inflammatory infiltrate was less but the myocardium developed significant hypertrophy with an increase in interstitial fibrosis and in 8 cases the morphological changes were those of dilated cardiomyopathy. From the morphological standpoint of this study we have shown some evidence that dilated cardiomyopathy can be the end result of acute myocarditis. It appears that not every case of acute myocarditis progresses to dilated cardiomyopathy and that steroid treatment does not necessarily prevent progression of myocarditis to dilated cardiomyopathy.

Spontaneous spinal epidural haematoma with spontaneous resolution.

Abstract: Spontaneous spinal epidural haematoma is of unknown aetiology, but it has been associated with hypertension. Treatment is surgical decompression but three cases of spontaneous recovery have been reported. We report the fourth such recovery in a 68 year old hypertensive woman.

'Biological' depression; because sleep fails?

Abstract: Although converting-enzyme inhibition is of established value in the management of patients with severe chronic congestive heart failure, troublesome adverse reactions occur frequently during the course of treatment and may cause physicians to interrupt effective therapy. The three most common adverse reactions that are seen in patients with heart failure following treatment with captopril and enalapril (symptomatic hypotension, functional renal insufficiency, hyperkalaemia) are predictable consequences of interfering with the homeostatic functions of the renin-angiotensin system, which evolved millions of years ago to preserve life in sodium-depleted states. It is not surprising, therefore, that these untoward effects can be prevented or reversed by increasing the dietary intake of salt or reducing the dose of concomitantly administered diuretics; their occurrence rarely requires discontinuation of drug therapy. Recognition of this link between sodium balance and the adverse effects of converting-enzyme inhibition is important, because most patients with severe heart failure who experience such untoward reactions can nevertheless be expected to improve clinically during long-term therapy, if effective treatment is not interrupted.

Mechanisms by which stress can lead to coronary heart disease.

Abstract: Much stress is of psychological origin and due to emotional arousal. The mechanisms by which anger, helplessness, or a sense of control and serenity exert their various neuroendocrine effects are discussed. Primacy is given to three systems; to the catecholamines, to testosterone and to cortisol. Evidence that they interact to accelerate the arteriosclerotic process is cited. The protective aspects of intimacy are discussed together with evidence that certain personality types promote it in the marital situation while others do not. It is suggested that the post-traumatic stress syndrome may relate to the coronary-prone personality for it involves an alexithymic disturbance of the emotional competence required for successful intimacy.

Iodine-induced hyperthyroidism in a patient with a normal thyroid gland.

Abstract: Iodine-induced hyperthyroidism can develop even in the presence of an otherwise normal gland. One of the less common sources of iodine is tablets of seaweed, sold over the counter without prescription. We report the case of a 72 year old female who developed clinical and laboratory evidence of hyperthyroidism while ingesting sea-kelp (Vitalia) tablets. Six months after stopping the tablets, the symptoms and laboratory evidence of hyperthyroidism had disappeared. No evidence of pre-existing thyroid disease was found.

Cerebral Blood Flow, Metabolism and Epilepsy

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Amiodarone and thyroid hormone metabolism.

Abstract: Amiodarone, an antiarrhythmic and anti-anginal agent, contains 75mg of organic iodine per 200mg active substance. The drug is deiodinated during its biotransformation, and it is estimated that a dose of 200mg releases 6mg of free iodine (Broekhuyzen et al., 1969). Consequently, the thyroid gland has to adjust itself to these pharmacological quantities of iodine. When amiodarone medication is discontinued, it may take months until the iodine excess is cleared from the body due to the very long elimination half-life (approximately 40-60 days) (Haffajee et al., 1983; Plomp et al., 1984). We will review the pharmacological and pathological effects of amiodarone on thyroid hormone metabolism, and discuss the relationship between the thyroidal effects of amiodarone and its mechanism of action.

Aluminium phosphide poisoning: a prospective study of 16 cases in one year.

Abstract: Sixteen patients suffering from aluminium phosphide poisoning were treated during the year from January 1985 to December 1985. These accounted for approximately half the total number of cases of acute poisoning. Profuse vomiting, pain in the upper abdomen and shock were the most common presenting features. Six patients succumbed to their illness. Analysis of various prognostic factors revealed that ingestion of 'unexposed' tablets of aluminium phosphide taken from a freshly opened bottle was associated with a greater risk of fatal outcome. Aluminium phosphide poisoning has become an important matter of public health in parts of India.

Male fertility in Crohn's disease.

Abstract: The fertility of 70 men with Crohn's disease and a group of age matched controls were compared. Crohn's disease was associated with a significant reduction in family size independent of steroid or sulphasalazine treatment.

Glucose intolerance during diuretic therapy in elderly hypertensive patients. A second report from the European Working Party on high blood pressure in the elderly (EWPHE).

Abstract: Five hundred and seven elderly hypertensive patients were followed for 1 year, 371 for 2 years and 270 for 3 years in a double-blind, randomized, controlled trial in which they received either placebo or 25-50 mg hydrochlorothiazide and 50-100 mg of triamterene daily. One third of the active treatment group also received 250 mg to 2 g methyldopa daily. After 1 year the active treatment group had an average increase in fasting blood sugar of 2.5 mg/dl compared with an average fall of 1.4 mg/dl in the placebo group (P = 0.01). The increase in blood sugar 1 hour and 2 hours after 50 g oral glucose tended to be greater in the actively treated group but these increases did not achieve statistical significance. The effects of diuretic treatment were established after one year and did not increase further over the next 2 years. Overall there was an increase in fasting blood sugar of 5 mg/dl in the active treatment group which occurred mainly in the first year. The hyperglycaemic effect of diuretics appeared to be partly or wholly related to potassium loss since, in both groups, impairment of glucose tolerance was most marked in those in whom serum potassium decreased. The measures of blood sugar were also positively related to systolic pressure before and after treatment.

The restless legs syndrome.

Abstract: The first description of the restless legs syndrome (RLS) is attributed to Thomas Willis in the 'London Practice of Physick' of 1685 (Ekbom, 1960). Here he wrote 'wherefore to some, when being a bed they betake themselves to sleep, presently in the arms and leggs, leapings and contractions of their tendons, and so great a restlessness and tossings of their members ensue, that the diseased are no more able to sleep than if they were in a place of the greatest torture'. In 1861 Whittmaack used the term anxietas tibiarum to describe nocturnal discomfort of the legs, which he considered was a common symptom of hysteria (Ekbom, 1945). The same phenomenon was called 'impatience musculaire' in the French literature (Ekbom, 1944; Bonduelle, 1952) and the leg jitters by Allison (1943). Ekbom's earliest descriptions of the RLS distinguished a common form which he called 'asthenia crurum paraesthetica' from a painful variant 'asthenia crurum dolorosa' (Ekbom, 1946). He identified the first of these in 34 cases. Paraesthesia with deep calf and shin discomfort started only when the legs were at rest and necessitated that they were moved to provide relief. He postulated that pregnancy was an aetiological factor and in some patients he diagnosed prostatitis, testosterone deficiency and the burning feet syndrome due to malnutrition. Ask-Upmark noted the disorder as a late effect of gastrectomy (Ask-Upmark & Meurling, 1955) and on the basis of anecdotal evidence of postural dependence of symptoms, suggested the cause was vascular congestion ofthe spinal cord (AskUpmark, 1959). Some authors doubted the existence ofa distinct syndrome; Purdon-Martin (1946) believed the symptoms were due to acroparaesthesia and Masland (1947) that they were a manifestation of myokymia. By 1960 Ekbom had studied 175 people whom he had identified with restlessness of the legs. He found that 5% of normal psychiatrically stable individuals were disturbed by restless sensations, but also believed it was symptomatic of anaemia, certain infectious diseases, diabetes, cold exposure or those taking phenothiazine drugs (Ekbom, 1945, 1950, 1960). A diabetic patient whose symptoms vanished on the side of a recent leg amputation was presented as evidence for a peripheral origin (Ekbom, 1961) and Bornstein (1961) speculated about abnormal connections with the reticular system. In recent years neuroleptic-induced akathisia has been compared with idiopathic RLS. Akathisia was originally described in its uncommon idiopathic form by Haskovec (1901) and later in relation to Parkinson syndromes (Sicard, 1923) and drugs such as promethazine (Sigwald et al., 1947) and the phenothiazines (Steck, 1954). It is characterized by a state of mental and motor restlessness which is accompanied by an irresistible compulsion to physically move about. Restlessness of the legs is common and similar to that occurring in idiopathic RLS, but inner restlessness of the mind and body is peculiar to akathisia. Confusion between these two conditions explains why promethazine and prochlorperazine have been considered both cause and ineffective remedy of RLS.

Angiotensin converting enzyme inhibitors in diabetes: experimental and human experience.

Abstract: Peripheral glucose metabolism was studied during the influence of elevated systemic kinin levels by either application of exogenous bradykinin (BK) or inhibition of endogenous kinin degradation by angiotensin converting enzyme inhibitors (ACEI). In infusion experiments in streptozotocin-diabetic rats, both BK (0.3 micrograms/min) and ACEI (300 micrograms captopril/100 g) showed a significant reduction of elevated blood glucose levels. In man, non-insulin dependent diabetics (NIDD) and healthy subjects in postoperative (POP) stress were examined. Peripheral insulin-sensitivity and muscular glucose balance were determined using the glucose clamp technique and the forearm technique. In NIDD as well as in POP subjects, impaired peripheral insulin responsiveness, as evaluated by whole body glucose consumption, was improved up to 50% by application of BK (80 micrograms/h i.v.) or ACEI (25 mg captopril p.o.), respectively. This was most probably due to accelerated muscular glucose uptake which was assessed in the same experiment and found to be increased 2- to 3-fold under these conditions. As a molecular basis for the observed effects on muscular glucose uptake, phosphofructokinase was found to be markedly stimulated by BK (8 X 10(-10)mol/l) in the isolated perfused rat heart, suggesting accelerated glycolytic flux. It may be concluded that ACEI increase muscular insulin responsiveness, thus being beneficial in insulin-resistant states as well as in hypertension. This metabolic effect is most probably due to elevated systemic kinin levels. Further investigations are required to evaluate the clinical relevance of these findings.

Plasma electrolytes in elderly patients taking fixed combination diuretics.

Abstract: Plasma potassium and sodium concentrations were measured in a group of elderly patients taking maintenance thiazide diuretic therapy alone, with a potassium supplement or in combination with a potassium sparing diuretic. Fixed dose combinations of a thiazide and potassium sparing diuretic did not significantly reduce the prevalence of hypokalaemia and the combination of amiloride-hydrochlorothiazide was associated with a disproportionate number of cases of hyponatraemia. The desirability of the current widespread use of fixed dose combination diuretics over less expensive single agents is questioned.

Arrhythmias in dilated cardiomyopathy.

Abstract: Sixty-five patients with dilated cardiomyopathy underwent 24 hour electrocardiographic monitoring: 62 (95.4%) showed ventricular arrhythmias and 52 (80%) complex ventricular arrhythmias (multiform ventricular extrasystoles, paired ventricular extrasystoles and ventricular tachycardia). Complex ventricular arrhythmias correlated significantly with some haemodynamic indices of ventricular dysfunction: patients with multiform and paired ventricular extrasystoles and with ventricular tachycardia had lower values of ejection fraction (31.9 +/- 11.8%, P = 0.002) and of cardiac index (2.9 +/- 0.7 litres/min/m2, P = 0.029) than the others (41.1 11.1% and 3.5 +/- 0.9 litres/min/m2 respectively). Patients were followed for a period of 30 +/- 18 months (20 days to 64 months). During follow-up 19 died and mortality was higher among patients with multiform and paired ventricular extrasystoles and/or ventricular tachycardia. Complex ventricular arrhythmias are frequent in dilated cardiomyopathy: ventricular tachycardia and multiform and paired ventricular extrasystoles seem to be related to a more depressed ventricular function and to a poor prognosis. The importance of antiarrhythmic treatment in these patients has still to be evaluated.

Crohn's colitis and sarcoidosis.

Abstract: We report a patient with both sarcoidosis and Crohn's colitis, an association not previously documented. We review the literature and discuss the areas of overlap in these two conditions.

The heart in Portuguese amyloidosis.

Abstract: A systematic investigation was performed in patients with familial amyloidotic polyneuropathy, Portuguese type (AFp) to assess the pattern and incidence of cardiac involvement. Of 327 patients investigated, ECG abnormalities were present in 285 (87.2%). Low voltage and QS pattern in V1, V2, V3 were found in 51.3% and 35.7% patients respectively. Conduction disturbances were present in 211 (64.5%). Sinus node disease, 1st degree and Wenckebach interventricular blocks were frequent. Complete atrioventricular block was observed in only 2 patients (0.6%). Left anterior hemi-block was present in 30.8%, left bundle branch block in 3.9%, left posterior hemi-block in 2.4% and right bundle branch block in 2.1%. Holter monitoring showed a much higher incidence of conduction disturbances, most of these occurring at night. The mean values of septum and posterior wall thickness and mass evaluated by echocardiography in 72 patients were normal. The systolic and diastolic global and regional functions, determined in 12 patients, analysing the echo by a digitization computer technique, were normal. In 7% a trivial pericardial effusion was observed. In 16 patients with ECG changes and normal echocardiograms the technetium 99m pyrophosphate scanning was negative. We conclude that the ECG is the most precise, sensitive and clinically useful method for detecting cardiac amyloidosis in patients with AFp. In spite of the rarity of congestive and restrictive patterns, the incidence and severity of conduction disturbances does not allow us to consider heart disease in AFp as a benign entity.

Stress and heart disease: evidence of associations between unemployment and heart disease from the OPCS Longitudinal Study.

Abstract: The OPCS Longitudinal Study has been used to study both overall and cause-specific mortality patterns in 1971-1981 among men and women directly or indirectly affected by unemployment in April 1971. Groups studied included men seeking work in 1971, the wives of men seeking work in 1971 and other women in the same households as a man seeking work in 1971. The findings of this project are summarized here and attention is focused on mortality from circulatory diseases, in particular ischaemic heart disease. The study provides evidence which could be seen as supporting hypotheses about relationships between stress and overall mortality, with a marked excess for suicides. The evidence with respect to ischaemic heart disease is positive but less convincing with excess mortality from this cause principally occurring among younger unemployed men and among the wives of men who were seeking work in 1971. Given the sharp contrasts in the pattern and levels of unemployment between 1971 and 1981 it is difficult to extrapolate from these findings to the present day.

Captopril in the treatment of hypertension in type I and type II diabetic patients.

Abstract: This investigation was performed in two groups of adult patients, 10 with type I and 10 with type II diabetes mellitus, all with arterial hypertension (160 to 200 mm Hg systolic and 95 to 120 mm Hg diastolic). Captopril, 50 mg twice a day, was administered for 12 weeks and was effective as monotherapy in 16 patients. Mean arterial pressure (+/- s.d.) in type I patients changed from 121.4 +/- 9.6 to 100.2 +/- 10.1 after 4 weeks and to 102.0 +/- 3.8 mm Hg after 12 weeks; in type II patients it changed from 132.8 +/- 5.7 to 123.9 +/- 13.5 after 4 weeks and to 109.1 +/- 11.1 mm Hg after 12 weeks. The differences were statistically significant. In only 4 patients was it necessary to add a thiazide after the first month of therapy. No significant change was induced by captopril in urine output, osmolar clearance, free water clearance inulin, and PAH clearances. No significant change was observed in serum and urine Na+, Cl-, Ca++ and Mg++, whereas a statistically significant reduction was found in the renal clearances of K+ and PO4-. No important change in serum aldosterone was found, while plasma renin activity was increased, as expected. No alterations in urine protein, glucosaminoglycans, gamma GT, and N-acetyl-beta-glucosaminidase were observed during follow-up. All patients maintained good metabolic control of their disease. No neutropenia and orthostatic hypotension were seen. Captopril appears to be an effective and safe drug for lowering blood pressure in diabetic patients, without affecting renal function, electrolyte balance and the metabolic control of diabetes.