Showing papers in "QJM: An International Journal of Medicine in 1989"

Clinical Features and Prognostic Indicators in Paediatric Cerebral Malaria: A Study of 131 Comatose Malawian Children

Abstract: We studied the relationship between presenting features and outcome in 131 Malawian children admitted with cerebral malaria (P. falciparum malaria and unrousable coma). A method was devised for the measurement of depth of coma in children too young to speak. Twenty patients (15 per cent) died and 12 (9 per cent) recovered with residual neurological sequelae. Presenting clinical signs significantly associated with adverse outcome (death or sequelae) were profound coma, signs of decerebration, absence of corneal reflexes, convulsions at the time of admission and age under three years. Laboratory findings of prognostic significance were hypoglycaemia, leucocytosis, hyperparasitaemia, elevated plasma concentrations of alanine and 5'-nucleotidase, and elevated plasma or cerebrospinal fluid lactate. A prognostic index based on eight of these risk factors that can readily be ascertained at the bedside or in a ward sideroom, was more accurately predictive of outcome than any single feature. Such an index may be valuable as a measure of severity of illness for establishing the comparability of study groups, and for evaluating the role of other factors in the pathogenesis of cerebral malaria.

Hypopituitarism following external radiotherapy for pituitary tumours in adults.

Abstract: The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.

The association of autoimmune disorders with inflammatory bowel disease.

Abstract: Medical records of patients with ulcerative colitis (n = 858), Crohn's disease (n = 378) and coeliac disease (n = 148) were examined to determine the prevalence of associated autoimmune disorders. Of outpatient controls (n = 300), 2 per cent had at least one autoimmune disorder, compared to 7 per cent with ulcerative colitis, 2 per cent with Crohn's disease and 6 per cent with coeliac disease. Inclusion of primary sclerosing cholangitis with the autoimmune disorders increased the overall prevalence in ulcerative colitis to over 9 per cent. The results provide further indirect evidence of involvement of autoimmune mechanisms in the pathogenesis of ulcerative colitis.

The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature.

Abstract: The prognostic markers in 87 consecutive patients with lupus nephritis who underwent renal biopsy are reported for five clinically relevant long-term outcomes--renal insufficiency, renal failure, death due to renal systemic lupus erythematosus, death due to non-renal SLE and death due to SLE, both renal and non-renal. We have demonstrated that a number of previously neglected or rarely studied predictors were important prognostic markers. These included the duration of renal disease before biopsy, overall severity of SLE, as well as the presence of vasculitis, hypertension or a comorbid ailment. Furthermore, the study confirms the predictive importance of serum creatinine, 24-h urinary excretion of protein, C3, and of the activity and chronicity indices on biopsy. However, overall a simple measure of tubulointerstitial disease was the best predictor obtained from biopsy. Prognostic models based on clinical data alone were developed for each of the five outcomes. The models amplify our clinical understanding of lupus nephritis. Markers of renal severity were most important in predicting renal outcomes such as renal insufficiency and renal failure. Prognostic factors less directly related to renal disease (comorbidity and vasculitis) were important predictors of fatality. A marker of immunologic disease activity (C3) was a valuable predictor for many of the outcomes. Thus markers of disease severity reflecting organ damage due to SLE and other comorbid conditions could be combined with markers of immunologic activity to predict a variety of outcomes of relevance to a clinician. When biopsy data obtained by light or electron microscopy were evaluated for their ability to add new predictive information to the clinical models, only a limited value for biopsy was noted. It is likely that this reflected the close correlational relationships between clinical and biopsy variables, the strong clinical models generated, and the inclusion in the clinical models of the previously neglected clinical variables, duration of renal disease before biopsy and the presence of vasculitis or comorbid disease.

Prognosis of Critically-ill Patients with Acute Renal Failure: APACHE II Score and Other Predictive Factors

Abstract: The survival from acute renal failure requiring renal replacement therapy was studied in 90 critically-ill patients admitted to an intensive care unit. Mean age (+/- SD) was 51 +/- 14.6 (range 17 to 81) years. Mechanical ventilation was required in 88 patients and 71 patients received total parenteral nutrition. Thirty-three per cent of patients left the intensive care unit alive and 24 per cent survived to leave hospital. Final survival was 20 per cent in medical patients (n = 49), 29 per cent in surgical patients (n = 38) and 100 per cent in obstetric patients (n = 3). Hypotension, requirement for inotropic support, oliguria and sepsis were all associated with a poorer prognosis. The mode of renal replacement therapy did not affect survival, but additional haemodialysis was required in 33 of 65 patients treated by continuous arteriovenous haemofiltration but none of 22 treated with continuous arteriovenous haemodialysis (p less than 0.001). APACHE II score was calculated for 87 patients. Mean APACHE II score was 26.1 +/- 6.9 (range 14 to 44). APACHE II score on admission predicted the likelihood of survival well. No patients with a score of more than 40 survived, compared to 40 per cent of those with scores of 10 to 19. Pre-existing organ insufficiency or immunosuppression meriting a CHE score of 5 was associated with a very poor survival (1 of 30 patients). APACHE II score is a reliable indicator of severity of illness and likelihood of survival in critically-ill patients with acute renal failure. The widespread adoption of APACHE II scoring for patients with acute renal failure requiring intensive care would facilitate medical audit and comparison of studies from various centres.

Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea.

Abstract: Computed tomography has been used to study the pharyngeal airway during tidal breathing in wakefulness and during obstructive apnoeas in Non-REM sleep in patients with obstructive sleep apnoea. In supine subjects, contiguous transverse 10 mm sections were taken perpendicular to the posterior pharyngeal wall with a 2.1 s scan time. Studies during wakefulness showed that the narrowest section of the pharyngeal airspace was in the region posterior to the soft palate and that the minimal airway cross-sectional areas were significantly reduced in the group of patients with obstructive sleep apnoea compared to the group of control subjects without obstructive sleep apnoea. The studies during sleep showed that in all patients, the airspace posterior to the soft palate was a site of obstructive apnoeas. The length of the obstructed segment varied between patients, extending below the level of the soft palate in half the patient group. Airway narrowing and obstruction was due to posterior displacement of the soft palate and the tongue in the majority of patients, although lateral displacement of the pharyngeal walls was also observed. No occlusion was observed in the laryngopharynx although there was narrowing of oro- and laryngopharyngeal apertures below the site of obstruction during obstructive apnoeas. The size of the oropharyngeal airspace during wakefulness did not predict the presence of airway occlusion below the level of the soft palate when asleep. The variability between patients in the site(s) of upper airway obstruction during obstructive apnoeas have important implications for the choice of appropriate treatment in patients with obstructive sleep apnoea.

The Haematological and Biochemical Changes in Severe Pulmonary Tuberculosis

Abstract: This study surveys the extent and severity of haematological and biochemical abnormalities which occurred in 265 patients with pulmonary tuberculosis, and records the haematological changes that occur with treatment. Anaemia was present in 60 per cent of patients, more frequently in males than in females. Leucocytosis with neutrophilia occurred in 40 per cent, lymphopenia in 17 per cent and monocytopenia in 50 per cent. Platelet count and erythrocyte sedimentation rate were elevated in 52 and 80 per cent respectively. Bone marrow aspiration and trephine biopsy were of limited diagnostic value. Ferritin and vitamin B12 levels were increased in 94 and 57 per cent of subjects respectively whilst serum and red cell folic acid were within normal limits in 83 per cent. The frequency of the important biochemical changes were hyponatraemia (43 per cent) and hypoalbuminaemia (72 per cent); alkaline phosphatase, aspartic transaminase and lactic dehydrogenase levels were elevated in approximately a third of patients possibly due to unsuspected dissemination. There was a close correlation between the acid-fast bacilli in sputum and abnormal values, particularly those of body weight, haemoglobin, platelet count, white cell count and erythrocyte sedimentation rate. Failure of these indices to return to normal was invariably associated with persistent excretion of acid-fast bacilli. We have shown that haematological and biochemical abnormalities in pulmonary tuberculosis are common and may be valuable aids to diagnosis. Some haematological markers also reflect response to treatment.

Fatal reactivation of chronic hepatitis B virus infection following withdrawal of chemotherapy in lymphoma patients.

Abstract: Four Chinese patients with non-Hodgkin's Iymphoma and asymptomatic chronic hepatitis B infection developed fulminant hepatitis three to four weeks after two to five courses of chemotherapy. One was initially positive for hepatitis B e antigen and three were positive for antibody to HBeAg. They had normal initial serum aminotransferase levels. In all four patients, the hepatic illness appeared to be caused by reactivation of hepatitis B virus replication as evidenced by the appearance of HBV DNA in serum at the onset of hepatitis, seroreversion from anti-HBe to HBeAg positivity, and the absence of other incriminating drugs or viral markers. All died within three weeks after the onset of jaundice. Serum HBV DNA level dropped to undetectable level as the hepatitis progressed. We postulate that potent cytotoxic therapy reactivated HBV replication and permitted widespread infection of hepatocytes. Upon withdrawal of chemotherapy, the immunologic rebound resulted in rapid destruction of infected hepatocytes and massive liver necrosis. Several methods for the prevention of such hepatic reactivation are discussed.

Autonomic Neuropathy and Chronic Liver Disease

Abstract: Autonomic neuropathy has been reported in association with alcoholic cirrhosis but there is no information on its occurrence in non-alcoholic liver disease. We have examined autonomic function in 64 patients with biopsy-proven liver disease (22 with alcoholic liver disease and 42 with non-alcoholic liver disease) together with 29 age-matched controls. Forty-five per cent of patients with alcoholic liver disease and 43 per cent with non-alcoholic liver disease showed evidence of parasympathetic damage; 11 per cent of patients with alcoholic liver disease and 12 per cent with non-alcoholic liver disease had sympathetic damage. Forty-five per cent of patients with alcoholic liver disease and 22 per cent with non-alcoholic liver disease had peripheral neuropathy on clinical examination. Sixty-eight per cent of those with peripheral neuropathy also had autonomic neuropathy. This study confirms that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggests that the neurological defect may be secondary to the disturbed liver function. The implications of these observations with regard to prognosis of chronic liver disease are discussed.

Comparison of the prevalence and associated features of abnormal albumin excretion in insulin-dependent and non-insulin-dependent diabetes.

Abstract: Overnight albumin excretion rates were measured in 940 diabetic patients, 416 with insulin dependent and 524 with non-insulin dependent diabetes, and in 106 healthy volunteers. A significantly higher number of non-insulin dependent diabetic patients had abnormal albumin excretion compared with the insulin-dependent group (X2 = 15.2, p less than 0.002). Ten per cent of non-insulin-dependent and 7 per cent of insulin-dependent diabetic patients had albumin excretion rates in the range 30-150 micrograms/min and thus were at risk of the cardiovascular and renal complications of diabetes. Six per cent of non-insulin-dependent and 5 per cent of insulin-dependent diabetic patients had albumin excretion rates above 150 micrograms/min and thus were entering the phase of clinical diabetic nephropathy. Multivariate analysis revealed that male sex and retinopathy in insulin-dependent diabetes, and systolic blood pressure and retinopathy and peripheral vascular disease in non-insulin-dependent diabetes, were significantly related to albumin excretion. Only one patient with insulin-dependent diabetes of less than 5 years known duration had an albumin excretion rate in the range 30-150 micrograms/min, whereas such an excretion rate indicating patients at risk was observed at all durations of non-insulin-dependent diabetes. It is possible that during the long silent phase of non-insulin-dependent diabetes, before diagnosis, significant renal damage occurred.

Clinical features of the sleep apnoea/hypopnoea syndrome.

Abstract: The sleep apnoea/hypopnoea syndrome has been reported to be rare in Britain. We have offered a clinical service for the diagnosis and treatment of this condition in Scotland for four years during which there has been an increase in referral rate from 19 patients in year 1 to 61 in year 4. We report the clinical features of the 80 patients. Seventy-eight snored and 70 were somnolent, each falling asleep at least once each day when not in bed. Ten reported falling asleep whilst driving or flying. Twenty-nine slept restlessly, 28 were not refreshed by sleep and 21 had nocturnal choking attacks. Ankle swelling was reported by 26 and 25 were hypertensive (diastolic BP > 95 mmHg). Two had hyperthyroidism and one acromegaly. Nineteen have been successfully treated by continuous positive airway pressure therapy at home. The data suggest that regional centres should be established in Britain to diagnose and treat this condition.

Diaphragm strength in the shrinking lung syndrome of systemic lupus erythematosus.

Abstract: The cause of the reduced lung volume in the 'shrinking lung' syndrome of systemic lupus erythematosus (SLE) was investigated in 12 patients with the condition. Nine patients described persistent episodes of pleuritic chest pain. Narrow section (3 mm) computed tomography of the thorax revealed no interstitial fibrosis or significant pleural disease. Assessment of diaphragmatic function using manoeuvres more reliable than the maximal occluded efforts previously used alone to assess respiratory muscle strength, showed that diaphragm strength was unequivocally normal in nine of 12 patients. In three, maximum transdiaphragmatic pressure was moderately reduced, but phrenic nerve stimulation demonstrated that this was due to incomplete activation of the diaphragm during a maximal voluntary effort, rather than to a primary abnormality of the diaphragm. Results of maximum lung recoil pressures and dynamic compliance, and analysis of the 12-s maximum voluntary ventilation, suggested a restriction in chest-wall expansion, although it was not possible to identify the underlying cause of this on the basis of our results. We conclude that the 'shrinking lung' syndrome of SLE is not explained by a primary abnormality of the diaphragm.

Chronic Mountain Sickness in Tibet

Abstract: A clinical syndrome identical to the chronic mountain sickness of the Andes occurs commonly in Lhasa, Tibet. It affects, almost exclusively, the immigrant Han population and develops after an average of 15 years' residence at high altitude. The early symptoms are attributable to polycythaemia--headache, dizziness, loss of memory and fatigue being prominent. In the later stages of the disease, dyspnoea and peripheral oedema develop. Haemodynamic investigations show pulmonary hypertension with a normal cardiac output and dilatation of the right ventricle in the long-established case. Respiratory gas studies provide evidence of alveolar underventilation and ventilation: perfusion inhomogeneity. Both clinical and investigatory data suggest that the earlier stages of the disease are dominated by polycythaemia, while cardiopulmonary involvement increases with the duration of the disease. The disease is rare in women and uncommon in Tibetans. Cigarette smoking appears to be a contributory factor.

Acute liver decompensation on withdrawal of cytotoxic chemotherapy and immunosuppressive therapy in hepatitis B carriers.

Abstract: Five chronic carriers of hepatitis B virus developed a fulminant hepatitis-like picture when immunosuppression or cytotoxic treatment, given for unrelated disorders, was withdrawn. Viral replication at the time of the final illness was confirmed in three of the five cases by measurement of serum HBV DNA or the presence of HBc antigen on liver biopsy. A cytoplasmic and nuclear pattern of HBc was seen in histological material during life, but at post-mortem was limited to a nuclear distribution, suggesting greater destruction of hepatocytes containing cytoplasmic HBc. In two of the cases, chronic liver disease was found at post-mortem, there being no previous clinical or laboratory abnormality, but it is unlikely that this was a factor in the development of the superimposed fulminating hepatitis-like illness. Immunosuppressive and cytotoxic agents must be used with extreme caution in any hepatitis B carrier, as withdrawal can precipitate acute decompensation regardless of whether or not there is underlying chronic liver disease.

Myocardial Infarction and Antiphospholipid Antibodies in SLE and Related Disorders

Abstract: The clinical and serological findings in 13 patients with myocardial infarction and antiphospholipid antibodies (the 'lupus anticoagulant', antibodies to cardiolipin, antibodies to phosphatidylethanolamine (one patient] seen by our unit and other units from 1984 to 1989, are presented (eight males and five females, ages ranging from 20 to 52 years). Five suffered myocardial infarction before the age of 30; four of these five were in their early 20s. Other risk factors such as excessive smoking (greater than 20 cigarettes a day) (two patients), long-term treatment with steroid (one) and use of oral contraceptives (one) were present. One patient had demonstrated a plasminogen activator deficiency and one a deficiency of protein C. Two patients developed myocardial infarction six to eight weeks after warfarin was discontinued for recurrent deep vein thrombosis. Six patients had SLE as defined by the revised 1982 criteria, three suffered from 'lupus-like' disease, while four patients conformed to a 'primary' antiphospholipid syndrome.

Fungal peritonitis complicating peritoneal dialysis: report of 27 cases and review of treatment.

Abstract: The clinical features, treatment and outcome of 27 cases of fungal peritonitis were studied. Twenty-one cases occurred in patients receiving CAPD and six in patients on intermittent peritoneal dialysis. Twenty-five cases were due to Candida spp., one was due to Trichosporon spp. and in one, both Candida and Trichosporon and an unidentified acid-fast bacillus were isolated. Clinical features of fungal peritonitis and bacterial peritonitis were the same. A direct comparison with patients without fungal peritonitis failed to reveal an increased incidence of diabetes mellitus. However, a history of recent bacterial peritonitis and antibiotic treatment was frequently obtained. We found that the combination of oral ketoconazole and intraperitoneal miconazole is successful in treating fungal peritonitis complicating peritoneal dialysis but catheter removal and replacement is often necessary. Analysis of the relationship between clinical outcome and various treatment strategies in cases reported in the literature and in our own showed that an initial trial of antifungal drugs consisting of oral ketoconazole and i.p. 5-fluorocytosine or miconazole is warranted in most cases before contemplating catheter removal.

An Analysis of Factors Predisposing to Neurological Injury in Patients Undergoing Coronary Bypass Operations

Abstract: In a prospective study of 312 patients undergoing elective coronary bypass surgery we evaluated 50 preoperative, intraoperative and postoperative factors with the aim of identifying predisposing causes for perioperative neurological morbidity. Factors which showed a significant association with the development of neurological complications included the duration and severity of heart disease before surgery; the presence of extracoronary vascular disease; history of cardiac failure; history of diabetes; difficulty in terminating bypass; intraoperative mean arterial pressure levels of less than 40 mmHg; a large drop in haemoglobin level during surgery; prolonged stay in the intensive therapy unit after operation; and abnormalities of blood pressure control in the postoperative period. The significance of these findings is discussed and a comparison made with data available from previous studies.

Changing Trends in Acute Renal Failure in Third-world Countries — Chandigarh Study

Abstract: The pattern of acute renal failure in third-world countries is changing albeit at a slower pace compared to that in developed countries. Of the 1862 patients with acute renal failure requiring dialysis between 1965 and 1986 in a north Indian centre, 60, 15 and 25 per cent were related to medical, obstetrical and surgical conditions respectively. Among the medical patients, diarrhoeal diseases which caused 23 per cent of the total number of cases of acute renal failure in the period 1965 to 1974 caused only 10 per cent in 1981 to 1986. In the same period, acute renal failure due to sepsis and drugs increased while that due to copper sulphate poisoning and intravascular haemolysis showed a downward trend. Obstetrical acute renal failure declined from 22 per cent in 1965 to 1974 to 9 per cent during the period 1981 to 1986. This decline was chiefly due to a fall in cases of septic abortion, puerperal sepsis and postpartum haemorrhage. Surgical acute renal failure increased from 11 per cent during the period 1965 to 1974 to 31 per cent in the 1980s, predominantly due to an increase in patients with obstructive uropathy. Despite these favourable trends, the pattern of acute renal failure in the third world continues to be different from that in the developed countries.

Wilson's disease presenting with features of hepatic dysfunction: a clinical analysis of eighty-seven patients.

Abstract: An analysis has been made of presenting symptoms and course in 87 patients with predominantly hepatic Wilson's disease. In 30 patients, in whom the diagnosis was made relatively quickly, response to treatment was excellent and all recovered although two had severe haemolytic crises. Mean age of onset was 11 years (range five to 22). Nine patients suffered toxic reactions to penicillamine and were then treated with trientine. In 22 patients the diagnosis was made after neurological symptoms had supervened; in 20 the signs of hepatic damage had disappeared despite the lack of treatment but in two hepatic signs persisted until the central nervous system was affected. In the 20 patients in whom signs of liver disease resolved spontaneously there was a time interval of from one to eight years before neurological signs developed. All 22 patients in a third group died of hepatic disease without central nervous system involvement. In 19 cases duration of the illness was brief and the diagnosis was made very late or at post-mortem examination. One patient survived with chronic progressive liver damage for 20 years; diagnosis was also made at post-mortem examination. Mean age at death was 15 years. The diagnosis was made retrospectively in 13 patients who died. In two of these the diagnosis was confirmed by determination of the liver copper concentration on tissue saved at postmortem examination; in the other 11 the diagnosis is probable since other siblings developed a similar illness, proven to be Wilson's disease. Age range for these patients was eight to 13 years. Duration of the illness from onset to death was nine days to four years (mean 10 weeks). There was no example of primary carcinoma of the liver in this series.

Extrapyramidal Reactions to Metoclopramide and Prochlorperazine

Abstract: SUMMARY We have investigated prospectively the incidence of extrapyramidal events amongst patients receiving ‘first’ prescriptions for metoclopramide (n=2557) and prochlorperazine (n=2811) from general practitioners in the Northern Region Using community pharmacists to capture prescriptions. There were 12 reports of acute dystonic–dyskinetic events following metoclopramide and the incidence of this reaction was significantly greater in those under 30 years than in those 30 years and over. Following prochlorpcrazine there were eight reports of Parkinsonism in patients whose ages were known, seven were over 60 years. The incidence in those over 60 years was significantly higher than in those less than 60 years.

Predicting the outcome of acute stroke: do multivariate models help?

Abstract: Data collected by a single observer on 362 patients taking part in an acute intervention trial were used to derive simple methods of predicting outcome in conscious stroke victims. The effectiveness of these univariate methods was then compared with that of multivariate models based on discriminant function analysis. The multivariate models were somewhat better at predicting death within the first month in newly-admitted patients, and in predicting lack of functional improvement between one and six months in those still in hospital at one month. Even so, these predictions could not be made with certainty and the improvements in probability offered by multivariate over univariate analysis are unlikely to be of practical benefit to the clinician. Single variables such as power in the affected arm and continence were as good as the discriminant functions at predicting discharge within the first month and first six months, respectively. The predictive power of these single simple clinical variables was validated in a separate group of 277 stroke patients. The various proposed methods of prognostication in stroke need to be compared in prospective studies, but until this is done, we recommend a simple approach using the best available clinical information.

Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: a controlled study using record linkage in Tayside.

Abstract: The relationship between non-stcroidal anti-inflammatory drugs (NSAIDs) and gastrointestinal events has been examined in Tayside by record linkage. From March to October 1983, 57 715 prescriptions for five NSAIDs (ibuprofen, indomethacin, naproxen, Osmosin and piroxicam) were issued to 25 959 patients. Their inpatient morbidity from 1 January 1983 to 31 December 1985 was compared to that of an equal number of control subjects matched for age, sex and general practitioner. Analysis revealed that NSAID takers were more likely to develop disease of the gastrointestinal system (ICD 520–579) and symptoms involving the gastrointestinal system (ICD 787). For females the relative risk was 1. 67 and for males 1. 28. The difference between NSAID takers and controls increased with age above 60 years and was more pronounced over 70 years. Perforation and haemorrhage of peptic ulcer and gastrointestinal haemorrhage was also higher among NSAID takers after prescription: this difference was dependent upon age but not related to sex. The morbidity of the two groups, control and subsequent NSAID takers, was comparable before the NSAID prescriptions were issued and the control rates remained constant throughout the study.

Characterization of the anaemia of chronic renal failure and the mode of its correction by a preparation of human erythropoietin (r-HuEPO). An investigation of the pharmacokinetics of intravenous erythropoietin and its effects on erythrokinetics.

Abstract: SUMMARY Studies were directed to characterization of the anaemia of renal failure of 11 patients on haemodialysis and determination of the way in which it is corrected by human erythropoietin derived from recombinant DNA expressed in Chinese hamster ovary cells (r-HuEPO) administered intravenously. Erythrokinetics before treatment showed that total red cell mass was below normal and that both erythron transferrin uptake and red cell survival were modestly reduced; treatment increased both total red cell mass and erythron transferrin uptake but did not change red cell survival in previously untransfused patients. When BFU-e and CFU-e from patient bone marrow were cultured in autologous serum we found no evidence for inhibitors of erythroid progenitor maturation in patient serum compared with normal. Erythroid expansion in response to r-HuEPO was not limited by the availability of iron, iron requirements for new red cell formation being met from stores (if adequate) or from oral iron supplements. In pharmacokinetic studies the plasma clearance of r-HuEPO could be expressed by a three-parameter exponential curve with T ½ range of 2. 3 to 7. 3 h. T ½ after the first dose of r-HuEPO was not significantly different from that after 14 to 54 weeks treatment when the erythron had expanded to a new steady state. Erythron transferrin uptake before treatment was related to endogenous production of erythropoietin estimated from the plasma clearance of the first dose of r-HuEPO administered intravenously. This finding suggested that the availability of erythropoietin was the main factor limiting expansion of the erythron. This conclusion was supported by the continuity of the relationship during the response to treatment.

Renal Biopsy in Patients with Unexplained Renal Impairment and Normal Kidney Size

Abstract: We report renal biopsy findings in 109 patients with unexplained renal impairment (serum creatinine greater than 0.15 mmol/l) and normal-sized non-obstructed kidneys. The most common histological lesions were interstitial nephritis, rapidly progressive glomerulonephritis and a variety of other types of glomerulonephritis. The groups could not be distinguished by the presence or absence of hypertension, haematuria, proteinuria, or features of systemic disease. However interstitial nephritis was found more frequently in patients presenting with one or none of these features and rapidly progressive glomerulonephritis in patients presenting with three or more. All four patients with none of these features had interstitial lesions. Fifty-two per cent of patients with interstitial nephritis improved and 60 per cent of the patients with rapidly progressive glomerulonephritis who received immunosuppressive treatment improved or remained stable with treatment. The benefits of a biopsy diagnosis were almost wholly confined to these two groups. Complications were recorded in nine patients - prolonged macroscopic haematuria in six and symptomatic perirenal haematomata in three. Six required blood transfusion. One required nephrectomy to control haemorrhage and subsequently died. Percutaneous renal biopsy is not without risk in patients with renal impairment but the benefits of diagnosing interstitial nephritis and rapidly progressive glomerulonephritis outweigh the disadvantages.

Adult Salicylate Poisoning: Deaths and Outcome in Patients with High Plasma Salicylate Concentrations

Abstract: The clinical features, plasma salicylate concentrations, acid-base abnormalities and other biochemical findings are presented for 97 patients who either died from acute salicylate overdosage or survived maximum recorded plasma salicylate concentrations of 700 mg/l or greater. These patients comprised 4 per cent of 2204 cases of salicylate poisoning admitted during the period 1975 to 1985 inclusive. Seven patients died (overall mortality 0.3 per cent); they were significantly older than the survivors, the mortality being as high as 33 per cent in patients over the age of 70 years. Delayed presentation, coma, hyperpyrexia, pulmonary oedema and acidaemia were more common in the fatal cases. Failure to hyperventilate appropriately may contribute to the development of acidaemia. The prognosis of acute salicylate poisoning cannot be determined from the plasma concentration of the drug alone. Clinical features, particularly impaired consciousness, and the arterial hydrogen ion concentration must be taken into consideration. Haemodialysis is the treatment of choice for severe salicylate intoxication and should be used more liberally than it is at present.

Vasulitis Complicating Cystic Fibrosis

Abstract: Twelve patients with skin vasculitis complicating cystic fibrosis are described. Seven of these were proven histologically and of these two had systemic vascultitis. Staining of vasculitic tissue by the avidin-biotin immunoperoxidase technique using both monoclonal and polyclonal antisera directed against Haemophilus influenzae, staphylococcus aureus and Pseudomonas aeruginosa did not consistently reveal any bacterial antigens in these tissues. In one patient the vasculitis appeared secondary to ranitidine. There was no evidence of autoimmune disease in any of the patients. Antineutrophil cytoplasmic antibodies were detected in the serum of 40 per cent of the patients with vasculitis complicating cystic fibrosis but in none of 61 controls with cystic fibrosis (but without vasculitis) matched for age and sex and with similar bacteriological flora of sputum.

Kidney biopsy in SLE. I. A clinical-morphologic evaluation.

Abstract: The relationship between renal morphology and clinical disease was analysed in 148 patients with SLE attending a lupus clinic. Patients were not selected for renal disease. Renal tissue was assessed according to the World Health Organization classification of lupus nephritis, the preseuce of active and chronic lesions was recorded and disease activity was measured according to a standard protocol. All sections of the classification were represented in this group of patients. Active and chronic lesions were more likely to occur among patients with Class III/IV (proliferative glomerulonephritis), than in any other category. Patients with Class III/IV biopsy were more likely to have evidence of clinical renal disease than patients in Class II (mesangial). However, almost half of the Class II patients had some evidence of renal disease, including elevated serum creatinine, as well as important non-glomerular lesions. Without biopsy they might have been thought to have proliferative lesions and been treated more aggressively. Two patients with proliferative glomerulouephritis had no clinical evidence of renal disease. Thus, at the time of biopsy results renal histological examination did not uniformly correlate with clinical renal disease.

Primary glomerulonephritis and pregnancy.

Abstract: Three hundred and ninety-five pregnancies undertaken by 238 women with primary glomerulonephritis between 1962 and 1987 were analysed to record fetal and maternal outcome and identify risk factors for a poor outcome. Of 398 fetuses, 26 per cent were lost (including therapeutic abortions), 24 per cent surviving infants were premature (less than or equal to 36 weeks gestation) and 51 per cent were term. Excluding therapeutic abortions, 20 per cent of fetuses were lost, 15 per cent after 20 weeks gestation. Fifteen per cent of 237 fetuses whose birth weight was recorded were small for gestational age: Deterioration in maternal renal function was seen in 15 per cent of pregnancies and in 5 per cent of women failed to resolve post partum. Only four women had impaired renal function recorded in the first-trimester and two of these were known to have renal impairment before pregnancy. Hypertension was recorded in 52 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 26 per cent and was severe in 18 per cent. Treated hypertension pre-dated 12 per cent of pregnancies and in 7 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. Forty-four women (18 per cent) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 59 per cent of pregnancies and was irreversible in 15 per cent of women. Comparison of pregnancies which occurred before or after renal biopsy revealed a significantly higher fetal loss rate after 20 weeks gestation in those pregnancies undertaken before the diagnosis of renal disease, and a significantly higher incidence of hypertension and increased proteinuria. Impaired renal function, early or severe hypertension or nephrotic range proteinuria was significantly associated with increased fetal loss, prematurity and fewer full-term infants. There was no significant difference in fetal outcome or maternal complications in pregnancy in patients with treated hypertension before pregnancy and those who were normotensive in the first-trimester. The highest incidence of fetal and maternal complications occurred in patients with primary focal and segmental hyalinosis and sclerosis and the lowest in non-IgA diffuse mesangial proliferative glomerulonephritis. The presence of severe vessel lesions on renal biopsy was associated with a significantly higher total fetal loss and fetal loss after 20 weeks gestation.

The frequency of gastrointestinal endocrine tumours in a well-defined population--Northern Ireland 1970-1985.

Abstract: The reported incidence of gastrointestinal endocrine tumours is variable. In Northern Ireland circumstances allowing such an assessment are favourable with a central diagnostic laboratory and register established to collect data on tumours from a well-defined population of 1.5 million people. From 1970 to 1985, 368 cases were recorded of which 85 per cent were carcinoid tumours. The annual incidence of carcinoid tumours was 1.3 per 100,000 of the population and the majority occurred in the appendix (61 per cent). No patients presented with the carcinoid syndrome. The annual incidence for other tumours was 0.12 per 100,000 for insulinomas; islet cell tumours of unknown type 0.07; Zollinger-Ellison syndrome 0.05; and multiple endocrine neoplasia (MEN) 0.05. There were two cases of VIPoma, one glucagonoma, one neurotensinoma and one tumour producing ACTH. It is possible that some tumours are more uncommon than others because of difficulty in diagnosis.