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Two papers that reported that the blood pressure drug ramipril was beneficial in patients with intermittent claudication due to peripheral artery disease have been retracted after an investigation found that data were fabricated by the studies’ lead author, Anna A Ahimastos, a researcher at the prestigious Baker IDI Heart and Diabetes Institute in Melbourne, Australia. The first paper,1 published in JAMA in …

When employees at the German drug firm Boehringer Ingelheim learnt that the conclusions of a company study clashed with a marketing claim that its new anticoagulant did not need monitoring, they sought to have the paper revised and even questioned whether it should be published at all, internal company documents released by a US court indicate. In an email one employee, whose name was redacted, complained that the paper would harm the company’s marketing efforts and make discussions with regulatory agencies more difficult. “Can’t this be avoided?” the employee asked. Another employee, Andreas Clemens, a medical team leader for the drug, wrote that he believed that the findings were important and should be published but with revision. “The world is crying for this information—but the tricky part is that we have to tailor the messages smart.” In another email Clemens expressed concern that the paper “could be a liability issue” for the company. The study involved dabigatran etexilate (marketed as Pradaxa), a thrombin inhibitor that is approved in the United States and Europe for the prevention of stroke and embolic events in patients with atrial fibrillation. One of the …

Research studies on the side effects of commonly prescribed drugs constituted the three most read papers published by the BMJ in 2005, according to an internal audit that assessed their use by readers. Studies that showed increased risk of myocardial infarction in patients taking cyclo-oxygenase-2 (COX 2) inhibitors and that explored the link between selective serotonin reuptake inhibitors and suicide came top. For the audit Sara Schroter, the BMJ 's senior researcher, analysed research papers using three measures: the number of citations a paper received, the number of times it was accessed on the web, and the number of rapid responses it generated. The top scoring paper was a case-control study that showed greater risk of myocardial infarction in patients taking the COX 2 inhibitor rofecoxib (Vioxx) and in patients taking diclofenac …

A paper chromatographic analysis in 60 patients with muscular dystrophy from 49 families and in 351 of their relatives showed a high incidence of generalized hyperaminoaciduria in both patients and relatives. There was a higher incidence of threoninuria in patients and their relatives than in controls. One family was found to have excess histidinuria and another excess lysinuria.

Objectives: To investigate patterns of self monitoring of blood glucose concentration in diabetic patients who use insulin and to determine whether frequency of self monitoring is related to glycaemic control. Setting: Diabetes database, Tayside, Scotland. Subjects: Patients resident in Tayside in 1993-5 who were using insulin and were registered on the database and diagnosed with insulin dependent (type 1) or non-insulin dependent (type 2) diabetes before 1993. Main outcome measures: Number of glucose monitoring reagent strips dispensed (reagent strip uptake) derived from records of prescriptions. First recorded haemoglobin A1c concentration in the study period, and reagent strips dispensed in the previous 6 months. Results: Among 807 patients with type 1 diabetes, 128 (16%) did not redeem any prescriptions for glucose monitoring reagent strips in the 3 year study period. Only 161 (20%) redeemed prescriptions for enough reagent strips to test glucose daily. The corresponding figures for the 790 patients with type 2 diabetes who used insulin were 162 (21%; no strips) and 131 (17%; daily tests). Reagent strip uptake was influenced both by age and by deprivation category. There was a direct relation between uptake and glycaemic control for 258 patients (with recorded haemoglobin A1c concentrations) with type 1 diabetes. In a linear regression model the decrease in haemoglobin A1c concentration for every extra 180 reagent strips dispensed was 0.7%. For the 290 patients with type 2 diabetes who used insulin there was no such relation. Conclusions: Self monitoring of blood glucose concentration is associated with improved glycaemic control in patients with type 1 diabetes. Regular self monitoring in patients with type 1 and type 2 diabetes is uncommon. Key messages Several studies have indicated the importance of self monitoring of blood glucose concentration for prevention of complications in patients with diabetes Uptake of reagent strips for self monitoring of blood glucose among diabetic patients who used insulin was low, with only 20% of patients with type 1 diabetes and 17% of those with type 2 diabetes obtaining enough strips to test blood glucose concentration once daily Reagent strip uptake depends on characteristics such as age and social deprivation category, and patient groups with low uptake should be identified and targeted There was a direct association between strip uptake in the previous 6 months and glycaemic control in patients with type 1 diabetes but not in those with type 2 diabetes

The benefits of thrombolysis in patients with acute myocardial infarction are time dependent, with a potential 48% reduction in mortality if treatment is received within an hour of onset of symptoms.1 The benefits diminish thereafter. However the “call to needle” standard set by the national service framework2 has been achieved for only a third of patients nationally because of lengthy ambulance journeys and delays in hospital. Prehospital thrombolysis may be the most feasible means of achieving timely reperfusion, and all published studies have shown the accuracy of diagnosis, patient selection, and administration of thrombolysis.3 The Joint Royal Colleges Ambulance Liaison Committee favours autonomous prehospital thrombolysis by paramedics as a long term objective.4 We tested the feasibility of physician assisted and autonomous models of paramedic prehospital thrombolysis.M View this table: Summary statistics for time from event to response (minutes) All 64 paramedics serving the study hospital took part in the study. Of these, 48 (75%) received formal training in recording 12 lead electrocardiograms, diagnosing ST …

EDITOR—The green paper Who Decides? highlights two central issues: whether advance directives should have a statutory basis, and how capacity should be assessed in patients who may be unable to make decisions for themselves.1 A potentially important problem brings these two issues together: how should doctors assess the capacity of a patient to complete an advance directive? Healthy people may not be well placed to make decisions concerning their future incompetent selves1 because …

To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function.Multivariate Cox regression analysis of data from a large multicentre trial.Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand.7311 patients with all required data available.Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years.1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressureor = 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients.This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.

Insulin glargine is a new insulin analogue with delayed absorption and a prolonged duration of action.1 A 34 year old woman who had had type 1 diabetes for six years had previously been treated with premixed biphasic isophane insulin (Humulin M3), twice a day. This regimen had been changed to a basal bolus regimen of Actrapid and Insulatard during pregnancy, but she subsequently resumed twice daily injections (but …

Chronic liver disease and hepatocellular carcinoma are major worldwide public health problems in countries with endemically high levels of viral hepatitis (B and C).1 However, even in western countries chronic liver disease is an emerging problem, due not only to viral hepatitis but also to the effects of lifestyle factors such as heavy alcohol consumption and obesity.2 3 Liver function tests are widely performed blood tests used in patients with suspected liver disease or unexplained illness and in some specific situations such as screening of blood donors. The most widely used tests are those used to detect the aminotransferases—alanine and aspartate—which are associated with hepatocellular injury. Raised concentrations may …

This paper reports a double-blind trial of a new antianginal drug, perhexiline. Fifty-five patients suffering from angina pectoris were studied for periods of 12 or 24 weeks in a cross-over comparison against a placebo in four centres in the United Kingdom and Ireland. Perhexiline was effective in most patients as judged by reducing the number of anginal attacks in 84% and the consumption of glyceryl trinitrate tablets in 64%. The major side effect, dizziness, noted in one-third of the patients, may be dose/body-weight related. Perhexiline is a valuable new agent for the treatment of patients with angina, especially those who do not respond to other antianginal agents.

Case records have been studied for the results of surgery in 294 patients operated on for inflammatory bowel disease during 1967-72 at 34 non-teaching hospitals within the North-east Metropolitan Hospital Region. All patients treated surgically for acute colitis and those treated for chronic disease by total colectomy were included. The postoperative mortality of the primary surgery was 23·7%. The mortality was 2·1% in patients treated by elective operation, 37·6% in patients coming to urgent operation, and 60·9% in patients treated by emergency operation. The three most important factors affecting the mortality were considered to be: increasing age of the patient, the presence of established colonic dilatation, and preoperative perforation of the colon.

Three cases are reported of tumour-like lesions of the liver in women who had been on oral contraceptives for long periods. These malformations have a prominent vascular component and may present with haemoperitoneum and shock. The possibility of an association between liver hamartomas and oral contraceptive therapy has to be considered.

Continuous intravenous infusion of small amounts of insulin has been used in the management of a series of patients with diabetic ketoacidosis. In 13 patients with a plasma glucose level on admission of 725 mg/100 ml (+/- 80 S.E. of mean) and an arterial pH of 7.07 +/- 0.05 a mean loading dose of 6.5 +/- 0.82 units of soluble insulin was administered intravenously, and thereafter a sustaining infusion of 6.5 +/- 0.82 U/hr was continued until ketosis was corrected and the plasma glucose fell below 300 mg/100 ml. The total insulin dose needed to achieve this was 39.2 +/- 6.6 units given over a 3 to 10-hour period. Plasma insulin was measured in patients who had not previously received insulin and the mean level at an infusion rate of 4 U/hr was 75.6 +/- 8.0 muU/ml. Plasma glucose fell at a regular rate of 101 +/- 11 mg/100 ml/hr, and ketosis improved in parallel. Plasma potassium was well maintained throughout treatment. This regimen of treatment was clinically effective and simple to follow.

Protein was found significantly more frequently in single urine samples from 504 patients with malignancy (290; 58%) than in 529 controls (119; 22%) (p less than 0.01). Median protein concentration was greater (p less than 0.001) in patients with neoplasia (0.14 g/l) than in controls (0.07 g/l). Actuarial analysis showed a median survival of 4.5 months in patients with proteinuria compared with 10 months in those without (p less than 0.001). The association between proteinuria and shorter survival was statistically significant for patients with gut tumours, lung tumours, and tumours at other sites analysed as a group. Patients with myeloma or urinary tract tumours were not studied. In many patients with malignancy the presence of proteinuria may be associated with a substantially reduced survival time.

In 11 patients receiving transplants of allogeneic bone marrow, the graft was successful in six. Nine patients developed infections, and six died-five of septicaemia and one of Pneumocystis carinii pneumonia. Fifty individual infections occurred. Predisposing factors included severe underlying diseases, long-term exposure to resistant hospital organisms, heavy immunosuppressive therapy, and graft-versus-host disease. Gram-negative bacilli and Candida albicans were the most common causative organisms. In every instance of septicaemia identical organisms were isolated from blood cultures and simultaneously obtained stool cultures. Infection with exogenous organisms often occurred in patients occupying conventional isolation rooms. Isolation of one patient for 45 days in a laminar air flow room prevented infection with exogenous organisms.

Some three-quarters of folate compounds in a normal mixed diet have a chain of seven glutamic acid residues (polyglutamates). The extent to which these forms of folate are absorbed and utilized by man is of considerable nutritional importance. These studies indicate that the polyglutamate forms were absorbed and utilized to about one-third of the extent of simpler (monoglutamate) forms, as judged by the serum folate levels after oral equimolar doses, by the amount incorporated into red cells in long-term studies, by the amount excreted into the urine, and by their capacity to initiate haematological responses in patients with folate-deficient megaloblastic anaemias.

Episodes of clotting that occurred in 22 patients on regular haemodialysis were studied over a six-month period. The venous pressure during dialysis and the radiology of the Teflon-Silastic arteriovenous shunt were found to be satisfactory guides for the management of the shunt. The failure of the shunt during the early stage was mainly due to technical reasons. Histological study of the excised vessels in removed long-term shunts showed that these had failed because of rigidity and thickening of the vessel wall due to calcium and iron deposits or chronic inflammation, or both.

Administration of nitrazepam (10 mg nightly), diazepam (15 mg/day), and chlordiazepoxide (15 and 30 mg/day) had no effect on steady-state plasma warfarin concentrations, the plasma half-life of warfarin, or anticoagulant control in patients and it appears safe to prescribe these agents to patients on long-term oral anticoagulants. Urinary excretion of 6 beta-hydroxycortisol, however, increased in two out of five patients given chlordiazepoxide. In rats pretreatment with chlordiazepoxide (40 mg/kg for four days) caused stimulation of liver microsomal enzyme activity but neither diazepam nor nitrazepam had this effect.

Dyspeptic symptoms, gastrointestinal bleeding, or the development of anaemia without dyspepsia in patients treated with indomethacin may be manifestations of peptic ulceration. Such manifestations occur with suppositories as well as with capsules. The ulcers in the present series tended to be prepyloric, and often aroused the suspicion of malignancy. Symptoms were promptly relieved and radiological healing occurred rapidly after withdrawal of the drug.

High-dose excretion urography has been carried out in 32 patients presenting with non-obstructive acute oliguric or non-oliguric renal failure. An early, dense, persisting nephrogram has been observed in all patients with acute uncomplicated tubular necrosis and in patients with acute oliguric pyelonephritis. This appearance is modified by the presence of pre-existing renal disease. Different patterns have been observed in patients with acute glomerular disease, severe renal ischaemia, and chronic glomerular disease. The study demonstrates that careful analysis of the evolution of the nephrogram in patients with acute renal failure provides valuable information as to the nature of the parenchymal disease.

In a titrated dose cross-over trial of debrisoquine and methyldopa in 38 hypertensive patients neither drug was superior in lowering supine or standing diastolic pressure with a minimum of side effects. Methyldopa caused significantly greater reduction of supine (P

Reduction in caloric intake to 400 a day for 72 hours resulted in a significant increase in the plasma bilirubin concentration in patients with Gilbert's syndrome and in normal subjects. This was due to an increase in unconjugated pigment. There was no significant increase in the bilirubin concentration in patients with liver disease or haemolytic anaemia.The increase in unconjugated bilirubin was signficantly greater in Gilbert's syndrome than in normals but only when the initial bilirubin concentration was raised. It was usually seen within 24 hours of reducing the caloric intake. An increase of 100% or more suggests that unconjugated hyperbilirubinaemia is due to Gilbert's syndrome. In the normal subjects the unconjugated bilirubin level did not exceed 1.0 mg/100 ml.The increase in unconjugated bilirubin concentration on reducing the caloric intake may be due to decreased hepatic bilirubin uridine diphosphate glucuronyl transferase activity, which was shown to be present in seven rats starved for 72 hours. The effect of a 400 calorie diet for 24 hours on the unconjugated bilirubin level may distinguish Gilbert's syndrome from other causes of unconjugated hyperbilirubinaemia.

Focal myocytolysis, a form of myocardial damage, has been found to occur in about 8% of patients dying of intracranial lesions. Electrocardiographic abnormalities in patients with brain damage may be due to this. The cause of focal myocytolysis remains unknown, but if it could be prevented it might avert the patient's death from cardiac arrest or arrhythmia. Moreover, more than a minimal degree of this type of damage to the heart might make it unsuitable for transplantation.

Methoxyflurane and nitrous oxide have been compared as obstetric analgesics. The inhaled concentrations of these agents, given continuously, were adjusted by an anaesthetist to maintain each patient at the optimum state between reaction to pain and consciousness. Assessments were made continuously.Though the anaesthetist's assessment showed no difference between the mean results, a greater proportion of the methoxyflurane patients were "satisfactory" for 90-100% of the time than of the nitrous oxide patients, particularly in regard to objective pain relief. The midwives' opinion of those who had "complete" pain relief supported this. Nausea was significantly less among methoxyflurane patients, and vomiting during labour occurred only in patients who had nitrous oxide. It is concluded that nitrous oxide and methoxyflurane given in a continuously adjusted concentration are almost equally effective as obstetric analgesics, though there are certain features which favour methoxyflurane.

Gall bladder and hepatic bile was sampled from 66 patients undergoing elective operations on the biliary tract. Fifty-one patients had cholesterol gall stones but only 59% of these were found to have bile which was supersaturated with cholesterol. Repeated sampling of hepatic bile from patients with T-tubes showed that the secretion of supersaturated bile was intermittent.These results indicate that it is impossible to separate patients with cholesterol stones from controls simply by examination of the lipid composition of their bile, since an appreciable number of bile samples from patients with cholesterol stones were unsaturated.The fact that cholesterol gall stones form when the bile is supersaturated with cholesterol only intermittently suggests that the gall bladder may also have a part in their formation.

Failure to maintain compensatory hyperventilation during anaesthesia in patients with metabolic acidosis results in an increase in PaCO(2), fall in blood pH, and a possible rise in plasma potassium. This sequence of events may account for unexplained operative deaths in patients in renal failure.

Stimulation of reticuloendothelial activity may benefit patients with cancer. Oestrogenic compounds are known to stimulate reticuloendothelial phagocytic activity in animals and a similar effect is demonstrated in patients. The depression of reticuloendothelial phagocytic activity which follows radiotheraphy in the treatment of cancer can be prevented by the simultaneous administration of stilboestrol. Possibly this could be associated with a more favourable response to therapy, and a controlled trial is needed to establish this.

In hyperthyroidism suppression and non-suppression of early radioiodine neck uptake by exogenous thyroid hormone after a course of antithyroid drugs does not indicate clearly those patients who will eventually relapse or have a remission. Sixty-four hyperthyroid patients have been followed up for two years after an 18 to 24 months9 course of carbimazole. Twenty-eight patients had suppressed at the end of the carbimazole course and 20 of these remained in remission for two years, and 36 were non-suppressed and 21 of these relapsed. Patients with the highest neck uptakes relapsed soonest after stopping treatment. Pronounced rebound occurred in neck uptakes at one month after stopping treatment, both in patients who relapsed and in those who remained in remission. By one year after stopping treatment those who remained in remission had shown a further fall in early neck uptake. In two patients who relapsed after exposure to stressful events no change in 20-minute radioiodine neck uptakes was found in relation to the supposed stress.

Strontium-85 scanning of suspected bone lesions in 81 patients has added to the criteria for the diagnosis of malignant and other lesions of bone. Of 46 patients with a previous history of malignant disease and skeletal symptoms negative radiological findings were recorded in 19, but nine of these had positive scans, eight of which when followed up over periods of up to four years proved to be metastatic. A similar prevalence of positive scans occurred in patients without a previous history of malignancy. Because of the anatomical localization of lesions made possible by this technique a tissue diagnosis was made in six patients, while fields of radiotherapy were altered in another seven. This technique can improve the management of patients with suspected bone disease.

To determine the validity of endogenous creatinine clearance as a measure of glomerular filtration rate in patients with renal disease 308 simultaneous determinations of inulin clearance and endogenous creatinine clearance were reviewed and analysed. The ratio of creatinine clearance/inulin clearance increased progressively with the decline in inulin clearance, while the finding of a normal endogenous creatinine clearance masked a definite but mild decrease of glomerular filtration rate in 42% of the patients and a moderate decrease of glomerular filtration rate in 23%. This indicates that with declining glomerular filtration rates the endogenous creatinine clearance progressively overestimates actual glomerular filtration rates. Hence a single determination of creatinine clearance can be misleading as a screening measurement of glomerular filtration rate.

Sixty cases of colonic carcinoma have been investigated for antitumour immunoreactivity. The tests employed were blood lymphocyte reactivity and complement-dependent serum cytotoxicity against cultured tumour cells, and immunofluorescence for membrane staining of viable tumour cells and cytoplasmic staining of dried tumour cells in films. Nineteen cases were positive by one or more tests and the most frequent positive response, lymphocytotoxicity, was detected in 8 of the 24 cases tested in this way. The lymphocytotoxicity persisted in a case tested three times over a year. Immunoreactivity against tumour cell surface, as by lymphocyte or serum cytotoxicity or membrane immunofluorescence, was restricted to colonic carcinomas but there was an additional element of individual specificity; cross-reactivity with other tissues and tumours was not observed. Lymphocytes from regional lymph nodes were non-reactive even in a case with positive blood lymphocyte cytotoxicity against the carcinoma cells.

A questionnaire was used to study the choice and use of gastric function tests by members of the British Society of Gastroenterology. Pentagastrin has largely replaced older drugs as the stimulant of choice for evoking maximal acid secretion. Insulin tests are being used in situations where they are unlikely to provide useful clinical information. Fewer physicians than surgeons measure gastric secretion, and they use tests less often. The reluctance of physicians to test patients with uninvestigated dyspepsia or gastric ulcer seems justified, but in patients having dyspepsia with negative x -ray films, or after gastrectomy or vagotomy, the greater investigative keenness of surgeons seems commendable. Only half the surgeons ever try to assess the completeness of their vagotomies, and in only one-third of this half is it their usual practice. Criticism is made of the practice of routine measurement of acid in patients with duodenal ulcer, and of the use of acid measurements to decide whether a patient should have surgery or which type of operation should be performed.

An oral glucose tolerance test has been used to compare carbohydrate metabolism in patients suffering from chronic duodenal ulceration with that in a matched group of normal subjects. A significantly greater rise in blood glucose concentration was observed in the duodenal ulcer group, and this was associated with a significantly greater output of insulin. The reason for these findings may be an abnormal secretion of one or more of the small-bowel hormones.

There are many conflicting reports concerning the frequency of systemic hypertension in patients suffering from mitral valve disease, and many theories concerning the relation between the two conditions. We have made a further study of the problem from the case records and necropsy reports of patients with

The time interval since previous anaesthesia was compared in a surgical population in South Wales and in patients who developed jaundice after halothane. There was a significant difference in the pattern of time interval since previous general anaesthetics in the surgical population and in those patients who developed jaundice after halothane. In the group who developed jaundice there was an “excess” of patients who had had a previous halothane anaesthetic within four weeks. Halothane should if possible be avoided in patients who have had it before, particularly if this was within the previous four weeks. In the case of repeat halothane anaesthetics within four weeks, the risk seems to lie between 1 in 6,000 and 1 in 22,000.

Iron absorption was measured in 28 patients, 19 of whom were anaemic. The mean absorption in the anaemic patients was 39% and in the non-anaemic patients 8%. Gastrointestinal blood loss was then measured in 26 of these patients. The mean estimated blood loss in the anaemic patients was 15 ml. a day and in the non-anaemic patients 3 ml. a day. In 16 of the 19 anaemic patients symptoms of anaemia were either the sole or the major complaint.

Sodium valproate has a simple chemical structure unlike other anticonvulsants. It has been given to 63 patients with various types of epilepsy whose attacks were frequent and of whom 40 had failed to respond to other anticonvulsants. Fits stopped completely in 27 patients (43%) and 14 (22%) showed a reduction of attacks by more than 50%. The best results were in patients with absences (typical and atypical) associated with spike and wave discharges on the electroencephalogram. Myoclonic epilepsies responded well and improvement occurred with tonic-clonic seizures and focal motor fits. There was little or no improvement in temporal lobe epilepsy. Sodium valproate given alone did not cause unwanted effects but it potentiated many other anticonvulsants. An unusual side effect was temporary hair loss. A number of patients became more alert, school performances improved, and the management of subnormal patients became easier.

The possible role of white blood cells in tissue ischaemia has attracted recent interest. White blood cells can block narrow vessels, particularly if perfusion pressure is reduced or if the cells become activated. To investigate the role of white blood cells in ischaemia microfiltration techniques were used to measure the flow properties of these cells in patients with severe leg ischaemia before and after amputation. Compared with controls white blood cells from patients showed impaired ability to flow through 8 micron and 5 micron pore filters. This applied to fractionated granulocytes and mononuclear cells as well as to unfractionated mixed white blood cells. White blood cells from blood draining the ischaemic leg had worse filterability than those from arm blood of the same patients. After amputation of the ischaemic leg there was definite improvement, the flow properties of the cells being no longer significantly different from controls. These abnormalities detected in white blood cells probably reflect activation of the cells by factors released in the ischaemic tissue. As activation alters the mechanical and adhesive properties of white blood cells, a vicious cycle of microcirculatory trapping at low perfusion pressure, activation, tissue damage, and further activation and trapping might contribute to the progressive worsening of tissue ischaemia.

Out of 50 consecutive untreated patients with diffuse toxic goitre 15 showed long-acting thyroid stimulator (LATS), 30 showed LATS protector only, and five showed neither. LATS protector was present in all the patients with LATS. Infiltrative ophthalmopathy was less common in patients with LATS protector only (40%) than in patients with LATS also (67%), but the difference was not significant. There was a correlation between LATS protector level and thyroid (131)I uptake rate factor (k(1)), the coefficient (r) being 0.68 (P0.001). LATS level showed no such correlation. The results support the hypothesis that LATS protector is a pathogenic thyroid stimulator in patients with diffuse toxic goitre.

We have used the (125)I-fibrinogen test to asses the value of an improved method of peroperative intermittent calf compression as a prophylactic measure against postoperative thrombosis. In a group of 99 patients over the age of 40 undergoing operations lasting more than 30 minutes the technique reduced the incidence of postoperative thrombosis by over 75%. In patients suffering from malignant disease, who are generally considered to be in the very high risk category, the reduction achieved was almost 90%.

Deoxyuridine (dU) suppression tests have been performed on virtually all marrow samples aspirated at this hospital over the past 12 months. Of the 110 samples studied 26 gave abnormal results, and these 26 samples came from patients deficient in either vitamin B(12) or folate. The dU suppression test was found to be of particular value in the diagnosis of vitamin B(12) or folate deficiency in non-anaemic patients with macrocytosis and equivocal changes in marrow morphology and in patients in whom the serum vitamin B(12) or red cell folate levels were within the normal range.

A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 μmol/l (100 μg/ml)), yet the variation in dosage was only sixfold (0·5-3·9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 μmol/l (244 μg/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs. Only 2 (5·4%) of the tolbutamide-treated patients and 10 (16·7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5·5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8·0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient. There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug. We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.

Cephaloridine serum half-life was determined in 11 patients undergoing maintenance haemodialysis. Three of them were anephric. The mean cephaloridine half-life was 10·4 hours. There was an inverse correlation between cephaloridine half-life and the duration of maintenance haemodialysis treatment. Reasons for this are discussed. The effect of haemodialysis with the Kiil dialyser on cephaloridine half-life was studied in three patients. Dosage recommendations for patients on maintenance haemodialysis are suggested.

"Capillary permeability" to serum albumin has been measured in patients with collagen vascular diseases by a method which compares the dilution of intravenously injected (131)I-human serum albumin and (51)Cr-R.B.C.s. The results indicate an increased capillary permeability comparable to that which occurs in patients with extensive inflammatory skin disease. We suggest that this increased capillary permeability may be the cause of the episodes of oedema which occur in patients with collagen vascular diseases such as disseminated lupus erythematosus, systemic sclerosis, dermatomyositis, polyarteritis nodosa, and rheumatoid arthritis. "Spontaneous periodic oedema" may be the presenting feature of collagen vascular disease and is due to increased capillary permeability.

In a combined historical and radiological survey gall stones were found in 23 out of 72 patients with disorders of the terminal ileum (31·9%). This is four to five times the expected incidence of cholelithiasis. In these patients the incidence of gall stones was not related to age, but did, however, increase with increased duration of the ileal disorder. Glycine/taurine conjugation ratios of bile salts in the bile were abnormally high in 10 out of 11 patients with ileal disorders. Both impaired bile salt recirculation and absorption of poorly soluble bacterially degraded bile salts are possible causes of cholelithiasis in these patients.

The accuracy of predicting fetal maturity by ultrasound cephalometry, radiology, and liquor studies in patients with unknown confinement dates has been compared. The best prediction was given by ultrasound cephalometry. Liquor studies were least helpful.

The finding of electrocardiographic (E.C.G.) abnormalities in patients with leptospirosis who show clinical evidence of cardiac involvement is well recognized. In a review of the subject Sodeman and Killough (1951) reported the unexpected dis covery of abnormalities in three patients without such clinical signs, and expressed the opinion that " an active interest in the [cardiovascular] system is necessary to establish involvement." The fact that an apparently normal E.C.G. taken in the first week of the illness might give such evidence if compared with a later record supported their thesis. Moreover, Mackay-Dick and Robinson (1957) subsequently demonstrated transient minor changes in the QRST complex in two out of six consecutive patients with uncomplicated leptospirosis.