The effect of bile acids on colonic myoelectrical activity. The effect of different concentrations of sodium cholate, sodium chenodeoxycholate and sodium deoxycholate on colonic myoelectrical activity was studied in 4 dogs. There was no statistically significant difference in percentage motility, motility index, basal pressure or mean slow wave frequency with either cholic or chenodeoxycholic acid (5--15 mM). Deoxycholic acid (15 mM), however, caused a marked increase in percentage motility (median control value 4.1, range 0--23; after installation, median value 27--0, range 20.6--45.0, P less than 0.001). This was accompanied by an increase in spike activity, but no alteration in mean slow wave frequency or basal pressure was seen. Cholestyramine inhibited the motor response. It appears that only deoxycholic acid affects both motility and absorption, presumably by different pathways, and may thus assume importance in disorders of colonic motility.


Chylous ascites and obstructive lymphoedema of the small bowel following abdominal radiotherapy. The case history of a patient who developed chylous ascites following abdominal irradiation for recurrent carcinoma of the colon is presented. Laparotomy revealed generalized radiation damage of the small bowel with a particularly severely affected segment of jejunum, from the serosal surface of which chyle was seen to be leaking. Mesenteric lymphangiography revealed an obstruction to lymphatic drainage in the mesentery. Resection of the worst affected segment of bowel prevented further development of chylous ascites.


Leucocyte counts in the diagnosis and prognosis of acute appendicitis in children. Preoperative total and differential leucocyte counts were made in 225 children with acute appendicitis, 50 children with a normal appendix and 100 children with acute abdominal pain which resolved without any therapy. When adjusted to age, neutrophilia in 96 per cent, 30 per cent and 32 per cent and leucocytosis in 41.8 per cent, 4 per cent and 3 per cent was noted in the respective groups, the levels being significantly higher in the acute appendicitis group than in the other two groups. Among children with appendicitis, infections were observed in 62.8 per cent of the group with leucocytosis and in 13.7 per cent of the group with a normal leucocyte count; the difference is statistically significant. It is suggested that in acute appendicitis neutrophilia supports the diagnosis and leucocytosis indicates the prognosis. The rate of infection increases as the total leucocyte count rises above the upper normal limit. The difference of opinions on the significance of leucocyte counts in acute appendicitis is discussed.


Controlled environment therapy in the management of lymphoedema: a case report. A case of surgically-treated elephantiasis of a lower limb is reported in which preoperative controlled environment therapy (CET) proved to be an effective, rapid method of reducing the oedema.


A new vascularized bone graft transferred by microvascular anastomosis as a free flap. We describe a new, versatile bone and soft tissue compound free flap which may be transferred quickly and simply and describe its use in the treatment of compound fracture of the tibia and fibula with non-union due to loss of bone. The iliac crest and overlying soft tissue is transferred to the leg in one stage by microvascular anastomosis of the deep circumflex iliac vessels to vessels in the leg.


The presentation of gastrointestinal lymphoma: study of a population. The clinical presentation and findings in 45 patients with lymphoma of the gastrointestinal tract occurring in an unselected population are described. Nineteen patients presented as emergencies with haemorrhage, perforation, pyloric stenosis or intestinal obstruction. Systemic symptoms, peripheral lymph node enlargement and hepatosplenomegaly were rare, and a preoperative diagnosis of lymphoma was seldom made. Endoscopy was superior to radiology in defining lesions in the stomach and duodenum. Lesions which were multicentric, or of unusual macroscopic appearance, were common in the small bowel, and these should raise the suspicion of lymphoma. Local and systemic recurrence was common, but was not always fatal. Patients with gastric lymphomas survived longer than those with intestinal disease.


Pneumatosis coli and sigmoid volvulus: a report of 4 cases. Pneumatosis coli is an uncommon disease which is frequently misdiagnosed and inappropriately treated. The condition can usually be managed conservatively but complications requiring surgical treatment are occasionally encountered. We describe 4 patients with pneumatosis coli and associated volvulus of the sigmoid colon. Some of the factors that may have contributed to pneumocyst formation in these 4 patients are discussed with reference to recent advances in our understanding of the pathogenesis of pneumatosis coli.


Multiple intestinal perforation due to Celestin tube. Two cases of multiple intestinal perforation caused by the nylon from the core of disintegrating oesophageal Celestin tubes migrating down the alimentary tract are described. It is suggested that Celestin tubes should not be used in patients likely to survive for more than a few months.


Postoperative hypoxaemia: oesophagectomy with gastric replacement. Pre- and postoperative arterial blood samples were analysed for oxygen partial pressure (PaO2) and carbon dioxide partial pressure (PaCO2) in a consecutive series of 21 patients subjected to two- or three-stage oesophagectomy for carcinoma of the oesophagus. The forced vital capacity (FVC) was measured at the same time. On the second postoperative day the PaO2 showed a fall to 65 per cent of the preoperative value followed by a gradual recovery to 78 per cent on the tenth postoperative day. After 13 weeks the PaO2 had recovered to 95 per cent of the preoperative value. The PaCO2 decreased in the early postoperative period but had returned to the preoperative level by the tenth day. The FVC showed a trend similar to the PaO2 with a reduction to 33 per cent of the preoperative value on the second postoperative day, 52 per cent on the tenth day and 85 per cent after 13 weeks.


Salmonellosis associated with late rupture of an aortofemoral bypass graft. Salmonella infection is a rare cause of rupture of the atherosclerotic abdominal aneurysm. A case never previously reported is presented in which salmonella infection occurred involving an aortofemoral bypass graft which had been inserted 10 years previously. The infection caused a leak in the region of the graft which presented as a haematoma in the thigh.


Haematemesis in infantile hypertrophic pyloric stenosis: the source of the bleeding. Thirteen infants with haematemesis associated with hypertrophic pyloric stenosis were investigated in order to elucidate the source of bleeding. All 13 patients showed endoscopic evidence of oesophagitis, moderate in 4 and severe in 9. No significant gastric mucosal lesion was found. It was concluded that the site of the haemorrhage was the oesophageal mucosa in all 13 infants. Eleven of the patients experienced troublesome postoperative vomiting.


The concept of disease.

The concept of disease. The connotations of the term "a disease" were investigated by studying the ways in which both medical and non-medical people used the word. A list of common diagnostic terms was read slowly to groups of non-medical academic staff of a university, secondary-school students, medical academics, and family practitioners, who then indicated whether they thought each word referred to disease.All groups rated illnesses due to infections as diseases, but the doctors, and particularly the general practitioners, were more generous in accepting as diseases the terms for non-infectious conditions. Apart from the nature of the cause, the most influential factor in determining whether or not an illness was considered to be a disease was the importance of the doctor in diagnosis and treatment.These findings provide further evidence that there is ambiguity about the meaning of the term disease. To the layman a disease seems to be a living agency that causes illness. Doctors have obviously accepted more heterogeneous defining characteristics but remain reluctant to adopt unequivocally nominalist ways of thought. The position is not unlike that in the physical sciences, in which there is a good precedent for distinguishing between the formal scientific and the everyday uses of terms such as "force" and "power."


Diet and Crohn's disease: characteristics of the pre-illness diet. Thirty newly diagnosed patients with Crohn's disease were interviewed about their habitual, pre-illness diet and compared with 30 healthy controls, matched for age, sex, social class, and marital status. The patients ate substantially more refined sugar, slightly less dietary fibre, and considerably less raw fruit and vegetables than the controls. A diet high in refined sugar and low in raw fruit and vegetables precedes and may favour the development of Crohn's disease.


Treatment of Crohn's disease with an unrefined-carbohydrate, fibre-rich diet. Thirty-two patients with Crohn's disease were treated with a fibre-rich, unrefined-carbohydrate diet in addition to conventional management and followed for a mean of four years and four months. Their clinical course was compared retrospectively with that of 32 matched patients who had received no dietary instruction. Hospital admissions were significantly fewer and shorter in the diet-treated patients, who spent a total of 111 days in hospital compared with 533 days in the non-diet-treated control group. Whereas five of the controls required intestinal operation, only one diet-treated patient needed surgery. This is in strong contrast to general experience with this disease. Treatment with a fibre-rich, unrefined-carbohydrate diet appears to have a favourable effect on the course of Crohn's disease and does not lead to intestinal obstruction.


Fibreoptic injection of oesophageal varices. A new technique for injecting sclerosant into oesophageal varices uses a flexible gastroscope. Once the gastroscope has been inserted a flexible tube with a window cut into its distal end is pushed down over the gastroscope until a varix protrudes through the window. The varix can then be injected with a needle passed down the biopsy channel of the gastroscope. Once the varices have all been injected in this way the tube is advanced to compress the injection sites and so help control bleeding. This method, using a flexible gastroscope, has proved easier and safer than the traditional method using a rigid gastroscope.


Pregnancy in patients presenting with hyperprolactinaemia. Ninety-two pregnancies occurred in 76 hyperprolactinaemic patients treated with bromocriptine. Half conceived within three months of attempted conception. There was no evidence of an increased rate of spontaneous abortion, fetal abnormality, or multiple pregnancy; the three twin pregnancies occurred in women who were additionally treated with clomiphene and human chorionic gonadotrophin. Thirty-one patients had radiological evidence of a pituitary tumour; 14 with major radiograph changes in the pituitary fossa or serum prolactin concentrations greater than 100 ng/ml received pituitary irradiation before conception. None of the latter showed evidence of enlargement of the tumour during pregnancy. In contrast two of the four patients with similar tumours but who were not irradiated developed visual field defects, one with gross destruction of the pituitary fossa. Prophylactic treatment to limit subsequent tumour expansion during pregnancy in patients with prolactinomas is indicated, and pituitary irradiation before conception appears to be a safe and effective method to achieve this goal.


Are breast-fed babies still getting a raw deal in hospital? After preliminary validation of test weighing under ward conditions the fluid intake and weight gain of 39 breast-fed and 25 artificially fed infants were compared. All were fed every four hours for six feeds a day, and the breast-fed infants received dextrose supplements only. The average intake and weight gain of the breast-fed group was significantly less than that of the group fed artificially.When cows'-milk supplements are withheld from breast-fed infants a four-hourly regimen provides insufficient stimulus to lactation for their needs in the first week of life. If more than lip service is to be paid to the mother who desires to breast-feed in hospital, early and more frequent feeding should be practised.


De novo acute infection and reactivation of hepatitis B virus in established cirrhosis. Five patients with cirrhosis proved by biopsy had clinical, biochemical, and serological evidence of an acute hepatitis B infection. In two the illness was fulminant and led to death. Only one patient completely recovered. Serological markers for the hepatitis B virus were absent before the onset of the acute illness in four patients, which suggested that a de novo infection had been acquired as a result of recent transfusions of blood or blood products. The fifth patient, who had Goodpasture's syndrome, had antibody to the core of hepatitis B virus, indicating previous exposure to the virus; his acute hepatitis may have been related to immunosuppressive drug treatment, which may have reactivated a dormant virus infection. Thus an acute type B viral hepatitis due to either a de novo or a reactivated infection may be superimposed on cirrhosis.


Verification of smoking history in patients after infarction using urinary nicotine and cotinine measurements. Urinary concentrations of nicotine and its major metabolite cotinine were measured in volunteers whose smoking habits were known to test the reliability of the measurements as indicators of current smoking. In the non-smokers detectable concentrations were always below the confidence limits set for the method, while in smokers the concentrations were always above these limits. After subjects stopped smoking cotinine appeared in the urine for longer than nicotine and was still detectable at least 36 hours after the last cigarette had been smoked. When this method was used to verify the smoking histories given by patients attending an infarction clinic it was estimated that 46-53% of previous smokers had actually stopped smoking compared with the 63% who said that they had done so. It is suggested that simultaneous assays of urinary nicotine and cotinine may be a useful means of verifying patients' current smoking habits.


Improving medication compliance: a randomised clinical trial. A medical monitor which recorded the date and hour each time a medicine bottle was opened was used to evaluate a programme for improving patients' compliance with their treatment. Eighty-two patients with glaucoma who had been prescribed pilocarpine eye drops three times daily to prevent visual loss were randomised into two groups. Both groups used the medication monitor during two 20-day periods, but before the second period the experimental group were given an education and tailoring programme in an attempt to improve their compliance. Nine patients missed the second treatment period and were excluded from the analysis. The patients in the experimental group showed significantly improved compliance when compared with the control group. The numbers of missed doses were reduced by about half, as was the proportion of time that exceeded the eight-hour dose intervals. Follow-up studies are needed to determine how long the improved compliance persists, but anyone considering setting up an education and tailoring programme should recognise the extent to which therapeutic efforts are wasted because of non-compliance.


Long-term urethral catheter drainage.

Long-term urethral catheter drainage. Long-term catheter management is best conducted by specially trained community staff, provided there is close liaison with the urologist. Patients, hospital staff, and the primary health care team all benefit. The scheme is cost-effective, more convenient for patients and relatives, and reduces the need for emergency calls to the general practitioner and hospitals. We advocate development of similar schemes in other districts.


Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. One hundred cases of severe paracetamol poisoning were treated with intravenous N-acetylcysteine (acetyl-cysteine). There was virtually complete protection against liver damage in 40 patients treated within eight hours after ingestion (mean maximum serum alanine transaminase activity 27 IU/1). Only one out of 62 patients treated within 10 hours developed severe liver damage compared with 33 out of 57 patients (58%) studied retrospectively who received supportive treatment alone. Early treatment and acetylcysteine also prevented renal impairment and death. The critical ingestion-treatment interval for complete protection against severe liver damage was eight hours. Efficacy diminished progressively thereafter, and treatment after 15 hours was completely ineffective. Intravenous acetylcysteine was more effective than cysteamine and methionine and noticeably free of adverse effects. It is the treatment of choice for paracetamol poisoning.


Haemodynamic effects of salbutamol in patients with acute myocardial infarction and severe left ventricular dysfunction. The haemodynamic effects of salbutamol infusions at rates of 10,20, and 40 micrograms/min were measured in 11 patients with acute myocardial infarction complicated by left ventricular failure. Four patients also had cardiogenic shock. Consistent increases were observed in cardiac outputs at all doses (up to 56% at 40 micrograms/min), while the mean systemic arterial pressure fell slightly (average 5 mm Hg), implying a reduction in peripheral vascular resistance. Changes in right atrial pressure and indirect left atrial pressure (measured as pulmonary artery end-diastolic pressure) were small and not significant. Analysis of data from individual patients showed that the greatest increment in cardiac output was reached at 10 micrograms/min in two cases, 20 microgram/min in three, and 40 micrograms/min in the remaining six. Heart rate at these doses increased by an average of only 10 beats/min. Salbutamol failed to reduce left ventricular filling pressure and cannot be recommended for the treatment of pulmonary oedema in acute myocardial infarction. The increase in cardiac output, however, was considerable, so that the drug may be important in the management of low-output states. This action is probably a result of peripheral arteriolar dilatation (itself a result of beta 2-adrenoreceptor stimulation) and is achieved with little alteration in the principal determinants of myocardial oxygen requirement.


The Scottish perinatal mortality survey. Perinatal deaths in single births that occurred in Scotland during 1977 were investigated by case-record analysis. Causes of death were divided into nine categories, an extended version of the Aberdeen classification being used. Out of 1012 single perinatal deaths, 265 were due to fetal abnormality, which in 140 cases was malformation of the central nervous system. Of the 747 normally formed infants, 446 weighed 1500 g or more, of whom 82 died intra partum and 154 were born alive. The largest single cause of death was low birth weight in normally formed babies whose mothers had no complications of pregnancy (302 cases). Of these babies, 103 (34%) were growth-retarded. Rhesus incompatibility (16 deaths) and maternal diabetes (seven deaths) were not major causes of perinatal loss. These results were thought to be valuable in illustrating the main causes of perinatal mortality and directing attention to important issues. Hence a modified version of the study is being continued to see whether yearly audit by regional assessors is a feasible and practical way of monitoring trends in perinatal mortality.


Monitoring of psychotropic drug prescribing in general practice. Over 1000 repeat prescriptions of psychotropic drugs, which were given without the doctor seeing the patient, were analysed from a population of over 100 000 patients during a two-week period. The analysis showed that the longer repeat prescribing had taken place the older the patient was likely to be and the less closely were they monitored by their general practitioner.


Changes in coronary risk factors during comprehensive five-year community programme to control cardiovascular diseases (North Karelia project). A comprehensive community programme to control cardiovascular diseases (CVD) in North Karelia, Finland, was carried out during 1972-7. The central intermediate objective of the programme was to reduce the prevalence of smoking, the serum cholesterol concentration, and raised blood-pressure values among the population of the area. The effect was evaluated by examining independent representative population samples in 1972 and 1977 in both the county of North Karelia and a matched control county. Over 10 000 subjects were studied each time, the participation rate being around 90%. The decrease that occurred in the risk factors, especially in men, was in general greater in North Karelia compared with the control county. When a multiple logistic function was used for the three risk factors an overall mean net reduction of 17% among men and 12% among women was observed in the estimated risk for coronary heart disease in North Karelia. This community programme effectively reduced the levels of the three main risk factors for CVD in the population, and thus mortality and morbidity from CVD should fall. This is assessed in further studies.


Changes in morbidity and mortality during comprehensive community programme to control cardiovascular diseases during 1972-7 in North Karelia. A comprehensive community programme studying the control of cardiovascular diseases (CVD) was carried out in North Karelia, Finland, between 1972 and 1977. The main objective was to reduce the mortality and morbidity of CVD, particularly in middle-aged men. Changes in the mortality and incidence of CVD were monitored by community-based registers of cases of acute myocardial infarction (AMI) and stroke and data on death certificates. During the programme the total mortality in the area decreased by 5% and the mortality from CVD decreased by 13% among men and 31% among women aged 30-64 years. The incidence of AMI fell by 16% among men and 5% among women, while that of cerebral stroke fell by 38% among men and 50% among women. Changes in mortality in North Karelia were compared with those in a matched control area; the difference between the two areas was not significant. The true effect of the programme cannot be deduced from these results, but mortality from CVD and the incidence of AMI and stroke fell during the five years studied. Thus the changes in mortality and morbidity of CVD accorded with the initial objectives of the programme.


Maternal perception of fetal motor activity. A technique using real-time ultrasound for comprehensive recording of fetal motor activity was used in 20 subjects in the third trimester of pregnancy. Maternal awareness of fetal movement correlated with the number of fetal parts contributing to the movement but not with maternal parity or obesity, gestational age, placental site, or duration of the fetal movement. Some subjects recorded fetal breathing, passive fetal displacement, and Braxton Hicks's contractions as fetal movement. Most of our subjects were consistent and accurate in their perception of major fetal movements, but a few were inconsistent and one was completely unaware of major fetal movements. These results suggest that kick counts kept by most mothers will be accurate. Low counts of fetal movement should be an indication for fetal monitoring by other means and not, unconfirmed, for intervention.


Haemorrheological response to plasma exchange in Raynaud's syndrome. Eight patients with Raynaud's syndrome were treated by weekly plasma exchange for four weeks using a Haemonetics Model 30 Blood Processor. The mean whole-blood viscosity at a shear rate of 0.77/s was significantly lower after treatment, and the mean index of red-cell deformability was significantly improved. In four patients studied serially the mean percentage fall in whole-blood viscosity after a single plasma exchange was 49% at 0.77/s but only 14% at 91/s. All patients noticed symptomatic improvement including healing of ischaemic digital ulcers. In six patients the number of digital arterial segments containing detectable blood flow was measured by directional Doppler; in all six the number increased. It is concluded that plasma exchange is an effective means of haemorrheological treatment and may be beneficial in patients with digital ischaemia.


Edinburgh Emergency Asthma Admission Service: report on 10 years' experience. In December 1968 an emergency service was begun in Edinburgh to expedite admission to hospital of patients with severe acute asthma. During the first 10 years requests were made to admit 112 patients to a respiratory unit with provision for intensive care on 360 occasions. Four of the patients died of their disease, one in hospital and three before admission. It was thought that the death rate would have been much higher had conventional admission procedures been observed. Owing to ethical objections to a controlled trial it was not possible to obtain substantive proof that the service reduced deaths from asthma. Nevertheless, there was strong circumstantial evidence that organised facilities for the immediate admission to hospital of patients with a history of life-threatening attacks would result in fewer deaths at home. Earlier admission also apparently reduced hospital mortality and the number of patients requiring tracheal intubation and mechanical ventilation. It is concluded that there is a prima facie case for an emergency asthma admission serivce similar to that operating in Edinburgh to be established in all cities and large towns.


Long-term survival of patients with breast cancer: a study of the curability of the disease. A retrospective analysis was made of 3878 cases of breast carcinoma first seen in Edinburgh from 1954 to 1964. During this time there was a policy to treat breast cancer by simple mastectomy and x-ray therapy, and over 90% of cases classified as international stages I and II were so treated. The mortality in these women was compared with that in an equivalent normal population using Scottish national age-specific death rates. For every year of follow-up within 20 years of initial treatment there was an excess mortality from all causes. There was an overall excess mortality of 58% among patients with breast cancer 15-20 years after initial treatment, and 20 times more deaths occurred in this period from breast cancer than in a normal population. For patients disease-free after 15 years there was still a 28% excess mortality from all causes. Factors known to be of major prognostic significance for five-year survivorship had less influence than might have been expected when the ratio of observed to expected deaths was considered for longer periods of follow-up. The effect of clinical staging (I, II, or III), though initially marked, largely disappeared by the 10th year of follow-up, and after allowing for age there was no evidence beyond 10 years of an effect on survival of the original stage of the disease. Similarly, the effect of tumour size on survival disappeared after 10 years. Women who were premenopausal at presentation still had a significant excess of deaths in the fourth quinquennium of follow-up. In the menopausal and postmenopausal groups combined there was still a small non-significant excess of deaths from all causes after 15 years but this almost disappeared when patients who had already relapsed were excluded. In terms of overall mortality only patients who have undergone the menopause before presentation and who are disease-free 15 years after primary treatment may prove to be cured by conventional techniques such as simple mastectomy and postoperative radiotherapy.


Gut hormones in tropical malabsorption.

Gut hormones in tropical malabsorption. Concentrations of various gut hormones were measured after a test breakfast in eight patients with severe tropical malabsorption and 12 controls. The patients with tropical malabsorption had greatly raised basal plasma motilin and enteroglucagon concentrations, but their postprandial release of both gastric inhibitory polypeptide and insulin was significantly reduced. The pattern of gut hormone release differed from that found in coeliac disease. The measurement of gut hormones, each of which has a specific site and function, thus throws new light on the pathophysiology of tropical malabsorption and may suggest approaches of treatment.


Pathogenesis of neonatal hyperbilirubinaemia after induction of labour with oxytocin. To determine the pathogenesis of neonatal hyperbilirubinaemia after oxytocin-induced labour venous cord blood from 95 healthy newborn infants was examined. Of these, 15 were delivered by elective caesarean section, 40 after spontaneous labour, and 40 after oxytocin-induced labour. There was no significant difference in any haematological or biochemical variable between the first two groups. Infants born after oxytocin-induced labour, however, showed clear evidence of increased haemolysis associated with significantly decreased erythrocyte deformability (P less than 0.001). In-vitro studies showed a time- and dose-related reduction in erythrocyte deformability in response to oxytocin. The findings suggest that the vasopressin-like action of oxytocin causes osmotic swelling of erythrocytes leading to decreased deformability and hence more rapid destruction with resultant hyperbilirubinaemia in the neonate.


Interaction between anticoagulants and contraceptives: an unsuspected finding. To assess the effects of oral contraceptives on anticoagulant treatment the prothrombin times of 12 patients were measured while they were taking both drugs simultaneously and while they were taking only anticoagulants. The mean prothrombin time ratio was significantly higher when patients were taking both drugs than when they were taking only anticoagulants and their doses of anticoagulant were significantly lower. During both periods most of the prothrombin values remained in the therapeutic range. These findings suggest that, contrary to the common belief that oral contraceptives diminish the effects of anticoagulants, contraceptives in fact potentiate the action of the anticoagulants.


General practice observed. A do-it-yourself medical centre. A group practice commissioned a local building company to build their own medical centre comprising 370 m2 (4000 ft2) of building with an adequate car park at a total cost of 60 000 pounds with design to completion in nine months. A bank loan for 10 years was assigned to the partnership and each partner made his own arrangements for repayment. The updated cost for June 1979 is 80 000-85 000 pounds. Building a centre in this way is professionally and financially rewarding.


How reliable is determination of ulcer size by endoscopy? The suface areas of 23 artificial ulcers in a rubber manikin and of 35 ulcers in 35 consecutive patients admitted for endoscopy of the upper gastrointestinal tract were estimated by six endoscopists. Of the 138 estimations made in the manikin 80% underestimated the true size of the ulcer: the mean (+/- SD) was -29 +/- 40%. The largest and the smallest estimate of the same ulcer by different endoscopists varied on average by a factor of 4.5 +/- 3.8, and the estimates by the same endoscopists of ulcers with the same size varied by a factor of 2.3 +/- 0.6. In the patients the scatter of the estimates was even larger, the mean factor being 7.8 +/- 6.3. Changes in ulcer size are therefore an unsuitable criterion for assessing ulcer healing. Even if consecutive examinations are performed by the same endoscopist, changes in ulcer area smaller than by a factor of 3 are not discernible.


Incidence of malignant melanoma of the skin in England and Wales and its relationship to sunshine. In most of England and Wales the incidence of malignant melanoma of the skin has risen rapidly in recent years, especially in women. Mean incidences in the 14 English health regions and Wales correlated negatively with latitude and positively with hours of sunshine, suggesting that exposure to sunshine was an important causal factor. Male and female incidences within a region tended to show similar yearly fluctuations, implying a common factor affecting the incidence in both men and women with a short latent period of action. This factor may be exposure to sunshine, which may cause melanoma after an induction period of about two years; for women the incidence of melanoma in the regions of England and Wales correlated positively with hours of sunshine two years earlier.


Self-monitoring of blood glucose in diabetic pregnancy. Admission to hospital is usually recommended to achieve the best possible diabetic control during pregnancy. We have used blood glucose monitoring at home to find out if patients can achieve equally good control outside hospital. Twenty-five consecutive diabetic patients were studied, of whom 20 had taken insulin before pregnancy. Six of their 14 previous pregnancies had ended in perinatal death. The 25 women performed 4247 blood glucose measurements during their pregnancies. Overall the mean blood glucose concentration was 7.1 mmol/l (128 mg/100 ml); before meals the mean was 6.5 mmol/l (117 mg/100 ml). Mean concentrations were lower in the third trimester, but at no stage was control in hospital significantly better than at home. The mean hospital stay before delivery was 22 days, and all patients had live babies. Monitoring blood glucose concentrations at home produces greater understanding and motivation among patients, improves control early in pregnancy, and shortens time spent in hospital.


Nuclear medicine in district general hospitals. Nuclear medicine is a recognised clinical specialty both nationally and internationally. Compared with other countries, it is inadequately developed in Britain, particularly in district general hospitals. To create clinical radioisotope services at district level physicians or radiologists with experience in nuclear medicine need to be trained and appointed. Such appointments would allow facilities to evolve that would provide either a comprehensive nuclear medicine service formed around a physician or an imaging service based on a radiologist. Such units would improve the care of patients at a reasonable recurring cost of 15 pounds--30 pounds per investigation.


Prevalence of gall stones at necropsy in nine British towns: a collaborative study. A prospective study of the prevalence of gall stones at necropsy in nine towns in England and Wales showed considerable geographical variations. The age- and sex-standardised prevalence ranged from 20.6% in Ipswich to 9.2% in Wakefield. The distribution of gall stones differed from that of all-cause mortality and was negatively correlated with that of mortality from ischaemic heart disease. Socioeconomic influences related to affluence do not appear to be major determinants of the distribution of gall stones.


Immunoreactive calcitonin in leukaemia.

Immunoreactive calcitonin in leukaemia. A radioimmunoassay was used to measure concentrations of immunoreactive human calcitonin (HCT) in plasma and leucocytes from patients with various leukaemic and myeloproliferative disorders. Plasma immunoreactive HCT concentrations were increased in 32 out of 33 patients with chronic granulocytic leukaemia (CGL) and in all eight patients with acute myeloid leukamia (AML) at presentation or in relapse. Out of 11 patients with other myeloproliferative disorders, eight had increased plasma immunoreactive HCT concentrations. Buffy-coat-cell extracts and culture media from peripheral leucocytes of patients with CGL also contained increased immunoreactive HCT concentrations. In contrast, plasma from patients with chronic lymphocytic leukaemia, acute lymphoblastic leukaemia, and AML in remission had low or undetectable immunoreactive HCT concentrations. Increased plasma and cellular concentrations of immunoreactive HCT may be a consequence of abnormal proliferation of myeloid cells and might prove to be valuable in predicting relapse in patients with myeloid leukaemias.


Praziquantel: a new schistosomicide against Schistosoma haematobium. The effectiveness of the new schistosomicide praziquantel was assessed in African schoolchildren infected with Schistosoma haematobium. They were stratified according to the severity of their infection and were then randomly allocated to treatment with two single-dose regimens (30 and 40 mg/kg) and a split regimen of two doses of 20 mg/kg given four hours apart. All three regimens were highly effective and produced few side effects. Children who initially had very high pretreatment egg loads showed a poorer therapeutic response at all dose levels, and further investigations are necessary to find the optimum dose. Because of its effectiveness in a single dose and lack of toxicity, praziquantel may prove to be the ideal schistosomicide.


Muscarinic receptors in the central nervous system of the rat. I. Technique for autoradiographic localization of the binding of [3H]propylbenzilylcholine mustard and its distribution in the forebrain. [3H]Propylbenzilylcholine mustard ([3H]PrBCM) is a synthetic, potent muscarinic antagonist, which binds specifically and irreversibly by means of a covalent linkage to muscarinic receptors. Ten micrometer coronal cryostat sections taken through unfixed rat brain at the level of the maximum extent of the caudate nucleus were mounted on glass slides and incubated with 2.4 nM [3H]PrBCM at 30 degrees C for 25 min. They showed a total binding of 3250 pmol/g protein, of which 2130 pmol/g protein was sensitive to pretreatment with 10-6 M atropine. The specific (atropine-sensitive) binding was saturable. Saturation was reached at 15 min, with a rate constant of 1.3 x 106 M-1 sec-1. Binding was unaffected by drugs acting at nicotinic receptors (D-tubocurarine, hexamethonium), or by physostigmine, but was inhibited by muscarinic drugs (pilocarpine, oxotremorine, 3-quinuclidinylbenzilate). Postfixation for 15 min in Carnoy's fixative reduced the specific binding by 10% and the non-specific by 50%. Prefixation (i.e. before incubation with [3H]PrBCM) with any fixatives containing formaldehyde largely prevented specific binding, but a range of concentrations of glutaraldehyde (2% to 0.05%) caused only small reductions in specific binding (e.g. 0.1% glutaraldehyde caused only a 6% reduction). Clear, regionally specific patterns of localization of specific label in light microscope autoradiographs could be obtained from cryostat sections prefixed with 0.1% glutaraldehyde, incubated with 2.4 nM [3H]PrBCM for 15 min at 30 degrees C, and postfixed for 15 min in Carnoy's solution. Of the 105 forebrain areas studied 12 had grain counts between 6 and 9 times the non-specific level and a further 30 had counts 4 to 6 times non-specific. The higher grain counts were in the external plexiform layer of the olfactory bulb, anterior olfactory nucleus, olfactory tubercle, pyriform cortex, stratum radiatum of the hippocampus, stratum moleculare of the dentate gyrus, lateral amygdaloid nucleus, cortico-amygdaloid transition zone, anteroventral thalamic nucleus, hypothalamic supraoptic nucleus, caudate-putamen, nucleus accumbens, and in laminae 3 and 6 of the neocortex (parietal region). There were high grain densities over the choroid plexus the lateral but not the third or fourth ventricles.


Muscarinic receptors in the central nervous system of the rat. II. Distribution of binding of [3H]propylbenzilylcholine mustard in the midbrain and hindbrain. The distribution of muscarinic receptors has been studied in the rat midbrain and hindbrain by counting silver grains in light microscope autoradiographs of the specific (atropine-sensitive) binding of [3H]propylbenzilylcholine mustard in cryostat sections. Of the 78 areas studied 6 had grain counts between 6 and 9 times the nonspecific level ("high"), and a further 15 had counts 4-6 times non-specific ("intermediate"). The basilar pontine nuclei and the ventral nuclei of the lateral lemniscus had high counts. Among the cranial nerve motor nuclei the facial and hypoglossal nuclei had high counts and the motor trigeminal nucleus and nucleus ambiguus had medium counts. The interpeduncular nucleus as a whole had low counts but there were two bands of intense staining on each side around the entry zone of the bundles of afferent cholinergic fibres from the habenula. Intermediate levels of binding occurred over the inferior colliculus and the superficial and intermediate grey layers of the superior colliculus. The molecular layer of the vestibulocerebellar vermis was distinctly labelled.


Muscarinic receptofs in the central nervous system of the rat. III. Postnatal development of binding of [3H]propylbenzilylcholine mustard. The postnatal development of muscarinic receptors has been studied in 7 selected areas from the brains of 1-17-day-old rats by counting silver grains in light microscope autoradiographs of the specific (atropine-sensitive) binding of [3H]propylbenzilylcholine mustard in cryostat sections. A major part of the adult receptor density is present at 1 day of age, a time when only a small fraction of the adult number of synapses has yet been formed. Of the areas studied the hypoglossal nucleus is the most precocious in muscarinic receptor development, and the dentate gyrus the latest (associated with the late development of the dentate granule cells). The pattern of receptor distribution changes with development. The caudate-putamen first develops receptor in patches, beginning at the lateral (ventricular) surface. The pontine nuclei develop receptor in a medial to lateral sequence. The maturation of the adult laminar pattern of the olfactory bulb depends on the alignment of cells (especially the mitral cells). The neocortex initially has uniform labelling throughout its depth, and later the labelling in layer 4 becomes relatively less dense (probably associated with the ingrowth of afferent fibres). The hippocampal formation first develops receptor evenly over the pyramidal cell dendrites; later receptor appears over the newly formed dentate stratum moleculare and becomes much reduced over the hippocampal stratum lucidum and stratum lacunosum-moleculare (probably associated with the ingrowth of afferent fibres from the dentate gyrus and entorhinal area). In the cerebellum muscarinic receptor is found only in the lobules which receive the primary vestibular afferents. In the neonate it is present in the granular layer, but this later disappears and is replaced by the adult pattern of labelling in the molecular layer.


Muscarinic receptors in the central nervous system of the rat. IV. A comparison of the effects of axotomy and deafferentation on the binding of [3H]propylbenzilylcholine mustard and associated synaptic changes in the hypoglossal and pontine nuclei. The reaction of axotomy has been studied in the rat hypoglossal nucleus by quantitative electron microscopical counts of numbers of synapses and by changes in muscarinic receptors assessed by counting silver grains in light microscope autoradiographs of the specific (atropine-sensitive) binding of [3H]propylbenzilylcholine mustard in cryostat sections. For the first 5 days after unilateral peripheral hypoglossal nerve axotomy the muscarinic ligand binding falls to 50% of control levels and then shows no further fall for up to 30 days. Synapse numbers decrease progressively over the first 10 days after operation, by which time they reach 50% of normal. Thus receptor changes reach completion at a time when synapse loss is still continuing. Later, both muscarinic ligand binding and synapse numbers recover to an extent which depends at least in part on the effectiveness of the peripheral nerve regeneration, suggesting that both the receptor and synapse changes may be dependent upon neuromuscular contacts. The reactions of muscarinic receptors to axotomy and deafferentation have been studied in the rat basilar pontine nuclei. Cerebellectomy, which causes axotomy of the pontine neurones and also removes their postsynaptic targets (the granule cells), causes no change in pontine muscarinic receptor over the first week after operation. This differs from the rapid fall in hypoglossal muscarinic receptors induced by axotomy. At longer survivals after cerebellectomy there is a partial loss of pontine muscarinic receptors associated with atrophy of the pontine neurones. Destruction of the neocortical afferents causes a loss of at least half of the synapses in the pontine neuropil. However, the light microscopic autoradiographic study revealed no obvious changes in the dentisy or distribution of the pontine muscarinic receptors from 4 days to more than 6 months after operation.


The role of the cholinergic system in the central control of thermoregulation in rats. Systemic and central administration of methacholine (a synthetic choline derivative) both produced dose-dependent decreases in rectal temperature in rats at all the ambient temperatures studied. Both at room temperature (22 degrees C) and in the cold (8 degrees C), the hypothermia in response to methacholine application was brought about by both a decrease in metabolic heat production and an increase in cutaneous circulation. In the heat (29 degrees C), the hypothermia was due solely to an increase in respiratory evaporative heat loss. Furthermore, the methacholine-induced hypothermia was antagonized by central pretreatment of atropine (a selective blocker of cholinergic receptors), but not by the central administration of either 6-hydroxydopamine (a relative depletor of catecholaminergic nerve fibers) or 5,6-dihydroxytryptamine (predominately a serotonin depletor). The data indicate that activation of the cholinergic receptors within brain with methacholine decreases heat production and (or) increases heat loss which leads to hypothermia in rats.


Modes of rouleaux formation of human red blood cells in polyvinylpyrrolidone and dextran solutions. The mechanics by which normal human erythrocytes join on a plastic cover slip into two cell doublets and larger aggregates of rouleaux were studied microscopically. Polyvinylpyrrolidone (PVP-360) or dextran (DX-70 or DX-110) were used as the rouleau agents. The minimum concentration of the rouleau-inducing agents required to form doublets was 1 g/L for PVP-360 and 5 g/L for the DXs. Three modes of interaction were observed in Ringer's solution with PVP or DX, cresting and flipping (involving no intercellular sliding) and a sliding mode of doublet formation (involving less gravitational work and less cellular deformation). The sliding mechanism occurred in suspensions with the lower concentrations of the rouleau agent but was also observed when geometric constraints prevented the nonsliding interaction of larger groups of cells in the higher concentrations of the rouleau agent. The technique provides a sensitive index for studying the combined effect of cellular flexibility and intercellular adhesion. Significant changes were observed for reduced membrane surface charge or reduced ionic calcium.


Behavioural effects of 6-hydroxydopamine-induced depletion of spinal noradrenaline. Bilateral injection of 6-hydroxydopamine (4 micrograms/2 microL) into the caudal medulla of rats reduced spinal noradrenaline (NA) to 6% of control values. No significant NA depletion was observed in the hippocampus, cortex, or cerebellum, and a small loss of NA was found in the hypothalamus. These lesions were found to elevate significantly threshold shock levels necessary to elicit jump responses, and they also abolished the reflexive alternating motor movements produced by decapitation. These data support the hypothesis that spinal NA mechanisms modulate reflexive motor movements. However, no significant effect of these lesions was found on either spontaneous or amphetamine-induced locomotor activity, suggesting that spinal NA does not play a significant role in these behaviours.


The effects of nitrous oxide on the developing hamster embryos. Pregnant hamsters were exposed to different concentrations of nitrous oxide during the period of organogenesis. Teratogenic effects were observed in a small but significant number of fetuses. Types of malformations included cleft palate, limb defects, gut herniation, and fetal edema. A dose-effect relationship was not observed. It is not clear from our observations whether the observed effect on the fetuses was due to the excess of nitrous oxide, hypoxia, or a combination of both. Comparison with published literature indicates that further studies on the effects of nitrous oxide in placental animals are needed.


Effect of cholecystokinin, secretin, and gastric inhibitory polypeptide on insulin release from the isolated perfused rat pancreas. The actions of gastric inhibitory polypeptide (GIP) on insulin release from the isolated perfused rat pancreas were compared with those of pure secretin and cholecystokinin (CCK). At dose levels physiologically achievable for GIP (1 ng/mL perfusate), infusions of CCK stimulated significant insulin release both on a weight (1 ng/mL) and a molar (770 pg/mL) basis. Although 50% as potent as GIP on a weight basis and 43% as potent on a molar basis, the insulin response to CCK was multiphasic and sustained for the duration of the infusion. The action of CCK, like that of GIP, was glucose dependent yielding no significant insulin release at a low perfusate glucose concentration (80 mg/dL). Irrespective of perfusate glucose concentration or dose (1 or 5 ng/mL), secretin failed to stimulate significant release of insulin from the perfused pancreas. It was concluded that secretin is ineffective as an incretin and that a physiological role for CCK in an enteroinsular axis awaits accurate measurement of circulating levels of immunoreactive CCK.


The irreversible binding of benzo[a]pyrene to rat liver macromolecules in vivo and in vitro: effects of agents that influence benzo[a]pyrene metabolism. The present study was carried out to determine the effects of agents that influence benzo[a]pyrene (BP) metabolism in vitro on the irreversible binding of BP to rat hepatic macromolecules in vivo. The irreversible binding of [3H]BP was found to be both dose and time dependent after its intraperitoneal administration to male Wistar rats. The SKF 525-A, at doses of 50 and 75 mg/kg, ip 3 h before BP, decreased the level of binding from control by 31 and 34%, respectively. At 35 mg/kg, SKF-525-A had no effect. Diethyl maleate (0.6 mL/kg, ip) and cysteine (150 mg/kg, ip), 30 and 5 min before BP, respectively, did not alter the binding of BP from control. Oral methadone treatment, previously shown to increase selectively epoxide hydrase activity in male Wistar rats, also failed to alter the amount of BP bound to hepatic macromolecules. 3-Methylcholanthrene (20 mg/kg per day, ip, for 2 days) administered 24 h before BP, decreased the level of binding from control by 30%. Parallel in vitro studies were carried out with the various agents used in vivo.


Norepinephrine, monoamine oxidase, and acetylcholinesterase in the rat jugular vein compared with other blood vessels. The observation that the rat jugular vein relaxed in response to norepinephrine but not to field stimulation prompted us to evaluate the extent of innervation in this tissue. The norepinephrine concentration in the jugular vein was about 10% of that in the mesenteric artery and vein. The low levels of norepinephrine were not due to higher monoamine oxidase activity relative to the enzyme activity in other blood vessels. In the jugular vein, as in heart and brain, serotonin was preferred substrate for monoamine oxidase whereas in the femoral vein, mesenteric vein, and mesenteric artery, phenylethylamine oxidation was greater. Based on kinetic and inhibitory studies with LY51641, a selective type A inhibitor, monoamine oxidase activity was not found to be uniform throughout the cardiovascular system. In addition to low levels of norepinephrine, acetylcholinesterase activity in the jugular vein was only 5 and 13% of the activity in the portal vein and mesenteric artery, respectively. Thus, we provide strong evidence that our inability to generate a response to field stimulation in the rat jugular vein results from the lack of functional innervation in this tissue. This information adds to the usefulness of this preparation for comparative studies of agents acting on the smooth muscle without the added complication of neuronal uptake mechanisms.


The reliability of rates of glucose appearance in vivo calculated from single tracer injections. The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-experimental equation which describes the changes in plasma glucose specific radioactivity.


The effect of magnesium-free solutions on the responses of the guinea pig urinary bladder to adenosine 5'-triphosphate and nerve stimulation. Exposure of the guinea pig urinary bladder to magnesium-free Krebs-Henseleit type solution for 60 min led to an increase in the responses of the tissue to added adenosine 5'-triphosphate (ATP). The responses of the tissue to histamine were unaffected. The atropine-resistant contractions due to nerve stimulation were potentiated at frequencies above 4 Hz when the response of the tissue was 60% of its maximum response. This would suggest that, although ATP does contribute to the responses of the tissue at high frequencies, it is not the transmitter of the noncholinergic nerves present in the bladder.


Biological activities of kinins modified at the N- or at the C-terminal end. A series of analogues of des-Arg9-bradykinin, modified at the N- or C-terminal end, were tested on rabbit aorta strips (receptor B1) and on cat ileum strips (receptor B2) in an attempt to find long-acting agonists and antagonists. It was found that the methylation or the amidation of the C-terminal carboxyl reduces the affinity and (only the amidation) the intrinsic activity of the agonists, while not changing significantly the duration of action of both agonists and antagonists. The addition of a Lys at the N terminal is accompanied by a marked increase of affinity, no changes of intrinsic activity, and a prolongation of the duration of action of agonists. Antagonists behave in a similar way as the agonists and show increased affinity; the time required for inducing full inhibition as well as the duration of action are significantly increased. The pharmacological and physiopathological implications of these results are discussed.


Influence of adrenalectomy and sex on the binding of 3-methylcholanthrene to cytosol macromolecules of rat liver. The retention of 3-methylcholanthrene (3-MC) in rat hepatic cytosol was significantly enhanced by adrenalectomy. In contrast, there was no significant difference in 3-MC retention in females as compared with males. 3-MC present in the cytosol fraction was bound to macromolecules and could be separated into three fractions by ion-exchange column chromatography.


Brain benzodiazepine levels following intravenous administration of [34]diazepam: relationship to the potentiation of purinergic depression of central nervous system neurons. Levels of [3H]benzodiazepine were measured in rat cerebral cortex following intravenous injection of [3H]diazepam using a dose and time schedule reported to elicit a marked potentiation of the depressant effects of iontophoretically applied 5'-AMP to rat cerebral cortical neurons. The levels of [3H]benzodiazepine obtained strongly suggest (i) that blockade of adenosine uptake as a mechanism for this potentiation is not consistent with the potency of diazepam as an inhibitor of adenosine uptake in vitro, and (ii) that a potentiative interaction of adenosine and diazepam may reflect the binding of these compounds to benzodiazepine receptors.


Effects of some divalent cations on motoneurones in cats. In cats under Dial, Co, Mn, La, and Sr were injected extracellularly near lumbosacral motoneurones. All tended to improve intracellular recording, but when the membrane potential was initially stable, Mn, and especially Co, had a moderate and reproducible depolarizing action. Both Mn and Co depressed excitatory postsynaptic potentials evoked by dorsal root stimulation. The prominent after-hyperpolarization (a.h.p.), which normally follows the motoneuronal action potential, was consistently and reversibly depressed by Mn and Co (as well as La), the underlying conductance increase being also diminished, but there was no significant reduction in the after-depolarization. By contrast, Sr tended to potentiate the a.h.p., especially when this was depressed by a previous injection of Co or Mn. Unlike the other cations, Co had a marked depressant effect on the action potential, particularly its rate of rise. Since the action potential could be immediately restored by hyperpolarization or by an injection of Sr (in the absence of depolarization), Co may enhance Na inactivation.


Amino acids and the synaptic pharmacology of granule cells in the dentate gyrus of the rat. Granule cells in the dentate gyrus in the hippocampi of anaesthetized rats were excited by stimulation of the contralateral hippocampus (the commissural input) and the ipsilateral entorhinal cortex (the perforant path). The cells were also activated by the electrophoretic administration of various amino acids. A selective antagonism of glutamate and perforant path excitations was obtained with glutamic acid diethylester, and of aspartate and other amino acid induced and commissural excitations with D- or DL-alpha-aminoadipate. An excitatory effect of alpha-aminoadipate which was sometimes observed was prevented by the gamma-aminobutyric acid antagonist bicuculline, and may be a disinhibitory phenomenon. The results lend support to the proposition that the transmitter of the perforant path is glutamate while that of the commissural fibres is aspartate.


The development of central nervous system control of the gill withdrawal reflex evoked by siphon stimulation in Aplysia. In older Aplysia, the central nervous system (CNS) (abdominal ganglion) exerts suppressive and facilitatory control over the peripheral nervous system (PNS) which initially mediates the gill withdrawal reflex and its subsequent habituation evoked by tactile stimulation of the siphon. In young animals, both the suppressive and facilitatory CNS control were found to be absent. In older animals, removal of branchial nerve (Br) input to the gill resulted in a significantly reduced reflex latency and, with ctenidial (Ct) and siphon (Sn) nerves intact, a significantly increased reflex amplitude and an inability of the reflex to habituate with repeated siphon stimulation. In young animals, removal of Br had no effect on reflex latency and with Ct and Sn intact, the reflex amplitude latency was not increased and the reflex habituated. Older animals can easily discriminate between different intensity stimuli applied to the siphon as evidenced by differences in reflex amplitude, rates of habituation, and evoked neural activity. On the other hand, young animals cannot discriminate well between different stimulus intensities. The lack of CNS control in young animals was found to be due to incompletely developed neural processes within the abdominal ganglion and not the PNS. The lack of CNS control in young Aplysia results in gill reflex behaviours being less adaptive in light of changing stimulus conditions, but may be of positive survival value in that the young will not habituate as easily. The fact that CNS control is present in older animals strengthens the idea that in any analysis of the underlying neural mechanisms of habituation the entire integrated CNS-PNS must be taken into account.


Effects of unilateral orchidectomy on rat epididymal delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase. The effects of unilateral orchidectomy on the adult rat epidiymal testosterone metabolizing enzymes, delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase, are investigated. Five weeks following unilateral orchidectomy, it is found that the activity of 3 alpha-hydroxysteroid dehydrogenase per organ is not altered, whereas delta 4-5 alpha-reductase activity decreased by more than 80% on the side of the orchidectomy. Neither accessory sex tissue weights, ventral prostate and seminal vesicles, nor the concentration of circulating testosterone, luteinizing hormone, follicle-stimulating hormone, or prolactin is altered by unilateral orchidectomy. These data indicate that (1) epididymal 3 alpha-hydroxysteroid dehydrogenase activity can be maintained by circulating androgens and that (2) the major factor regulating delta 4-5 alpha-reductase activity is not a substance secreted by the testes into the peripheral circulation. It is suggested that a substance directly secreted into the epididymis by the testis regulates epididymal delta 4-5 alpha-reductase activity.


Clinical and pathological features of six cases of sarcoidosis presenting with renal failure. Six patients with biopsy-proven renal sarcoidosis presented with renal failure of unknown origin; in none was the diagnosis of sarcoidosis initially considered. The serum creatinine concentration at the time of presentation ranged from 265 to 1380 mumol/l (3.0 to 15.6 mg/dl), with a mean of 787 mumol/l (8.9 mg/dl). Although only two patients were hypercalcemic at the time of presentation, the 24-hour urinary excretion of calcium was increased in three of the four patients in whom it was measured, and renal calculi were present in one case. Renal biopsy revealed interstitial nephritis and tubular atrophy in all cases, as well as nephrocalcinosis in three cases and noncaseating granulomas negative for acid-fast bacilli in four cases. In each patient steroid therapy led to a rapid improvement in renal function (mean post-treatment serum creatinine level 274 mumol/l [3.1 mg/dl]). The follow-up period ranged from 8 months to 8 years (mean 3.0 years). In three patients renal function remained stable with low-dose steroid therapy. In two cases recurrent hypercalcemia and deteriorating renal function accompanied steroid withdrawal but resolved with its reinstitution. In one additional case reversible deterioration in renal function accompanied tapering of the steroid dose; however, there was no hypercalcemia.This report emphasizes the importance of considering sarcoidosis in the differential diagnosis of acute renal failure of unknown origin. Long-term follow-up of such patients is essential, as relapse is common.


Surface soil as a potential source of lead exposure for young children. Soil analyses revealed an elevated lead content in the surface soil of three British Columbia cities. The lead accumulations were largely attributed to dustfall from a nearby large lead-zinc smelter in Trail and to automotive traffic in Nelson and Vancouver. Although the mean concentrations of lead in the soil were relatively low at Nelson (192 parts per million [ppm]), in selected areas of Vancouver with heavy traffic they were similar to those found within 1.6 km of the large smelter at Trail (1545 and 1662 ppm respectively). In a study conducted in 1975, children aged 1 to 6 years in Trail and Nelson were found to have higher mean blood lead levels than grade nine students. The findings of the later study support the view that particulate lead in surface soil and dust accounted for most of the greater lead absorption in the younger children.


Predicting improvement in stroke patients referred for inpatient rehabilitation. An historical prospective study of prediction of improvement and final disposition of 105 patients with a stroke was carried out over a 2-year period in the rehabilitation service of a hospital providing long-term care. Patients were referred a mean of 37.8 days after the stroke, and were evaluated for total function and for mental status, perception, communication and motor ability at the time of admission and every 2 to 3 weeks thereafter. At the time of admission 26% of the patients were able to care for themselves; at the time of discharge 59% were able to do so, but 44% of these could not return home, primarily because of unfavourable social and environmental circumstances. In contrast, 35% of the patients unable to care for themselves went home because their families were willing to provide extra care. Neither the total function score nor the neurologic subtest scores at the time of admission predicted improvement. The presence of sphincter control and a lower age were the only significant predictors of improvement.