Biomedical subjects
Publications and source records attributed to I Simpson.
A case is presented where spontaneous rupture of a uterine arteriovenous malformation into the peritoneal cavity presented as an acute abdomen with fetal distress in late pregnancy. This is thought to be the first reported case of its type.
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The distribution of LDL receptors within subcellular compartments of isolated rat adipose cells and the effects of insulin on their expression have been assessed. By immunoblotting with specific anti-rat LDL receptor antibodies, LDL receptors were 2.3- and 4.5-fold enriched in endoplasmic reticulum-rich high-density microsomes (HDM) and Golgi complex-rich low-density microsomes (LDM), respectively, compared to plasma membranes (PM). This distribution was similar in cultured cells in which total receptors were increased 2.5-fold compared to freshly isolated cells. After correction for enzyme recoveries, LDL receptors were distributed approximately 4% in HDM, approximately 73% in LDM, and approximately 23% in PM. Insulin decreased total LDL receptors in adipose cells approximately 44%, with a 48% and 49% decrease in HDM and LDM, respectively, without any changes in PM. In contrast, insulin caused an increase of glucose transporters in PM while also decreasing glucose transporters in LDM. When adipose cells were depleted of potassium to inhibit receptor-mediated endocytosis, insulin again caused a decrease of LDL receptors in LDM but now increased LDL receptors in PM. Insulin increased the rate of LDL receptor synthesis approximately 24%, but decreased their half life approximately 40%. Thus, in isolated adipose cells the majority of LDL receptors appear to be located in an intracellular compartment that co-sediments with the Golgi complex rather than located in the PM. The LDL receptors localized in intracellular compartments seem to be functionally regulated as insulin acutely diminishes the number of receptors by apparently accelerating their rate of degradation through, as yet, incompletely determined mechanisms.
We have previously reported that oxygen free radical scavengers protect rat islet cells from damage by cytokines and we interpreted these findings as suggesting the involvement of oxygen free radicals but did not directly measure indices of free radical activity. In this study, we report on malondialdehyde, an end product of lipid peroxidation, in rat islets incubated with cytokines. The individual cytokines, interleukin 1 (1 U/ml), tumour necrosis factor (10(2) U/ml), and interferon gamma (10(2) U/ml) inhibited insulin release but did not increase islet malondialdehyde levels. Combination of these cytokines however, produced significant increases in islet malondialdehyde and this was accompanied by islet necrosis. Furthermore, an inhibitor of lipid peroxidation, U78518E, significantly decreased the cytokine-induced increase in islet malondialdehyde and protected islet Beta cells from destruction by the cytokine combination of interleukin 1, tumour necrosis factor and interferon gamma. These findings suggest that the cytotoxic action of cytokines on islet Beta cells may result from free radical production and lipid peroxidation in the islet cells.
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From 1970 to 1989, 121 children with mediastinal masses of various sorts were seen in the Department of Pathology, Royal Children's Hospital, Melbourne. The series is considered representative of the true incidence of these conditions in the state of Victoria, which had an average paediatric population during the time of this series of 900,000 children. The commonest cause of a mediastinal mass was NHL (36 cases). This was followed by HD (24 cases), then neuroblastoma and ganglioneuroma (16 and 9 cases respectively), duplication cysts (10 cases), teratomas (7 cases), neurofibroma (4 cases) and lymphangioma (3 cases). A great variety of rare conditions made up the remainder of the series and included mediastinal abscess, thymic cyst, pericardial cyst, accessory lobe of lung, plasma cell granuloma, fibromatosis, paravertebral Ewing's tumour, carcinoid tumour and neurofibrosarcoma. Presentation of the children with NHL was often acute with respiratory distress, while the child with HD was usually older and symptoms were more often systemic than local. The surgeon's role in diagnosis of these most frequently encountered mediastinal masses can be crucial and biopsy when indicated must be carried out with great care to produce material that is adequate for diagnosis and for the performance of cell marker studies and chromosome analysis. Neuroblastoma (NBL) and ganglioneuroma (GN) together were the third largest group. Children with neuroblastoma were usually young; 15 of the 18 cases were less than 2 years old. One-third of the infants with neuroblastoma presented with paraplegia and one-third with respiratory symptoms including wheeze, stridor and respiratory difficulty. Three children had Horner's syndrome. Prognosis of children with thoracic neuroblastoma is very good and contrasts with the poor outlook for those with abdominal neuroblastoma. Stage at presentation is probably the most important single prognostic variable. Ganglioneuroma presents at a later age than neuroblastoma and symptoms may be present for a long time or may be completely absent. Catecholamines, usually raised in neuroblastoma, are mostly normal in ganglioneuroma. Duplication cysts were the next most frequent group. Symptoms can often be acute and life threatening, although in three of our ten cases the cyst was an incidental finding on chest X-ray. However, only three of our patients had a normal respiratory examination. Teratomas were usually large and more often benign than malignant. Excision is the mandatory treatment and is usually curative. Although teratomas in young infants are often cellular and composed of many immature tissue types, their behaviour is benign.(ABSTRACT TRUNCATED AT 400 WORDS)
The present study was undertaken to investigate the effect of U-74006F on malondialdehyde (a by-product of lipid peroxidation) in subarachnoid clot. Eighteen cynomolgus monkeys were divided into three groups of six each. There were two U-74006F-treated groups, receiving doses of 0.3 or 1.0 mg/kg, and a placebo-treated group. Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and placement of subarachnoid clot around the middle cerebral artery (MCA). Treatment was administered intravenously every 8 hours for 6 days. Seven days after the experimental subarachnoid hemorrhage (SAH), angiography was repeated and the animals were killed. In the placebo-treated group, significant vasospasm occurred in the MCA on the side of the clot (p less than 0.01). After U-74006F treatment at both dosages, significantly less vasospasm developed in the clot-side MCA (p less than 0.01). The content of malondialdehyde was measured by both the thiobarbituric acid test and high-performance liquid chromatography (HPLC). Comparing the two methods, HPLC proved to be more accurate than the thiobarbituric acid test, especially for measurement of low concentrations of malondialdehyde. In the placebo-treated group, the malondialdehyde content was significantly increased in the Day 7 clot (p less than 0.05). In contrast, malondialdehyde content in freshly prepared clot was very low. In the 0.3-mg/kg U-74006F group, the malondialdehyde content of clot was significantly less at Day 7 compared to clot from the placebo-treated group (p less than 0.05). Although the malondialdehyde content of clot from the 1.0 mg/kg U-74006F-treated group was less than that of placebo, it was not significantly so. Malondialdehyde was not detected in the actual vessel wall of the MCA of any group. These results suggest that lipid peroxidation in subarachnoid clot may play a role in the pathogenesis of vasospasm and that the salutary effects of U-74006F in vasospasm may be mediated by a reduction of lipid peroxidation in SAH.
The design of the study was to determine whether an increased blood flow as seen in shunt lesions could serve as a stimulus for the secretion of atrial natriuretic factor (ANF). Since atrial pressure, flow, and dilatation are closely related, an experimental ductus arteriosus model was utilized, in which acute changes of flow are assumed not to dilate the left atrium. In six dogs, a Dacron graft was constructed between the main pulmonary artery and the innominate artery. Constricting and releasing the tape around the graft adjusted the amount of "ductal" shunting. The total pulmonary flow and the shunt flow were measured by electromagnetic-flow transducers around the aortic root and around the graft. Plasma ANF concentration was measured from both cardiac atria. The size of the left atrium was determined from echocardiographic measurements made from a short-axis view. The total pulmonary flow varied between 1.2 and 5.8 1/min. The highest measured ANF was 396 pg/ml, and this was from the left atrium when the pressure was 18 mmHg, the highest left atrial pressure recorded. The highest right atrial pressure (5 mmHg) also correlated with the highest right-atrial level of ANF (366 pg/ml). The right atrial pressure had a significant correlation with plasma ANF concentration (R = 0.43, p less than 0.05). Pulmonary flow and plasma ANF concentration did not correlate; neither did left atrial size and ANF levels in 16 flow states where the size was measured. In the absence of atrial dilatation there was minimal stimulus for ANF secretion. A transient increase of left atrial pressure, without a concomitant significant atrial dilatation, did not serve as a significant stimulus for ANF secretion.
Gastric aspiration was performed continuously overnight and at hourly intervals during the daytime in 20 healthy male volunteers. Medications used included enisoprost 100, 200 or 400 micrograms, misoprostol 200 micrograms and placebo, given at bedtime. Each dose of enisoprost markedly inhibited nocturnal mean acid output, hydrogen ion activity, pH and peptic activity. The duration of these effects was up to 10 h. Misoprostol, given at bedtime, also decreased acid secretion, but the effect was significantly less than that observed with any of the doses of enisoprost. A dose-response effect for enisoprost was found for the mean nocturnal hydrogen ion activity and pH, as well as for maximum pH attained. Although enisoprost, given at bedtime, had a marked inhibitory effect on acid and pepsin secretion for the overnight interval, this did not result in rebound hyperacidity or a rise in serum total gastrin concentration. The results of this study suggest that enisoprost should be tested by clinical trial for the treatment of peptic ulcer disease.
Endocarditis is a recognized complication of both temporary and permanent indwelling right atrial catheters. Endocardial damage by the catheter may result in non-bacterial thrombotic endocarditis. Sterile vegetations composed of platelets and fibrin may become infected, either by direct spread of bacteria along the catheter, or following an episode of bacteraemia. Bacteria in infected vegetations may be protected from phagocytosis by a 'roof' of fibrin. Echocardiography is a valuable non-invasive method of diagnosis and may be used to monitor the resolution of vegetations and valve function. The right atrial catheter produces reflections which must be distinguished from cardiac abnormalities. We report a case of infective endocarditis in a patient with severe aplastic anaemia and a permanent indwelling right atrial catheter which was managed conservatively.
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Plasma levels of B beta 15-42 peptide and fibrinopeptide A (FPA) were measured as indicators of plasmin-mediated fibrin(ogen)olysis and thrombin activity of fibrinogen in 34 middle-aged men, at rest and following a standard exercise test. In the group as a whole no significant changes in B beta 15-42 or FPA were noted after exercise. When the group was subdivided into men with (n = 20) and without (controls n = 14) coronary heart disease, exercise-stimulated thrombin and plasmin generation was found only in the control group who exercised for a significantly longer duration. The rise in B beta 15-42 was related to both the intensity and duration of exercise. Similar increases in plasma fibrinolytic activity (fibrin plate) occurred in both groups and no other differences in the components of the fibrinolytic system (plasminogen, alpha 2-antiplasmin, fibrin degradation product) were noted either after exercise or between the groups. Exercise in normal middle-aged men is associated with modest thrombin and plasmin activation.
Obstruction of a Bjork-Shiley mitral valve prosthesis occurred in a 41 year old woman due to pannus tissue growing over the valve and impairing disc opening. The unusual intermittent nature of the obstruction was clearly demonstrated by Doppler ultrasound. The pannus was excised and the valve prosthesis replaced successfully with a Carpentier-Edwards xenograft.
A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.
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The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.
The exercise tolerance of the survivors of a consecutive group of 100 patients in a renal dialysis and transplant programme was compared with the prevalence of cardiac abnormalities detected by exercise testing, echocardiography, and radionuclide angiography. Fifty four patients attended for investigation 27 (SD 7) months after starting renal replacement therapy. Forty three of them (80%) were receiving antihypertensive treatment. Their performance on a bicycle ergometer exercise test was compared with that of 62 normal subjects and the patients divided into five groups of decreasing ability. The exercise tolerance of the patients was very poor, only 17 performing within the normal range. Impairment in exercise capacity was not explained by the type or quality of renal replacement therapy. Fourteen patients developed ischaemic electrocardiographic changes on exercise. Left ventricular ejection fraction was assessed by gated blood pool scanning in 37 patients; all nine of the patients with an abnormally low radionuclide ejection fraction also had abnormal exercise tolerance. Satisfactory M mode echocardiograms were obtained from 45 of the patients, and only two were normal. Left ventricular hypertrophy was detected in 25 (56%) of the echocardiograms, and abnormalities indicating impaired left ventricular function were common and widespread. Grouping all the abnormal cardiac features together for the patients in each exercise group showed a striking linear trend of increasing proportion of cardiac abnormalities with worsening exercise tolerance among the five exercise groups (p less than 0.001). The proportion of patients becoming unemployed within one year of starting renal replacement therapy similarly increased, from nil to 60% from the best exercise group to the most incapacitated. Twenty nine of the original cohort of 100 patients subsequently died, cardiovascular disease accounting for 12 (41%) of these deaths. Diminished exercise tolerance in patients receiving renal replacement therapy is strongly associated with cardiac abnormalities and reduced employment prospects.