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Biomedical subjects

F R Smith

Publications and source records attributed to F R Smith.

At least 55 records · Page 3Linked to original sources

Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers.

Sevoflurane was submitted to phase-1 studies in man following extensive testing in animal species during maintenance, was administered with oxygen to produce one hour of anesthesia in six healthy adult male volunteers. Respiratory and cardiovascular functions, the electroencephalogram, arterial blood gases, blood sevoflurane, inorganic fluoride and total, nonvolatile fluorine concentrations, and inspired and mixed expired sevoflurane concentrations were measured during exposure. Concentrations of expired sevoflurane, blood and urinary fluoride, and total nonvolatile fluorine metabolites were also measured after anesthesia. During exposure spontaneous respiratory frequency increased 28 per cent, respiratory minute volume changed insignificantly, and PaCO2s averaged 50 torr. PaCO2s remained near 400 torr. Arterial systolic blood pressure declined an average of 17 per cent. Pulse rate changed insignificantly. After an hour of exposure arterial blood serum inorganic fluoride concentrations averaged 22 microM and plasma nonvolatile organic fluorine concentrations averaged 9.1 mg/l, or 61.3 microM. Uptake of sevoflurane averaged 94 (+/- 63 SD) mmol. Following exposure 37 (/+- 12) mmol of unaltered sevoflurane were estimated to be excreted in exhaled air and 0.90 mmol of inorganic fluoride were excreted in the urine. Recoveries in exhaled air and urine averaged 51.5 (+/- 22.4) per cent of uptake. There was no significant drug-exposure-related change in the chest radiogram, electrocardiogram, electroencephalogram, urinalysis results, complete blood count, prothrombin time, serum electrolytes, transaminases, or hepatic and renal functions during four weeks following exposure compared wth preexposure values. Sevoflurane produced anesthesia of excellent quality; it appears to undergo limited biotransformation and to have little or no systemic toxicity.

Adult↗

Sodium valproate and bone marrow suppression.

Bone marrow suppression developed in a patient while she was on a regimen of sodium valproate. In addition, she had high titers of platelet autoantibodies and a coagulopathy, both recognized complications of valproate therapy. It is postulated that this drug was also responsible for the marrow suppression.

Adult↗

Pasteurella multocida meningitis.

Pasteurella multocida appears to be a very rare cause of meningitis. The bacterium has morphological similarities with other causative organisms, particularly Haemophilus influenzae, and its apparent rarity may be due partly to misidentification. This case, only the fourth reported from the United Kingdom, could not be distinuished clinically from the meningitis, owing to other pyogenic bacteria.

Adult↗

Choriocarcinoma of the stomach.

A 23-year old woman with primary choriocarcinoma of the stomach presented with abdominal pain and massive hepatomegaly. Serum levels of CEA and serum and urine levels of beta-HCG were markedly elevated. Immunoperoxidase staining for CEA and HCG reveal both to be present in morphologically typical carcinoma cells. This suggests that serum beta-HCG may be a useful tumor marker of gastric carcinoma.

Adult↗

Prediction of the parameters of whole body cholesterol metabolism in humans.

Total body turnover of cholesterol was studied in 54 subjects by fitting a three-pool mathematical model to plasma decay curves of 32--49 weeks duration following [14C]cholesterol injection. Fifteen subjects were normal, 10 hypercholesterolemic, 21 hypertriglyceridemic, and 8 had both hypercholesterolemia and hypertriglyceridemia; 21 had a familial form of hyperlipidemia. In every subject in this heterogeneous population, the three-pool model gave the best fit for the data. An extensive search was conducted for relationships between model parameters and physiological variables (body size, serum lipid levels, age, and sex). Both linear and nonlinear relationships, and those involving interactions between pairs of variables, were explored. Fifty different forms of the model parameters and 53 forms of the physiological variables were examined. To guard against declaring statistical significance when none was present, subjects were first randomly divided into two matched groups. In the first (hypothesis-generating) group of 36 subjects, more than 100,000 regression equations were considered for each form of the model parameters. Twenty-one highly significant equations were found that were then tested in the second group (hypothesis-testing, 18 subjects). Eighteen of the 21 equations were found to be significant; of these, 6 were selected that accounted for a large part of the observed variation in the four model parameters for which equations were found (production rate (PR), and the sizes of pool 1, pool 3, and total exchangeable body cholesterol). The major determinant of cholesterol PR was body weight alone (r = 0.80). No function of serum lipid levels significantly influenced PR. Both body weight and serum cholesterol level entered into the equations for cholesterol mass. Age influenced the size of pool 3. Serum triglyceride level only had an effect on the size of pool 1. Since these equations were generated in one group of subjects and tested in another, they can be considered a confirmed set of predictive equations.

Adult↗

Localization of a vasoactive intestinal peptide-producing tumor with selective venous sampling.

A case of vasoactive intestinal peptide-producing adenoma of the tail of the pancreas (VIP) successfully managed by surgical resection is presented. Peripheral venous VIP levels correlated with the severity of the diarrhea. Intraoperatively, the VIP levels in the splenic and portal veins were 485 and 100 pg./ml., respectively. These data suggest that preoperative selective transhepatic venous catheterization for VIP sampling might be used to establish the site of VIP production and, thereby, direct surgical management. This technic requires further evaluation regarding its role in this clinical setting.

Adenoma↗

Normal levels of fibrinopeptide A in patients with primary hyperlipidemia.

Fibrinopeptide A (FPA) levels were measured in a group of 130 controls and patients with various types of primary hyperlipidemia to investigate whether an increased steady state level of thrombin activity is present in hyperlipidemic patients. In a subset of 56 subjects, levels of clotting factors II, VII, and X were measured as well. FPA levels in hyperlipidemic patients were not significantly different from those of control subjects. Furthermore, on multiple regression analysis, no significant relationships were found between FPA levels and the concentrations of serum cholesterol or triglyceride, or log triglyceride levels. Statistically significant relationships were found between all three clotting factor levels and triglyceride concentration. The correlation coefficients for these relationships, however, were low, so that the correlations are of questionable pathophysiological significance. A weak relationship also was found between the plasma levels of cholesterol and of factor II. Thus, although small increases in various clotting factors may be found in patients with hyperlipidemia, plasma FPA levels are normal. These data indicate that hyperlipidemia is not associated with a steady state of increased thrombin activity in vivo in humans.

Cholesterol↗

Meckel's diverticulum. Vagaries of technetium scanning.

A case of a Meckel's diverticulum is described in a young man presenting with abdominal pain and gastrointestinal bleeding. Methods of arriving at the diagnosis preoperatively are reviewed. A false-negative as well as a true-positive small bowel series and technetium scan were obtained in this case. The factors influencing technetium uptake by a Meckel's diverticulum are reviewed.

Abdomen↗

Hyperlipidemia and premature arteriosclerosis.

In the last decade, understanding of the relationship between plasma lipoprotein concentrations and arteriosclerosis has advanced considerably. Prospective and case-control epidemiologic studies in the general population have established a direct correlation between low density lipoprotein and an inverse correlation between high density lipoprotein concentrations and the risk of coronary disease. Detailed studies of patients and families with genetic hypercholesterolemia, hypertriglyceridemia, and combined hypercholesterolemia hypertriglyceridemia have identified subpopulations at particular risk. Skin fibroblast lines from patients with genetic hyperlipidemias have been used to provide important new information on the regulation by plasma lipoproteins of cellular cholesterol metabolism. We are entering a phase of investigation where epidemiological and biochemical data supplement each other in such a way that the old hypothesis linking plasma lipids to atherosclerosis has new life.

Age Factors↗

Vitamin-A reversal of abnormal dark adaptation in cirrhosis. Study of effects on the plasma retinol transport system.

Of 26 patients hospitalized with mild to moderate alcohol-associated cirrhosis, 14 had dark-adaptation abnormalities consistent with marginal vitamin-A status. The response of dark adaptation and the plasma retinol transport proteins, retinol-binding protein and prealbumin, was studied in 12 of these patients after daily oral vitamin-A supplements of 3300 microgram. Vitamin-A supplementation was associated with significant (p less than 0.05-0.005) improvement in dark adaptation and increased plasma concentrations of retinyl esters, retinol, and retinol-binding protein. Thus in patients with cirrhosis and marginal vitamin-A status, supplemental vitamin-A therapy appears to stimulate retinol-binding protein release from the liver. This enhancement of plasma retinol transport and delivery of retinol to peripheral tissues such as the retina is one of several factors that may serve to optimize vitamin-A nutritional status in patients with cirrhosis.

Dark Adaptation↗