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Biomedical subjects

P Bennett

Publications and source records attributed to P Bennett.

At least 181 records · Page 10Linked to original sources

Comparison of methods for determination of testosterone and non-protein bound testosterone in men with alcoholic liver disease.

The serum concentrations of testosterone and of non-protein bound testosterone were determined in 28 men with alcoholic liver disease having normal to decreased serum albumin concentrations and normal to raised SHBG concentrations. Serum testosterone concentrations determined with two radioimmunoassays using different purification procedures and antibody batches did not differ significantly and correlated significantly (r=0.91; p less than 0.001). The median serum concentration of non-protein bound testosterone was 0.265 nmol/l (range 0.068-0.495 nmol/l) when determined by equilibrium dialysis and 0.232 nmol/l (range 0.042-0.610 nmol/l) when calculated according to the law of mass action. This difference is insignificant. The concentrations of non-protein bound testosterone determined by the two methods correlated significantly (r=0.83; p less than 0.001). In the calculation of non-protein bound testosterone, the actual serum albumin concentration can be replaced by a fixed albumin concentration (r=0.99; p less than 0.001). Further, in these patients the serum concentration of non-protein bound testosterone can be expressed by the testosterone/SHBG ratio (r=0.97; p less than 0.001).

Dialysis↗

The structure of C-protein and X-protein molecules and a polymer of X-protein.

C-protein and X-protein are components of the thick filaments in vertebrate skeletal muscles and occupy similar locations in different fibre types. We find that the molecules are both rods about 30 to 40 A wide, but they differ significantly in their lengths, the X-protein molecule being about 350 A long and the C-protein molecule about 280 A. This suggests they are not isoforms. The short length of the C-protein molecule implies that it cannot act in the thick filament as a length-determining agent by a simple vernier mechanism. X-protein associates at low ionic strength (KCl concentration less than 0.07 M) but, unlike C-protein, forms long ordered polymers. These have been examined by electron microscopy to gain information on the molecular shape and on how the molecules interact. The polymers are helically twisted ribbons with a repeat distance along the axis of 660 A. The cross-section of the ribbon is approximately elliptical with major and minor axes of 405 A and 166 A, respectively. From an analysis of the micrographs by optical diffraction, we deduce that the molecules run across the face of the ribbon at an angle of about 15 degrees to the diameter and lie on a two-stranded helix. Models for the polymer are discussed in which the molecules are slightly bowed outwards and bind to each other only at their ends. We suggest that interactions similar to those in the polymer might occur in the thick filaments of muscle, and propose that at each axial position where X-protein attaches along the myosin filament, three X-protein molecules might form an approximately triangular ring around the filament backbone. The appearance of the X-protein polymers is similar to that of the twisted structures called paired helical filaments that make up the neurofibrillary tangles associated with dementia of the Alzheimer type.

Animals↗

Diabetes in Wallis Polynesians: a comparison of residents of Wallis Island and first generation migrants to Noumea, New Caledonia.

A comparative study of diabetes, impaired glucose tolerance and obesity was undertaken in samples of rural Wallisians of Wallis Island and first generation Wallisian migrants in the urban centre of Noumea, New Caledonia. Approximately 20-25% of the adult population of the 2 communities was included in the study. Wallisians in Noumea tended to be more obese than those in Wallis (particularly females). The prevalence of diabetes was 7 and 4 times higher in Noumea compared to Wallis for males and females respectively. Differences in the extent of obesity appeared to account for some of the difference in prevalence of diabetes, but other environmental factors (such as constituents of the diet, and exercise) must be operative as well. The results of this study are consistent with previous findings concerning environmental determinants of diabetes in Pacific populations.

Adult↗

Serum sex hormone concentrations in insulin dependent diabetic women with and without amenorrhoea.

Abnormal steroid secretion may contribute to anovulation in insulin dependent diabetic patients with amenorrhoea. We have measured serum sex hormone-binding globulin (SHBG) and free and bound oestrogen and androgen levels in 17 such patients. As controls we included 17 patients with insulin dependent diabetes mellitus and normal menstrual cycles, 21 regularly menstruating normal women (both sampled during early follicular phase), and 23 non-diabetic patients with amenorrhoea. The diabetic patients with normal cycles had significantly higher serum concentrations of delta 4-androstenedione and testosterone than the normal women (P less than 0.01). The amenorrhoeic diabetics in contrast had significantly lower serum concentrations of SHBG, 5 alpha-dihydrotestosterone and free and total oestradiol-17 beta than either group of menstruating women (P less than 0.05), and significantly lower concentrations of delta 4-androstenedione (P less than 0.01), dehydroepiandrosterone sulphate (P less than 0.01), testosterone (P less than 0.01), and oestrone (P less than 0.05), than the cycling diabetics. The two amenorrhoeic groups had similar free and bound sex hormone concentrations except that delta 4-androstenedione levels were significantly lower in the diabetics (P less than 0.01). We conclude that the low sex hormone levels in diabetic women with amenorrhea may be due to suppression of the hypothalamic-pituitary axis in view of the impaired LH secretion found in these patients and that excess androgen secretion seems not to be of aetiological importance in amenorrhea related to diabetes mellitus. The decreased steroid levels in amenorrheic diabetics is due to their suppressed ovarian function while the increased androgen levels in diabetics with regular cycles are probably of ovarian origin.

Adolescent↗

Abnormal androgen and oestrogen metabolism in men with steroid sulphatase deficiency and recessive X-linked ichthyosis.

Serum levels of sex hormone binding globulin (SHBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulphate, oestradiol, oestrone, oestrone sulphate, FSH, and LH were measured in 20 steroid sulphatase-deficient men with recessive X-linked ichthyosis and in normal men. The serum oestrone sulphate level was significantly higher than normal in the patients (P less than 0.0001). In affected men, there was a tendency towards higher dehydroepiandrosterone sulphate levels and no decline with age was seen in the patients as opposed to normal men (interaction: P less than 0.025). Serum androstenedione, and oestradiol levels were lower than normal in the patients (P less than 0.0005 and P = 0.055, respectively), while their LH level was higher than normal (P less than 0.0005). The serum levels of SHBG, total and free testosterone, dihydrotestosterone, oestrone, and FSH were not significantly different from normal in the icthyotic patients. We suggest that the observed abnormalities in these patients are a consequence of the enzyme deficiency which severely impairs the ability of tissues to hydrolyse steroid sulphates.

Adult↗

A comparison of psychological and medical treatment of the irritable bowel syndrome.

Twenty-four subjects completed a study comparing the efficacy of a psychological treatment package suggested by Latimer (1983) and the best medical regime available in the treatment of the Irritable Bowel Syndrome (IBS). Initial anxiety levels were high in both groups and were reduced in the psychological, but not medical, condition. IBS symptoms and associated behaviours were reduced equally in both conditions.

Adult↗

Monoclonal antibodies against the human epidermal growth factor receptor from A431 cells. Isolation, characterization, and use in the purification of active epidermal growth factor receptor.

A431 cells have been used as an immunogen for generating monoclonal antibodies against the epidermal growth factor (EGF) receptor. Two immunoglobulin M and eight immunoglobulin G3 anti-EGF receptor antibodies were cloned. All ten antibodies immunoprecipitated biosynthetically labeled mature A431 cell EGF receptor and were able to recognize the receptor in Western blotting. However, none of the antibodies immunoprecipitated precursor polypeptides of the A431 cell EGF receptor, neither did they recognize EGF receptors from human foreskin fibroblasts, human placenta, nor a human-mouse hybrid cell expressing EGF receptor. The antibodies were found to bind to glycolipids from A431 cells and it was shown that the determinant involved was the blood group A antigen. It appears that this determinant is present on both the EGF receptor and glycolipids of A431 cells but is not expressed on EGF receptors from other human cells tested. One of the monoclonal antibodies raised was used for immunoaffinity purification of the EGF receptor. The procedure took advantage of the carbohydrate nature of the antigenic determinant by employing sugar-specific elution. The mild conditions permitted the purification of A431 cell EGF receptor (70-80% pure) that possessed an intrinsic EGF-stimulated tyrosine kinase activity with a specific activity of about 20 nmol/min/mg.

ABO Blood-Group System↗

Glucose tolerance and ancestral genetic admixture in six semitraditional Pacific populations.

Population-based data on 1,842 subjects from six semitraditional Pacific communities, collected in the years 1978-1983, have been compared in order to examine the hypotheses that differences in the distribution of plasma glucose concentration between populations are to some extent genetically determined, and that non-Austronesian (NAN) Melanesians are relatively resistant to glucose intolerance. Semitraditional communities were chosen for study so that the comparison would be minimally confounded by either known or as yet undetermined environmental factors associated with nontraditional living, the effects of which may vary between populations. The samples were also selected so as to provide a gradient of proportional NAN and AN admixture. They were drawn from the following regions: the highlands of Papua New Guinea, New Caledonia, Fiji, the Wallis Islands, Western Samoa, and Kiribati (formerly the Gilbert Islands). The Papua New Guinea highlanders, of entirely NAN ancestry, were regarded as the baseline population. A gradient of increasing mean 2-hr plasma glucose concentration was observed across the six populations and differences persisted between populations, after controlling for age and obesity. Variations in diet, physical activity, and degree of sociocultural modernization were not considered a sufficient or consistent explanation of these findings and they therefore lend tentative support to the hypothesis of a genetic component to variability in glucose tolerance. The relationship between population estimates of glucose tolerance and estimates of the genetic distance from the baseline NAN Melanesian sample was examined. With the notable exception of Fiji, there was evidence of a linear correlation between the two parameters.

Female↗

The Pima infant feeding study: breastfeeding and respiratory infections during the first year of life.

Initial episodes of upper respiratory infection, otitis media, and pneumonia identified from medical records in the first year of life were analysed in relation to feeding practices (ascertained by maternal interview in 1978) among 571 infants born 1960-1977 on the Gila River Reservation. The odds ratio of developing a first episode of upper respiratory infection or otitis media during the first year was less than unity for infants exclusively breastfed for four months compared to exclusively bottlefed infants after logistic regression adjustment for seasonality, birthweight, and adverse social conditions (OR = 0.64). This benefit was evident during the first four months of life (OR = 0.61) and during the second four months (OR = 0.48). However, a significant benefit of early exclusive breastfeeding was no longer demonstrable during months 9-12. Exclusive breastfeeding for four months marginally reduced risk of pneumonia after adjustment for covariates. The data suggest that breastfeeding of infants in early life is associated with reduced risk of respiratory infection.

Arizona↗

The Pima Infant Feeding Study: breast feeding and gastroenteritis in the first year of life.

In 1978, a retrospective study of infant feeding was conducted among 257 Pima Indian women of reproductive age, who were residing on the Gila River Reservation, Arizona. With data on infant feeding patterns from 683 infants born 1950-1977 to the Pima Indian women, infants were classified into one of five feeding groups based on the duration breast-fed and time of introduction and duration bottle-fed. History of severe diarrhea/diarrhea with dehydration/diarrhea and vomiting was abstracted from the infant's medical record and classified as a case of gastroenteritis. The risk of developing a first such episode during the first year of life was compared between the exclusively bottle-fed and each of the other four feeding groups. The odds ratio of gastroenteritis during the first year was significantly less than unity for infants exclusively breast-fed for four months before adjustment (odds ratio = 0.49) and after adjustment for adverse social conditions and seasonality (odds ratio = 0.51). Similarly, univariate analysis and multiple logistic regression analysis of gastroenteritis from birth through four months revealed estimates of the odds ratio that were significantly less than unity for infants exclusively breast-fed for four months (odds ratio = 0.33 and 0.30, respectively). Although a trend of decreasing gastroenteritis with increasing breast feeding was noted across all other feeding groups, the rates of first episodes of gastroenteritis did not significantly differ among all other feeding groups and the bottle-fed. Thus, exclusive breast feeding for four months is associated with reduced risk of early first episodes of gastroenteritis among infants in a less developed community in the United States.

Adolescent↗

Advance prediction of transthoracic impedance in human defibrillation and cardioversion: importance of impedance in determining the success of low-energy shocks.

The purposes of this study were to evaluate a method that predicts transthoracic impedance in advance of defibrillating shocks in humans and to assess the importance of transthoracic impedance in low-energy defibrillation. Via defibrillator electrodes we applied 31 kHz current to the chest during the defibrillator charge cycle, before the defibrillating shock was actually delivered. The current flow was limited by transthoracic impedance; a microprocessor monitored the predischarge current flow and determined the predischarge impedance by calibration against known resistance values. Actual impedance to the defibrillating shock was also determined and compared with the predicted impedance. With this approach we predicted impedance in 19 patients who received 66 shocks for ventricular and atrial arrhythmias. Predicted impedance (y) correlated very well with actual impedance (x):y = .90x + 11.3; r = .97. To determine the importance of impedance in defibrillation and cardioversion, we prospectively gathered data from 96 patients who received shocks of various energies for ventricular or atrial arrhythmias. In patients with high transthoracic impedance (greater than 97 omega), low-energy shocks (less than or equal to 100 J) for ventricular defibrillation had only a 20% success rate as opposed to a 70% success rate for low-energy shocks in patients with low or average impedance (p less than .05). We conclude that transthoracic impedance can be accurately predicted in advance of defibrillation and cardioversion. This method permits the preshock identification of patients with high impedance in whom attempts to defibrillate with low-energy shocks are inappropriate.

Arrhythmias, Cardiac↗

Development of an organic affective syndrome during a hyperbaric diving experiment.

The authors describe the clinical and pharmacologic management of a patient who developed an organic affective syndrome during a simulated deep-diving experiment. The physiological complexities of deep-diving research are reviewed, as well as the neuropsychiatric symptoms of the high pressure nervous syndrome.

Atmosphere Exposure Chambers↗

The acute and long term effect of the H2-receptor antagonists cimetidine and ranitidine on the pituitary-gonadal axis in men.

We have investigated the effect on the human pituitary-gonadal axis of the H2-receptor antagonists cimetidine 300 mg and ranitidine 50, 100, and 200 mg by i.v. bolus, or treatment for 6 months with either cimetidine (1000 mg/day for 1.5 months followed by 400 mg/day for 4.5 months) or ranitidine (200-400 mg/day for 1.5 months followed by 100-200 mg/day for 4.5 months). Administration of the H2-antagonists (i.v.) to normal men did not cause any release of LH, FSH, or testosterone. Long-term treatment with cimetidine of duodenal ulcer patients caused a significant rise in basal LH (6 weeks) and FSH secretion (11 weeks). Following reduction of the cimetidine dose LH and later FSH returned to pre-treatment values. However, despite reduction of the cimetidine dose, the LH and FSH responses to LHRH stimulation were still significantly higher after 6 months of treatment compared with pre-treatment responses. No changes were found in basal or in LHRH stimulated testosterone or dihydrotestosterone secretion. Treatment with the more potent H2-antagonist ranitidine did not cause any change in basal or in LHRH stimulated LH and FSH secretion. The effects on LH and FSH secretion observed during cimetidine treatment might therefore be caused by other mechanisms than blockade of H2-receptors. It is possible that cimetidine, having anti-androgen properties, blocks pituitary or hypothalamic androgen receptors.

Adult↗

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis.

The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely with galactose elimination capacity (r = 0.54; P less than 0.001), serum albumin (r = -0.53; P less than 0.001), plasma factor II + VII + X (r = 0.62; P less than 0.001), indocyanine green clearance (r = -0.71; P less than 0.001), and hepatic blood flow (r = -0.61; P less than 0.01) and correlated directly with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.

Administration, Oral↗