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Biomedical subjects

G R Wright

Publications and source records attributed to G R Wright.

At least 19 recordsLinked to original sources

Sorption of fluoroacetate (compound 1080) by Colestipol, activated charcoal and anion-exchange in resins in vitro and gastrointestinal decontamination in rats.

The sorption of sodium fluoroacetate (FA) by activated charcoal (AC) and 5 anion exchange resins (AERs) was tested in 2 simulated gastrointestinal (GI) fluids. Each sorbent was incubated with FA in a shaker-water-bath at 37 C for 24 h. Supernatant was removed and filtered, and the concentration of FA was determined by gas chromatographic detection of the dichloroaniline derivative. Under simulated gastric conditions (0.1 M HCl at approximately pH 1.5), the sorbents removed the following proportions of FA from solution: Carbosorb AC, 87 +/- 2%; cholestyramine, 28 +/- 7%; colestipol, 96 +/- 0%; Amberlite IRA-96, 70 +/- 2%; DEAE-Sephadex, 7 +/- 4%; Chitosan, 66 +/- 2%. Under simulated intestinal conditions (0.05 M sodium phosphate at approximately pH 7.4), binding was as follows: Carbosorb AC, 68 +/- 4%; cholestyramine, 53 +/- 5%; colestipol, 46 +/- 2%; AmberliteIRA-96, 10 +/- 20%; DEAE-Sephadex, 64 +/- 7%; Chitosan, 5 +/- 2%. All findings differed significantly from control, with the exception of Amberlite IRA-96 and Chitosan in phosphate buffer, and DEAE-Sephadex in HCI. In a second study, rats were given 5 mg FA/kg, and then gavaged with 2 g/kg Carbosorb AC, colestipol or bentonite. Over 4 h, the area under the curve of serum FA versus time (AUC) decreased by 39% in the rats treated with colestipol and 42% in those treated with bentonite. In contrast, Carbosorb AC did not affect the AUC,yet increased Tmax In another study, mortality was assessed 96 h after rats were orally dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb AC, colestipol or water immediatey or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingiy, the 30-min delay resulted in lower mortality in colestipol-treated rats, (approximately 38%) compared to 100% in the group treated with Carbosorb AC. Before any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive care setting. The potential for synergistic effects with 2 or more sorbents also warrant investigating.

Adsorption↗

Hormone therapy in women in the menopause transition. Randomised, double-blind, placebo-controlled trial of effects on body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium.

OBJECTIVE: To determine whether hormone treatment of women during the menopause transition induces changes in body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium. DESIGN: Prospective, randomised, placebo-controlled, double-blind, 12-month study, with crossover at 6 months. SETTING: Outpatient clinic of a city hospital. PARTICIPANTS: 105 apparently healthy women in the menopause transition (40-52 years), with menstrual function, who were experiencing minor menopausal symptoms, were selected from the general population by advertising. INTERVENTIONS: Active arm--oral conjugated oestrogens (0.625 mg daily) and cyclic medroxyprogesterone acetate (10 mg daily) on Day 14-27 of each menstrual cycle; placebo arm--placebos of both medications. MAIN OUTCOME MEASURES: Excess change from baseline associated with active compared with placebo treatment for all variables; effect of order of treatment. RESULTS: Baseline biochemical values were similar for both treatment-order groups, but baseline blood pressures and body weights were higher in the group receiving placebo first. With treatment, there were no differences in overall values for body weight and blood pressure (P > 0.4), and order of treatment had no significant influence (P > 0.3). There were no differences in total and low density lipoprotein cholesterol levels, overall or with order of treatment. Active treatment increased high density lipoprotein (HDL) cholesterol levels (overall and when placebo was given first; P = 0.001), and triglyceride levels (when active treatment was given first; P = 0.03). There was no overall treatment effect, but a significant order-of-treatment effect, on antithrombin III activity (mean levels were decreased by active treatment to a greater extent when it was given first; P = 0.02). The endometrium showed only physiological changes regardless of treatment. CONCLUSIONS: The lack of significant excess change in anthropometry, lipoprotein levels, antithrombin III activity, and endometrial histology in women given hormone treatment compared with placebo is reassuring. The increase in HDL cholesterol level is an extra benefit. Our study provides conclusive evidence that hormone treatment does not produce weight gain in women during the menopause transition.

Adult↗

Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer.

Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity.

Carrier Proteins↗

Fluoroacetate content of some species of the toxic Australian plant genus, Gastrolobium, and its environmental persistence.

Gas chromatography confirmed the relatively high concentrations of fluoroacetate found in toxic Gastrolobiums, a genus of indigenous Australian plants. Fluoroacetate concentration in these plants ranged from 0.1 to 3875 micrograms/g (ppm) dry weight, with young leaves and flowers containing the highest concentrations. However, there was considerable intrastand variation between individual plants of at least two species with coefficients of variation ranging from 94% to 129%. Despite the high concentrations of fluoroacetate in many species, only one of nine soil samples collected from beneath these plants contained fluoroacetate. None of the 16 water samples collected from nearby streams and catchment dams contained fluoroacetate. This suggests that fluoroacetate does not persist in this environment. Fluoroacetate was also found in the genus Nemcia, and very low levels of fluoroacetate (ng/g) were detected in the foodstuffs, tea and guar gum. The latter indicates that other plant species may produce biologically insignificant amounts of fluoroacetate.

Australia↗

Orthodontics as a risk factor for temporomandibular disorders (TMD). II.

Debate about orthodontic treatment as a risk factor for temporomandibular disorders (TMD) led to this study. This report, the second in a series, concerns findings from a longitudinal study in which 30 new orthodontic patients have been enrolled annually since 1983. The method of Helkimo was used to collect TMD data before initiation of orthodontic treatment, and at annual intervals after debanding. Treatment was by fixed edgewise appliances. Data from a pretreatment and at least one posttreatment Helkimo examination were available for 109 patients. Follow-up data were available for 92 patients in the first year after debanding, with the corresponding sample sizes declining to 56, 33, 19, 11, and 7 for the second through the sixth posttreatment years, respectively. Primary analyses involved comparison of mean scores from the Helkimo 25-point dysfunction index scale. There were no significant differences between mean pretreatment and posttreatment Helkimo scores for any of the various groupings except for small, clinically unimportant improvements seen in the 12 to 24 month subgroup of 55 patients and in the 48 to 60 month subgroup of 11 patients. With average follow-up time of about 2 years for the 109 patients, 90% had Helkimo scores that stayed the same or improved, and 10% had scores that increased or worsened from 2 to 5 Helkimo points. We conclude that the orthodontic treatment experienced by our sample was not an important etiologic factor for TMD.

Adult↗

A comparison of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene expression in head and neck squamous cell carcinomas.

The proto-oncogenes c-erbB-2 and epidermal growth factor (EGF) receptor which encode 2 closely homologous transmembrane glycoproteins have been found amplified and/or overexpressed in a range of epithelial malignancies. In a series of 46 head and neck squamous cell cancers (SCCs), immunohistochemical reactivity for the EGF receptor was detected in all cases, particularly at the invading edge of cellular islands of SCC and in the basal cells of normal adjacent squamous epithelium. Southern blot analysis demonstrated EGF receptor gene amplification in 3 cases. In contrast, strong membrane staining for the c-erbB-2 oncoprotein was not detected in any sample, and there were no cases of c-erbB-2 gene amplification. Despite a close structural and (presumed) functional homology between these 2 receptor-oncoproteins in the development of malignancy, we report that their expression in SCCs is markedly different. Furthermore, unlike the situation for breast cancer, quantitation of the c-erbB-2 or EGF receptor oncoproteins is unlikely to yield important prognostic information in this group of patients.

Adult↗

Transferrin receptor expression in primary superficial human bladder tumours identifies patients who develop recurrences.

A group of 65 patients with superficial bladder carcinoma was followed for 2 years and tumour recurrence rate was correlated both with transferrin receptor status of the initial primary tumour and with the results of voided urine cytology. Nine of 24 patients with transferrin receptor negative tumours had recurrences compared with 30 of 41 patients with transferrin receptor positive tumours. This difference was highly significant. Urine cytology at presentation was also predictive of further tumour formation: of 30 patients who were transferrin receptor positive and had positive urine cytology, 25 developed recurrences.

Adult↗

Respiratory gas exchange during positive pressure breathing and rapid decompression to simulated altitudes of 18.3 and 24.4 km.

Respiratory gas exchange was studied, using the technique of mass spectrometry, during events of slow and rapid decompression of human subjects to simulated altitudes of 60,000 and 80,000 ft (18.3 and 24.4 km, respectively). Positive breathing pressures and G-suit counterpressures were employed in three series of decompression experiment. Low levels of inspired carbon dioxide and nitrogen reflected the rebreathing of gases throughout the experiments. Application of a positive breathing pressure of 70 torr, accompanied by a jerkin pressure equal to breathing pressure and a G-suit counterpressure of four times the breathing pressure on the trunk and limbs, respectively, maintained alveolar oxygen at physiologically safe levels during decompression to 60,000 ft (18.3 km) altitude. Similarly, 80 torr positive breathing pressure, in combination with four times the breathing pressure in the G suit, adequately satisfied the requirements for oxygen during rapid decompression to 80,000 ft (24.4 km) simulated altitude.

Aerospace Medicine↗

Narcotic effects of nitrous oxide and compressed air on memory and auditory perception.

Three experiments were conducted to examine the effects of 35% N2 O (nitrous oxide) on human memory and auditory perception. In Experiment I, dichotic listening performance was found to be impaired. Experiment II used the same technique but was controlled for attenuation of sound transmission in the middle ear. No impairment was found. The perceptual effect found in Experiment I was peripheral, not central, and N2O did not impair short-term memory (STM). Experiment III used one-trial free recall of a word list. The shapes of the serial position curves were interpreted as indicating that N2O impairs long-term memory (LTM) but not STM. Experiment III provided no evidence, using cued recall, that the LTM deficit was due to impaired retrieval. Comparing these results with those for compressed air led to the conclusion that both N2O and hyperbaric nitrogen display an identical pattern of effects. A reason for the decrement found in some N2O STM studies may have been confounding the measurement of STM with that of LTM.

Atmospheric Pressure↗

Carbon monoxide, nicotine and the 'safer' cigarette.

15 healthy adults (5 women, 10 men) have been exposed to each of four experimental conditions: rebreathing of air or carbon monoxide, and the smoking of two low-nicotine (0.3 mg) or medium-nicotine (1.2 mg) cigarettes. The dose of carbon monoxide selected (80 ml) had no effect on resting heart rate or electrocardiogram, nor did it modify the exercise heart rate, ventilation, oxygen consumption or electrocardiogram. Both types of cigarette produced variable changes in the blood carboxyhaemoglobin level, increments being greatest in heavy smokers, and least in former smokers, pipe and cigar smokers, Gains of carboxyhaemoglobin were less with low-nicotine than with medium-nicotine cigarettes. Both types of cigarette produced some increase of resting heart rate, but the smoking of two cigarettes was insufficient to modify the exercise heart rate, ventilation, or oxygen consumption. The electrocardiogram also showed no signs of ischaemia during either rest or effort. It is suggested that, for the light and moderate smoke, the 'safest' cigarette may be one with a low tar and a very low nicotine yield. On the present data, this would also induce only small increments of blood carboxyhaemoglobin levels.

Adult↗