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Biomedical subjects

J R Hayes

Publications and source records attributed to J R Hayes.

At least 91 records · Page 5Linked to original sources

The effect of plasma glucose control by continuous subcutaneous insulin infusion or conventional therapy on retinal morphology and urinary albumin excretion.

The effect of plasma glucose control on retinal morphology, urinary albumin excretion and related haematological and lipid measurements was studied prospectively for 30 weeks in 17 patients with insulin-dependent diabetes mellitus. All had background diabetic retinopathy (BDR) and absence of albustix positive proteinuria: 9 were allocated to a continuous subcutaneous insulin infusion (CSII) group and 8 to a conventional therapy (CT) group. There was a sustained reduction (p less than 0.01) in haemoglobin A1 (HbA1) in the CSII group, but not in the CT group. Mean HbA1 over the 30 week study period was lower (p less than 0.05) in the CSII (8.9 +/- 0.3%) than the CT group (10.2 +/- 0.5%). Retinal morphology assessed by fluorescein angiography improved after 30 weeks in one patient in the CSII group, but in most patients it remained the same or deteriorated. The patient with the best plasma glucose control developed a small area of neovascularisation. Less deterioration in retinopathy was not related to better plasma glucose control. Urinary albumin excretion, plasma viscosity, plasma fibrinogen, red cell deformability and plasma lipids did not change in either the CSII or CT group. In the 7 patients selected from both groups who achieved the best control there was a reduction in urinary albumin and LDL cholesterol.

Adolescent↗

Nutrient interaction with drugs and other xenobiotics.

Drugs and other xenobiotics (foreign compounds) are consumed with food, presenting the potential for interactions that may modify the biological activity of both nutrients and xenobiotics. The complexities associated with the biological fate of both classes of compounds yield a multitude of potential interactions, making the prediction of specific interactions a complicated task. However, the similarities between the biological processes involved in the biological fate of both xenobiotics and nutrients allow a logical approach to the understanding and prediction of interactions. For example, for either a xenobiotic or nutrient to produce a systemic effect, it must be absorbed. There are similarities between the factors that influence the availability and absorption of both xenobiotics and nutrients. It is at these points of similarity that interactions are most likely to occur. This is also true for the other major processes involved with the biological fate of both xenobiotics and nutrients, such as distribution, metabolism, and excretion. An understanding of these processes and the most likely points of interaction is the first step in understanding and acquiring predictive ability of the potential interactions between nutrients and drugs, as well as other xenobiotics.

Absorption↗

Naphthalene toxicity in CD-1 mice: general toxicology and immunotoxicology.

Random bred CD-1 mice were used to evaluate the acute oral toxicity and subchronic toxicity of naphthalene administered in corn oil. The acute oral LD50 of naphthalene was 533 and 710 mg/kg in male and female mice, respectively. Subchronic toxicity was evaluated with 14- and 90-day daily oral gavage studies. Doses utilized in the 14-day study were 27, 53, and 267 mg/kg, with the latter representing one-half of the male LD50. Both males and females demonstrated a 5-10% mortality and depressed body weight at the high dose only. Males had decreased thymus weights, and females had decreased spleen and increased lung weights at the high dose only. Other organ weights were unaffected at any dosage level. Serum enzyme and electrolyte levels were not altered in a dose-related manner. To assess the potential immunotoxicity of naphthalene the following screen was utilized: humoral immune response, response to mitogens, delayed hypersensitivity response, popliteal lymph node response, bone marrow stem cell number, and DNA synthesis. No evidence of immunotoxicity was demonstrated. The 90-day study employed daily oral doses of 5.3, 53, and 133 mg/kg. There was no treatment-related mortality in either sex, nor was body weight affected. Organ weights were not affected in males, and females showed reduced spleen weights only at the high dose. Serum enzyme and electrolyte levels, as well as the immunotoxicity screen, indicated that naphthalene doses up to one-fourth the LD50 for 90 days failed to elicit consistent statistically significant and biologically relevant compound-related effects. A screen of the effects of the 90-day naphthalene treatment on various aspects of the hepatic drug metabolizing system indicated no alterations, with the exception of a specific dose-related inhibition of aryl hydrocarbon hydroxylase activity in both male and female mice.

Animals↗

Glomerular filtration rate in children: determination from the Tc-99m-DTPA renogram.

Analysis of the Tc-99m-DTPA renogram is usually limited to calculating the relative function of each kidney. To develop a method to determine the absolute glomerular filtration rate (GFR), various methods of analyzing the renogram were examined to determine which gave the best correlation with GFR. That regression could then be used to predict GFR without the need for blood samples. Fifty children were studied using Tc-99m-DTPA renograms and GFR measured simultaneously by plasma disappearance. The renogram variables were adjusted for detector sensitivity and for dose divided by weight, which was used as an index of plasma concentration. GFR correlated better with the slope of the second phase than with the area under the renogram curve. For the best correlation with GFR (using background subtraction and depth correction) r = .971 and the mean residual = 4.8 ml/min. For GFR normalized for body surface area (using background subtraction and no depth correction) r = .954 and the mean residual = 9.1 ml/min/1.73 m2. This method can accurately estimate GFR from the renogram in children.

Adolescent↗

Neonatal phenobarbital administration results in increased cytochrome P450-dependent monooxygenase activity in adult male and female rats.

The effects of neonatal exposure to phenobarbital during the first five days after birth on the enzymatic activity of the adult male and female rat liver P450-dependent monooxygenase system were investigated. Although liver weight per 100 grams of body weight and total hepatic microsomal protein content were not altered in adult rats treated neonatally with phenobarbital, both sexes did show significant increases in cytochrome P450 content, cytochrome P450 reductase activity, cytochrome c reductase activity, ethoxycoumarin-O-deethylase activity and in the activity of a specific glucuronyl-transferase. Several of these activities were increased to a larger extent in the females, suggesting that females may be more sensitive to this phenomenon.

Age Factors↗

Antiestrogen basicity--activity relationships: a comparison of the estrogen receptor binding and antiuterotrophic potencies of several analogues of (Z)-1,2-diphenyl-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-butene (tamoxifen, Nolvadex) having altered basicity.

A series of N-substituted (Z)-1,2-diphenyl-1-[4-(2-aminoethoxy)phenyl]-1-butenes, analogues of the antiestrogen tamoxifen (Nolvadex), in which the side-chain basicity is varied over a wide range, has been prepared to probe the importance of basicity in evoking estrogen antagonism. All of the compounds, except the pyrrole analogue 14, were found to possess significant antiestrogenic activity in the rat, as measured by their ability to inhibit estrogen-induced uterine growth. This implies that in the tamoxifen series the level of side-chain basicity, at least in the Lowry-Brønsted sense, is not a determining factor in the estrogen antagonist potencies of these compounds.

Animals↗

Treatment of common gynecologic-endocrinologic symptoms by allergy management procedures.

The technique of managing allergies by optimum-dose (provocative neutralization) testing and treatment using aqueous progesterone has been studied in 132 women having progesterone-related symptoms due to the menstrual cycle, pregnancy, or exogenous hormone administration. When extremely small doses of progesterone (0.0016 mg or below, up to maximum of 2.5 mg) were administered following determination of specific dose requirement by skin testing, startlingly rapid and effective clearing of symptoms was observed. With these individualized doses, symptoms cleared completely or almost completely within 30 minutes in the majority of patients. A single-blind technique was employed to rule out placebo effect. Some common problems found to respond well to the procedure were nausea and vomiting during pregnancy (100%), premenstrual syndrome (96%), and dysmenorrhea (84%).

Dysmenorrhea↗

Tamoxifen aziridines: effective inactivators of the estrogen receptor.

Two analogs of the antiestrogen tamoxifen, which bear a chemically reactive aziridine function in place of the dimethylamino group, bind to the estrogen receptor from rat uterus and from MCF-7 human breast cancer cells and appear to react irreversibly with the receptor at the estrogen binding site, in a time-and concentration-dependent fashion. BEcause these compounds are effective receptor inactivators in uterus and breast cancer cells, they should prove to be useful probes for investigating the role of receptor in regulating cellular responses to estrogen and in studying the dynamics of estrogen receptor synthesis and turnover.

Animals↗

Factitial bleeding: successful management with psychotherapy.

A young female nurse presented with unusual upper and lower-gastrointestinal bleeding, shown to be factitial. Following detection, she was successfully confronted and treated with psychotherapy. A plan for successful management of the Munchausen syndrome is discussed.

Adult↗