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Biomedical subjects

F J Hayes

Publications and source records attributed to F J Hayes.

26 records · Page 2Linked to original sources

Effects of nifedipine treatment on the renin-angiotensin-aldosterone axis.

Nifedipine is a commonly used agent in treating hypertension and angina because of its vasodilator properties. An inhibitory role of nifedipine on aldosterone (Aldo) biosynthesis has been documented in in vitro studies. This study was designed to examine the impact of a sustained release nifedipine formulation on Aldo biosynthesis and its clinical consequences. Early and late effects of nifedipine on Aldo, PRA, and Aldo/PRA ratio levels were studied in a single blind, placebo-controlled, 10-day pilot study. Ten normotensive subjects and 10 patients with hypertension were studied. Blood samples for the measurement of Aldo and PRA were obtained at 2-h intervals for 10 h on a control day and on days 1 and 8 of nifedipine treatment for the determination of baseline, early, and late values. Placebo was administered at 0800 h on the first and second days of the study, whereas nifedipine (60 mg/day) was given for the following 8 days. The Aldo/ PRA ratio was used as a sensitive indirect index of the responsiveness of Aldo secretion to adrenal stimulation with angiotensin. Compared to those on the control day, a significant rise in the integrated PRA levels occurred on the first day of nifedipine treatment, with a further rise observed on the eighth day of the treatment in the normotensive subjects (1.1 +/- 0.6, 1.7 +/- 1.2, and 2.5 +/- 1.8 ng/mL.h on the control day and the first and eighth days of treatment, respectively; P < 0.05) and by the eighth day in the hypertensive subjects (2.2 +/- 2.8 and 4.0 +/- 4.1 ng/mL.h; P < 0.05). A significant rise in integrated Aldo levels occurred in the normotensive subjects on the eighth day of nifedipine treatment (control day, 319 +/- 187; eighth day of nifedipine, 363 +/- 167 pmol/L; P < 0.05) and in the hypertensive subjects (426 +/- 219 and 535 +/- 284 pmol/L; P < 0.05). This was associated with a significant lowering of the Aldo/PRA ratio on the first day of the treatment, with further lowering on the eighth day in the normotensive (435 +/- 454, 269 +/- 209, and 182 +/- 107; P < 0.05) and by the eighth day in the hypertensive subjects (716 +/- 833 and 305 +/- 315; P < 0.05). When individual time points were examined in the normotensive subjects, Aldo/PRA levels were significantly lower on day 8 of nifedipine treatment at 1000, 1200, and 1400 h than corresponding values on the control day. The fall in the Aldo/PRA ratio during nifedipine treatment indicates that the previously reported in vitro inhibition of Aldo biosynthesis in adrenal cells is reproduced in vivo. In the absence of nifedipine, it is likely that Aldo levels would be higher for any given level of PRA. It is probable that the Aldo inhibition and the vasodilatatory effect of nifedipine combine to bring about the lowering of blood pressure. Drugs that inhibit renin-angiotensin axis activity are likely to be particularly effective when additional lowering of blood pressure is required.

Aged↗

Aggressive thyroid cancer associated with toxic nodular goitre.

Reports of concurrent thyrotoxicosis and thyroid cancer have appeared in the last three decades. While most of the tumours have been clinically inconsequential, it has been suggested that thyroid carcinomas arising in patients with Graves' disease tend to behave aggressively, while those associated with toxic nodular goitre follow a more benign course. We report a contrary clinical experience with four cases of thyrotoxicosis associated with metastatic thyroid cancer, two of which were fatal. All four patients had toxic nodular goitre. Thyroid eye signs were uniformly absent. Two patients had received 131I therapy; none had other history of irradiation to the head or neck. Antimicrosomal and antithyroglobulin antibodies were absent in all four patients. Thyroid-simulating immunoglobulin, which was measured in one patient, was also absent. Histopathological examination of the resected thyroid glands revealed two papillary cancers. one mixed anaplastic/papillary and one anaplastic cancer. All four patients had cervical node involvement and one had pulmonary metastases. Both patients with anaplastic carcinoma succumbed to their disease within 6 months: neither of the patients with papillary cancer had disease recurrence after 2 and 4 years, respectively. The experience reported here of aggressive thyroid cancer associated with toxic nodular goitre may represent coincidence or, alternatively, it may represent the early recognition of a change in the natural history of toxic nodular goitre.

Adult↗

Rapid liquid chromatographic-mass spectrometric assay for oxymetazoline in whole rat blood.

A rapid HPLC-electrospray mass spectrometric assay for the quantitation of oxymetazoline in whole rat blood has been developed. Sample preparation was a single liquid-liquid extraction after addition of a deuterated internal standard (IS) and pH adjustment. An aliquot of reconstituted extract was injected onto a narrow-bore octadecyl reversed-phase column at a flow-rate of 400 microliters/min. Using a 20:1 post-column split, 5% of the eluent was introduced into the mass spectrometer interface. Elution of the analyte and IS occurred in less than 2 min. This rapid separation was made possible because of the sample cleanup and the selectivity of the mass spectrometric detection. The [M+H]+ ions for oxymetazoline (m/z 261) and [2H9]oxymetazoline (m/z 270) were detected using selected ion monitoring. The linear range of the assay was 0.67-167 ng/g of blood and the limit of quantitation with a 0.30-g sample was 1.0 ng/g. The assay permitted the analysis of nine samples per hour with the requisite sensitivity and selectivity and was used to determine the blood pharmacokinetics of oxymetazoline in rats dosed via intravenous and intranasal routes.

Animals↗

Simultaneous immunoassay using electrochemical detection of metal ion labels.

The concept of a simultaneous dual analyte immunoassay based on two different metal ion labels is demonstrated. The model system consists of two proteins, human serum albumin (HSA) and immunoglobulin G (IgG). Bismuth and indium ions have been coupled to these proteins through the bifunctional chelating agent diethylenetriamine-pentaacetic acid (DTPA). A maximum molar labeling ratio of 6:1 and 10:1 was obtained for HSA and IgG, respectively. Following a competitive equilibrium between unlabeled and labeled protein for a limited amount of specific antibody immobilized on polystyrene, the bound metal ion labels were released by acidification and detected by differential pulse anodic stripping voltammetry (ASV). Limits of detection for HSA and IgG are 1.8 and 0.6 microgram/mL, respectively. Application of the dual immunoassay to human serum samples gave results that were comparable to those obtained by nephelometry.

Antibodies↗

Diabetes mellitus in an adult cystic fibrosis population.

Medical records of 132 patients attending an adult cystic fibrosis (CF) clinic were analysed to define the prevalence and clinical significance of diabetes mellitus (DM) in CF. Eighty four (63.6%) had normal blood glucose levels, 30 (22.8%) had hyperglycaemia only during intercurrent illness and 18 (13.6%) had DM. No significant differences were noted between the diabetic and non-diabetic groups for age, gender, height, weight, body mass index (BMI), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) and pancreatic supplementation. Patients with hyperglycaemia during intercurrent illness had significantly lower BMI, FEV1% and FVC% than those with normal blood glucose levels. Of the diabetics four were managed on diet, three received oral hypoglycaemic agents and eleven were insulin requiring. The prevalence of DM in CF is considerable, severity of CF does not correlate with development of overt DM, and CF patients should be screened for DM by an oral glucose tolerance test on reaching adulthood.

Adult↗

Thoracic polyradiculopathy--abdominal wall swelling and sensory symptoms in diabetes mellitus.

We describe two patients with type 2 diabetes who presented with abdominal pain secondary to thoracic polyradiculopathy. In the first patient abdominal pain occurred in association with marked abdominal distension; extensive negative gastrointestinal investigations were performed before the correct diagnosis was made by electromyography showing thoracic paraspinal muscle denervation. In the second case, truncal sensory symptoms alone were evident at the time of diagnosis of diabetes mellitus. While muscle laxity was absent, extensive paraspinal muscle denervation was detected. Tolrestat, an aldose reductase inhibitor, was associated with good clinical response of symptoms due to peripheral neuropathy and thoracic polyradiculopathy. The pathogenesis of thoracic polyradiculopathy is uncertain but is likely to be the result of multiple infarcts along the course of thoracic spinal nerves accounting.

Abdominal Muscles↗

Diabetes mellitus in an adult cystic fibrosis population.

Medical records of 132 patients attending an adult cystic fibrosis (CF) clinic were analysed to define the prevalence and clinical significance of diabetes mellitus (DM) in CF. Eighty four (63.6%) had normal blood glucose levels, 30 (22.8%) had hyperglycaemia only during intercurrent illness and 18 (13.6%) had DM. No significant differences were noted between the diabetic and non-diabetic groups for age, gender, height, weight, body mass index (BMI), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) and pancreatic supplementation. Patients with hyperglycaemia during intercurrent illness had significantly lower BMI, FEV1% and FVC% than those with normal blood glucose levels. Of the diabetics four were managed on diet, three received oral hypoglycaemic agents and eleven were insulin requiring. The prevalence of DM in CF is considerable, severity of CF does not correlate with development of overt DM, and CF patients should be screened for DM by an oral glucose tolerance test on reaching adulthood.

Adult↗