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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 631 records · Page 35Linked to original sources

Cellular growth and metabolic adaptations to nutrient stress environments in tumor microregions.

Heterogeneity of cell subpopulation growth was significantly modulated by different oxygen and glucose environments and necrosis in multicellular tumor spheroids of rodent and human origin. PO2 profiles within spheroids measured with microelectrodes showed major differences associated with different oxygen and glucose supply conditions, indicating important interactions of these two substrates affecting oxygen consumption rates and cellular viability. Cellular interactions in association with the development of growth quiescence and differentiation changed oxygen consumption rates and slopes of PO2 profiles within spheroids. Protein synthesis in monolayer cells in culture was severely inhibited when exposed to extreme hypoxia, but certain proteins were synthesized at increased rates. Many of these oxygenated regulated proteins can also be induced by glucose deprivation. The data demonstrate cellular and subcellular changes in tumor models in vitro because of variations in oxygen and glucose supply. Many of these changes would be expected to occur in tumor microregions in vivo and could have important consequences for therapeutic responsiveness.

Animals↗

A measurement of w for 150 MeV protons in nitrogen and argon.

Ionisation chamber dosimetry for proton radiation therapy requires accurate measurements of w, the average energy necessary to produce an ion pair for protons in the therapeutic energy range of 30-240 MeV. In this investigation, such measurements were made at the Harvard Cyclotron Laboratory for 150 MeV protons in nitrogen and argon with an accuracy of 2%. Ionisation and energy loss were measured simultaneously in a gas cell 1 m in length. A parallel plate ionisation chamber situated inside the gas cell was used to measure ionisation, and the energy loss was determined from time-of-flight and range measurements. The data indicate that w is 26.5 +/- 0.6 eV/(ion pair) for argon and 36.3 +/- 0.8 eV/(ion pair) for nitrogen. These results are consistent with measurements at lower energies.

Argon↗

The ability of the serum thyrotrophin receptor antibody (TRAb) index and HLA status to predict long-term remission of thyrotoxicosis following medical therapy for Graves' disease.

In agreement with previous authors we found patients with Graves' disease to have an increased incidence of the DR 3 antigen. We could find no association, however, between the presence of the antigen and relapse after carbimazole treatment. A concordant HLA status and thyrotrophin receptor antibody (TRAb) index, obtained at either 6 or 12 months after the start of treatment could only predict cases of relapse and remission in a minority of patients making this of very limited clinical use. The TRAb index obtained at 12 months after the start of medical therapy could accurately predict cases of relapse and remission for the next 3 years in 24/30 patients studied.

Adult↗

Beat frequency of cilia from sites of purulent infection.

Mucociliary clearance depends on the interaction between cilia and mucus; it is delayed in the presence of purulent secretions. Nasal mucociliary clearance was examined by the saccharin method and nasal ciliary beat frequency by a photometric technique. Four groups were studied: normal controls, patients with bronchiectasis without nasal symptoms, patients with chronic mucopurulent sinusitis alone, and patients with chronic mucopurulent sinusitis and bronchiectasis. Nasal mucociliary clearance was prolonged in infected patients. Cilia obtained from the site of purulent secretions were found to beat more slowly in vitro (mucopurulent sinusitis 12.1 Hz, mucopurulent sinusitis and bronchiectasis 11.6 Hz), than those obtained from normal controls (14.3 Hz) and from patients with bronchiectasis alone (13.6 Hz). The cause of the ciliary slowing seemed most likely to be the release of host factors during the inflammatory response, rather than the particular organism isolated. Ciliary slowing may contribute to the observed delay of mucociliary clearance in conditions in which purulent secretions are present.

Adolescent↗

Effect of cigarette smoking on nasal mucociliary clearance and ciliary beat frequency.

Despite the in vitro ciliotoxicity of tobacco smoke and the abnormal mucociliary clearance found in smoking related chronic bronchitis, studies of mucociliary clearance in healthy smokers have produced variable results. The nasal mucociliary clearance of saccharin and the in vitro nasal ciliary beat frequency were studied in healthy smokers and non-smokers. One of 29 smokers had a nasal mucociliary clearance time of over 60 minutes; in the remaining 28 the mean (SD) clearance time was 20.8 (9.3) minutes, which was significantly longer (p less than 0.001) than the mean time of 11.1 (3.8) minutes in 27 lifelong non-smokers. There was no significant difference between the mean nasal ciliary beat frequency of 10 smokers and 10 non-smokers. There were no significant differences in mean ciliary beat frequency or mean nasal mucociliary clearance time after 10 healthy non-smoking volunteers had smoked two cigarettes each, exhaling the smoke through their nostrils. Unless there is a prompt reversal of any ciliotoxic effect of tobacco smoke when cilia are removed for in vitro examination, the defective clearance seen in chronic cigarette smokers seems unlikely to be due to slowed ciliary beat frequency. It may be due to reduction in number of cilia or to change in the viscoelastic properties of mucus. The failure to detect any acute effect of tobacco smoke is in keeping with this hypothesis.

Adult↗

Hypothalamic localization of multiunit electrical activity associated with pulsatile LH release in the rhesus monkey.

Abrupt increases in electrical activity can be recorded from the medial basal hypothalamus of the rhesus monkey and these bursts are correlated with a pulse of LH release from the anterior pituitary. In this study we have localized the tips of the electrodes from which such electrical activity can be recorded and have attempted to correlate the placement with the presence of immunoreactive LHRH neurons and axons. Electrodes associated with bursting activity were found as far rostral as the suprachiasmatic nucleus and as far caudal as the premammillary nuclei. The majority were found in the medial basal hypothalamus including the region of the arcuate nucleus, the retrochiasmatic zone and the dorsal aspect of the median eminence. The tips of the electrodes were associated with either LHRH neurons or axon bundles. Negative electrodes (those not associated with bursting electrical activity) which did not exit through the ventral surface of the brain nor enter the ventricle were found in the same regions of the hypothalamus as positive electrodes. Although it is tempting to associate the bursting electrical activity with the LHRH neurosecretory system, such a correlation cannot yet be made.

Animals↗

Regional myocardial and organ blood flow after myocardial infarction: application of the microsphere principle in man.

A physiologic means of measuring the distribution of cardiac output and regional myocardial blood flow has been developed that uses human albumin microspheres labeled with carbon-11 (11C) and external detection with positron emission tomography. Ten patients with previous myocardial infarction were studied to investigate the level of blood flow in normal and infarcted segments of the heart. After diagnostic catheterization, 4 to 6 mCi of 11C on 2 to 3 million sterile microspheres (15 to 20 micron) were mixed and injected into the apex of the left ventricle during timed withdrawal of arterial blood to obtain reference flow values. Regional activity in brain, heart, lungs, liver, spleen, and kidneys was measured tomographically. Blood flow was calculated based on the relationship between total activity in a reference flow and tissue activity in tomograms of each organ (ml/min/100 g). No adverse effects were noted after injection of the microspheres. Successive myocardial tomograms showed no loss of activity. There were no significant differences in flow values in matched regions of paired organs. Mean cerebral flow was 52.4 +/- 10.0 ml/min/100 g in the frontal lobes, 54.4 +/- 8.8 in the temporal lobes, 67.6 +/- 8.2 in the occipital lobes, and 53.0 +/- 9.4 in the basal ganglia. Flow was 16.0 +/- 8.4 ml/min/100 g (range 0 to 40.0) in the center of infarcted myocardium and 82.0 +/- 32.0 in the remote segments. This method meets most of the demands for use of microspheres to measure tissue blood flow. The wide range of flow values in infarcted myocardium may be a function of infarct size, spatial resolution, or pathologic evidence of islands of viable tissue. Patients with angina had high flow values in the infarcted segment, whereas those with heart failure had significantly lower values. Surviving myocardium in the region of the infarct may need to be considered if patients complain of angina, particularly when treatment is aimed at preserving ventricular function.

Adult↗

The development of thyrotoxicosis (Graves' disease) during immunosuppression for autoimmune haemolytic anaemia.

A patient is described who developed thyrotoxicosis (Graves' disease) during immunosuppressive therapy for acquired autoimmune haemolytic anaemia. The fact that the two conditions may be associated should be recognised. Long-term immunosuppressive therapy does not prevent the development of immunoglobulins of IgG type postulated to be aetiologically involved in Graves' disease.

Adult↗

Endocrine effects of low dose aminoglutethimide with hydrocortisone--an optimal hormone suppressive regimen.

The endocrine effects of aminoglutethimide 125 mg twice daily and hydrocortisone 20 mg twice daily were assessed in 45 postmenopausal women with advanced breast cancer. Oestrone and oestradiol levels were suppressed by 60% within 2 weeks and suppression was maintained for more than 6 months of chronic treatment. In contrast to conventional dose AG with hydrocortisone, or low dose AG without hydrocortisone, delta 4 androstenedione was suppressed by 65%. This effect may contribute to optimal oestrogen suppression.

Aminoglutethimide↗

Low dose aminoglutethimide (125 mg twice daily) with hydrocortisone for the treatment of advanced postmenopausal breast cancer.

Aminoglutethimide 125 mg twice daily and hydrocortisone 20 mg twice daily was used to treat 76 postmenopausal women with advanced breast cancer. There were 4 CR, 17 PR (objective response rate 28%). Highest response was in soft tissue. CNS toxicity was less than with conventional dose AG (drowsiness 7% v. 31%), although the incidence of rash was equivalent. Previous responders to tamoxifen had a higher response (33%) than previous non-responders (9%). The lower toxicity and maintained efficacy suggest that this should be the standard dosage regimen.

Aged↗

Assessment of a time-resolved fluoroimmunoassay for thyrotropin in routine clinical practice.

We assessed the use of a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) system to measure thyrotropin (thyroid-stimulating hormone, TSH) in routine clinical practice. The assay is simple and precise, with intrabatch CV of less than 10% down to 0.1 milli-int. unit/L. When compared with free thyroxin, total thyroxin, and triiodothyronine measurements in 142 patients, the present assay most sensitively indicated hyperthyroidism and, in conjunction with free thyroxin, most sensitively indicated hypothyroidism. Free thyroxin was the most specific assay (lowest number of falsely increased or decreased results) in detecting thyroid disorders, with a specificity of 93.6% as compared with 85.1% for TSH, 81.9% for thyroxin, and 77.6% for triiodothyronine.

Evaluation Studies as Topic↗