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Biomedical subjects

R J Winter

Publications and source records attributed to R J Winter.

At least 55 records · Page 3Linked to original sources
PubMed1989

To what extent should a hospital ethics committee be involved in hospital policy formation?

The extent to which a HEC becomes involved with policy formation depends in large measure on the credibility the committee has within the institution. Although on the basis of training, insight, or experience the HEC is in an ideal position to formulate policy, premature involvement in this area can jeopardize the effectiveness of the HEC in other areas which are equally if not more important. To the extent that the HEC does engage in policy formation it must do so with considerable political as well as ethical acumen.

Ethics↗
PubMed1989

Atrial natriuretic peptide levels in plasma and in cardiac tissues after chronic hypoxia in rats.

1. Atrial natriuretic peptide (ANP) levels were measured in cardiac tissues and in plasma from adult rats exposed to chronic alveolar hypoxia for periods of 2 h, 24 h and 7 days. Levels were also measured in rats that were maintained in hypoxia for 7 days and then returned to air for 24 h. 2. Plasma ANP was not altered at 2 h but was significantly increased at both 24 h and at 7 days. Plasma ANP in animals exposed to hypoxia for 7 days was normal 24 h after returning to air breathing, despite the persistence of indices of pulmonary hypertension. 3. No significant right atrial hypertrophy was observed under these conditions of chronic hypoxia. A reduction in right atrial ANP content was found at 24 h and was accompanied by a decrease in the number of electrondense granules per right atrial muscle cell. After exposure to hypoxia for 7 days, right atrial ANP and granule number was not different from control, and no alteration was found in right atrial ANP level after removal from the hypoxic environment. 4. No significant right ventricular hypertrophy was produced by exposure to hypoxia for 2 or 24 h. In the former group ventricular ANP had decreased significantly compared with control. Right ventricular hypertrophy was found in both the hypoxic groups after exposure for 7 days, when selective increases in right ventricular ANP content were found. 5. These findings are consistent with the hypothesis that ANP release occurs on exposure to chronic hypoxia and is independent of the associated cardiac hypertrophy and pulmonary vascular remodelling. The findings may have relevance to the natriuresis and reported changes in the renin-angiotensin-aldosterone axis under hypoxic conditions.

Animals↗
PubMed1989

Atrial natriuretic peptide concentrations in hypoxic secondary pulmonary hypertension: relation to haemodynamic and blood gas variables and response to supplemental oxygen.

Plasma atrial natriuretic peptide concentrations, measured in samples drawn from the pulmonary artery, were raised in nine of 17 patients with hypoxic pulmonary hypertension but normal right atrial pressures at rest. No relationship was seen between atrial natriuretic peptide concentrations and mean pulmonary artery or right atrial pressure, or calculated pulmonary or systemic vascular resistance. Patients with the most severe hypoxaemia tended to have higher plasma atrial natriuretic peptide concentrations; three patients with no past history of oedema had concentrations more than twice the upper limit of normal. Treatment with supplementary oxygen for 30 minutes reduced pulmonary vascular resistance in all patients but had no significant effect on plasma atrial natriuretic peptide concentration. These findings suggest that atrial natriuretic peptide may be a factor in the control of sodium and water balance in hypoxic cor pulmonale, where the determinants of individual susceptibility to peripheral oedema are not well understood.

Aged↗
PubMed1988

De novo cardiac beta adrenoceptor synthesis in adult rats under normoxic and hypoxic conditions.

Bromoacetylalprenololmenthane (BAAM), an alkylating irreversible beta adrenoceptor antagonist, was used to study in vivo beta adrenoceptor synthesis in adult rat left ventricle under normoxic and hypoxic conditions. In normoxic conditions cardiac beta adrenoceptor density decreased by 50% 15 h after treatment and recovered to control values after about 250 h. A similar decrease in receptor density and pattern of recovery was found in environmental hypoxia. Neither hypoxia nor treatment with BAAM had a significant effect on the dissociation constant of the radioligand. These results show that cardiac beta adrenoceptor synthesis occurs rather slowly and suggest that alteration of the rate of receptor synthesis in hypoxic states is not a major determinant of reported changes in density.

Adrenergic beta-Antagonists↗
PubMed1987

Circulating molecular variants of growth hormone in childhood.

Human growth hormone (hGH) is known to consist of several molecular forms. We examined the molecular nature of circulating hGH in 18 normal children and compared the resulting patterns to those previously obtained in adults. hGH secretion was stimulated with L-dopa, the hormonal forms were extracted from plasma by immunoadsorbent chromatography, and their molecular nature was analyzed by polyacrylamide gel electrophoresis. Circulating monomeric hGH consisted of 73% hGH22K, 16% hGH20K, and 10% of an acidic hGH from (N alpha-acylated or deamidated hGH). These relative proportions are indistinguishable from those found in the plasma of adults. No age or sex differences in the circulating hGH pattern were found. We conclude that the types and proportions of hGH forms in the blood of normal children are the same as those previously established in adults. These data provide a framework against which children with postulated structurally abnormal ("bioinactive") hGH can be compared.

Adolescent↗
PubMed1987

Absence of the plasma growth hormone-binding protein in Laron-type dwarfism.

We recently described a specific, high affinity binding protein (BP) for growth hormone (GH) in normal human plasma. Little is known about the source, regulation and biological role of this BP. Because its specificity is similar to that of the GH receptor, we considered the possibility that it represented a circulating receptor subunit or fragment. Laron-type dwarfism is a rare disorder characterized by severe growth failure, resistance to GH, and GH receptor deficiency. To probe the relationship between the receptor and the circulating binding protein, we measured the binding of GH to plasma from a child with Laron-type dwarfism and compared it with that in plasma of normal children and adults. Normal plasma samples were supplemented with unlabeled GH to the endogenous GH level in the plasma of the Laron patient to yield comparable saturation of the BP. After incubation of plasma with radiolabeled GH, bound GH was separated from free GH by gel filtration on Sephadex G-100. There was no detectable binding (less than 1.5%) of GH in the plasma of the Laron-type dwarf, whereas in normal children the bound GH fraction averaged 24.0 +/- 6.1% (mean +/- SD). Thus, the GH-BP is either absent or functionally abnormal in Laron-type dwarfism. This finding suggests that the circulating GH-BP is related to and/or may be derived from the GH receptor. Alternatively, it is possible that the BP plays an as yet poorly understood pivotal role in the promotion of somatic growth.

Carrier Proteins↗
PubMed1986

Tissue specific modulation of beta-adrenoceptor number in rats with chronic hypoxia with an attenuated response to down-regulation by salbutamol.

The number of beta-adrenoceptors and their affinity for the radioligand 125I-labelled cyanopindolol (125I-CYP) were measured in crude membrane preparations of left ventricle, spleen and lung from Wistar rats exposed to 28 days continuous hypoxia. beta-Adrenoceptor density in the left ventricle was not significantly altered after exposure to chronic hypoxia (binding site maxima, Bmax.: normoxic control 36 SEM 5, hypoxic 24.8 SEM 2 fmol/mg of protein). There was no change in beta-adrenoceptor number in the spleen in response to chronic hypoxia (Bmax.: normoxic control 76 SEM 19 fmol/mg of protein, hypoxic 80 SEM 15 fmol/mg of protein). Chronic hypoxia resulted in a significant increase in beta-adrenoceptor number in lung tissue (binding site maxima, Bmax.: normoxic control 406 (SEM 31) fmol/mg of protein; hypoxic 535 (SEM 30) fmol/mg of protein, P less than 0.01 without change in the dissociation constant (KD) of the radioligand. beta-Adrenoceptor subtypes in lung homogenates were studied by establishing displacement curves for 125I-CYP by ICI 118551 (a selective beta 2-antagonist). A significant difference was seen in the proportion of beta 1-/beta 2-adrenoceptor subtypes after hypoxia (normoxic control 66 SEM 2.5%, hypoxic 79 SEM 2.4% beta 2-adrenoceptors, P less than 0.01). alpha 1-Adrenoceptor number in lung membranes was measured with 125I-labelled 2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone (125I-HEAT). No difference was seen in the number of alpha 1-receptors in normoxia and in chronic hypoxia [Bmax.: normoxic control 48 (SEM 3), hypoxic 48 (SEM 5) fmol/mg of protein].(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1985

Clearance of 99m-technetium-labelled DTPA in asbestos-exposed subjects without clinical or radiological evidence of interstitial lung disease.

The half-time clearance of an inhaled aerosol of 99m-technetium-labelled diethylene triamine pentacetate from lung to blood (T1/2LB) was measured using a gamma camera in 20 non-smoking subjects (mean age 54, range 40-69 years) with previous occupational asbestos exposure, but no clinical or radiological evidence of asbestosis, and 20 non-smoking normal subjects (mean age 54, range 40-62). Mean T1/2LB was 44.7 minutes (range 12-102) in exposed subjects, significantly less than 57.2 minutes (range 30.5-109) in normal subjects (P less than 0.05). There was no correlation between age and T1/2LB in either group. In exposed subjects T1/2LB showed a weak rank correlation with the membrane component of DLco (Dm) (r = 0.40, P less than 0.05) but no significant correlation with FVC, TLC, DLco, Kco, resting Pao2 or change in Pao2 on exercise. In six exposed subjects T1/2LB was shorter than in any of the normal subjects. These six did not differ from the other 14 exposed subjects in any physiological variables. T1/2LB is abnormal in some asbestos-exposed subjects without clinical, radiological or physiological evidence of asbestosis. Follow-up will show whether it is an early indicator of development of interstitial lung disease.

Adult↗
PubMed1985

Ventilatory saving by external chest wall compression or oral high-frequency oscillation in normal subjects and those with chronic airflow obstruction.

Oscillation of the air within the lungs at high frequency is associated with an increased clearance of CO2. Because of the high frequency and low volume of these oscillations, spontaneous breathing is unhindered and the technique has potential value as a supplement to ventilation. High-frequency oscillations were superimposed upon tidal breathing by using a loudspeaker attached to a mouthpiece (oral high-frequency oscillation, OHFO) or by external chest wall compression (ECWC). We set out (a) to compare the changes in ventilation and breathlessness by using OHFO and ECWC in normal subjects with those in patients with chronic airflow obstruction (CAO), and (b) to relate the pattern of saving to the resonant frequencies of the respiratory system as a whole (for, 5-10 Hz in normal subjects, 16-26 Hz in CAO) and those of the ribcage (foc, 70 Hz). OHFO reduced minute ventilation (VE) by up to 46% in normal subjects (P less than 0.01) and 29% in CAO (P less than 0.01) without any rise in CO2. ECWC reduced VE by 27% in normal subjects (P less than 0.01) and 16% in CAO (P less than 0.01) without a rise in CO2. High-frequency oscillation by either method relieved breathlessness in those with CAO and was comfortable and well tolerated. In normal subjects for was discrete and varied little with respiration. Maximum savings occurred around for (5-10 Hz). In CAO, there was no obvious single resonant frequency and flow and pressure signals were intermittently in phase over a band of about 10 Hz. Thus the reductions in minute ventilation were only loosely related to for (13-26 Hz). Neither group reduced VE at foc (65-75 Hz). OHFO has considerable potential in the management of patients with CAO, where it may be of value as an assistance to breathing and in the relief of breathlessness. ECWC, although effective in principle, is impractical by our methods and awaits the development of an acceptable delivery system.

Adult↗
PubMed1985

Immune complex-mediated cutaneous vasculitis in a scar--the importance of local anatomical factors.

A vasculitic rash developed on the legs and arms of a 47 year old woman. Similar vasculitic lesions also erupted in a scar sustained ten years previously. Circulating immune complexes consisting of IgG were detected by Clq binding. We discuss the factors involved in the localization of vasculitic lesions, and in particular stress the role of microvascular injury.

Antigen-Antibody Complex↗
PubMed1985

Effect of oral high frequency ventilation by jet or oscillator on minute ventilation in normal subjects.

Normal subjects were asked to breathe through an open ended tube while high frequency oscillations were superimposed on tidal breathing via a side arm, either an eight inch (20 cm) loudspeaker or a jet ventilator being used. Both systems were comfortable and well tolerated. Spontaneous minute ventilation fell by 19-46% at frequencies up to 33 Hz without a rise in transcutaneous PCO2. Maximum ventilatory savings occurred at 1.6 Hz with the jet ventilator (p less than 0.01) and at a frequency corresponding to respiratory system resonance with the loudspeaker. This suggests that during oral high frequency ventilation pulmonary gas exchange is improved and leads to more efficient carbon dioxide excretion for a given minute ventilation. This technique provides a practical and simple method of supplementing breathing in conscious subjects, and it may also have application in the management of patients with acute or chronic respiratory failure, where intubation and conventional ventilation might be avoided.

Adult↗
PubMed1985

Asbestosis: assessment by bronchoalveolar lavage and measurement of pulmonary epithelial permeability.

Thirty two patients with asbestosis were assessed by means of bronchoalveolar lavage (27 patients) and the half time clearance from lungs to blood (T1/2LB) of an inhaled aerosol of diethylenetriamine pentacetate (DTPA) labelled with technetium 99m (32 patients). T1/2LB was also measured in 20 non-smoking normal individuals and 17 smokers without a history of exposure to asbestos. Thirteen patients (46%) showed an increase in the percentage of neutrophils with or without an increase in the percentage of eosinophils and eight (29%) showed an increased percentage of lymphocytes. The number of neutrophils plus eosinophils expressed as a percentage of the total count was positively correlated with the length of the history of disease (r = 0.53, p less than 0.025) and greater percentages were associated with more severe impairment of lung function. Smokers had lower percentages of lymphocytes than non-smokers (p less than 0.002) and showed increased proportions of neutrophils and eosinophils more often than non-smokers (p less than 0.05). In 18 non-smokers with asbestosis the mean T1/2LB was 33.8 (range 10.0-62.0) minutes, significantly less than 57.2 (30.5-109) minutes in 20 non-smoking normal subjects (p less than 0.002). In non-smokers shorter T1/2LB correlated with a longer time since first exposure to asbestos (r = -0.65, p less than 0.005), longer duration of exposure (r = -0.70, p less than 0.001), and a shorter time since last exposure (r = 0.59, p less than 0.01). Shorter T1/2LB was also associated with increased inflammatory activity as shown by higher bronchoalveolar lavage cell counts (r = -0.53, p less than 0.025) and higher combined percentages of neutrophils, eosinophils, and lymphocytes (r = -0.47, p less than 0.05). The techniques of bronchoalveolar lavage and measurement of inhaled solute clearance may be useful in assessing inflammatory activity in asbestosis.

Adult↗
PubMed1985

Use of the flexible film isolator as a single circuit hypoxic chamber for small animals.

PVC isolators are now widely used for housing animals and provide a readily available pretested air-tight chamber (Pendry, 1984; Trexler, 1984). We have adapted a flexible film isolator for use as a hypoxic chamber for small animals. The environment within the chamber can be easily and continuously monitored with indwelling probes, obviating the need for a separate circuit for gas analysis. This design has been used for long-term studies of chronic hypoxia.

Animals↗
PubMed1985

Virilizing adrenocortical tumors in childhood: eight cases and a review of the literature.

Eight cases of adrenocortical tumor are presented with a review of the literature. Although such tumors are rare, they are important causes of inappropriate virilization and Cushing's syndrome in childhood. Clinical virilization with or without hypercortisolism was found in all eight children, who were 5 years old or younger. Excessive linear growth was noted, despite evidence of hypercortisolism. Serum levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and cortisol were elevated in all cases tested and appear to be useful diagnostic alternatives to the more traditional determinations of urine 17-ketosteroids and 17-hydroxycorticosteroids. Abdominal sonography and computed tomography have proven to be reliable tools for tumor localization. Surgical resection was the definitive therapy in all patients, and perioperative steroid replacement was essential. Histologic diagnosis appeared to have little bearing on prognosis, and the majority of pediatric patients have had clinically benign disease. At a mean follow-up of 3 years, seven of the eight children were alive and had no evidence of tumor recurrence.

17-Hydroxycorticosteroids↗