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Biomedical subjects

R J Winter

Publications and source records attributed to R J Winter.

At least 19 recordsLinked to original sources
PubMed1992

Positive end expiratory pressure via a portable system in thoracic dystrophy.

The provision of positive end expiratory pressure, via a unique portable system, in the long term management of a child with thoracic dystrophy is reported. The system uses low gas flow enabling a reduction in equipment and simplification of the circuit as compared with a standard continuous positive airways pressure system.

Abnormalities, Multiple↗
PubMed1992

Chronic hypoxia impairs soluble guanylyl cyclase-mediated pulmonary arterial relaxation in the rat.

We have examined the effects of exposing rats to hypoxia (10% fractional inspired O2 concentration) for 2 and 7 days on endothelium-dependent and -independent vasodilation and also on the ability of guanosine 3',5'-cyclic monophosphate (cGMP) to activate cGMP-dependent protein kinase (G-kinase) in rat conduit pulmonary arteries (PA). The ability of acetylcholine (ACh) and sodium nitroprusside (SNP) to both relax PA rings and elevate tissue cGMP levels was significantly attenuated in PA from hypoxic animals. The ability of atrial natriuretic peptide to relax and generate cGMP in PA rings was unchanged by hypoxia. Relaxation and elevation of cGMP levels induced by SNP in aortic rings was unaltered by hypoxia. Similarly, hypoxia did not alter the concentration-dependent activation by exogenous cGMP of G-kinase. We conclude that chronic exposure of rats to hypoxia results in a selective impairment of soluble guanylyl cyclase in rat PA, leading to an attenuation of ACh- and SNP-induced cGMP accumulation and relaxation.

Animals↗
PubMed1992

Effects of natriuretic peptides and neutral endopeptidase 24.11 inhibition in isolated perfused rat lung.

We have studied the acute effect of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) on pulmonary vascular tone in normoxia and acute hypoxia in the absence and presence of a specific inhibitor of neutral endopeptidase 24.11 (NEI, UK 73, 967, candoxatrilat; Pfizer) in the isolated and blood-perfused rat lung preparation. Baseline pulmonary artery pressure (Ppa) was 16.4 +/- 0.3 mm Hg in lungs from normoxic control rats and 22.5 +/- 0.3 mm Hg in lungs from rats kept in hypoxia (FIO2 = 10%) for 7 days. Acute hypoxic pulmonary vasoconstriction (HPV delta Ppa) was similar in normoxic control rats (9.5 +/- 0.6 mm Hg) and chronically hypoxic rats (9.8 +/- 0.9 mm Hg). NEI at 0.07 and 0.2 mg had no effect on baseline Ppa or HPV delta Ppa. Synthetic BNP at 10 nM had no effect on baseline Ppa but produced a 2.8 +/- 0.2 mm Hg reduction in HPV delta Ppa alone and 2.7 +/- 0.2 mm Hg reduction in the presence of 0.07 mg NEI in normoxic control rats. In contrast, ANP at 10 nM produced a significantly greater decrease in HPV delta Ppa in the presence of 0.07 mg NEI (4.8 +/- 0.3 mm Hg, p < 0.05) compared with ANP alone (2.9 +/- 0.4 mm Hg), and similar results were also observed in chronically hypoxic rats. Thus, BNP has a vasodilator effect similar to that of ANP in the pulmonary circulation. Inhibition of neutral endopeptidase 24.11 augments the effects of ANP on HPV but does not influence the pulmonary vascular responses to BNP.

Animals↗
PubMed1991

Resident, faculty, and residency program development. An integrated approach through annual retreats.

Retreats during residency training have evolved as an escape from the daily routine. Recognizing that the retreat format could also be used as a foundation for program design and personal development, we have designed annual retreats for each of the 3 years of pediatric residency training. The sessions vary in length and agenda, but serve as the basis for an ongoing effort fostering growth and maturation of the department and its component participants. The effectiveness of the program (and the morale of the residents) is greatly influenced by this program.

Chicago↗
PubMed1991

An outbreak of aspergillosis in a general ITU.

Over a 5-month period, six patients in a general intensive therapy unit became colonized by Aspergillus species including Aspergillus fumigatus, and invasive infection occurred in at least two of them. Broncho-alveolar lavage was unhelpful in discriminating between infection and colonization. The source of infection was presumed to be disturbance of an accumulation of spores in fibrous insulation material above the perforated metal ceiling. Patients in such units without clearly identifiable defects of defence against infection may be at risk from aspergillosis. The risk can be reduced by improved hospital design, satisfactory ventilation and thorough regular cleaning of environmental surfaces.

Adult↗
PubMed1991

Effects of continuous infusion of atrial natriuretic peptide on the pulmonary hypertension induced by chronic hypoxia in rats.

1. The effects of the continuous infusion of atrial natriuretic peptide on the development of pulmonary hypertension were studied in rats exposed to chronic hypoxia. 2. Continuous intravenous infusion of two doses of synthetic rat atrial natriuretic peptide, 300 ng/h per rat (0.10 pmol/h per rat) and 800 ng/h per rat (0.28 pmol/h per rat), attenuated the development of pulmonary hypertension in rats exposed to chronic hypoxia (fractional concentration of oxygen in inspired air = 10%) for 7 days: (i) the pulmonary artery pressure (mean +/- SD) in the vehicle-treated hypoxic group was 45 +/- 6 mmHg compared with 28 +/- 6 mmHg in the vehicle-treated normotoxic group (n = 8, P less than 0.001); (ii) treatment with atrial natriuretic peptide in normoxia did not alter the pulmonary artery pressure, systemic blood pressure or heart rate; (iii) treatment with atrial natriuretic peptide in hypoxia resulted in a lower pulmonary artery pressure in the group treated with 800 ng of atrial natriuretic peptide/h per rat (38 +/- 8 mmHg, P less than 0.05 compared with the vehicle-treated hypoxic group) without affecting the systemic blood pressure or heart rate. 3. Chronic hypoxia resulted in an extension of vascular smooth muscle towards the periphery of the lung with the development of muscle in normally non-muscularized vessels (remodelling).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neutral endopeptidase 24.11 inhibition reduces pulmonary vascular remodeling in rats exposed to chronic hypoxia.

Inhibition of the metabolism of endogenous atrial natriuretic peptide (ANP), by continuous infusion of a specific inhibitor of neutral endopeptidase (membrane metalloendopeptidase E.C. 3.4.24.11), UK 73,967 (candoxatrilat), was undertaken in rats, in which chronic hypoxia was used as a stimulus to induce pulmonary hypertension and right ventricular hypertrophy. Inhibition of neutral endopeptidase 24.11 with low-dose and high-dose UK 73,967 (NEI) increased endogenous plasma ANP by greater than 155% during the development of pulmonary hypertension. NEI treatment reduced mean pulmonary arterial pressure in hypoxia as follows: vehicle 26.6 +/- 4.0 mm Hg; low-dose NEI 22.7 +/- 1.9 mm Hg, and high-dose NEI 22.6 +/- 2.5 mm Hg (both p less than 0.01 compared with hypoxic vehicle); however, it was without effect on pulmonary arterial pressure in normoxia (17.6 +/- 2.2 mm Hg) or on systemic blood pressure. The development of right ventricular hypertrophy was also reduced in both groups treated with NEI (right ventricular weight/left ventricular weight: 0.43 +/- 0.03 vehicle; 0.40 +/- 0.02 low-dose NEI and 0.40 +/- 0.02 high-dose NEI, both p less than 0.05 compared with vehicle). Remodelling of the pulmonary vasculature, characterized by extension of the muscle within the small pulmonary arteries toward the periphery of the lung, was reduced by NEI treatment (percentage of thick-walled peripheral vessels; 19.2 +/- 3.1% vehicle; 10.4 +/- 2.3% low-dose NEI and 8.1 +/- 1.8% high-dose NEI, both p less than 0.001 compared with vehicle). In the isolated blood perfused rat lung pulsed doses of NEI had no effect on pulmonary vascular tone in the absence of ANP. Specific inhibition of the enzyme neutral endopeptidase reduces vascular remodelling, the development of pulmonary hypertension, and right ventricular hypertrophy. Endogenous ANP modulates vascular remodelling in vivo. Retarding the metabolism of endogenous ANP through inhibition of neutral endopeptidase 24.11 represents a potential approach toward therapy. g

Animals↗
PubMed1991

Long-term prospective evaluation of offspring of diabetic mothers.

We have suggested that altered maternal metabolism may affect the subsequent anthropometric and neuropsychological development of children who were in utero during disturbances in maternal fuel economy. This study reports the physical growth through 8 yr of age and the neuropsychological development through 4 yr of age in offspring of diabetic mothers (ODM). At birth, 50% of infants had weights greater than 90th percentile for gestational age. By 12 mo, length and weight were similar to the general population. Height remained normal until 7 yr of age, when it became slightly greater than average. After 5 yr of age, relative weight increased dramatically, and by 8 yr of age, half of the ODM had weights greater than 90th percentile. This childhood obesity in ODM is correlated with maternal prepregnant weight and independently with amniotic fluid insulin at 32-38 wk gestation. The Brazelton Neonatal Behavioral Assessment Scale (BNBAS) was administered to 185 newborn ODM. Significant correlations were found between poorer second- and third-trimester glycemic regulation and lower scores in three of four newborn BNBAS dimensions. The Stanford-Binet Intelligence Scale was measured in 102 ODM at 4 yr of age. We found an inverse correlation between childhood IQ and second- and third-trimester maternal lipid metabolism (serum free fatty acids and beta-hydroxybutyrate). This correlation is not explained by adverse perinatal events, socioeconomic status, maternal IQ, ethnicity, or diabetes type. These long-range associations between altered maternal metabolism and childhood growth and development continue to support Freinkel's hypothesis of fuel-mediated teratogenesis.

Aging↗
PubMed1990

Expression of neural cell adhesion molecule immunoreactivity in hypertrophic myocardium.

Myocardial neural cell adhesion molecule (N-CAM) is temporally regulated, being expressed during cardiac morphogenesis and innervation and suppressed in the adult heart. We have investigated the plasticity of N-CAM expression in hypertrophic muscle using the rat model of chronic hypoxia to selectively induce right ventricular hypertrophy over a 14 day time course. Sarcolemmal and intercalated disc N-CAM immunostaining was more extensive in the ventricular myocardium of hypoxic rats compared to normoxic controls. Quantitative assessment of the immunoreactivity in tissue extracts demonstrated a selective increase in the amount of N-CAM immunoreactivity in the hypertrophic myocardium of the right ventricle of rats exposed to hypoxia and this was associated with an increase of the 125 kDa isoform. We conclude that myocardial hypertrophy may be a factor influencing N-CAM expression in the heart and adhesion molecules may have a role in cardiac remodelling.

Animals↗
PubMed1990

Quantitative immunocytochemistry shows calcitonin gene-related peptide-like immunoreactivity in lung neuroendocrine cells is increased by chronic hypoxia in the rat.

We have previously shown that the vasodilator calcitonin gene-related peptide (CGRP) is increased in pulmonary neuroendocrine cells in response to hypoxia. To quantify the change, we have now examined lung of adult male Wistar rats exposed to hypoxia (FIO2 = 0.1) for 1 wk and littermate controls. Sections of lung were immunostained simultaneously using rabbit antiserum to rat alpha-CGRP with the peroxidase antiperoxidase technique. The area and integrated optical density of each group of endocrine cells were measured using an image analyzer. For each animal, the summed integrated optical density of endocrine cells divided by the sum of their areas was used as a measure of CGRP-like immunoreactivity. The intensity of immunostaining of endocrine cells in the respiratory portion of the lung was 43% greater than that of endocrine cells along the conducting airways (P less than 0.001). The intensity of staining was increased by approximately 12% (P less than 0.04) after 7 d of hypoxia with no apparent difference in the response of central and peripheral endocrine cells. Measurements of staining intensity of CGRP-coupled agarose beads indicated that a 12% change in staining intensity corresponded to a 15 to 20% change in the concentration of CGRP or CGRP-like immunoreactive material. The supra-optimal dilution technique (measurement of the increase in the number of immunoreactive cells upon sequential immunostaining with a supra-optimal and then an optimal dilution of primary antiserum) detected the increase in CGRP-like immunoreactivity after 7 d of hypoxia with a high degree of statistical significance (P less than 0.005) using the same number of sections.

Animals↗