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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 343 records · Page 19Linked to original sources
PubMed1982

Bronchial hypersecretion in preterm neonates.

During an 18-month period, 11 preterm infants with birthweights between 700 and 1560 g (mean 1.2 kg) developed excessive tracheobronchial secretions during intensive care. No single obstetric factor was incriminated. Copious, viscous, tracheobronchial secretions were noted at about 5 days during mechanical ventilation via endotracheal tube causing recurrent segmental collapse, hypoxia, and hypercapnia (median peak PCO2 13.5 kPa). All infants were treated with frequent bronchial lavages and continued intermittent positive pressure ventilation, together with high concentrations of oxygen. No infant died, but morbidity was high. Tracheostomy was performed on 2 infants (one at age 3 months, because of severe croup) and 2 others had clinical or physiological evidence of upper airways narrowing. Follow-up studies showed that this group had more problems of airways obstruction throughout the first year of life as well as increased lung stiffness. The hypersecretion group showed a higher incidence of chronic lung disease. Likely aetiological factors were sought. Contamination of the mechanical ventilation equipment by detergent and activated glutaraldehyde was found; this could have been a contributory factor.

Airway Obstruction↗
PubMed1982

Pulmonary sequelae of neonatal respiratory distress in very low birthweight infants: a clinical and physiological study.

Twenty infants, mechanically ventilated in the neonatal period for respiratory distress syndrome, were compared with 15 healthy controls, matched for birthweight(less than 1501 g) but greater in mean gestational age. Clinical features and lung mechanics (by whole body plethysmography) were recorded at 6-monthly intervals until about one year. THe neonatal course of the mechanically ventilated infants was commonly complicated by tracheobronchial hypersecretion and the later course by a fairly high incidence of lower respiratory tract illness. In this group, thoracic gas volume, dynamic compliance, pulmonary and airways conductance were all abnormal during the middle 4 months of the first year and reverted towards normal towards the end of the first year. The control group had normal lung mechanics. Early lung function tests were of limited value in predicting later lower respiratory tract illness, which was more common in boys, after neonatal mechanical ventilation for longer than 24 hours or raised ambient oxygen for longer than 5 days. There were few predictive physical signs. In this group of very low birthweight infants, respiratory distress syndrome of sufficient severity to require mechanical ventilation led to significant physiological and clinical disturbances of lung function which lasted into the second 6 months of life and which were particularly severe in those who had recurrent lower respiratory tract illness.

Female↗
PubMed1982

Antenatal dexamethasone and subsequent lung growth.

Long-term effects on lung size and lung mechanics were sought in a 12-month follow-up study of 15 infants of very low birthweight (less than 1500 g), 7 of whom had been exposed to antepartum dexamethasone (mean dose 21 mg). None of the infants had significant neonatal respiratory disease. No differences were found between the dexamethasone-treated and control groups for thoracic gas volume, dynamic pulmonary compliance, or airways resistance during the first year of life. This suggests that the growth and development of the lungs are not adversely affected by antepartum exposure to dexamethasone.

Body Weight↗
PubMed1982

Hyperventilation-induced asthma: evidence for two mechanisms.

The mechanism by which airway cooling induces airflow obstruction in asthmatic subjects has not yet been established. Using a pair of isocapnic hyperventilation challenges, with a 40-minute interval, we looked for the presence of a refractory period in 19 asthmatic patients (aged 9-18 years). The subjects fell into two groups. The eight in the "non-refractory" group showed less than a 25% reduction in response to the second challenge, but the 11 in the "refractory" group showed at least a 35% reduction. Twelve subjects also performed a hyperventilation challenge after cholinergic blockade with inhaled ipratropium bromide. In five, in whom no refractoriness after hyperventilation was seen, there was a significant protection from cholinergic blockade (p less than 0.05). In these a vagal (cholinergic) reflex seems likely. The remaining seven, who had a refractory period, received no significant protection from cholinergic blockade and therefore no evidence for the presence of any cholinergic mechanism. We conclude that two mechanisms are responsible for hyperventilation-induced asthma, one of which is a vagal reflex while mediator release may be the other.

Adolescent↗
PubMed1982

Transcapillary exchange of molecular weight markers in the postglomerular circulation: application of a barrier-limited model.

The permselectivity of the postglomerular capillary wall was studied by performing pulse-injection multiple indicator-dilution experiments on dog kidneys in vivo, using simultaneous injection of T1824-labeled albumin (plasma reference), creatinine (extracellular reference), and one or two radioactively labeled indicators: raffinose (595 dalton), vitamin B12 (1,357 dalton), or inulin (approximately 5,000 dalton). The urine transit patterns superimposed for all these except albumin, suggesting equal permeability for these molecular weight markers at the level of the glomerular filtration barrier. But the renal vein mean transit times progressively decreased. Therefore, their apparent interstitial volumes of distribution decrease with increasing molecular weight. This could be due to several factors acting singly or in combination: reduced capillary permeability in the postglomerular microcirculation; restricted diffusion in the postglomerular interstitium; or excluded volume effects. Evidence suggested that the effect was due to a combination of permeability and exclusion volume effects. To assess the validity of this assumption, the barrier-limited model was compared with the experimental data. The results were analyzed (both hydropenic and mannitol-diuretic dogs) and best fits calculated using two independent parameters, permeability and excluded volume. For permeability (X10(-4) cm/s, mean +/- SD) the range of values was always greater than or equal to 15 for creatinine and raffinose, and greater than or equal to 12 for B12. The permeability for inulin was 6.9 +/- 1.4. When interstitial volume excluded was expressed as percentage of the volume available to creatine, the excluded volume was negligible for raffinose and B12 but 12 +/- 5% for inulin. During mannitol diuresis the permeability for creatinine and raffinose remained high, but the values tended to decrease for B12. The permeability of inulin decreased to 2.9 +/- 0.09. Mannitol diuresis increased the excluded volume of inulin but did not alter the creatinine, raffinose, or B12 value.

Animals↗
PubMed1982

2-Deoxy-D-glucose transport in dog kidney.

Osmotically active brush border membrane (BBM) and antiluminal membrane (ALM) vesicles prepared from dog kidney cortex were used to investigate transport of 2-deoxy-D-glucose (2DG). A parallel in vivo study was carried out using the pulse-injection multiple indicator-dilution technique. Single-pass indicator-dilution experiments demonstrate both luminal and antiluminal interactions for 2DG. The antiluminal interaction is blocked by large systemic doses of phlorizin (100-200 mg/kg). With plasma glucose concentration in the range of 4-5 mM fractional luminal extraction of 2-[14C]DG relative to simultaneously filtered creatinine is 25 +/- 2%. This luminal extraction can be inhibited by raising plasma glucose concentration to approximately 30 mM and by administration of low systemic doses of phlorizin (6-8 mg/Kg). 2DG uptake into BBM vesicles equilibrates into the same intravesicular volume as D-glucose. A definite Na+ component of 2DG uptake can be defined which is more sensitive to inhibition by phlorizin than by phloretin and is also inhibited by D-glucose and alpha-methyl-D-glucoside but not by L-glucose. But compared with D-glucose, the Na+-dependent BBM uptake of 2DG is greatly reduced. 2DG uptake into ALM vesicles is independent of Na+, is more sensitive to inhibition by phloretin than by phlorizin, and is also blocked by cytochalasin B but not by alpha-methyl-D-glucoside. Influx of 2-[14C] DG into ALM vesicles is increased by preloading with unlabeled D-glucose. Conversely influx of D[14C]glucose into ALM vesicles is accelerated by preloading with unlabeled 2DG. ALM influx of radiolabeled 2DG is accelerated by D-glucose, 3-O-methyl-D-glucose, D-galactose, and unlabeled 2DG but not by alpha-methyl-D-glucoside. The specificity of inhibition and countertransport results from in vivo and in vitro experiments are consistent with the proposal that 2DG shares a common carrier mechanism with D-glucose at each of the opposing membrane surfaces.

Animals↗
PubMed1982

Problems in measurement of thoracic gas volume in infancy.

Thoracic gas volume (TGV) was measured with a whole-body plethysmograph in 20 infants at functional residual capacity (FRC) and at a series of higher lung volumes achieved by artificial inflation of the lungs with known volumes of air after airway occlusion. There was a discrepancy between the corrected values of TGV measured at high and low lung volumes in nine infants; in six cases TGV measured at high lung volumes exceeded that measured at FRC, and in three cases it was reduced when compared with the measurement made at FRC. These changes were not related to age, size, or clinical status and could be explained by airway closure at FRC, combined with an uneven distribution of pleural pressure.

Gases↗
PubMed1982

The drugging of the Third World.

This article reports an investigation of the promotion of more than 500 products marketed by over 150 pharmaceutical companies in the United States, Great Britain, Latin America, Africa, and Asia. In contrast to the promotional material provided to physicians in the United States and Great Britain, material presented to physicians in Third World countries was found to be marked by gross exaggeration of product effectiveness and minimized or completely omitted potential hazards. No substantial differences could be found between multinational and domestic companies, brand-name and generic firms, or companies based in capitalist nations and those in socialist or communist-bloc countries in terms of the adequacy and accuracy of their promotion. Little evidence was found to support industry claims that the discrepancies in promotion reflect the different policies of various drug regulatory agencies. Much of the promotion concerned "luxury products," including costly tonics and appetite stimulants marketed in poor countries where the pressing need is for food. Bribery of influential physicians and key governmental officials may play an important role in irrational drug promotion and use in the Third World. Some of the proposed corrective approaches to this problem are examined.

Advertising↗
PubMed1982

In vivo determination of cellular uptake in the kidney.

This paper describes the application of the pulse injection, multiple indicator dilution method to the study of cellular uptake in the kidney in vivo. By using the uptake of sugars and amino acids as specific examples, a rationale is provided that outlines the use of the technique in distinguishing luminal compared to antiluminal uptake. The site of cellular uptake processes cannot be localized by using a whole-organ approach such as the indicator dilution method; nevertheless, for sugars the correlation between in vivo studies and vesicle uptake measurements carried out with purified brush border and antiluminal membrane fractions confirms that the indicator dilution experiments reflect events that are occurring at the level of the proximal tubule in dog kidney. Because of the heterogeneity of tubular flow and substrate concentration profiles along the length of the nephron, it is difficult to use in vivo methods for carrying out kinetic studies on substrate uptake at the luminal surface. By contrast, a strong argument is made that uptake at the contraluminal surface of the proximal tubule can be optimally studied by using the single-pass indicator dilution method. The particular advantages are that the orientation of the basolateral membrane is known and also that uptake fluxes can be measured over short periods of time, i.e., less than 5 s. As an experimental example, uptake of glutamine in the kidney is discussed, and by a combination of indicator dilution methodology and arteriovenous extraction measurements combined with computer simulation and mathematical modeling, an approach is developed for the purposes of deriving unidirectional substrate fluxes at opposing nephron surfaces.

Animals↗
PubMed1981

Interaction of phlorizin and sodium with the renal brush-border membrane D-glucose transporter: stoichiometry and order of binding.

The order and stoichiometry of the binding of phlorizin and sodium to the renal brush-border membrane D-glucose transporter are studied. The experimental results are consistent with a random-binding scheme in which the ratio of phlorizin- to sodium-binding sites is one-to-one. When the kinetics of phlorizin binding are measured as a function of increasing sodium concentration no significant variation is found in the apparent number of binding sites; however, the apparent binding constant for phlorizin decreases rapidly from approximately 16 microM at [Na] = 0 to 0.1 microM at [Na] = 100 mM and approaches 0.05 microM as [Na] leads to infinity. The experimental data are fit to a random carrier-type model of the coupled transport of sodium and D-glucose. A complete parameterization of the phlorizin binding properties of this model under sodium equilibrium conditions is given.

Animals↗
PubMed1981

Luminal and antiluminal transport of glutamine in dog kidney: effect of metabolic acidosis.

We have studied the luminal acid antiluminal transport of glutamine and glutamate with the pulse injection multiple indicator dilution technique in normal dogs and in dogs with acute and chronic acidosis. The single-pass experiments yield estimates of unidirectional influx at each nephron surface. The kidney of normal dogs extracts 57% of the arterial glutamine load; 23% of this extraction is due to luminal reabsorption and 34% to antiluminal uptake from the peritubular circulation. After the total net extraction by the kidney is determined from arteriovenous differences and blood flow measurements, in normal dogs, the net antiluminal flux is calculated to be negative, indicating that at least part of the glutamine reabsorbed is returned to the renal venous circulation across the antiluminal membrane. In acutely acidotic dogs, the situation is similar, but a 30% to 40% fall in renal hemodynamics (blood flow and GFR) is observed with secondary reduction in luminal and antiluminal uptake. In chronically acidotic dogs, the unidirectional luminal and antiluminal uptakes of glutamine are similar to that observed in normal animals, but the calculated efflux across the antiluminal membrane is drastically reduced. These findings suggest that (l) a cellular transport mechanism for glutamine exists at the antiluminal pole of the renal tubule and dominates the luminal uptake process in normal animals; (2) cellular transport of glutamine (luminal and antiluminal) does not play a role in the renal adaptation to metabolic acidosis; (3) the intrarenal utilization of glutamine acts as a metabolic sink for this amino acid, which in turn regulates its net uptake by the kidney; and (4) the total uptake of glutamine limits ammoniagenesis in this species.

Acidosis, Renal Tubular↗
PubMed1981

Oxatomide and exercise-induced asthma in children: the value of serial exercise tests.

Two groups of eight asthmatic children carried out serial treadmill exercise tests at 2-hourly intervals, after double-blind premedication with oxatomide (2 mg/kg by mouth), sodium cromoglycate powder (20 mg by inhalation) or matched placebo preparations. The drugs were studied in one group up to 6 hr and in the other group (omitting sodium cromoglycate) from 4 to 10 hr after administration. Peak expiratory flow rate was measured before and after exercise to give an index of exercise-induced asthma. Oxatomide had a slight but significant bronchodilator effect. After a lag period of up to 4 hours, oxatomide exerted a significant protective effect against exercise-induced asthma which lasted until at least 8 hr. At 10 hr after ingestion, the effect had gone. A mean maximum diminution of exercise-induced asthma of 49% was found, in comparison with placebo. Oral oxatomide after a lag period, exerts a significant protective effect against exercise-induced asthma. The relevance of these observations for the clinical management of asthma remains to be determined.

Asthma↗
PubMed1981

Congenital hypertension due to unilateral renal vein thrombosis.

A boy was found on the day of birth to have hypertension and radiological evidence of calcification of the left renal vein. Persistent hypokalaemia and hyper-reninaemia in the presence of a small left kidney and normal right kidney led to the decision to perform a left nephrectomy. The biopsied specimen showed old calcified renal vein thrombosis with accompanying medullary necrosis. Postoperatively hypertension resolved.

Humans↗