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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 271 records · Page 15Linked to original sources

Hypoxaemia in wheezy infants after bronchodilator treatment.

The response of the bronchi to nebulised salbutamol was measured in five recurrently wheezy infants. Changes in oxygenation (measured by pulse oximeter and transcutaneous PO2 electrodes) and carbon dioxide (measured by transcutaneous PCO2 electrode) were recorded at the same time. Neither nebulised saline nor salbutamol caused any changes in the measurements of airway function. A significant drop in mean oxygen saturation of 2% and of transcutaneous oxygen tension of 1.3 kPa occurred after nebulised salbutamol. No significant change occurred in measurements of transcutaneous carbon dioxide tension, nor was there any significant change in any of these measurements after 2.5 ml of nebulised saline had been given as a control. These results suggest that nebulised salbutamol may cause significant hypoxaemia, in wheezy infants probably by inducing ventilation/perfusion disturbance.

Albuterol↗

Ipratropium bromide and airways function in wheezy infants.

The airway response to nebulised ipratropium bromide was studied in 17 chronically or recurrently wheezy infants aged 4-15 months. The peripheral airway response was assessed by the change in maximum flow at functional residual capacity (Vmax FRC) and the upper and central airway response by the change in specific airways resistance. The significant reduction in specific airways resistance after treatment with ipratropium bromide signified an improvement in central and upper airway function. No change was found, however, in Vmax FRC and hence in peripheral airway function. It seems that, as in older subjects, inhaled antimuscarinic, anticholinergic drugs have their maximum effect on the large airways, and this may explain their lack of effect in the management of acute bronchiolitis.

Airway Resistance↗

Nedocromil sodium and exercise induced asthma.

Serial exercise tests were carried out by 12 children with asthma on two study days. After a control exercise test either nedocromil sodium 4 mg or placebo were given double blind by metered dose inhaler. Highly significant inhibition of exercise induced asthma occurred after nedocromil, lasting for over two hours.

Adolescent↗

Airway responsiveness in wheezy infants: evidence for functional beta adrenergic receptors.

The effect of nebulised salbutamol on the bronchial response to nebulised histamine was studied in five wheezy infants aged 3-12 months. The response to doubling concentrations of up to 8 g/l of histamine was assessed by the change in the maximum flow at FRC (VmaxFRC), measured by flow-volume curves produced during forced expiration with a pressure jacket. The concentration of histamine required to provoke a 30% fall in VmaxFRC (PC30) was measured. All of the infants responded to low concentrations of histamine during control tests before and after nebulised saline (mean PC30 1.07 and 0.51 g/l). On a separate day there was a similar response to histamine before salbutamol (PC30 0.57 g/l), but after salbutamol the response was completely abolished up to the maximum concentration of histamine in all subjects (PC30 greater than 8 g/l). Thus wheezy infants have highly effective beta 2 adrenoceptors in intrathoracic airways.

Albuterol↗

Paradoxical response to nebulised salbutamol in wheezy infants, assessed by partial expiratory flow-volume curves.

Lower airway responses to nebulised bronchodilators were studied in 18 chronically or recurrently wheezy infants, aged 3-15 months, by means of partial forced expiratory flow-volume manoeuvres performed with an inflatable jacket. Maximum flow at functional residual capacity (FRC) (VmaxFRC) was used as the index of intrathoracic airways function. Peak expiratory flow rate was also measured. Baseline airways resistance and lung volume were determined during quiet breathing in an infant whole body plethysmograph. Measurements were made on separate days before and after nebulised salbutamol 2.5 mg with nebulised saline as control. The results were paradoxical: there was no change in VmaxFRC after saline, but a significant decline in VmaxFRC was found after salbutamol. Peak expiratory flow remained unchanged. These observations suggest that under conditions of forced expiration intrathoracic airways function may be further impaired by nebulised bronchodilator treatment in wheezy infants. When nebulised bronchodilator drugs are used to treat severe airways obstruction in infancy, careful monitoring is essential.

Airway Resistance↗

Bronchial responsiveness to histamine in wheezy infants.

Little is known about airway responsiveness in infancy. The bronchial response to incremental doses of nebulised histamine (to a maximum dose of 8 g/l) was measured in 11 wheezy infants with a mean age of 8.7 months. The study was repeated after a 30-40 minute recovery period in seven infants and again on a separate day in 10. The index of response was the provoking concentration of histamine that produced a 30% fall in the maximum expiratory flow at functional residual capacity (PC30), taken from partial forced expiratory flow-volume curves produced in a pressure jacket. Nine of 11 infants had a PC30 of less than 8 g/l. The response was consistent between tests in both the nine responders and the two who failed to respond at 8 g/l. The PC30 was lower in infants with more severe baseline airway obstruction. Spontaneous recovery after challenge was complete in 30 minutes in seven of eight infants studied. The highest doses of histamine caused changes in the configuration of the flow-volume curves and symptomatic cough and wheeze in addition to a change in forced flow rates. This study provides clear evidence of intrathoracic airway responsiveness to histamine in infancy.

Bronchi↗

Role of the oesophagus in asthma induced by the ingestion of ice and acid.

Twelve Asian patients with a history of asthma exacerbated by ingestion of ice and acidic drinks were selected for study. To determine the site of response to ingested ice and acid they were challenged with ice or dilute hydrochloric acid, which was orally retained on one day and swallowed on another. On a third day a placebo was given. The airway response was assessed by measuring FEV1 and the provocative concentration of histamine that reduced the FEV1 by at least 20% (PC20). There was no significant change in FEV1 or histamine PC20 after placebo or the orally retained challenges for the group as a whole or for any individual. After the ice and hydrochloric acid had been swallowed there was a small but statistically significant mean fall in FEV1, increasing to a maximum 90 minutes after ingestion, together with a significant increase in bronchial responsiveness. As conditioning of the inspired air would have been similar after orally retained and after swallowed ice or acid, the response is likely to be due to oesophageal stimulation. The mechanism of the response to oesophageal stimulation is unclear, but the slow time course seems to preclude a simple neural reflex.

Acids↗

Evidence of digoxin metabolism by the kidney.

By performing single pass experiments in the dog, we could identify by thin layer chromatography a digoxin metabolite produced by the kidney. In vitro studies verify that this new species is produced by the brush border membrane of the renal tubular cell.

Animals↗

Postglomerular capillary solute flux restricted by shape and charge in the dog.

The permselectivity characteristics of the postglomerular (PG) microcirculation in dog kidney were investigated employing 3H-labeled cationic (DEAE) and anionic sulfated dextrans (dextran-SO4) ranging from 19 to 29 A Stokes-Einstein Radius. With the use of the multiple-indicator dilution (MID) technique, a bolus injection was made into the left renal artery and timed serial samples were obtained from renal venous and urine outflows. The injection solution contained 125I-labeled albumin (plasma reference), [14C]inulin and/or creatinine (glomerular and interstitial references), and a test [3H]dextran probe. A control run was carried out with tracer, then charge interaction was analyzed by repeating the MID run with excess unlabeled compound or after protamine sulfate infusion. After loading, renal vein recovery and mean transit time (t) were unchanged relative to [14C]inulin for [3H]dextran-SO4. But excess DEAE resulted in reduced recovery and decreased t for [3H]DEAE. After protamine sulfate, the renal vein and urine recoveries of [3H]dextran-SO4 decreased and the renal vein t increased. These findings demonstrate saturable anionic binding sites in the PG microcirculation. Under conditions where charge interaction was eliminated, the ratio of renal vein t for 125I-albumin to cationic or anionic dextran was always less than its ratio to neutral dextran, implying a larger apparent volume of distribution. We concluded that PG capillaries also limit solute flux on the basis of shape.

Animals↗

Factors affecting the urinary excretion of albumin in insulin-dependent diabetes.

To determine the specificity of the urine excretion of albumin as a measure of glomerular permeability in early insulin-dependent diabetic nephropathy, the effect of variable glomerular filtration and urine flow rates on albumin, beta 2-microglobulin excretion, and the fractional renal clearance of neutral dextran (Stokes Einstein Radius 24-46 A) was examined. Five insulin-dependent diabetic subjects with normal glomerular permeability (albumin excretion less than 30 micrograms/min) and one with elevated albumin excretion (195 micrograms/min) were studied pre and post strict glucose control with constant subcutaneous insulin infusion for 7 days. The albumin excretion in the 5 subjects never exceeded 30 micrograms/min during wide variations in glomerular filtration and urine flow rates. A positive correlation between beta 2-microglobulin excretion and urine flow (r = 0.81), and glomerular filtration (r = 0.77) rates was observed. In contrast, albumin excretion showed no correlation, indicating different factors affect the excretion rate of albumin and beta 2-microglobulin. Therefore, elevated albumin excretion (greater than 30 micrograms/min) in insulin-dependent diabetes is due to increased glomerular permeability and not changes in glomerular filtration and urine flow rates, and the albumin/ beta 2-microglobulin ratio may not be a valid indicator of changing glomerular permeability. The fractional neutral dextran clearances remained unchanged with variation in glomerular filtration and urine flow rates. The sieving curve was identical in all subjects for neutral dextran 40 A, the size of albumin, suggesting that reduced glomerular charge selectivity may contribute to increased albuminuria in progressive diabetic glomerulosclerosis.

Adult↗

Isolation and partial purification of a Na+-dependent phlorizin receptor from dog kidney proximal tubule.

This paper describes a new method for solubilization and partial purification of a Na+-dependent phlorizin receptor from dog kidney proximal convoluted tubule. Selective solubilization is carried out with 0.1% Na+-deoxycholate followed by complete solubilization with 0.5% deoxycholate. The 100,000 X g supernatant of the deoxycholate extract is then subjected to a combination of chromatofocusing and gel exclusion chromatography. Purification is monitored by a new column assay which permits detection of the Na+-dependent high affinity phlorizin receptor in solubilized preparations. Na+-dependent phlorizin binding exhibits the same characteristics on the column assay as in intact brush border vesicles. Binding is temperature-dependent, inhibited by proteolytic agents, Na+-dependent, and inhibited by excess cold phlorizin and D-glucose but not L-glucose. Quantitation of specific binding at different stages of the isolation procedure indicates a final purification of approximately 80-140-fold compared to intact brush border membrane fragments. Enrichment of specific phlorizin binding is paralleled by enrichment of a 61-66-kDa polypeptide on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. It is postulated that this polypeptide contains both the Na and the sugar specific binding site and represents a subunit of the intact Na+-dependent glucose transporter from dog kidney proximal tubule brush border membrane.

Animals↗

Centrifugal cytology: a new technique for urine cytology.

A new technique, centrifugal cytology, appears to have a high recovery rate of malignant cells from voided urine specimens resulting in a high probability of early disease detection and should be considered a good supplement to cytoscopic evaluation of high-risk populations.

Centrifugation↗

Biochemical investigation of the pathogenesis of Heymann nephritis.

This study describes biochemical comparison of proximal tubule antigens from the brush border membrane (BBM) of dog and rat kidney. The purpose was to determine if a difference in BBM composition could explain the inability to produce either active or passive Heymann Nephritis in the dog. Although the membrane composition as revealed by coomassie blue staining on 4 to 11 per cent polyacrylamide electrophoresis varied considerably between rats and dogs, polyclonal antibodies (rabbit anti-rat, rabbit anti-dog) against purified BBM from both species immunoprecipitated five identical polypeptides. Four bands were visualized between 70 kd and 170 kd; but the major polypeptide had an apparent molecular wt of approximately 460 kd. This high molecular wt constituent and three of the other peptides were bound specifically to lentil lectin column, confirming their glycoprotein nature. Only the 460 kd polypeptide was immunoprecipitated by monoclonal antibody against gp 330. Since both rat and dog BBM contain gp 330, believed to be the sole pathogenic antigen in Heymann Nephritis, we conclude that failure to produce active or passive Heymann Nephritis in the dog using the same protocol that is successful in rats cannot be attributed to differences in antigenic make-up of the brush border membrane.

Animals↗

Regulation of lateral flagella gene transcription in Vibrio parahaemolyticus.

Two distinctly different organelles of locomotion are produced by Vibrio parahaemolyticus. The polar flagellum is responsible for motility in a liquid environment (swimming), and the lateral flagella enable the bacteria to move over surfaces (swarming). Synthesis of lateral flagella occurs when V. parahaemolyticus is grown on agar media but not when it is grown in liquid media. We used lux (luminescence gene) fusions to conveniently and sensitively analyze the factors which influence transcription of lateral flagella genes (laf). Transposon mini-Mu lux was used to mutagenize V. parahaemolyticus and to generate laf::lux transcriptional fusions. Mutants with insertions of mini-Mu lux in laf genes were defective in the swarming phenotype and produced light when the bacteria were propagated on agar media, but not when cells were grown in liquid media. Thus, surface-dependent expression of lateral flagella synthesis is controlled by regulation of transcription. Such fusion strains were also used to further define the environmental conditions which induce laf gene expression. Cultivation on media solidified by gelling agents other than agar also induced light production in fusion strains, as did growth on a variety of hydrophilic membrane filters suspended over liquid media. Growth at an air-surface interface was not necessary for expression since embedding the fusion strains in agar was also effective. Furthermore, induction of laf gene transcription could also be accomplished by increasing the viscosity of the liquid medium by the addition of a high-molecular-weight polymer such as polyvinylpyrrolidone. Increase in luminescence of the fusion strains was detected within 30 min of initiation of the inducing circumstance, and reversal of induction, e.g., by dilution of the viscous medium, resulted in a rapid decline in the rate of increase in luminescence. Conditions that induced luminescence in the fusion strains also induced the synthesis of lateral flagella in wild-type V. parahaemolyticus. The growth environment of the genes, and it appears that the signal that triggers laf expression is physical rather than chemical in nature. Possibilities for a sensing mechanism are discussed.

Agar↗

Effect of tracheobronchial suction on respiratory resistance in intubated preterm babies.

Measurements of the resistance, time constant, and compliance of the respiratory system were made in 25 mechanically ventilated, preterm babies on 32 occasions, using the single breath technique. Patients were classified according to the level of respiratory resistance by reference to a population of 36 babies studied over the first two days of life before airway secretions had become apparent. There was a highly significant fall in both the resistance and time constant measurements after tracheobronchial suction or lavage for infants whose pretreatment values of resistance were greater than the reference mean. When tracheobronchial toilet was effective in removing secretions the changes in resistance and time constant values were again significant. No changes in compliance values were noted. Severe but clinically inapparent mucous obstruction of the airways was revealed in two infants by a progressively rising respiratory system resistance during continuous monitoring. The need for and efficacy of tracheobronchial suction and lavage could be determined by such techniques for monitoring the resistance of the respiratory system during mechanical ventilation.

Airway Resistance↗