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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 253 records · Page 14Linked to original sources

Histamine-induced airway obstruction in infancy: changes in oxygenation.

In seven recurrently wheezy infants who were found to be histamine-responsive during bronchial challenge, changes in oxygenation (by oximeter and transcutaneous PO2 electrode) and carbon dioxide tension (by transcutaneous PCO2 electrode) were concurrently measured. The histamine challenge consisted of doubling concentrations administered by nebulizer for 1 min at 5-min intervals, up to a maximum concentration of 8 g/L. The response was determined from maximum expiratory flow using a squeeze technique. Significant mean reductions in transcutaneous oxygen tension of 0.9 +/- 0.7 kPa and 1.5 +/- 0.9 kPa were seen respectively at half the provoking concentration and at the provoking concentration of histamine that caused a significant reduction in maximum expiratory flow rates. The reduction in oxygen saturation of 4.8 +/- 3% was also significant at the provoking concentration. No significant change in transcutaneous carbon dioxide tension was seen. These results suggest that acute histamine-induced airway obstruction causes significant ventilation/perfusion disturbance in wheezy infants. Oxygen monitoring should be performed during bronchial challenge tests in infancy.

Blood Gas Monitoring, Transcutaneous↗

Lung volume changes during histamine-induced bronchoconstriction in recurrently wheezy infants.

Respiratory inductance plethysmography was used to estimate changes in functional residual capacity (FRC) in seven recurrently wheezy infants undergoing histamine challenge. Inhalations of normal saline and doubling concentrations of histamine were given up to and including the provoking concentration (PC) that caused a significant fall in maximum flow at FRC (Vmax FRC) as measured using the inflatable jacket technique. Below the PC histamine in general caused small increases in FRC [9.4 +/- 7.6 ml (mean +/- SD) at half the provoking concentration]. However, larger increases were seen at the provoking concentration (26.6 +/- 15.6 ml). Inspection of flow-volume curves obtained before and after the larger changes in FRC suggested that the reduction in airflow measured by the change in Vmax FRC was underestimated.

Bronchial Provocation Tests↗

Variable expression of extracellular polysaccharide in the marine bacterium Pseudomonas atlantica is controlled by genome rearrangement.

Production of extracellular polysaccharide by the marine bacterium Pseudomonas atlantica is a variable trait. Strains that produce extracellular polysaccharide (EPS(+)) have a mucoid colony phenotype, but during cultivation in the laboratory nonmucoid, EPS(-) variants arise that have a crenated colony morphology. This change is reversible since crenated variants rapidly switch to the original mucoid phenotype. We have cloned the locus (eps) controlling variable expression of EPS production by screening a recombinant cosmid library for clones that restore EPS production in the crenated variant. By using eps as a probe of genomic structure in variant strains, expression of EPS production was found to be controlled by a specific DNA rearrangement. Insertion of a 1.2-kilobase-pair DNA sequence in the eps locus results in EPS(-), whereas excision of the sequence restores the EPS(+) phenotype. Properties of the rearrangement suggest the involvement of a mobile genetic element. The possible significance of this DNA rearrangement to the survival of P. atlantica in the ocean is discussed.

Journal Article↗

Assessment of a new valveless infant ventilator.

A new valveless ventilator, which uses an air jet to provide the driving force for positive pressure ventilation, was used on 13 newborn babies (10 of very low birthweight) who had severe respiratory disease. The ventilator differs from 'true' jet ventilators in that its driving gas does not take part in gas exchange. Functionally it is a pressure pre-set, time-cycled ventilator, whose performance is characterised by the rapid and precise maintenance of both inspiratory and expiratory airway opening pressure. All the babies had progressively worsening respiratory failure (mean values of arterial pCO2 were 9.46 kPa, with a pH of 7.14, and an inspired oxygen concentration of 92.5%) on conventional mechanical ventilation. On the new ventilator, with the same settings, there was a dramatic and highly significant improvement within 20 to 30 minutes (mean values of arterial pCO2 were 6.45 kPa, pH 7.26, and inspired oxygen concentration 85.7%). This improvement was maintained. The new ventilator represents an important advance in the management of babies with severe respiratory failure.

Carbon Dioxide↗

Airway responsiveness in low birthweight children and their mothers.

In a prospective study on a cohort of 7 year old children of low birth weight (under 2000 g at birth), we observed an increased prevalence of airway responsiveness to histamine compared with a reference population of unselected, local schoolchildren. The airway responsiveness to histamine was significantly related to a history of asthma in first degree relatives (natural parents and siblings) in both groups of children, but not to that of the mothers. There was no increase in the prevalence of maternal asthma, a family history of asthma, or airway responsiveness in the mothers of low birthweight children. We were unable to find evidence to support the hypothesis that maternal smooth muscle irritability (uterine and airway) has a causative role in the premature labour in the mothers and in subsequent bronchial hyper-responsiveness in their prematurely born children.

Asthma↗

In vivo characterization of insulin uptake by dog renal cortical epithelium.

In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: [3H]dextran greater than 70 kDa (plasma reference), [14C]inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below [14C]inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching [14C]inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM.

Animals↗

Variability of the perceived sense of effort in breathing during exercise in patients with chronic obstructive pulmonary disease.

The present study examined the reproducibility with which subjects with stable chronic obstructive pulmonary disease (COPD) scale the sense of effort involved in breathing during exercise. The sense of effort was assessed in 6 subjects with COPD during bicycle exercise continued to a symptom-limited maximal work load using a conventional category scale. Reproducibility of the sensory experience was assessed by comparing results obtained from 3 incremental work tests, 2 on the same day and a subsequent test performed within 1 to 10 days. During all trials in all subjects, sensory scores correlated closely with both minute ventilation and oxygen consumption (r greater than or equal to 0.92 for both VE and VO2). The average coefficients of variation for the maximal Borg Score and Borg Score at 2 min of exercise for the group as a whole were 3 +/- 1 and 3 +/- 2% (SE), respectively. Variability in sensory scores was not significantly different on exercise trials performed either within or between days. Furthermore, variability of sensory scores, oxygen consumption, heart rate, or minute ventilation were similar. We conclude that when using a category scale in subjects with COPD, the perceived sense of effort in breathing during exercise is highly reproducible, correlates closely with physiologic measures defining the intensity of exercise, and is no more variable than physiologic parameters typically measured during an exercise test.

Aged↗

Inhibitory effects of volume expansion performed in vivo on transport in the isolated rabbit proximal tubule perfused in vitro.

To examine the renal tubular sites and mechanisms involved in the effects of hypooncotic volume expansion (VE) on renal electrolyte excretion, we performed clearance and isolated tubular perfusion studies using intact and thyroparathyroidectomized (TPTX) rabbits. We also examined the effect of VE on luminal brush border transport. In the microperfusion studies, proximal convoluted (PCT) and straight (PST) tubules were taken from rabbits without prior VE or after 30 min of 6% (body wt) VE. Acute VE increased the percentage excretion of Na, Ca, and P in TPTX animals and the percentage and absolute excretions of these ions in intact rabbits. In PST from VE animals, fluid flux (Jv) was depressed compared with Jv in PST from nonVE rabbits: Jv = 0.18 +/- 0.03, (VE) vs. 0.31 +/- 0.03 nl/mm.min, (nonVE) P less than 0.02. Phosphate transport (Jp) in the PST from VE animals was also depressed: JP = 1.58 +/- 0.10 (VE) vs. 2.62 +/- 0.47 pmol/mm.min, (nonVE) P less than 0.05. Similar results were obtained with TPTX animals. In the PCT from VE animals, Jv was decreased (0.49 +/- 0.10 (VE) vs. 0.97 +/- 0.14 nl/mm.min, (nonVE) P less than 0.02), but JP was not affected significantly. Transport inhibition was stable over approximately 90 min of perfusion. In the brush border vesicle studies, sodium-dependent phosphate transport was inhibited compared with that in control animals, at the 9-, 30-, and 60-s time points. These findings indicate that the inhibition of renal ionic transport by VE occurs in both PCT and PST and is, in part, the result of a direct effect of VE on tubular transport mechanisms.

Animals↗

The question of autism in an atypical infant.

The evaluation and brief treatment of a less-than-a-year-old girl whose parents were concerned she was autistic is described. We review what is known about the initial symptoms of autism and consider how early it is feasible to make a diagnosis. We outline the domains of cognitive, language, and social development that ought to be monitored given concern about autism and explain how we evaluated these domains in our home-based intervention. Finally, we consider possible explanations for this infant's recovery from a serious early disturbance in social relatedness.

Autistic Disorder↗

Effects of quinidine on the renal tubular and biliary transport of digoxin: in vivo and in vitro studies in the dog.

Quinidine is known to inhibit the renal clearance of digoxin without affecting glomerular filtration rate. The renal interaction between these drugs was investigated by a combination of in vivo and in vitro methods. The uptake of digoxin by brush border membrane vesicles was not affected by quinidine. Similarly, digoxin did not inhibit the uptake of the cation N-methylnicotinamide by these vesicles and did not alter the binding kinetics of digoxin to the Na+, K+-adenosine triphosphatase by the antiluminal membrane vesicles. By using the in vivo multiple indicator dilution technique transtubular transport of digoxin was documented; renal-artery infusion of quinidine did not affect the recovery of digoxin in the renal vein or urine. Clearance studies documented that the decrease in the renal clearance of digoxin is paralleled by a significant fall in renal blood flow evidenced by a decrease in p-aminohippuric acid clearance. It is concluded that quinidine inhibits the renal excretion of digoxin not by competition at the tubular cell membrane level, but rather by decreasing renal blood flow. A parallel decrease in biliary clearance of digoxin is documented and may suggest a similar mechanism.

Animals↗

Nucleotide sequence of the regulatory locus controlling expression of bacterial genes for bioluminescence.

Production of light by the marine bacterium Vibrio fischeri and by recombinant hosts containing cloned lux genes is controlled by the density of the culture. Density-dependent regulation of lux gene expression has been shown to require a locus consisting of the luxR and luxI genes and two closely linked divergent promoters. As part of a genetic analysis to understand the regulation of bioluminescence, we have sequenced the region of DNA containing this control circuit. Open reading frames corresponding to luxR and luxI were identified; transcription start sites were defined by S1 nuclease mapping and sequences resembling promoter elements were located.

Amino Acid Sequence↗

Characteristics of nurse anesthetists working with and without anesthesiologists.

All professionally active certified registered nurse anesthetists (CRNAs) in four geographically representative states were surveyed by mail and telephone in 1981, and response rate of greater than or equal to 70% was obtained for each state. CRNAs who worked with anesthesiologists (Group I) were compared with those who worked in hospitals with no anesthesiologists (Group II). More than 75% of both groups were employed by hospitals, but Group II CRNAs (15.5% of respondents) were nearly five times as likely to practice on an independent, fee-for-service basis. Members of Group II worked predominantly in hospitals in small or rural communities and, compared with those in Group I, were more likely to be male and older, less likely to hold a baccalaureate degree, and less likely to use invasive monitoring techniques. Nearly 50% of Group II had no standing consulting relationship with an anesthesiologist. A consultation network supported by telecommunications deserves consideration as a means of providing CRNAs who work independently in small rural hospitals with a cost-effective team approach to anesthesia care.

Adult↗

Phosphate regulation of gene expression in Vibrio parahaemolyticus.

The synthesis of a major outer membrane protein, OmpP, in Vibrio parahaemolyticus was induced by growth in media deficient in phosphate. The gene, ompP, encoding this protein was cloned. Synthesis of OmpP in Escherichia coli was regulated by the availability of phosphate, and this control required the function of pho regulatory genes of E. coli. Analysis of gene fusion strains constructed by mutagenesis with transposon mini-Mulux revealed that ompP was transcriptionally regulated in V. parahaemolyticus. Impaired growth of a strain with an ompP defect was observed in media which contained large linear polyphosphates as the phosphate source. This and other evidence suggested that OmpP functions as a porin channel for the entry of phosphate into the cell. A number of other proteins or activities were induced by phosphate limitation including hemolysin, phospholipase C, and phosphatase activities. A regulatory locus controlling expression of phosphate-regulated genes was identified and cloned. This regulatory locus cloned from V. parahaemolyticus was shown to complement E. coli strains with defects in pho regulatory genes.

Bacterial Outer Membrane Proteins↗