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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 163 records · Page 9Linked to original sources
PubMed1993

Inflammatory cells in the lungs of premature infants on the first day of life: perinatal risk factors and origin of cells.

Neither the origin of leucocytes in the premature newborn airway nor their relationship to perinatal factors has been adequately determined. In order to sample airway cells, modified bronchoalveolar lavage was performed on 74 intubated infants of < 32 weeks' gestation and < 24 hours of age. Cells were counted, stained and, in a small separate group of six infants, four boys and two girls, probed for the Y chromosome with suitable control samples. Perinatal risk factors for increased airway cellularity were analysed by multiple regression. Premature rupture of membranes of more than 24 hours' duration was independently associated with increased numbers of airway leucocytes (n = 74). More than 90% of airway leucocytes from four boys with pulmonary inflammation were positive for the Y chromosome indicating that the cells were of fetal rather than maternal origin.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Pulmonary inflammatory cells in ventilated preterm infants: effect of surfactant treatment.

The aim of this study was to determine the effect of surfactant treatment on the number and distribution of inflammatory cells in bronchoalveolar lavage fluid (BALF) from mechanically ventilated preterm infants over the first week of life in relation to the subsequent development of chronic lung disease (CLD). The study included 25 babies who received surfactant on clinical grounds and 29 babies of similar severity who did not. BALF was collected on days 1, 3, 5, and 7 after birth. Cell counts were performed and differentials were calculated on 300 cells. CLD was equally common in both treatment groups. Of the 54 infants, 29 (53%) who developed CLD had a higher incidence of patent ductus arteriosus and air leak and needed a higher concentration of inspired oxygen on the fifth and seventh days of life. Babies who developed CLD had more polymorphonuclear leucocytes and fewer macrophages on days 5 and 7 than those who recovered. Surfactant treatment was associated with a higher total white cell count on day 3. Between days 3 and 7, macrophage numbers were higher in surfactant treated babies, whatever the pulmonary outcome. This data suggests that CLD was associated with persistence of high numbers of polymorphonuclear leucocytes in BALF at the end of the first week. Surfactant treatment caused a persistent increase in macrophage numbers. The association between persistent neutrophilia and CLD was unaffected by surfactant treatment.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Bronchoalveolar lavage fluid glutathione in intubated premature infants.

Lower concentrations of uncorrected glutathione in the bronchoalveolar lavage fluid were found on the first day of life in seven infants who subsequently developed chronic lung disease when compared with 27 infants who did not require supplemental oxygen at 36 weeks' postconceptional age. The concentration of glutathione on the first day was independent of gestational age. These preliminary results suggest that glutathione accumulates in the lung epithelial lining fluid of preterm infants and that a relative deficiency may predispose to lung injury.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Energy-dependent transport of digoxin across renal tubular cell monolayers (LLC-PK1).

Digoxin secretory transport across renal tubular cell monolayers (LLC-PK1) grown on permeable filters was characterized. Metabolic inhibitors reduced total and specific basolateral to apical (B-A) flux of digoxin and conversely increased the apical to basolateral (A-B) flux. The specific transport of digoxin from the basolateral to the apical compartment was saturable, with a maximum velocity of transport of 184.5 +/- 38.0 pmol.cm-2.h-1 and a Michaelis-Menten constant (Km) of 14.1 +/- 1.6 microM. In addition, B-A flux of digoxin resulted in accumulation of digoxin in the apical compartment against the concentration gradient. P-Glycoprotein inhibitors such as quinidine, verapamil, vincristine, and cyclosporine increased the net A-B flux and inhibited the total B-A flux without affecting the nonspecific flux significantly. Tetraethylammonium, a prototype substrate for an organic cation transport system, had no such effect. Our results suggest that digoxin undergoes transepithelial secretion by an energy-dependent, carrier-mediated process in renal tubules, a process that seems to be distinct from the tetraethylammonium transport system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Vascular exchange in the kidney. Regional characterization by multiple indicator tomography.

In previous work with the method of multiple indicator dilution (MID), we have established that a spatially distributed model of transcapillary exchange proposed by Goresky, Ziegler, and Bach (GZB) accurately describes, at the in vivo whole-organ level, the handling of extracellular indicators in the canine renal cortex. To date, however, it has not been possible to assess the key hypothesis that GZB corresponds to the actual local mechanism of exchange in vivo and is not just a compact summary of the kidney's average whole-organ behavior. By adapting the MID method to high speed computed tomography (CT), we are now able to report that the GZB mechanism is an accurate description of renal cortical transcapillary exchange down to volumes of cortical tissue comprising no more than a few per cent of the total cortical mass, i.e., containing no more than a few thousand nephrons. A small bolus of iohexol (radiopaque extracellular indicator) or iodipamide ethyl ester microparticles (radiopaque plasma indicator) injected into the renal artery was followed by CT as it passed through the kidney and into the renal vein. Time-attenuation value curves of the two contrast media obtained from the renal vein and from regions of interest in the cortex were then modeled with the GZB mechanism and with a more complex formulation that includes GZB as a limiting case. When applied to the data, the models converged to GZB as the best fit for each region examined. The GZB mechanism is found to provide excellent agreement with the regional data.

Animals↗
PubMed1993

Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects.

The interrupter technique is a non-invasive method for measuring airway calibre. Since the calculation of interrupter resistance (Rint) is critically dependent upon the analysis of the mouth pressure/time (Pmo(t)) curve obtained after flow interruption, we wanted to assess the relative merits of four different analyses of Pmo(t) curves, obtained under basal conditions and following methacholine-induced airway narrowing, in 10 healthy adults. Four methods of analysing the Pmo(t) curves were used to calculate Rint values: RintC-a smooth curve fit with back-extrapolation; RintL-two-point linear fit with back-extrapolation; RintEO-calculated from the pressure change after the post-interruption oscillations had decayed (end-oscillation); and RintEI-calculated from the pressure change at the end of the period of interruption. The airway response measured with the four Rint methods was compared with plethysmographic airway resistance (Raw). The sensitivity of the methods was determined by calculating a sensitivity index (SI), the change in resistance after challenge expressed in multiples of baseline standard deviation. Values of RintC were similar to Raw values under all conditions. Resistance values from the remaining Rint methods significantly exceeded Raw (mean basal difference: 0.13-0.34 kPa.l-1 x s; mean difference after challenge: 0.12-0.42 kPa.l-1 x s. Raw was the most sensitive method for detecting bronchoconstriction (doubling of Raw was equivalent to SI of 10.5). Of the Rint methods, RintEI gave the highest sensitivity index (SI = 3.1), with a 42% mean change; RintC produced the greatest proportionate change after challenge (55%), but with a lower SI (2.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Demonstration of renal tubular flow by selective angiographic computed tomography.

A high-speed computed tomography scanner was used to study the bulk flow of a small bolus of nonionic contrast medium through the renal tubules of five dogs. A 0.5-mL bolus of iohexol 300 (150 mg iodine) was injected rapidly into the renal artery, and transverse images of the kidney were obtained at 15-second intervals over 300 seconds. The mean attenuation values measured in regions of interest in the papilla and the cortex were displayed as a function of time. Curves from the papillary regions of interest showed two peaks, the first corresponding to the passage of the bolus through the loops of Henle that extend into the papilla and the second to the passage of the bolus through the terminal collecting tubules. The cortical regions of interest showed the cortical return peak, which corresponded to the passage of the bolus through the distal convoluted tubules. The peaks generated by this method can be used to measure the transit times of the bolus from the glomeruli to the loops of Henle in the papilla, from the loops of Henle to the distal convoluted tubules, and from the distal convoluted tubules to the distal collecting tubules. The mean total transit time in dehydrated dogs was 169 seconds. The method is compared with contrast-enhanced magnetic resonance imaging (with gadolinium diethylenetriaminepentaacetic acid), which has been used by other researchers for the same purpose.

Animals↗
PubMed1992

The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin.

Digoxin, a widely used cardiac glycoside with a low therapeutic index, is known to interact with a large and diverse group of co-administered drugs, frequently leading to toxic accumulation of the glycoside. Establishing the mechanism(s) of these interactions, therefore, has potential clinical significance. The present studies implicate P-glycoprotein, the MDR1 gene product overexpressed in multidrug resistant cells, as the apical membrane protein responsible for the renal secretion of digoxin and provide an explanation for the occurrence of digoxin toxicity in the presence of certain co-administered medications. Since digoxin is considered a prototype for endogenous digitalis-like glycosides, the results also allow for speculation that endogenous digitalis-like glycosides may be the natural substrates for P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit.

We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers (MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Of the droplets emerging from the MDI, Aerochamber, and ET tube, 18% of the initial dose was in droplets less than 4.7 microns. Assuming that the test-lung model accurately reflects in vivo deposition, the combination of MDI and Aerochamber appears to be an extremely effective way of delivering budesonide aerosol to ventilated newborn infants.

Aerosols↗
PubMed1992

A new regime in the management of gastroschisis.

In this review of 24 patients with gastroschisis, we illustrate a regime of management with a low morbidity and no mortality. The essence of the technique relies on antenatal diagnosis, intrauterine transfer, and a planned cesarean section with immediate repair performed at 37 to 38 weeks' gestation. Although the operation may be technically easier at lower gestational ages, we believe the concomitant increase in complications such as respiratory distress syndrome outweigh the advantage of easier surgery. The results of this series compare favorably with other published results.

Abdominal Muscles↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of syphilis. Infectious Diseases Society of America and the Food and Drug Administration.

Syphilis is caused by Treponema pallidum, a spirochetal bacterium pathogenic only for humans. The clinical course of disease is divided into three stages interspersed by periods of latency. Penicillin remains the treatment of choice for all stages of infection; tetracycline or erythromycin may be used as therapeutic alternatives in defined circumstances. Patients enrolled in clinical trials should be evaluated clinically, microscopically, and serologically for the presence of the spirochete. All participants, after undergoing counseling and giving informed consent, should be tested for infection with human immunodeficiency virus. Specific criteria exist for diagnosis of syphilis and response to therapy. It may be desirable to perform a small, uncontrolled, open trial of a new anti-infective drug for the collection of preliminary evidence of efficacy. A larger-scale, randomized, active-control comparative clinical trial is necessary to prove efficacy.

Animals↗
PubMed1992

The luxR gene product of Vibrio harveyi is a transcriptional activator of the lux promoter.

Expression of the lux operon from the marine bacterium Vibrio harveyi is dependent on cell density and requires an unlinked regulatory gene, luxR, and other cofactors for autoregulation. Escherichia coli transformed with the lux operon emits very low levels of light, and this deficiency can be partially alleviated by coexpression of luxR in trans. The V. harveyi lux promoter was analyzed in vivo by primer extension mapping to examine the function of luxR. RNA isolated from E. coli transformed with the Vibrio harveyi lux operon was shown to have a start site at 123 bp upstream of the first ATG codon of luxC. This is in sharp contrast to the start site found for lux RNA isolated from V. harveyi, at 26 bp upstream of the luxC initiation codon. However, when E. coli was cotransformed with both the lux operon and luxR, the start site of the lux mRNA shifted from -123 to -26. Furthermore, expression of the luxR gene caused a 350-fold increase in lux mRNA levels. The results suggest that LuxR of V. harveyi is a transcriptional activator stimulating initiation at the -26 lux promoter.

Bacterial Proteins↗
PubMed1992

Bronchial responsiveness and lung function in infants with lower respiratory tract illness over the first six months of life.

The aim of this study was to determine whether increased bronchial responsiveness to histamine is associated with lower respiratory tract illness (one or more episodes of wheeze or cough, or both) in infancy. Fifty four normal newborn infants who had at least one atopic parent were recruited. At a median age of 6.5 months, 45 infants, 23 with a history of lower respiratory tract illness, and 22 without, underwent pulmonary function testing during a symptom free period. The maximum flow at functional residual capacity (VmaxFRC) was calculated from partial forced expiratory flow volume curves using the squeeze technique. Bronchial responsiveness to increasing doses of histamine was assessed by determining the provoking concentration which caused a 30% decrease in VmaxFRC (PC30). The length adjusted VmaxFRC was lower for symptomatic infants before the challenge (median 125 ml/s; 95% confidence intervals (CI) 85 to 164 ml/s) compared with control infants (median 215 ml/s; 95% CI 159 to 298 ml/s). There was no significant difference in PC30 between symptomatic infants (median 10.3 g/l; 95% CI 2.8 to 23.8 g/l) and control infants (median 16.5 g/l; 95% CI 2.4 to 27.9 g/l). Bronchial responsiveness to histamine can be shown in most infants early in life and is independent of lower respiratory tract symptoms including wheezing.

Bronchi↗
PubMed1992

Delivery of therapeutic aerosols to intubated babies.

Delivery of drug aerosols to the lungs of ventilated neonates by metered dose inhaler and spacer (Aerochamber) and ultrasonic nebuliser (Pentasonic) was assessed using sodium cromoglycate. The mean proportion of a known intratracheal dose of sodium cromoglycate excreted in the urine of four intubated infants was 37.5%. After assuming that 38% of the sodium cromoglycate aerosol reaching the neonatal lung will be excreted in the urine, three puffs (15 mg) delivered by metered dose inhaler and spacer resulted in a pulmonary dose of 258 micrograms (1.7%, n = 7). A dose of 20 mg (4 ml) sodium cromoglycate ultrasonically nebulised over five minutes into the inspiratory limb of a standard ventilator circuit produced a pulmonary dose of 257 micrograms (1.3%, n = 7). Of two in vitro lung models assessed, a combination of filter and neonatal test lung was superior to a multistage impactor in estimating the in vivo pulmonary sodium cromoglycate dose delivered by metered dose inhaler and spacer (243 micrograms v 1740 micrograms).

Aerosols↗
PubMed1992

Atopy, bronchial responsiveness, and symptoms in wheezy 3 year olds.

Fifty children with at least one hospital admission for acute lower airway obstruction in the first 2.5 years of life were assessed at 3 years of age to determine the relationship between atopy, bronchial responsiveness, and the pattern of their symptoms. Bronchial responsiveness was measured by assessing the effect of inhaled metacholine, using the change in transcutaneous oxygen tension (PtCO2) as an indirect measure of response. Symptom patterns were defined by the number of wheezing episodes associated with colds and the presence or absence of cough or wheeze unrelated to viral infections. Forty per cent of the children were found to be atopic by skin prick test or history. In contrast to the situation found in older children and adults, the non-atopic children had significantly greater bronchial responsiveness (lower mean concentration of methacholine causing a 20% fall in PtCO2, the PC20) than the atopic children and significantly more of them had an onset of respiratory symptoms in the first year of life. Cough and wheeze in the absence of colds was more frequently found in the atopic children as was the use of continuous medication. However, the number of reported acute episodes of wheeze associated with colds was the same in the two groups. The findings of the study suggest that in this hospital based group of children, acute wheeze associated with colds in the first three years of life is independent of the finding of atopy and that bronchial responsiveness in this age group may have a different pathogenesis from that in older subjects.

Blood Gas Monitoring, Transcutaneous↗
PubMed1992

Repeatability of methacholine challenge in asthmatic children measured by change in transcutaneous oxygen tension.

BACKGROUND: The airway response to bronchial provocation may be evaluated by monitoring the fall in transcutaneous oxygen tension (PtcO2) but the repeatability of this method has not been rigorously assessed. METHODS: To determine the repeatability of this indirect method of assessment, bronchial challenge was performed with methacholine in nine children with stable asthma (age range 6-12 years) and was repeated 24 hours later. The response was determined by the fall both in forced expiratory volume in one second (FEV1) and in PtcO2. A modified tidal inhalation protocol was used in which quadrupling concentrations of methacholine were given, thereby reducing the time taken for the full challenge by almost half. The concentrations of methacholine that provoked a 20% decrease in FEV1 (PC20FEV1) and 15% and 10% falls in PtcO2 (PC15PtcO2, PC10PtcO2) were calculated. RESULTS: Repeatability measures, assessed as the 95% range for a single determination, were +/- 0.96 and +/- 1.12 doubling concentration differences respectively for PC15PtcO2 and PC10PtcO2 and +/- 0.80 for PC20FEV1. CONCLUSION: This challenge method using quadrupling concentrations and an indirect assessment of the response by PtcO2 was sufficiently repeatable for clinical use and compared favourably with repeated challenge assessed by FEV1. The PtcO2 method is simple and effort independent, and should prove particularly useful for measuring bronchial reactivity in young children.

Asthma↗
PubMed1992

Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin.

We studied the in vivo luminal and contraluminal uptake of [3H]digoxin in dog kidney using the single-pass multiple indicator dilution method. A bolus tracer of 125I-albumin (plasma reference), creatinine, or L-[14C]glucose [extracellular reference (ecf)] and [3H]digoxin (or [3H]ouabain) was injected into the left renal artery, and timed serial samples were collected from the left renal vein (basolateral uptake) and left and right ureters (luminal uptake). [3H]ouabain was excreted solely by filtration and exhibited saturable and irreversible binding at the basolateral surface. Uptake of [3H]digoxin across the basolateral membrane was large and nonsaturable. Despite urine flow-dependent reabsorption and approximately 20% protein binding, the urine recovery ratio for [3H]-digoxin/glomerular (ecf) marker was 0.97 +/- 0.04 (n = 29), indicating net digoxin secretion. After intravenous infusions of cyclosporin in Cremophor EL (0.5-3.5 microM), the urine recovery ratio decreased in a dose-dependent manner from control values of 1.13 +/- 0.06 (n = 12) to 0.62 +/- 0.03 (n = 14). There was no change in the relative renal vein recovery. Left renal artery infusion of quinidine (37.5 micrograms.min-1.kg-1) decreased the relative urine recovery of [3H]digoxin by 46% (n = 6) but had no effect on postglomerular extraction. Cyclosporin and quinidine are known inhibitors of P-glycoprotein. But digoxin did not compete with [3H]azidopine for binding in rat brush-border membranes or membranes prepared from the multidrug-resistant cell line CHRC5. The exact mechanism for renal digoxin secretion remains to be determined, but our results point to a luminal localization of this secretory system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗