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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 109 records · Page 6Linked to original sources
PubMed1996

Cellular activation of mesangial gelatinase A by cytochalasin D is accompanied by enhanced mRNA expression of both gelatinase A and its membrane-associated gelatinase A activator (MT-MMP).

Activation of gelatinase A represents a crucial regulatory step in the control of its enzymic activity. Rat kidney mesangial cells secrete predominantly latent gelatinase A that can be activated following treatment with cytochalasin D. In the present paper we provide new evidence, using reverse transcription-PCR, that treatment of rat mesangial cells with cytochalasin D enhances the steady-state level of mRNA of the membrane-type matrix metalloproteinase (MT-MMP), as well as of gelatinase A, with no change in the level of tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA. Since the TIMP-2 protein level is reduced in conditioned medium from cytochalasin D-treated cells, the results of the present study are consistent with a model in which the action of cytochalasin D is to cause extracellular gelatinase A and TIMP-2 to be sequestered at the plasma membrane, forming a heterotrimeric complex with MT-MMP. In this manner, TIMP-2 may assume a bifunctional role causing: (i) inhibition of gelatinase A in the extracellular compartment; and (ii) guiding gelatinase A to activation through a membrane association with MT-MMP.

Animals↗
PubMed1996

Occlusion maneuver to detect the relative contribution of the rib cage and abdomen to tidal volume using respiratory inductive plethysmography in infants.

Respiratory inductive plethysmography (RIP) records movements of the rib cage (RC) and abdomen (AB). A calibration procedure is needed to determine their relative contribution to tidal volume. We evaluated the hypothesis that the relative contribution of the RC and AB could be defined from respiratory efforts made during a brief occlusion of the airways in 10 infants aged 6.5-19 months, who were studied in quiet sleep. Six occlusions were performed during tidal breathing, with and without a pneumotachograph (PNT) and face mask in place. We analyzed the periods of occluded respiratory effort when RC and AB were in opposite directions (paradoxical movements), plotting RC vs. AB and performing a least-squares linear regression to estimate the ratio of the coefficients of AB/RC. Multiple linear regression of AB and RC over tidal volume during about 100 seconds of tidal breathing provided a reference standard. A ratio of 1 means that AB and RC make equal contributions to tidal volume. The feasibility of the occlusion maneuver was poor; only 51% of occlusions with PNT and 54% without led to a paradoxical movement with a good fit (r > 0.9). The mean coefficient of variation (range) was 9.35% (3.9-15.3%) with PNT and 12.1% (2.5%-26.3%) without it. The accuracy was very poor, with the mean AB/RC value being 0.94 with occlusions and 2.39 with multiple linear regression. The mean difference was 1.45 (SD 0.80), yielding 95% confidence limits for the difference of 0.12-3.01. We concluded that, due to its very poor accuracy and feasibility, the occlusion technique is not a useful method to calibrate RIP in infancy.

Abdomen↗
PubMed1996

Effectiveness of budesonide aerosol in ventilator-dependent preterm babies: a preliminary report.

The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.

Administration, Inhalation↗
PubMed1996

Changes in respiratory rate affect tidal expiratory flow indices in infants with airway obstruction.

Among the tidal expiratory flow measurements that have been suggested as surrogate tests for airway obstruction, a short time to reach peak tidal expiratory flow (t(pef)) is the most widely used. Time to peak expiratory flow is most often expressed as the ratio between t(pef) and total expiratory time (t(e)). As te strictly depends inversely on respiratory rate (RR), we studied the hypothesis that an increase in RR (and a fall in t(e)) with the development of airway obstruction during methacholine or histamine challenge in infants could mask a decrease of t(pef) when expressed as t(pef)/t(e). Thirty-three infants (ages 6.5-23 months) with recurrent wheeze were studied during sedated sleep. Runs of tidal breathing and maximal expiratory flow at FRC (V(maxFRC)) measured by the squeeze technique were obtained before and after the challenge. All infants responded to the challenge: the median fall in P(tCO2) was 25%, and it was 43% in V(maxFRC). RR increased from a median value of 31.1 to a median of 35.1 breaths/min. Both t(pef) and t(e) were significantly shorter after the challenge (P < 0.001 and 0.004, respectively); however, the decrease in t(pef)/t(e) was not significant (P=0.081). The change in t(pef)/t(e) was positively correlated with the change in RR (r = 0.51, P = 0.003). To analyze better the effect of changes in RR on various indices, we divided the patients into two groups: in 17 subjects with a small increase in RR (< 10%), t(e) did not change significantly, while t(pef) and t(pef)/t(e) did; in 16 subjects with a more marked increase in RR (> or = 10%), the shortening of te masked the simultaneous shortening of t(pef), so that t(pef)/t(e) did not change. These data demonstrate that t(pef)/t(e) cannot be reliably used to evaluate changes in airway obstruction when concomitant changes in RR occur.

Airway Obstruction↗
PubMed1996

Gastric smooth muscle tumors: diagnostic dilemmas and factors affecting outcome.

We reviewed the 46 gastric stromal tumors that were treated at our institution between 1958 and 1992. The most common presenting symptoms were gastrointestinal bleeding, pain, and fatigue or malaise. The tumors ranged from 4 to 150 mm, with surgery most often being a wedge excision or partial gastrectomy. Abdominal computed tomography was the most specific diagnostic test obtained preoperatively. Factors associated with decreased survival included size >/= 8 cm (p = 0.02), more than 0-3 mitoses per 10 HPF (p < 0. 001), positive margins or unresectability (p = 0.008), and tumor pathologic grade II or more (p = 0.004). These tumors have an unpredictable behavior. Surgical resection with negative margins remains the best therapy, but resection for palliation is sometimes indicated as it can be associated with prolonged survival.

Adult↗
PubMed1996

Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity.

OBJECTIVE: Pulmonary fibrosis is a prominent feature of chronic lung disease of prematurity (CLD). We sought to determine the influence of the potent profibrotic cytokine transforming growth factor beta-1 (TGF-Beta 1) on the development of CLD. METHODS: We determined the concentration of active and total TGF-Beta 1 in bronchoalveolar lavage fluid obtained from 18 infants who subsequently had CLD (mean gestation, 25.7 weeks; birth weight, 816 gm) 15 (29.8 weeks, 1493 gm) who recovered from the respiratory distress syndrome, and 7 (35.1 weeks, 2441 gm) control infants. RESULTS: The concentration of both active and total TGF-Beta 1 was increased in the infants with CLD when compared with the respiratory distress syndrome and control groups. The increase in active and total TGF-Beta 1 was greatest on day 4 of age, when infants who eventually had CLD were compared with those who did not progress to CLD (active TGF-Beta 1, 39.5 vs 4.6 ng/ml; total TGF-Beta 1, 43.8 vs 13.8 ng/ml). In addition, immunocytochemistry studies localized pan-TGF-Beta to alveolar macrophages obtained by bronchoalveolar lavage. CONCLUSIONS: These observations indicate that TGF-Beta 1 may contribute to the fibrotic response that is observed in the lungs of infants who have CLD.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Description of a one step staggered reannealing method for directional cloning of PCR-generated DNA using sticky-end ligation without employing restriction enzymes.

A novel method is described for ligation of PCR products into vectors. It utilizes formation of sticky end sequences compatible with those generated on the plasmid. Four primers are used: two primers are designed to contain the desired sequence of the sticky end plus the sequence of the gene and the other two primers contain the same sequence as the first two primers without the additional bases. The primers are paired to create two PCR products containing the additional bases in a staggered 5' position. Following melting and reannealing, the newly formed products contain the additional sequences as sticky overhangs compatible with the sticky ends of the plasmid.

Animals↗
PubMed1996

A portable device based on the interrupter technique to measure bronchodilator response in schoolchildren.

A new device for measuring airway resistance following brief airflow interruption (Microlab 4000; Micromedical Ltd, UK) was evaluated in 25 asthmatic school children in comparison with well-established methods. Airway resistance was measured during brief airflow interruption (Rint), before and after administration of salbutamol 200 micrograms by metered-dose inhaler, and in the spirometric parameters, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), and total respiratory system resistance at 6 Hz (Rrs,6) measured by the forced oscillation technique (FOT). The sensitivity index (SI) (mean change/baseline standard deviation) was calculated for each subject. At baseline, interrupter conductance, the reciprocal of Rint, correlated well with FEV1 (r = 0.837; p < 0.001) and PEF (r = 0.773; p < 0.001), and Rint correlated highly with Rrs,6 (r = 0.942; p < 0.001). The median intrasubject coefficient of variation of the interrupter method was higher than the FOT or either spirometric parameter; Rint 11%, Rrs,6 9%, FEV1 5% and PEF 5%. However, the sensitivity to detect change after bronchodilator, expressed as the median SI, did not differ significantly between measurements: Rint 3.5, Rrs,6 3.6, FEV1 2.4 and PEF 3.0. A significant response (SI > 2) was shown by the interrupter in 22 of the subjects compared with 16 by FEV1. The interrupter technique is useful for assessing changes in airway calibre in asthmatic school children, with a sensitivity at least as good as standard methods. Such a device could be of particular value in those too young to perform spirometry.

Airway Resistance↗
PubMed1996

Evaluation of a new interrupter device for measuring bronchial responsiveness and the response to bronchodilator in 3 year old children.

The interrupter technique for measuring airway resistance is non-invasive and convenient, and therefore ideally suited for the assessment of induced changes in airway calibre in preschool children. The aim of this study was to evaluate a commercially available interrupter device (based on Microlab 4000), which calculates the interrupter resistance (Rint) from pressure and flow following a brief interruption of expiration during quiet breathing. The repeatability of Rint was assessed, and its response to methacholine challenge and the bronchodilator salbutamol were compared with an indirect technique, the fall in transcutaneous oxygen tension (Ptc,O2), using the sensitivity index (SI, i.e. the change after challenge expressed in multiples of the baseline standard deviation) in 12 wheezy children (aged 3 yrs +/- 2 months). The mean (SD) baseline value of Rint was 0.91 (0.20) kPa.L-1.s. Short-term repeatability and baseline variability were satisfactory for Rint (intraclass correlation coefficient = 0.6; mean intrasubject coefficient of variation = 13%). Although 10 of the 12 subjects obtained a significant response using Rint at maximal bronchoconstriction (i.e. SI > 2), overall, Rint was five times less sensitive than Ptc,O2 (geometric mean SI: Rint 3 vs Ptc,O2 16; p < 0.0001). Reversal of obstruction with administration of a bronchodilator was clearly demonstrated in almost all subjects: Rint after challenge (mean +/- SD) 1.25 (0.22) kPa.L-1.s; after salbutamol 0.78 (0.19) kPa.L-1.s; p < 0.001. In conclusion, the convenient interrupter resistance method appears more promising for detecting bronchodilator responses than induced bronchoconstriction in wheezy preschool children; however, measurement of transcutaneous oxygen tension provides a reliable indirect means of detecting induced airway obstruction in this age-group.

Airway Resistance↗
PubMed1996

Acute frontal lobe syndrome and dyscontrol associated with bilateral caudate nucleus infarctions.

BACKGROUND: A 67-year-old man presented with acute onset of spatial and temporal disorientation, memory loss and associated episodic dyscontrol. Investigations showed infarctions of both caudate nuclei. This patient presented a unique opportunity to study the relationship between the lesions, his behaviour, and neuropsychological testing. METHOD: Single case report. Investigations included interviews to determine cognitive impairment, i.e. WAIS-R, MMSE, and neurological examination. RESULTS: Extensive neuropsychological testing revealed severe impairment on tasks requiring planning, memory or abstract thought. These findings are very similar to those seen in Huntington's disease. CONCLUSIONS: A neurobiological hypothesis is proposed to account for his symptoms, and recent discoveries in the basic sciences used to inform his management.

Aged↗
PubMed1996

Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity.

Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1 beta and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants (median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four (38 wk, 2690 g) control infants. IL-1 beta and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1 beta, 4.6 versus 1.1 ng/mL, p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p < 0.05). Immunocytochemistry of lavage cells for IL-1 beta, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1 beta and IL-8 mRNA was similar in both groups. These results suggest that IL-1 beta, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Mapping the genes for haloperidol-induced catalepsy.

The strain means for haloperidol-induced catalepsy were determined in the 26 strain BXD recombinant inbred series. The ED50 values ranged from 0.55 mg/kg (strain 30) to 7.9 mg/kg (strain 2). Heritability for the catalepsy response was 0.78 and the number of effective loci was estimated to be four. The strain means were correlated with the strain distribution patterns for 1300 marker loci of known chromosomal location and polymorphic between the C57Bl/6J and DBA/2J strains. Six quantitative trait loci (QTLs) were identified at P < .01. Two of the six QTLs were confirmed in a sample of B6XD2 F2 animals (n = 144), phenotyped for haloperidol response and genotyped for microsatellites closely linked to the QTLs. The confirmed QTL on chromosome 4 is near the b locus. The confirmed QTL on chromosome 9 is closely linked to Drd2, the D2 dopamine receptor gene. One hundred of the F2 individuals were phenotyped for D2 dopamine receptor binding using the ligand [125I] epidepride as the ligand. Consistent with previous results, the nonresponsive F2 individuals showed modestly higher receptor binding in all brain regions examined: the nucleus accumbens core, the nucleus accumbens shell, the lateral caudate putamen, the dorsomedial caudate putamen, the substantia nigra zona compacta and the ventral tegmental area. The DBA/2J allele of the chromosome 9 QTL was associated with higher receptor binding in all brain areas except the ventral tegmental area. Overall, the data illustrate that either near or part of Drd2 is a QTL which has significant effects on both haloperidol response and D2 dopamine receptor binding. However, the data also illustrate that most of the genetic variance in either haloperidol response or D2 dopamine receptor binding is not associated with Drd2.

Animals↗
PubMed1996

[Retinal grafts: biological problems and clinical stakes].

Retinal transplantation, formerly perceived as unrealistic, has become over the past decade a major clinical and biological undertaking in several laboratories and eye clinics. We describe the insights gained through the pioneering experimental works of Del Cerro et al, Turner et al, Gouras et al, Aramant et al, Lund et al e.g. the survival of transplants, the lack of immune response to photoreceptors, their integration and expression of neuronal markers, but also the dysplastic arrangement into rosettes and the lack of a definitive proof for functionality. Our laboratory has undertaken to establish the trophic and synaptic functions of sheets of photoreceptors transplanted, as described by Silverman et al, in the subretinal space of mutant rd mice carrying a retinal degeneration similar to human retinitis pigmentosa. Clinical applications to this condition as well as in cases of end-stage age related macular degeneration are discussed.

Animals↗
PubMed1996

Measuring quality of life for young children with asthma and their families.

In assessing therapeutic interventions in asthma we have become increasingly aware of the importance of measuring outcomes which relate to patient experience of illness and its impact on their lives. These patient oriented assessments are usually defined as "quality of life" measures. There are good reasons for wanting to measure the impact of disease on people with asthma. Quality of life is likely to be related to health behaviour, such as adherence to therapy and use of health resources. Quality of life may be a stronger predictor of these behaviours than objective symptoms. Thus, in evaluating health-related interventions, quality of life is an important dimension of outcome measurement. Adult measures are now frequently used but there has been less development of measures suitable for children. Important issues in measuring quality of life for children include the development of age-appropriate scales, measurement of the impact of illness on the whole family, and the relationship between child's report and proxy report. Recently developed asthma specific scales for children include the Child Asthma Questionnaire (CAQ), and the Paediatric Asthma Quality of Life Questionnaire (PAQLQ). The PAQLQ comprises a form directly assessing child quality of life and a form assessing paediatric care-givers (usually a parent). The impact of child asthma on the family as a whole may be particularly important not only for comparing benefits of different interventions, but also for predicting outcomes, such as medical help-seeking.

Adult↗
PubMed1996

[A new technique for isolation of photoreceptor layer].

OBJECTIVE: If somebody wants to start the research of photoreceptor transplantation, first of all, the pure photoreceptor layer should be obtained. The pure photoreceptor is the key of retinal transplanting experiment for accurate analyses and good results. We present the pure photoreceptor layer isolation technique. METHOD: A vibratome, a special machine for tissue and cell isolation, was used for retinal isolation and pure photoreceptor cells were harvested. RESULTS: The pure photoreceptor cell layers of mice, rats, rabbits, monkeys and human have been obtained by this new technique. CONCLUSIONS: By the technique, 100 per cent of pure photoreceptor cells could be isolated, and the manipulation is simple and reliable.

Animals↗
PubMed1995

Intensive care for critically ill elderly: mortality, costs, and quality of life. Review of the literature.

The literature on outcomes of intensive care for the elderly with regard to intensive care unit utilization, mortality, hospital costs and charges, and quality of life after intensive care were reviewed. Publications in the English literature, which evaluated intensive care and included elderly populations, were obtained from review of Index Medicus and MEDLINE. We conclude that age alone is not an acceptable predictor of critical illness with regard to mortality and quality of life of survivors. A therapeutic trial and appropriately discontinuing life support may lead to better utilization of intensive care. Additional data are needed on long-term mortality and quality of life after hospital discharge.

Aged↗
PubMed1995

Identification of H-ras mutations in urine sediments complements cytology in the detection of bladder tumors.

BACKGROUND: Urinary cytology has long been used as a noninvasive screen for the detection of urinary tract cancer but is limited by the generation of false positive and false negative results. More recently, molecular changes associated with urothelial neoplastic progression have been identified in DNA from urine sediments, demonstrating an alternative approach for identifying neoplastic change in the bladder. PURPOSE: The purpose of this prospective study was to determine the value of detection of H-ras (also known as HRAS) mutations in urine sediment DNA as a clinical indicator of tumor presence, recurrence, and/or progression. METHODS: Urine sediments were collected from 100 patients presenting with bladder tumors, with follow-up samples collected from 19 patients. DNA extracted from urine sediments was analyzed for changes in exon 1 of the H-ras gene, using single-strand conformation polymorphism (SSCP) analysis. A representative number of aberrant H-ras/SSCP migrating bands were excised and sequenced to confirm the presence of a mutation. Human bladder specimens were obtained from patients (93 of the 100 patients initially and 18 of the 19 patients studied by follow-up) and histologically evaluated for tumor content and grade. RESULTS: Mutations in exon 1 of the H-ras gene were detected in urine sediments from 44% (44 of 100) of the patients; concordant results were obtained by cytologic analysis, where 33% (31 of 93) of the patients displayed positive cytology. Analysis of the distribution of abnormalities with tumor grade revealed greater detection of low-grade (1-2) lesions using ras analysis (47%) compared with cytology (16%). In contrast, cytology was more effective in identifying the presence of carcinoma in situ. Combined results from these two approaches substantially increased the sensitivity of tumor detection, resulting in the identification of tumors in 60% of patients. CONCLUSIONS: Identification of H-ras mutations in DNA from urine sediments facilitates the detection of low-grade bladder tumors and, in combination with cytology, increases the overall tumor detection from 33% to 60%. Preliminary results in patient follow-up suggest that detection of H-ras mutations may have some clinical utility in detecting the presence of abnormal cells in the absence of an overt lesion following cystoscopy or positive cytology.

Base Sequence↗