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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cloning of a novel gene in the human kidney homologous to rat munc13s: its potential role in diabetic nephropathy.

Glomerular mesangial cells (MC) are believed to play a pivotal role in development of diabetic nephropathy. We employed differential display reverse transcription polymerase chain reaction (DDRT-PCR) comparing human MC grown under 25 mM and 5.5 mM D-glucose and osmolarity control as a first step to identify possible candidate genes regulated by hyperglycemia. This strategy resulted in cloning of a novel gene in human MC, human munc13 (hmunc13), a human homologue of rat munc13s with the N-terminal segment similar to munc13-1 and the C-terminal segment more similar to munc13-2. Hmunc13 is also expressed in human kidney cortical epithelial cells. By using relative RT-PCR and Northern blot, we have confirmed that expression of hmunc13 in MC is up-regulated by high D-glucose treatment. Together with previous reports that munc13s binds to diacylglycerol (DAG) and that hyperglycemia increases DAG levels, these findings point to a potential role of hmunc13 in mediating some of the acute and chronic changes in MC produced by exposure to hyperglycemia.

Amino Acid Sequence↗
PubMed1998

Anterior cervical osteophytes as a cause of pharyngeal stage dysphagia.

OBJECTIVE: To describe the association of anterior cervical osteophytes impairing epiglottic movement as an etiology of pharyngeal stage dysphagia. DESIGN: A retrospective chart review. SETTING: An academic affiliated Veterans Affairs Medical Center. PATIENTS: Veterans 60 years of age or older referred to speech pathology for dysphagia evaluation. RESULTS: Of 376 veterans evaluated consecutively since 1990, 40 patients had dysphagia determined to be secondary to cervical bony protuberances. The evaluation and management of three cases with functional consequences at level C3-5 with no dysphagia etiology present are described. CONCLUSION: Cervical osteophytes need to be considered in the differential diagnosis of dysphagia in older people.

Aged↗
PubMed1998

Soluble L-selectin concentration in bronchoalveolar lavage fluid obtained from infants who develop chronic lung disease of prematurity.

AIMS: To explore the changes in neutrophil adhesion molecule expression and release into bronchoalveolar lavage fluid (BAL) obtained from infants who developed chronic lung disease (CLD). METHODS: BAL fluid was obtained from 37 infants: 18 (median gestation 26 weeks, birthweight 835 g) who developed CLD, 12 (29 weeks, 1345 g) with respiratory distress syndrome (RDS) and seven control infants (33 weeks, 2190 g). RESULTS: Soluble L-selectin (sL-selectin) in BAL fluid from the CLD and non-CLD groups was similar immediately after birth, but in infants who subsequently developed CLD, sL-selectin remained persistently increased (at day 7: CLD 42.6 vs RDS 6.0 ng/ml, p < 0.05; CLD vs controls 1.5 ng/ml; p < 0.05). CD11b/CD18 expression on neutrophils obtained by BAL increased with time to reach a maximum at 17 days of age in infants who developed CLD. CONCLUSIONS: These results suggest that leucocyte traffic persists in infants who develop CLD and may have an important part to play in the pathogenesis of CLD.

Analysis of Variance↗
PubMed1998

Arachidonic acid potentiates the feedback response of mesangial BKCa channels to angiotensin II.

The influence of arachidonic acid (AA) on the feedback regulation of mesangial contraction by large Ca(2+)-activated K+ channels (BKCa) was determined through single-channel analysis using the patch clamp method. The mesangial BKCa is a low-gain negative feedback inhibitor of contraction that is activated in response to agonist-induced Ca2+ transients and membrane depolarization. AA activated BKCa in cell-attached patches in a dose-dependent manner with a maximal effect at 400 nM and a half-maximal response at 49 nM. In inside-out patches, AA directly activated BKCa with a maximal effect at 400 nM. BKCa was activated significantly in response to addition of 100 nM ANG II in the presence but not the absence of AA. Since it was shown previously that fatty acids stimulated both soluble and membrane-bound guanylyl cyclase, we determined whether AA activated BKCa by interfering with cGMP-mediated signal transduction pathways. It was previously shown that 10 microM cGMP, via cGMP-dependent protein kinase, activated BKCa in a biphasic manner with an early increase in probability of a channel existing in an open state (Po) and a subsequent inactivation mediated by protein phosphatase 2A (PP2A). We found that 10 microM dibutyryl-cGMP enhanced BKCa activity in an additive manner with saturating concentrations (400 nM) of AA. Moreover, the inactivation phase mediated by PP2A was not abolished. Thus AA does not affect the phosphorylation/dephosphorylation regulatory cycle for BKCa. It is concluded that AA potentiates the ANG II feedback response of BKCa by a mechanism that is independent of the phosphorylation cycle.

Angiotensin II↗
PubMed1998

Irregularities and power law distributions in the breathing pattern in preterm and term infants.

Unlike older children, young infants are prone to develop unstable respiratory patterns, suggesting important differences in their control of breathing. We examined the irregular breathing pattern in infants by measuring the time interval between breaths ("interbreath interval"; IBI) assessed from abdominal movement during 2 h of sleep in 25 preterm infants at a postconceptional age of 40.5 +/- 5.2 (SD) wk and in 14 term healthy infants at a postnatal age of 8.2 +/- 4 wk. In 10 infants we performed longitudinal measurements on two occasions. We developed a threshold algorithm for the detection of a breath so that an IBI included an apneic period and potentially some periods of insufficient tidal breathing excursions (hypopneas). The probability density distribution (P) of IBIs follows a power law, P(IBI) approximately IBI-alpha, with the exponent alpha providing a statistical measurement of the relative risk of insufficient breathing. With maturation, alpha increased from 2.62 +/- 0.4 at 41. 2 +/- 3.6 wk to 3.22 +/- 0.4 at 47.3 +/- 6.4 wk postconceptional age, indicating a decrease in long hypopneas (for paired data P = 0.002). The statistical properties of IBI were well reproduced in a model of the respiratory oscillator on the basis of two hypotheses: 1) tonic neural inputs to the respiratory oscillator are noisy; and 2) the noise explores a critical region where IBI diverges with decreasing tonic inputs. Accordingly, maturation of infant respiratory control can be explained by the tonic inputs moving away from this critical region. We conclude that breathing irregularities in infants can be characterized by alpha, which provides a link between clinically accessible data and the neurophysiology of the respiratory oscillator.

Abdominal Muscles↗
PubMed1998

High-frequency respiratory impedance measured by forced-oscillation technique in infants.

Measurements of respiratory input impedance (Zin) in infants using forced oscillations at the airway opening up to 256 Hz have been shown to include a first antiresonance (ar,1). We wondered whether features derived from high-frequency Zin change during methacholine-induced airway obstruction in infants, whether those changes could be explained by a lumped parameter model as in dogs (providing a value for respiratory resistance [Rrs]), or whether they are similar to Zin data in human adults with airway obstruction. In 13 wheezy infants (age 58 +/- 19 wk) Zin(omega) was assessed at baseline, and in nine infants after methacholine challenge, using a provocation dose defined by fall of more than 30% in VmaxFRC (rapid chest-compression technique). Following methacholine challenge, VmaxFRC decreased significantly (p < 0.0005), the frequency at which ar,1 occurred ( far,1) increased significantly (p = 0.0007), and the relative maximum in the real part at far,1 [Zinre( far,1)] increased significantly (p = 0.02), whereas Rrs did not change. We conclude that in wheezy infants ar,1 is highly sensitive to changes in lung mechanics. Although ar,1 cannot be explained by a simple lumped-parameter model, it is likely due to wave propagation phenomena, as in human adults. In either case, far,1 potentially contains information about airway wall compliance, which is important for the understanding of flow limitation in infant wheezing disorders.

Airway Resistance↗
PubMed1998

Differences in airway wall compliance as a possible mechanism for wheezing disorders in infants.

High-frequency input impedance measurements (Z(f)) provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. Using the high-speed interrupter technique (HIT), we have shown that it is possible to measure high-frequency Z(f) in infants up to 900 Hz, including antiresonant phenomena which are known to be related to wave propagation velocity. This implies that the first antiresonant frequency (far,1) is a function of airway wall compliance. Since, airway wall mechanics are particularly important for the flow limitation phenomena, we wondered whether we could find evidence that airway wall properties were important for the occurrence of flow limitation during incremental methacholine challenge in infants. We measured Z(f) from 32-900 Hz and maximal flow at functional residual capacity (V'maxFRC) by the rapid chest compression technique in 10 infants (aged 36-81 weeks) with wheezing disorders. far,1 increased significantly at very low doses of mch before any decline could be detected in V'maxFRC. We hypothesize that these changes in far,1 are determined by mch-induced decrease in airway wall compliance. High-speed interrupter technique in combination with rapid chest compression technique can be used to study developmental differences in airway function (particularly of airway wall properties) and their contribution to airway disease and response to bronchodilator therapy in infants.

Adult↗
PubMed1998

High-frequency respiratory input impedance measurements in infants assessed by the high speed interrupter technique.

High-frequency input impedance (Z(f)) measurements, including antiresonances, provide useful noninvasive information on airway geometry and especially airway wall mechanics in the canine and human adult respiratory system. A knowledge of airway wall mechanics would be particularly important in understanding flow limitation phenomena in infants. High-frequency Z(f) has not been measured in infants above 256 Hz, because the high impedance of the infantile respiratory system would be expected to result in low amplitudes of oscillatory flow at higher frequencies. The aim of this study was to develop a technique to measure high-frequency Z(f) in infants and to elucidate the nature of the antiresonance phenomena in the Z(f) spectrum in infants. Z(f) was measured from 32-900 Hz during rapid airflow interruption by the high-speed interrupter technique (HIT) in 18 infants (aged 24-149 weeks) with wheezing disorders. The HIT enables the excitement of higher flow amplitudes at high frequencies using a pseudostep forcing function. In all infants Z(f) showed a mean (SD) first antiresonance (far,1) of 172 (35) Hz (real part of Z(f) at far,1 (Z(f)re(far,1)): 4.9 (1.1) kPa x L(-1) x s) and in five infants a second antiresonance (far,2) of 564 (51) Hz (Z(f)re(far,2): 2.0 (0.7) kPa x L(-1) x s). The antiresonances were found to be related to wave propagation in the airways (acoustic antiresonances), because they increased by a factor of approximately 2 when He-O2 was inhaled. This implies that far,1 and its harmonics are a function of airway wall compliance. In conclusion, the first and second antiresonances may be helpful in understanding flow limitation in wheezing disorders in infants, because flow limitation is related not only to airway diameter but also to airway wall compliance.

Adult↗
PubMed1998

Issues relating to children born prematurely.

Preterm infants suffer increased risk of acute and chronic respiratory disorders. In patients with chronic lung disease or severe bronchopulmonary dysplasia, long-term respiratory morbidity and pulmonary dysfunction into late childhood and early adulthood have been reported. This includes symptomatic morbidity (recurrent cough and/or wheeze) and lung function abnormalities such as increased resistance to airflow, airway hyperresponsiveness, and increased propensity to air-trapping. To date, no clinically significant association between prematurity and classical atopic asthma has been demonstrated. Therefore, interventions should primarily focus on the reduction of wheezing disorders and lung function abnormalities in children born prematurely. In order to design interventions in the foetal and early neonatal period or during childhood the potential risk factors for long-term morbidity need to be carefully identified at different age groups: factors which affect pre- and postnatal lung growth, airway inflammation, viral infections, air pollution and others. Future research issues should include well-conducted prospective follow-up programmes which will identify major risk factors in specific populations. Early intervention will provide information on disease mechanisms and on new prophylactic as well as therapeutic strategies.

Bronchial Hyperreactivity↗
PubMed1998

Follicular and Hürthle cell carcinoma: predicting outcome and directing therapy.

BACKGROUND: Follicular thyroid cancer is a heterogeneous disease including follicular and Hürthle cell and tumors with and without vascular and major capsular invasion. Analyses of prognosis and risk groups have been criticized for not taking these differences into account. METHODS: Retrospective analysis was done of 240 patients treated from 1940 to 1997. RESULTS: Ninety-two patients without vascular or major capsular invasion followed up for a median of 14 years had no recurrences or deaths. In the remaining 148 patients, 32 had Hürthle cell and 116 had follicular cell carcinoma. Patients with Hürthle cell carcinoma were significantly older (55 vs 47 years; P = .0014). Lymphatic metastases did not influence outcome. Patients who were at high risk by age and sex, metastases, extent, and size had a 20-year survival rate of 36% for follicular and 35% for Hürthle cell carcinoma; patients at low risk had 20-year survival rates of 94% and 89%, respectively, with no significant difference between follicular and Hürthle cell carcinoma. Recurrences were treated successfully in 33% of patients with follicular carcinoma but never cured in patients with Hürthle cell carcinoma. Bilateral versus unilateral operation or radioiodine for ablation did not alter outcome. CONCLUSIONS: Follicular and Hürthle cell carcinoma with minimal capsular invasion behaved benignly. Age and sex, metastases, extent, and size risk criteria differentiate strongly between patients with high-risk and low-risk follicular and Hürthle cell carcinoma. Controlling for risk factors, Hürthle cell and follicular cell carcinomas have similar prognoses.

Adenocarcinoma, Follicular↗
PubMed1997

Glutathione and neonatal lung disease.

Glutathione (GSH) was measured using HPLC-electrochemical detection in bronchoalveolar lavage fluid from 28 neonates for up to 21 days after birth. GSH levels varied from 0.1-11.2 mumol l-1 (with a geometric mean concentration of 1.3 mumol l-1). GSH in epithelial lining fluid was estimated using the urea dilution method at 15.0 mumol l-1 (range 0.5-196 mumol l-1), which is significantly lower than observed in adult subjects. There was an L shaped relationship between GSH and the two markers of oxygen therapy, oxygen index and FiO2. The lowest GSH levels were associated with the group of infants with the most severe airways problems who required high oxygen.

Bronchoalveolar Lavage Fluid↗
PubMed1997

Recruiting older adults for clinical trials.

More than 400 community-dwelling older adults were recruited into a clinical trial which compared the effectiveness of diagnosis and treatment through geriatric assessment with that provided through usual community physician care. Six recruitment methods were utilized: referrals, solicitations, presentations, media, mailings, and fliers. Each method is described and its results reported in terms of numbers recruited, yield, and cost per participant. The most efficient method was referrals; the method producing the largest number was presentations; the least effective method was fliers. Problems and solutions are discussed, and guidelines for recruiting older adults are suggested. These guidelines include: monitoring with accompanying adaptation, targeting the groups most likely to benefit, providing incentives, and reducing uncertainty among potential participants.

Advertising↗
PubMed1997

Acute renal failure due to indinavir crystalluria and nephrolithiasis: report of two cases.

Two patients with oliguric acute renal failure (ARF) attributed to crystalluria and nephrolithiasis with obstructive uropathy caused by the human immunodeficiency virus protease inhibitor indinavir are described. In both patients, ARF resolved with administration of intravenous fluids. One patient required urologic intervention to relieve bilateral ureteral obstruction.

Acute Kidney Injury↗