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Steven M Scharf

Publications and source records attributed to Steven M Scharf.

10 recordsLinked to original sources
PubMed2006

Feasibility of retinoids for the treatment of emphysema study.

BACKGROUND: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. METHODS: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 +/- 12.0% of predicted] and CT density mask (38.5 +/- 12.8% of voxels <- 910 Hounsfield units) [mean +/- SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. RESULTS: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. CONCLUSIONS: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time- and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.

Aged↗
PubMed2005

Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats.

RATIONALE AND OBJECTIVES: Obstructive sleep apnea (OSA) is associated with oxidative stress and myocardial dysfunction. We hypothesized that the chronic intermittent hypoxia (CIH) component of OSA is sufficient to lead to these adverse effects. METHODS AND RESULTS: Rats were exposed to CIH (nadir O2, 4-5%) for 8 hours/day, 5 days/week, for 5 weeks. Results were compared with similarly handled controls (HC). Outcomes included blood pressure (tail cuff plethysmograph), echocardiographic and invasive measures of left-ventricular (LV) function, and indices of oxidative stress that included levels of myocardial lipid peroxides and Cu/Zn superoxide dismutase. Blood pressure was greater in CIH (n=22) than in HC (n=22) after 2 weeks of exposure (136+/-12 vs. 128+/-8 mm Hg; p<0.05). However, the difference disappeared by 5 weeks (127+/-13 vs. 127+/-13 mm Hg). LV weight/heart weight was greater with CIH (CIH, 0.52+/-0.05; HC, 0.47+/-0.06; p<0.005). Echocardiograms revealed LV dilation, as well as decreased LV fractional shortening (CIH, 29.7+/-9.8%; HC, 37.4+/-7.1%; p<0.001). LV end-diastolic pressure was increased with CIH (CIH, 13.7+/-5.5; HC, 8.0+/-2.9 mm Hg; p<0.001), decreased LV dp/dtmax (CIH, 5072+/-2191; HC, 6596+/-720 mm Hg/second; p<0.039), and decreased cardiac output (CIH, 48.2+/-10.5; HC, 64.1+/-10.9 ml/minute; p<0.001). LV myocardial lipid peroxides were greater (CIH, 1,258+/-703; HC 715+/-240 microm/mg protein; p<0.05) and LV myocardial superoxide dismutase levels were lower (CIH, 10.3+/-4.9; HC, 18.6+/-8.2 U/mg protein; p<0.05) with CIH. CONCLUSIONS: CIH leads to oxidative stress and LV myocardial dysfunction.

Animals↗
PubMed2005

Prevalence of concomitant sleep disorders in patients with obstructive sleep apnea.

We determined the prevalence of concomitant sleep disorders in patients with a primary diagnosis of obstructive sleep apnea (OSA). We retrospectively analyzed 643 patients, aged > or =18, with a primary diagnosis of OSA, evaluated by sleep specialists, in whom clinical and polysomnographic data were derived using standardized techniques by reviewing data from a standardized database and clinical charts. Concomitant sleep disorders were listed according to the International Classification of Sleep Disorders (American Academy of Sleep Medicine, 2000). The mean age was 48.5+/-13.5 years and 55% were male. Racial distributions were African-Americans 51.8% and Caucasian 47%. Indices of disordered breathing were respiratory disturbance index 32.4+/-30.4/h sleep and time <90% O(2) saturation 44.5+/-81.6 min. Thirty-one percent of patients had a concomitant sleep disorder. The most common were inadequate sleep hygiene (14.5%) and periodic limb movement disorder (PLMD, 8.1%). Of patients with other sleep disorders, 66.8% had treatment initiated for these disorders. Predictors of inadequate sleep hygiene (logistic regression) were: age (each decade OR=0.678, P=0.000000), gender (for M, OR=0.536), and the presence of at least one other major system disorder (OR=2.123, P=0.0015). Predictors of PLMD were: age (each decade OR=0.794, P=0.0005), gender (for M, OR=0.433, P=0.004), and total sleep time (for each 10 min, OR=0.972, P=0.0013). We conclude that approximately one third of patients with sleep apnea have another identifiable sleep disorder, usually requiring treatment. This suggests that practitioners evaluating and treating sleep apnea ought to be prepared to deal with other sleep disorders as well.

Female↗
PubMed2004

Comparison of primary-care practitioners and sleep specialists in the treatment of obstructive sleep apnea.

We wished to determine if being treated for sleep apnea by a sleep specialist increased patient awareness or long-term continuous positive airway pressure (CPAP) compliance. We performed a retrospective telephone survey and laboratory chart review in patients with a diagnosis of sleep apnea evaluated either at a laboratory in which only sleep specialists can order polysomnography (University Specialty Hospital, noted as USH) or at a laboratory serving the medical community at large (Kernan Hospital, noted as K). Both laboratories are under the same medical director, use the same policies and procedures, equipment, and technician pool. One hundred three patients participated in the survey (approximately 37% of those contacted), 59 from USH and 44 from K. The groups were comparable in terms of demographics, presenting complaints, and apnea severity. In patients treated by sleep specialists, awareness of the disease process was greater and the evaluation was timelier than in patients treated by generalists. However, there was no difference between the groups' long-term self-reported CPAP acceptance or compliance. The most robust predictor of continued CPAP use was the patient's self-report of feeling better.

Adult↗
PubMed2004

Racial differences in clinical presentation of patients with sleep-disordered breathing.

We characterized differences in severity, presentation, and treatment compliance in sleep-disordered breathing (SDB) between African Americans (AA) and Caucasians (W). We retrospectively analyzed demographics, proxy measures of socioeconomic position, concurrent illness, presenting complaints, polysomnographic data including respiratory disturbance index (RDI) and time less than 90% O2 saturation (T90), and acceptance of and long-term compliance with CPAP therapy. Over 1 year there were 128 AA, 102 W, and 3 "other." AA were younger (44.9+/-14.1 vs. 49.2+/-14.5 years; P=0.022), had greater body mass index (BMI) (39.7+/-10.7 vs. 33.4+/-9.2 kg/m2; p<0.0001), and reported lower estimated median household income (MHI) than W ($33,365+/-15,236 vs. $52,641+/-20,209; p<0.0001). OSA was more severe among AA: (median RDI: AA 32.9, W 29.1 events/h; p=0.008; median T90: AA 17.6 vs. W 5.3 per minute; P=0.006). However, after adjustment for BMI and MHI, differences between AA and W in RDI were not significant. Equal frequencies of AA and W accepted and were compliant with CPAP. We conclude that while AA present with more severe OSA than W this was accounted for by factors known to influence OSA severity. Further, there were no racial differences in accepting and adhering to therapy with CPAP.

Adolescent↗
PubMed2003

Body composition and resting energy expenditure in clinically stable, non-weight-losing patients with severe emphysema.

STUDY OBJECTIVES: To characterize the metabolic status of weight-stable and clinically stable individuals with advanced emphysema. PATIENTS: Seventy-nine patients with severe emphysema (FEV(1), 29 +/- 13% of predicted [mean +/- SD]) evaluated for enrollment in the National Emphysema Treatment Trial and 20 age-matched healthy subjects were studied. SETTING: Pulmonary function laboratory of university-affiliated teaching hospital. INTERVENTIONS: Data collection. MEASUREMENTS AND RESULTS: We measured lung function, body composition, serum leptin levels, serum tumor necrosis factor receptors (sTNF-Rs), resting oxygen consumption (RVO(2)) normalized to weight in kilograms (RVO(2)/kg), and RVO(2) normalized to fat-free mass (FFM) [RVO(2)/FFM]. The patient group and healthy group had similar age, body mass index (BMI), and body composition. RVO(2)/kg, RVO(2)/FFM, and sTNF-R levels were higher in patients compared to healthy subjects. There were no differences in serum leptin levels between emphysematous and healthy subjects, and there was no correlation between leptin and sTNF-R and RVO(2)/kg. Furthermore, both groups had similar gender-related differences in FFM, percentage of body fat, and serum leptin levels. Patients with lower BMI showed the greatest differences from control subjects in RVO(2)/kg. CONCLUSION: In weight-stable subjects with advanced emphysema, RVO(2)/kg and RVO(2)/FFM were higher compared to healthy subjects, especially in those with BMI in the lower end of the normal range. RVO(2)/kg and RVO(2)/FFM did not correlate with leptin or sTNF-R levels. These data show that a higher metabolic rate is found in patients with emphysema who are clinically and weight stable. Thus, hypermetabolism is a feature of the disease and not sufficient to lead to weight loss.

Aged↗
PubMed2002

Hemodynamic characterization of patients with severe emphysema.

In 120 patients with severe emphysema evaluated for participation in the National Emphysema Treatment Trial, pulmonary hemodynamics and ventricular function were assessed. Pulmonary function tests were (%predicted): FEV(1) = 27%; residual volume = 224.6%; diffusion capacity = 26.7%. In 90.8% of patients, end-expiratory pulmonary artery mean pressure was > 20 mm Hg; in 61.4%, end-expiratory wedge pressure was > 12 mm Hg. Cardiac index was normal. Mean pulmonary artery pressure correlated inversely with arterial PO(2), and severity of emphysema, and directly with wedge pressure. Multiple stepwise regression revealed that arterial PO(2) was not an independent predictor of mean pulmonary artery pressure. No correlation was found between indices of emphysema severity and PA pressures. Diastolic ventricular pressures were increased without evidence of systolic dysfunction. We conclude that (1) elevations of pulmonary vascular pressures are common, (2) pulmonary hypertension may be related to factors other than hypoxia, (3) pulmonary hypertension does not impair resting systemic O(2) delivery, and (4) elevated cardiac diastolic pressures do not represent systolic dysfunction.

Aged↗
PubMed2002

Improvement in spirometry following lung volume reduction surgery: application of a physiologic model.

According to a previously published theoretical model of emphysema, the ratio of RV to TLC (RV/TLC) reflects the size mismatch between the hyperinflated lungs in the disease and the surrounding chest. The model suggests that RV/TLC is an important predictor of improvement in FVC and that increased FVC is an important determinant of increased FEV(1) after lung volume reduction surgery (LVRS). We tested these predictions in 13 patients undergoing LVRS, in whom we made detailed measurements of lung mechanics. Using stepwise regression, we found that RV/TLC was the only preoperative independent predictor of the increase in FVC. Seventy percent of the increase in FEV(1) was attributable to increased FVC, with the remainder due to increased FEV(1)/FVC. In a separate group of 78 LVRS patients evaluated with standard preoperative pulmonary function tests, RV/TLC again was found to correlate with the increase in FVC, and changes in FEV(1) were also due largely to changes in FVC. However, RV/TLC was not predictive of the increase in FEV(1) among the group of 78 patients, because FEV(1)/FVC in patients with a low preoperative RV/TLC often increased despite little change in FVC. These findings support the proposed mechanism for increased FVC following LVRS. They also illustrate the limitations of the model, and suggest further hypotheses for selecting patients who may benefit from surgery.

Aged↗