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Biomedical subjects

R S Goldstein

Publications and source records attributed to R S Goldstein.

At least 19 recordsLinked to original sources
PubMed1999

Differential expression of Islet-1 in neural crest-derived ganglia: Islet-1 + dorsal root ganglion cells are post-mitotic and Islet-1 + sympathetic ganglion cells are still cycling.

The Islet-1 antigen is an early marker of differentiation of neural tube cells, and is expressed in many other embryonic cells as well. It had been reported that Islet-1 is expressed only in post-mitotic sympathetic neuroblasts in vitro, unlike other differentiation markers. We have double-labeled St. 23 chick embryos for bromodeoxyuridine (BrDU) and Islet-1 and found that neural tube and dorsal root ganglion (DRG) cells express Islet-1 after leaving the cell cycle, while sympathetic ganglion (SG) cells express Islet-1 while still dividing.

Animals↗
PubMed1999

Generic and specific measurement of health-related quality of life in a clinical trial of respiratory rehabilitation.

The purpose of this study was to compare the performance of measures of health-related quality of life in a randomized controlled trial of respiratory rehabilitation versus conventional community care for patients with chronic airflow limitation. The study included 89 stable patients with moderate to severe chronic airflow limitation with measurement of health status at 12, 18, and 24 weeks. Outcomes included two disease-specific (the Oxygen Cost Diagram and the Chronic Respiratory Questionnaire [CRQ]) measures, a generic health profile (the Sickness Impact Profile [SIP]), and two utility measures (the Standard Gamble and the Quality of Well-Being index [QWB]). Of the measures, only the four domains of the CRQ (dyspnea, fatigue, mastery, and emotional function) showed statistically significant differences (P < or = 0.05) between treatment and control groups. Correlation between change in the CRQ and change in other relevant measures, including the 6-minute walk test and global ratings of change in dyspnea, fatigue, and emotional function were generally weak to moderate (from 0.19 to 0.51). All correlations between change in the QWB, SIP, and Standard Gamble and other measures were very weak or weak (up to 0.30). Correlation between change in the three generic measures were all very weak (<0.15). The results suggest that unless investigators include responsive and valid disease-specific measures of health-related quality of life in controlled trials in chronic diseases, they risk misleading conclusions about the effect of treatments on health status.

Health Care Surveys↗
PubMed1999

Overviews of respiratory rehabilitation in chronic obstructive pulmonary disease.

The purpose of this study was to critically appraise overviews of respiratory rehabilitation in chronic obstructive pulmonary disease (COPD) in order to verify to what extent they convey evidence-based information helpful in implementing new rehabilitation programmes. A Medline search (1985-September 1995) for overviews related to rehabilitation, exercise therapy, education and/or psychological support in COPD was conducted. Chapters of major textbooks of respiratory medicine were also included. The search was limited to the English literature. Two independent reviewers assessed the overviews according to a validated index of scientific quality of research overviews using the following criteria: 1) the literature search method; 2) the inclusion criteria for original articles in the overview; 3) the validity assessment of the original articles; 4) the synthesis of findings; and (5) the conclusion of the overview. Thirty-eight overviews were included. Overall, the methodological quality of the overviews was low (quality score: median 2/7; range 1-5). In only one overview did the author state that the work was based on the results of a literature search. The methodological quality of the primary studies included in the overviews was not included in any of the reviews. The conclusions were only partially supported by the results extracted from the cited primary studies. The widespread application of respiratory rehabilitation in chronic obstructive pulmonary disease should be preceded by demonstrable improvements in function attributable to the intervention. Evidence-based overviews of the literature could assist in implementing new rehabilitation programmes.

Evidence-Based Medicine↗
PubMed1998

Bile duct obstruction is not a prerequisite for type I biliary epithelial cell hyperplasia.

Biliary obstruction, produced by common bile duct ligation or alpha-naphthylisothiocyanate (ANIT) treatment in rats, has been associated with the development of type I biliary epithelial cell (BEC) hyperplasia. However, the exact mechanism(s) by which bile duct obstruction lead(s) to this proliferative lesion are not clear. The present studies were designed to determine if cholestasis, in the absence of biliary obstruction, would result in type I BEC hyperplasia. Male Sprague-Dawley rats were given a single oral dose of 150 mg/kg ANIT or i.v. doses of estradiol glucuronide (E2-17G; 21 mumol/kg/h for 48 h) to produce obstructive and non-obstructive cholestasis, respectively. E2-17G treatment resulted in cholestasis that was comparable in extent and duration to that observed following ANIT treatment. E2-17G and ANIT treatments produced comparable increases in serum bile acids (55- to 60-fold) and activities of ALT (36- to 38-fold), ALP (4- to 5-fold), and 5'-nucleotidase (7- to 11-fold), respectively, compared to controls. Both ANIT and E2-17G also increased serum bilirubin concentrations. ANIT treatment resulted in significant increases in biliary glucose concentrations that were associated with BEC damage/necrosis and obstruction of the bile duct lumen. Conversely, no evidence of BEC damage was observed in E2-17G-treated rats. Nonetheless, BEC hyperplasia was observed in the majority of rats following treatment with either ANIT or E2-17G, assessed by light microscopy and by BrdU immunohistochemistry. These data indicate that E2-17G treatment produces nonobstructive cholestasis and type I BEC hyperplasia, suggesting that biliary obstruction is not a prerequisite for type I BEC hyperplasia in rats. Differences in the time of onset of hyperplasia were observed: hyperplasia was noted immediately following 48 h of E2-17G-induced cholestasis but occurred several days after ANIT-induced cholestasis had subsided. Since the magnitude/duration of cholestasis was similar in the two models but the temporal association between cholestasis and type I BEC hyperplasia were different, these data suggest that the proliferative stimulus may be different in the two models and that E2-17G-induced type I BEC hyperplasia may not be attributed solely to cholestasis.

1-Naphthylisothiocyanate↗
PubMed1998

The influence of 6 months of oral anabolic steroids on body mass and respiratory muscles in undernourished COPD patients.

STUDY OBJECTIVE: To evaluate the influence of oral anabolic steroids on body mass index (BMI), lean body mass, anthropometric measures, respiratory muscle strength, and functional exercise capacity among subjects with COPD. DESIGN: Prospective, randomized, controlled, double-blind study. SETTING: Pulmonary rehabilitation program. PARTICIPANTS: Twenty-three undernourished male COPD patients in whom BMI was below 20 kg/m2 and the maximal inspiratory pressure (PImax) was below 60% of the predicted value. INTERVENTION: The study group received 250 mg of testosterone i.m. at baseline and 12 mg of oral stanozolol a day for 27 weeks, during which time the control group received placebo. Both groups participated in inspiratory muscle exercises during weeks 9 to 27 and cycle ergometer exercises during weeks 18 to 27. MEASUREMENTS AND RESULTS: Seventeen of 23 subjects completed the study. Weight increased in nine of 10 subjects who received anabolic steroids (mean, +1.8+/-0.5 kg; p<0.05), whereas the control group lost weight (-0.4+/-0.2 kg). The study group's increase in BMI differed significantly from that of the control group from weeks 3 to 27 (p<0.05). Lean body mass increased in the study group at weeks 9 and 18 (p<0.05). Arm muscle circumference and thigh circumference also differed between groups (p<0.05). Changes in PImax (study group, 41%; control group, 20%) were not statistically significant. No changes in the 6-min walk distance or in maximal exercise capacity were identified in either group. CONCLUSION: The administration of oral anabolic steroids for 27 weeks to malnourished male subjects with COPD was free of clinical or biochemical side effects. It was associated with increases in BMI, lean body mass, and anthropometric measures of arm and thigh circumference, with no significant changes in endurance exercise capacity.

Administration, Oral↗
PubMed1997

In vivo NGF treatment increases proliferation in the primary sympathetic ganglia of chick embryos.

Nerve growth factor (NGF) is considered to be a target-derived survival or differentiation factor for neural crest cells of the sympathoadrenal lineage. However, exogenous NGF was found to have a positive effect on the size of the primary sympathetic ganglia (PSG) of the chick embryo, well before sympathetic innervation of the periphery. We have determined the cellular mechanism of NGF's action on the PSG by quantifying both proliferation and apoptosis. The proportion of PSG cells in S-phase is nearly double in NGF-treated embryos compared to that in controls, strongly suggesting that NGF acts as a mitogenic factor. NGF reduced the low level of apoptosis at this stage as well. Since trkA has not been detected in the avian sympathetic ganglia until later in development, we suggest that these early effects of exogenous NGF may be mediated by the low-affinity neurotrophin receptor, p75, which is expressed from neural crest migration stages.

Animals↗
PubMed1997

Interpreting small differences in functional status: the Six Minute Walk test in chronic lung disease patients.

Functional status measurements are often difficult to interpret because small differences may be statistically significant but not clinically significant. How much does the Six Minute Walk test (6MW) need to differ to signify a noticeable difference in walking ability for patients with chronic obstructive pulmonary disease (COPD)? We studied individuals with stable COPD (n = 112, mean age = 67 yr, mean FEV1 = 975 ml) and estimated the smallest difference in 6MW distances that was associated with a noticeable difference in patients' subjective comparison ratings of their walking ability. We found that the 6MW was significantly correlated with patients' ratings of their walking ability relative to other patients (r = 0.59, 95% confidence interval [CI]: 0.54 to 0.63). Distances needed to differ by 54 m for the average patient to stop rating themselves as "about the same" and start rating themselves as either "a little bit better" or "a little bit worse" (95% CI: 37 to 71 m). We suggest that differences in functional status can be statistically significant but below the threshold at which patients notice a difference in themselves relative to others; an awareness of the smallest difference in walking distance that is noticeable to patients may help clinicians interpret the effectiveness of symptomatic treatments for COPD.

Aged↗
PubMed1997

The components of a respiratory rehabilitation program: a systematic overview.

OBJECTIVE: To determine the contribution of the various components of a rehabilitation program to the improvement of exercise capacity and health-related quality of life (HRQL) in patients with COPD. DATA SOURCES: MEDLINE (1966 to April 1996) was searched. Abstracts presented at international conferences were also hand searched for additional relevant trials. Bibliographies of the retrieved articles were reviewed. Experts in rehabilitation were consulted to uncover unpublished trials. STUDY SELECTION: Randomized controlled trials (RCTs) of exercise training, breathing exercises, education, and psychosocial support in patients with COPD were primarily included if (1) the treatment effect of a specific component of a rehabilitation program could be isolated, and (2) exercise capacity, HRQL, compliance with medical therapy, and/or knowledge about the disease were measured. DATA SYNTHESIS: A best-evidence synthesis was conducted; 22 RCTs contributed to the analysis. We found the following: (1) the patients exposed to interventions that included exercise training improved their functional exercise capacity and HRQL; (2) exercise training was muscle specific; (3) the evidence to support inspiratory muscle training and other breathing exercises as an adjunct to exercise training in COPD remains equivocal; (4) the contribution of education has not been well addressed; and (5) psychosocial support reduced dyspnea acutely and, when used as an adjunct to rehabilitation, promoted compliance with an exercise regimen and improved HRQL. CONCLUSION: Respiratory rehabilitation is likely to improve functional exercise capacity and HRQL if it includes exercise training and psychosocial support. Further research is required to better define the types and intensity of exercise as well as the influence of respiratory muscle training and patient education.

Breathing Exercises↗
PubMed1997

Proportional assist ventilation and exercise tolerance in subjects with COPD.

STUDY OBJECTIVE: This study determined whether proportional assist ventilation (PAV) applied during constant power submaximal exercise could enable individuals with severe but stable COPD to increase their exercise tolerance. DESIGN: Prospective controlled study having a randomized order of intervention. SETTING: Pulmonary function exercise laboratory. PARTICIPANTS: Ten subjects with severe stable COPD (mean [SD]: age=59 [6] years; FEV1=29 [7]% predicted; FEV1/FVC=33 [7]%; thoracic gas volume=201 [47]% predicted; diffusion of carbon monoxide=36 [10]% predicted; PaO2=76 [8] mm Hg; and PaCO2=41 [4] mm Hg). INTERVENTION: Each subject completed five sessions of cycling at 60 to 70% of their maximum power. The sessions differed only in the type of inspiratory assist: (1) baseline (airway pressure [Paw]=0 cm H2O); (2) proportional assist ventilation (PAV) (volume assist=6 [3] cm H2O/L, flow assist=3 [1] cm H2O/L/s); (3) continuous positive airway pressure (CPAP) (5 [2] cm H2O); (4) PAV+CPAP; and (5) sham (Paw=0 cm H2O). MEASUREMENTS AND RESULTS: Dyspnea was measured using a modified Borg scale. Subjects reached the same level of dyspnea during all sessions but only PAV+CPAP significantly (p<0.05) increased exercise tolerance (12.88 [8.74] min) vs the sham session (6.60 [3.12] min). Exercise time during the PAV and CPAP sessions was 7.10 [2.83] and 8.26 [5.54] min, respectively. Minute ventilation increased during exercise but only during PAV+CPAP was the end exercise minute ventilation greater than the unassisted baseline end exercise minute ventilation (36.2 [6.7] vs 26.6 [6.4] L/min, respectively; p<0.05). CONCLUSIONS: In this study, PAV+CPAP provided ventilatory assistance during cycle exercise sufficient to increase the endurance time. It is now appropriate to evaluate whether PAV+CPAP will facilitate exercise training.

Aged↗
PubMed1997

Economic analysis of respiratory rehabilitation.

STUDY OBJECTIVE: We report on the incremental costs associated with improvements in health-related quality of life (HRQL) following 6 months of respiratory rehabilitation compared with conventional community care. DESIGN: Prospective randomized controlled trial of rehabilitation. SETTING: A respiratory rehabilitation unit. PARTICIPANTS: Eighty-four subjects who completed the rehabilitation trial. INTERVENTION: Two months of inpatient rehabilitation followed by 4 months of outpatient supervision. MEASUREMENTS AND RESULTS: All costs (hospitalization, medical care, medications, home care, assistive devices, transportation) were included. Simultaneous allocation was used to determine capital and direct and indirect hospitalization costs. The incremental cost of achieving improvements beyond the minimal clinically important difference in dyspnea, emotional function, and mastery was $11,597 (Canadian). More than 90% of this cost was attributable to the inpatient phase of the program. Of the nonphysician health-care professionals, nursing was identified as the largest cost center, followed by physical therapy and occupational therapy. The number of subjects needed to be treated (NNT) to improve one subject was 4.1 for dyspnea, 4.4 for fatigue, 3.3 for emotion, and 2.5 for mastery. CONCLUSION: Cost estimates of various approaches to rehabilitation should be combined with valid, reliable, and responsive measures of outcome to enable cost-effectiveness measures to be reported. Comparison studies with the same method are necessary to determine whether the improvements in HRQL that follow inpatient rehabilitation are cheap or expensive. Such information will be important in identifying the extent to which alternative approaches to rehabilitation can influence resource allocation. A consideration of cost-effectiveness from the perspective of NNT may be useful in the evaluation of health-care programs.

Aged↗
PubMed1996

Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease.

BACKGROUND: Respiratory rehabilitation is increasingly recognised as an important part of the management of patients with chronic obstructive pulmonary disease (COPD). The widespread application of such programmes should be preceded by evidence of directly attributable improvements in function. We assessed the effect of respiratory rehabilitation on exercise capacity and health-related quality of life (HRQL) in patients with COPD. METHODS: We carried out a meta-analysis of randomised controlled trials of respiratory rehabilitation in patients with COPD that assessed functional or maximal exercise capacity, HRQL, or both. Respiratory rehabilitation was defined as exercise training (for at least 4 weeks) with or without education, psychological support, or both. The most commonly used measure for HRQL was the chronic respiratory questionnaire, in which responses were presented on a 7-point scale. The control groups received no rehabilitation. Within each trial and for each outcome an effect size was calculated; the effect sizes were then pooled by a random-effects model. The overall effect of treatment was compared with its minimum clinically important difference (MCID)--defined as the smallest difference perceived as important by the average patient. FINDINGS: We included 14 trials. Significant improvements were found for all the outcomes. For two important features of HRQL, dyspnoea and mastery, the overall treatment effect was larger than the MCID: 1.0 (95% CI 0.6-1.5) and 0.8 (0.5-1.2), respectively, compared with an MCID of 0.5. For functional exercise capacity (6-min walk test), the overall effect was 55.7 m (27.8-92.8), and for maximum exercise capacity (incremental cycle ergometer test), 8.3 W (2.8-16.5). Functional exercise capacity showed heterogeneity that could not be explained by the sensitivity analyses. INTERPRETATION: Respiratory rehabilitation relieves dyspnoea and improves the control over COPD. These improvements are clinically important. The value of the improvement in exercise capacity is not clear. Respiratory rehabilitation is an effective part of care in patients with COPD.

Exercise Therapy↗
PubMed1996

Rescue of sensory ganglia that are programmed to degenerate in normal development: evidence that NGF modulates proliferation of DRG cells in vivo.

The dorsal root ganglia (DRG, spinal ganglia) are a metameric series of structures that develop from neural crest cells within the dorsal somitic mesoderm. A striking element of patterning within this meristic series is the disappearance of the five or six most rostral DRG early in the embryonic development of birds and mammals. The transient DRG have been named "Froriep's ganglia" after their 19th century discoverer (reviewed in Lim et al., 1987). The ontogeny of the longest surviving Froriep's ganglion of the chick embryo, DRG C2, has recently been examined in detail (Rosen et al., 1996). At St. 18 (Embryonic Day (E)2.5+), the C2 DRG had the same shape and volume as permanent ganglia C5 and C6. C2's development first diverged from that of normal DRG at St. 19 (E3-), when C2 was observed to be half the size and shaped differently from its neighbors, and its peripheral nerve root began to degenerate. Both lower proliferation and higher apoptosis rates contribute to the reduced size of C2 compared to normal DRG at St. 19-20. One-third fewer C2 cells were found to be in S-phase when compared to neighboring ganglia, and apoptotic cells were more than three times more abundant in C2 than in conventional DRG at this stage. Since growth factors modulate both proliferation and apoptosis, we postulated that these molecules and/or their receptors might be responsible for the difference in fate between C2 and C5. In order to begin to evaluate this hypothesis, we have now treated embryos with nerve growth factor (NGF) in ovo. NGF treatments partially rescued C2, producing a 50% reduction in the normal difference in size between C2 and C5 at St. 23. At least part of this rescue could be accounted for by increased levels of proliferation in the NGF-treated C2 compared to those in control embryos. Proliferation in normal DRG C5 was unaffected by NGF application. NGF treatment rescued DRG cells in both C2 and C5 from cell death. Staining of pycnotic nuclei revealed that NGF dramatically reduced the death in the C2 ganglia. In addition to providing insight into the early patterning of the DRG, our results shed new light on the best-studied neurotrophic factor, NGF. Our finding is the first direct evidence for a role for NGF in control of DRG cell proliferation in vivo.

Animals↗