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Biomedical subjects

R S Goldstein

Publications and source records attributed to R S Goldstein.

At least 37 records · Page 2Linked to original sources

Appropriateness of domiciliary oxygen delivery.

OBJECTIVE: Almost every country in the developed world has a domiciliary oxygen program. Whether recipients meet program criteria has not been rigorously studied. DESIGN: Cross-sectional survey. PARTICIPANTS: Two hundred thirty-seven patients receiving domiciliary oxygen in the Ontario Ministry of Health Home Oxygen Program (HOP). METHODS: A respiratory therapist visited the patients' homes and administered questionnaires, obtained resting arterial blood gas measurements, and conducted a standardized home exercise test while monitoring oxygen saturation using an oximeter. MEASURES OF OUTCOME: We evaluated the extent to which patients met HOP criteria that are based on the inclusion criteria of randomized trials showing the life-prolonging effects of domiciliary oxygen. We also assessed the extent to which the patients' oxygen prescription was consistent with the results of rest and exercise testing. RESULTS: Ninety-six of 237 participants (40.5%; 95% confidence interval, 34.3 to 46.8) did not meet criteria for home oxygen. Patients aged < or = 70 years were more likely to meet criteria (71 of 105 patients; 67.9%) than those > 70 years old (70 of 132 patients; 53.0%). The proportion of patients meeting criteria was similar whether the referring physician was a specialist (71 of 112 patients; 62.5%) or a primary-care physician (69 of 123 patients; 56. 1%). A very important health benefit from oxygen was identified among 82% of those who met criteria and 88% of those who did not. Patients received higher flow rates than our criteria suggested were appropriate. Agreement between the independently assessed oxygen prescription at rest and the patients' report of oxygen use was extremely poor (chance-corrected agreement [kappa], 0.17), as was agreement concerning optimal exercise flow rates (kappa, 0.26). CONCLUSIONS: Current procedures for administration and reimbursement of home oxygen result in a large proportion of recipients not meeting criteria, as well as the prescription of excessive oxygen flow rates. These results are likely to apply to many jurisdictions and suggest a large potential for more efficient resource allocation.

Age Factors↗

Plasticity of axial identity among somites: cranial somites can generate vertebrae without expressing Hox genes appropriate to the trunk.

Classic studies have shown that the presomitic mesoderm is already committed to a specific morphological fate, for example, the ability to generate a rib. Hox gene expression in the paraxial mesoderm has also been shown to be fixed early and not susceptible to modulation by an ectopic environment. This is in contrast to the plasticity of Hox expression in neuroectodermal derivatives. We reexamine here the potential of somites for morphological plasticity by transplanting the cranial (occipital) somites 1-4, that normally produce small contributions to the skull, to the trunk of avian embryos. Surprisingly, the transposed cranial somites are able to form reasonably normal vertebral anlage. In addition, the cranial somitic mesoderm produces intervertebral disks, structures not normally found in the skull. These somites are however unable to generate some elements of the vertebrae, such as the costal process. In contrast to the morphogenetic plasticity of the occipital somites, their characteristic inability to support survival of dorsal root ganglia was not significantly modified by posterior transplantation. Dorsal root ganglia initially developed and then degenerated with the same morphological stages as normally observed. In striking contrast to the plasticity of morphology, we found that all four members of the of the fourth paralogous group of Hox genes that are expressed endogenously at the level of the graft are not upregulated in the caudad-transposed cranial mesoderm. It therefore appears that genes other than those of the Hox family normally expressed at this axial level control the position-specific morphogenesis of ectopic vertebrae formed from cranial somites. In evolutionary terms, the present results imply that occipital somites that were incorporated into the "New Head" retain the ability to develop according to their original morphogenetic fate, into vertebrae.

Animals↗

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↗

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↗

Expression of ACC oxidase genes differs among sex genotypes and sex phases in cucumber.

Ethylene has been implicated as a sex-determining hormone in cucumber: its exogenous application increases femaleness, and gynoecious genotypes were reported to produce more ethylene. In this study, three full-length ACC oxidase cDNAs were isolated from cucumber floral buds. RFLP analysis of a population that segregates for the F(femaleness) locus indicated that CS-ACO2 is linked to F at a distance of 8.7 cM. Expression of two of the genes, CS-ACO2 and CS-ACO3, was monitored in flowers, shoot tips and leaves of different sex genotypes. In situ mRNA hybridization indicated different patternsof tissue- and stage-specific expression of CS-ACO2 and CS-ACO3 in developing flowers. CS-ACO3 expression in mid-stage female flowers was localized to the nectaries, pistil and in the arrested staminoids, whereas CS-ACO2 transcript levels accumulated later and were found in placental tissue, ovary and staminoids. In male flowers, petals and nectaries expressed both genes, whereas ACO2 expression was strong in pollen of mature flowers. In young buds, strong expression was observed along developing vascular bundles. Four sex genotypes were compared for CS-ACO2 and CS-ACO3 expression in the shoot apex and young leaf. FF genotypes had higher transcript levels in leaves but lower levels in the shoot apex and in young buds, as compared to ff genotypes; the shoot-tip pattern is, therefore, inversely correlated with femaleness, and the possibility of a feedback inhibition mechanism underlying such correlation is discussed. The two CS-ACO genes studied displayed a differential response to ethrel treatment in different organs and sex genotypes, further demonstrating the complexity of the mechanisms controlling ethylene production during cucumber floral development.

Amino Acid Oxidoreductases↗

Trends in the epidemiology of COPD in Canada, 1980 to 1995. COPD and Rehabilitation Committee of the Canadian Thoracic Society.

PURPOSE: To describe trends in the epidemiology of COPD in Canada from 1980 to 1995, in terms of perceived prevalence, mortality, and hospital morbidity. DATA SOURCES: We limited the analysis to data related to chronic bronchitis, emphysema, or chronic airway obstruction not classified elsewhere, and excluded asthma (Ninth International Classification of Diseases, codes 490 to 492 and 496). The perceived prevalence rate of COPD was derived from the 1994-1995 National Health Survey. Mortality and hospital morbidity data (from 1980 to 1995) were obtained from the Health Statistics Division of Statistics Canada. RESULTS: From the National Health Survey, it was estimated that 750,000 Canadians had chronic bronchitis or emphysema diagnosed by a health professional. Prevalence rates were the following: ages 55 to 64 years, 4.6%; ages 65 to 74 years, 5.0%; > or =75 years, 6.8%. From 1980 to 1995, the total number of deaths from COPD increased from 4,438 to 8,583. Although the age-standardized mortality rate remained stable throughout this period in men (around 45/100,000 population), it doubled in women (8.3/100,000 in 1980 to 17.3/100,000 in 1995). There were 55,782 hospital separations in 1993-1994 with COPD as the primary discharge diagnosis (compared to 42,102 in 1981-1982). In people aged > or =65 years, the age-specific hospital separation rate increased over this period, especially in women > or =75 years (from 504/100,000 to 1,033/100,000). The average in-hospital length of stay was 9.6 days in 1981-1982 and 8.3 days in 1993-1994. CONCLUSION: COPD represents a major health issue in Canada and will likely remain so for decades. Physician and non-physician health professionals who provide health care, as well as those who fund it must actively encourage approaches for primary and secondary prevention of this condition as well as approaches shown to be effective in addressing its associated impairment, disability, and handicap.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗