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Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 19 recordsLinked to original sources
PubMed2001

An auroral flare at Jupiter.

Jupiter's aurora is the most powerful in the Solar System. It is powered largely by energy extracted from planetary rotation, although there seems also to be a contribution from the solar wind. This contrasts with Earth's aurora, which is generated through the interaction of the solar wind with the magnetosphere. The major features of Jupiter's aurora (based on far-ultraviolet, near-infrared and visible-wavelength observations) include a main oval that generally corotates with the planet and a region of patchy, diffuse emission inside the oval on Jupiter's dusk side. Here we report the discovery of a rapidly evolving, very bright and localized emission poleward of the northern main oval, in a region connected magnetically to Jupiter's outer magnetosphere. The intensity of the emission increased by a factor of 30 within 70 s, and then decreased on a similar timescale, all captured during a single four-minute exposure. This type of flaring emission has not previously been reported for Jupiter (similar, but smaller, transient events have been observed at Earth), and it may be related directly to changes in the solar wind.

Journal Article↗
PubMed2001

Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences.

The identification of clones within bacterial populations is often taken as evidence for a low rate of recombination, but the validity of this inference is rarely examined. We have used statistical tests of congruence between gene trees to examine the extent and significance of recombination in six bacterial pathogens. For Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus, the congruence between the maximum likelihood trees reconstructed using seven house-keeping genes was in most cases no better than that between each tree and trees of random topology. The lack of congruence between gene trees in these four species, which include both naturally transformable and nontransformable species, is in three cases supported by high ratios of recombination to point mutation during clonal diversification (estimates of this parameter were not possible for Strep. pyogenes). In contrast, gene trees constructed for Hemophilus influenzae and pathogenic isolates of Escherichia coli showed a higher degree of congruence, suggesting lower rates of recombination. The impact of recombination therefore varies between bacterial species but in many species is sufficient to obliterate the phylogenetic signal in gene trees.

Alleles↗
PubMed2001

Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration.

BACKGROUND: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia. METHODS: We studied the activity and core-body temperature rhythms in a cohort of 38 male patients with a clinical diagnosis of probable Alzheimer disease (AD) approximately 2 years before death. These patients were later given a confirmed diagnosis of AD (n = 23), frontotemporal degeneration (FTD) (n = 9), or diffuse Lewy body disease (DLB) with mixed AD or FTD pathologies (n = 6) after autopsy and neuropathological examination. Physiological rhythms of patients with AD and FTD were then compared with a group of normal, elderly men (n = 8) from the community. RESULTS: Alzheimer patients showed increased nocturnal activity and a significant phase-delay in their rhythms of core-body temperature and activity compared with patients with FTD and controls. The activity rhythm of FTD patients was highly fragmented and phase-advanced in comparison with controls and apparently uncoupled from the rhythm of core-body temperature. CONCLUSIONS: Patients with AD and patients with FTD show different disturbances in their rhythms of activity and temperature compared with each other and with normal elderly patients.

Age Factors↗
PubMed2001

Conflict resolution at the University of Ottawa Faculty of Medicine: The Pelican and the sign of the triangle.

In 1997 the University of Ottawa Medical School adopted a conflict-resolution policy for informally dealing with complaints of abuse, harassment and intimidation, sexual harassment, and scientific misconduct or misappropriation of intellectual property. In collaboration with the university's Faculty of Law, general conflict-resolution workshops were given for faculty and administration and mediation training was provided to medical faculty designated "complaint officers" under the policy. In this article, the authors describe the policy and training and then analyze the first major incident arising after the policy's implementation: the publication of disrespectful misogynist material in The Pelican, a medical student society newsletter. The Pelican incident is used as a "lessons learned" case study both in terms of its multiple outcomes and as an opportunity to pinpoint some important policy and practical considerations that emerged in implementing a conflict-resolution policy. The article also describes the results of a learning environment survey conducted after the Pelican incident.

Conflict, Psychological↗
PubMed2001

Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease.

Regular short-acting inhaled beta-agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 microg albuterol. All patients received regular ipratropium bromide at 20 microg per puff in 2 puffs four times daily, beclomethasone at 250 microg per puff or equivalent corticosteroid in 2 puffs twice daily, and open-label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 microg per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol daily). Despite greater beta-agonist use, patients showed similar results during treatment and control periods for all outcomes. Differences between active and placebo periods were: FEV1: -0.04 L (95% confidence interval [CI]: -0.09 to 0.01 L); slow vital capacity: 0.04 L (95% CI: -0.12 to 0.20 L); 6-min walk test distance: -3.1 m (95% CI: -16.8 to 10.5 m); and Chronic Respiratory Questionnaire scores for dyspnea: 0.02 (95% CI: -0.13 to 0.16); fatigue: -0.02 (95% CI: -0.25 to 0.20); mastery: 0.01 (95% CI: -0.20 to 0.24); and emotional function: 0.02 (95% CI: -0.20 to 0.24). We found that in patients with COPD, use of regular short-acting inhaled beta-agonists resulted in twice as much beta-agonist use without physiologic or clinical benefit as did use on an as-needed basis.

Administration, Inhalation↗
PubMed2001

Nutritional intervention in COPD: a systematic overview.

OBJECTIVE: We conducted a systematic overview of randomized controlled trials (RCTs) to clarify the contribution of nutritional supplementation for patients with stable COPD. METHODS: RCTs were identified from several sources, including the Cochrane Airways Group register of RCTs, a hand search of abstracts presented at international meetings, and consultation with experts. Two reviewers independently selected trials for inclusion, assessed quality, and extracted the data. RESULTS: Twenty-one reports were classified according to the type, duration of supplementation, and the presence of anabolic substances. High carbohydrate meals were associated with an increase in carbon dioxide production and a decrease in exercise capacity. Short-term crossover studies in which diets of various compositions were administered supported the notion that high carbohydrate loads increase the stress on the ventilatory system. The influence of longer-term supplementation (> 2 weeks) on weight, anthropometry, and exercise capacity varied, without there being a consistent effect. Lean body weight was only occasionally reported and health-related quality of life too rarely to be included as an outcome. The influence of recombinant human growth hormone was disappointing. Anabolic steroids increased body weight and lean body mass, but had little influence on exercise capacity. CONCLUSION: This systematic overview in patients with COPD supports the notion that those with marginal ventilatory reserve might benefit from a dietary regimen in which a high percentage of calories are supplied by fat. Although there are reports of the benefits of nutritional repletion, trials of > 2 weeks failed to show consistent benefit on body weight. Evaluating nutritional repletion is hampered by the absence of information regarding body composition, exercise, and health-related quality of life. Growth hormone has not been shown to be useful. Further studies are needed to refine the beneficial effects of anabolic steroids as adjunctive agents together with nutritional support and exercise.

Anabolic Agents↗
PubMed2000

A comparison of chronic pain patients and controls on traumatic events in childhood.

PURPOSE: The purpose was to examine the incidence of traumatic events in childhood, such as sexual and physical abuse, in a chronic pain group and a control group of hospital employees without chronic pain. METHOD: Ninety two patients with chronic pain, age range 20-62, were consecutively recruited from the outpatient clinics of a rehabilitation hospital and a general hospital. Ninety eight hospital employees, age range 20-62, were consecutively recruited from the employee health office of a rehabilitation hospital. All participants responded to nine questions related to sexual, physical and verbal abuse in childhood and completed the Childhood Traumatic Events Scale. A logistic regression with age, gender, sexual, physical, and verbal abuse, death of a family member, childhood illness, major upheaval before age 17, as independent variables were used to predict membership in the pain group contrasted with the control group. RESULTS: Child abuse was reported in the childhood history by 54.4% of the chronic pain group, compared with 21.4% of the control group. A logistic regression showed that after adjusting for gender and age, sexual and verbal abuse were statistically significant predictors of being a member of the pain group. Odds ratios were sexual abuse: 2.67, p < 0.05, CI 1.00-7.14. Verbal abuse: 4.39, p < 0.001, CI 1.93-9.97. A logistic regression was modelled to predict child abuse when gender was taken into account. The results of the logistic regression showed that pain was a significant predictor for sexual abuse after adjusting for gender and age: odds ratio 4.37, p < 0.001, CI 1.80-10.60. Gender was not a statistically significant predictor for sexual abuse, after adjusting for pain and age: odds ratio 2.92, p < 0.072, CI 0.91-9.42. CONCLUSIONS: A history of physical, sexual and verbal abuse is more likely to occur in a chronic pain group than in a control group of hospital employees. Although child abuse is reported to be as high as 25% in the general American population, the statistics for chronic pain patients are twice as high as in the general population. The mechanisms for abuse include age, gender, and early family environment.

Adult↗
PubMed2000

Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction. The THROMBO Investigators.

Thrombosis contributes to recurrent coronary events in patients after acute myocardial infarction (AMI), but prognostic significance of thrombogenic factors by gender is unknown. This study aimed to determine gender-related differences in the prognostic significance of thrombogenic factors for predicting cardiac events (nonfatal reinfarction or cardiac death) in postinfarction patients. Blood levels of the following factors were measured 2 months after AMI in 791 men and 254 women: fibrinogen, von Willebrand factor, factor VII and VIIa, plasminogen activator inhibitor, D-dimer, cholesterol, apolipoprotein A-1, apolipoprotein B, lipoprotein(a), triglycerides, and high-density lipoprotein cholesterol. After adjustment for clinical covariates, levels of apolipoprotein A, high-density lipoprotein cholesterol, fibrinogen, and factor VIIa were significantly higher in postinfarction women than men. During a mean 26-month follow-up, there were 67 cardiac events (8.5%) in men and 14 (5.5%) in women (p = 0.11). In the multivariate Cox model, elevated levels of factor VIIa were a significant predictor of cardiac events in women (p = 0.022) but not in men (p = 0.80), with significant gender-related effect (hazard ratio 2.80 vs 0.92, respectively; p <0.05). D-dimer had prognostic value in men (p = 0. 006) but not in women (p = 0.36), although the difference between hazard ratios for men and women was not significant (2.35 vs 1.58, respectively; p = 0.49). In conclusion, elevated levels of factor VIIa are associated with an increased risk of recurrent cardiac events in postinfarction women, but not in men. D-dimer is more predictive for cardiac events in postinfarction men than women. These observations indicate possible gender-related differences in the pathophysiologic mechanisms of recurrent cardiac events.

Apolipoproteins↗
PubMed2000

Psychiatric disorders and impairment in the children of opiate addicts: prevalances and distribution by ethnicity.

This study examined rates of psychiatric disorders and impairment in 283 children, aged 6 to 17, of 69 Caucasian, 45 African-American, and 47 Hispanic-American methadone maintenance patients. Children were evaluated by direct and/or parental interview with the K-SADS-E. Final DSM-III-R diagnoses and Global Assessment Scale (C-GAS) were assigned by best estimate. Substantial lifetime prevalences of mood (21%), anxiety (24%) and disruptive disorders (30%), school problems (37%), and global impairment (C-GAS < 61) (25%) were observed in the children of opiate-dependent patients. There were few differences between ethnic groups. Effects of proband gender and major depression and their interactions with ethnicity on risk for childhood psychopathology were also examined. The results suggest children of patients in treatment for opiate dependence from diverse ethnic groups are at risk for psychopathology. Programs for early detection and intervention should be devised and evaluated.

Adolescent↗
PubMed2000

Variability of outer membrane protein P1 and its evaluation as a vaccine candidate against experimental otitis media due to nontypeable Haemophilus influenzae: an unambiguous, multifaceted approach.

Candidate vaccine antigens for preventing otitis media caused by nontypeable Haemophilus influenzae (NTHI) should possess one or more conserved epitopes. We sought to evaluate the candidacy of P1, a surface-expressed outer membrane protein knowing that this antigen is subject to diversifying selection. Therefore, we selected NTHI strains from among >500 phylogenically variant isolates representative of the diversity found in natural populations of H. influenzae. Twenty-three variants of P1 (</=95% similarity) were identified among 42 strains. When chinchillas were immunized with recombinant P1 (rP1) obtained from one of these isolates (BCH-3), all animals developed antibodies specific for rP1. Immunized animals were protected against disease when challenged with BCH-3, but not with an ompP1 mutant of BCH-3 or a strain (BCH-2) possessing a heterologous P1 (91% identity). We conclude that (i) while P1 induces protection against NTHI-mediated otitis media, development of a polyvalent vaccine reflecting the variability of P1 would be necessary to construct an efficacious vaccine and (ii) use of a phylogenically characterized collection of representative isolates in concert with gene sequencing, cloning, gene inactivation, and animal testing offers an efficient, rational, and rigorous strategy for evaluating the potential problems associated with variability of vaccine targets and specificity of related immune responses.

Amino Acid Sequence↗
PubMed2000

Drinking water turbidity and gastrointestinal illness in the elderly of Philadelphia.

STUDY OBJECTIVE: To investigate the association between drinking water quality and gastrointestinal illness in the elderly of Philadelphia. DESIGN: Within the general population, children and the elderly are at highest risk for gastrointestinal disease. This study investigates the potential association between daily fluctuations in drinking water turbidity and subsequent hospital admissions for gastrointestinal illness of elderly persons, controlling for time trends, seasonal patterns, and temperature using Poisson regression analysis. SETTING AND PARTICIPANTS: All residents of Philadelphia aged 65 and older in 1992-1993 were studied through their MEDICARE records. MAIN RESULTS: For Philadelphia's population aged 65 and older, we found water quality 9 to 11 days before the visit was associated with hospital admissions for gastrointestinal illness, with an interquartile range increase in turbidity being associated with a 9% increase (95% CI 5.3%, 12.7%). In the Belmont service area, there was also an association evident at a lag of 4 to 6 days (9.1% increase, 95% CI 5.2, 13.3). Both associations were stronger in those over 75 than in the population aged 65-74. This association occurred in a filtered water supply in compliance with US standards. CONCLUSIONS: Elderly residents of Philadelphia remain at risk of waterborne gastrointestinal illness under current water treatment practices. Hospitalisations represent a very small percentage of total morbidity.

Aged↗
PubMed2000

Skeletal muscle fiber quality in older men and women.

Whole muscle strength and cross-sectional area (WMCSA), and contractile properties of chemically skinned segments from single fibers of the quadriceps were studied in 7 young men (YM, 36.5 +/- 3. 0 yr), 12 older men (OM, 74.4 +/- 5.9 yr), and 12 older women (OW, 72.1 +/- 4.3 yr). WMCSA was smaller in OM compared with YM (56.1 +/- 10.1 vs. 79.7 +/- 13.1 cm(2); P = 0.031) and in OW (44.9 +/- 7.5; P < 0.003) compared with OM. Age-related, but not sex-related, differences in strength were eliminated after adjusting for WMCSA. Maximal force was measured in 552 type I and 230 type IIA fibers. Fibers from YM (type I = 725 +/- 221; type IIA = 792 +/- 271 microN) were stronger (P < 0.001) than fibers from OM (I = 505 +/- 179; IIA = 577 +/- 262 microN) even after correcting for size. Type IIA fibers were stronger (P < 0.005) than type I fibers in YM and OM but not in OW (I = 472 +/- 154; IIA = 422 +/- 97 microN). Sex-related differences in type I and IIA fibers were dependent on fiber size. In conclusion, differences in WMCSA explain age-related differences in strength. An intrinsic defect in contractile proteins could explain weakness in single fibers from OM. Sex-related differences exist at the whole muscle and single fiber levels.

Adult↗
PubMed2000

Carbohydrate malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints.

BACKGROUND: Carbohydrate malabsorption of lactose, fructose and sorbitol has already been described in normal volunteers and in patients with functional bowel complaints including irritable bowel syndrome. Elimination of the offending sugar(s) should result in clinical improvement. OBJECTIVE: To examine the importance of carbohydrate malabsorption in outpatients previously diagnosed as having functional bowel disorders, and to estimate the degree of clinical improvement following dietary restriction of the malabsorbed sugar(s). METHODS: A cohort of 239 patients defined as functional bowel complaints was divided into a group of 94 patients who met the Rome criteria for irritable bowel syndrome and a second group of 145 patients who did not fulfill these criteria and were defined as functional complaints. Lactose (18 g), fructose (25 g) and a mixture of fructose (25 g) plus sorbitol (5 g) solutions were administered at weekly intervals. End-expiratory hydrogen and methane breath samples were collected at 30 minute intervals for 4 hours. Incomplete absorption was defined as an increment in breath hydrogen of at least 20 ppm, or its equivalent in methane of at least 5 ppm. All patients received a diet without the offending sugar(s) for one month. RESULTS: Only 7% of patients with IBS and 8% of patients with FC absorbed all three sugars normally. The frequency of isolated lactose malabsorption was 16% and 12% respectively. The association of lactose and fructose-sorbitol malabsorption occurred in 61% of both patient groups. The frequency of sugar malabsorption among patients in both groups was 78% for lactose malabsorption (IBS 82%, FC 75%), 44% for fructose malabsorption and 73% for fructose-sorbitol malabsorption (IBS 70%, FC 75%). A marked improvement occurred in 56% of IBS and 60% of FC patients following dietary restriction. The number of symptoms decreased significantly in both groups (P < 0.01) and correlated with the improvement index (IBS P < 0.05, FC P < 0.025). CONCLUSIONS: Combined sugar malabsorption patterns are common in functional bowel disorders and may contribute to symptomatology in most patients. Dietary restriction of the offending sugar(s) should be implemented before the institution of drug therapy.

Adult↗
PubMed1999

Elimination of non-viable 6-thioguanine-sensitive T cells from viable T cells prior to PCR analysis.

The study of T cell clones at the genomic level is expanding our understanding of their role in diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). We have been carrying out genotypic analysis by PCR of hypoxanthine phosphoribosyltransferase (hprt) mutations in these cells. Mutant T cells in the population can be cloned on the basis of their resistance to the cytotoxic drug, 6-thioguanine-(6-TG). A difficulty is that the majority of primary human T cells are capable of only limited growth ex vivo, even in the presence of 'feeder' cells. PCR analysis of DNA from such clones is made difficult by the limited number of viable mutant (drug-resistant) T cells and the large number of dead (drug-sensitive) mononuclear cells and feeder cells. DNA from the 'dead' cells remains sufficiently intact for many weeks in culture and can represent a significant source of background in PCR analysis. Here we describe a method employing hypotonic shock and micrococcal nuclease that reliably eliminates non-viable 6-TG-sensitive cells, allowing the study of the hprt gene in < 200 T cells by PCR.

Arthritis, Rheumatoid↗
PubMed1999

An epidemic of burkholderia cepacia transmitted between patients with and without cystic fibrosis.

Burkholderia cepacia is an important pathogen in cystic fibrosis (CF) and an infrequent cause of nosocomial infection in non-CF patients. This report describes a large hospital outbreak that appeared to involve both patient groups, a previously unrecognized phenomenon. Ribotype restriction fragment length polymorphism (RFLP) profiles and pulsed-field gel electrophoresis-resolved macrochromosomal RFLPs were analyzed, a ribotype-based phylogenic tree was constructed, and case-control and cohort studies were performed. A single dominant clone was found in both CF and non-CF groups. Phylogenic analysis suggests that it has evolved independently and that such highly transmissible strains can emerge rapidly and randomly. Acquisition risk in the CF patients was linked to hospitalization (odds ratio=5.47, P=.0158, confidence interval=1. 28-26.86) and was associated with significantly increased mortality rates. Infection control policies must now consider this threat of transmission between non-CF and CF patients.

Adolescent↗
PubMed1999

Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy.

Changes in human immunodeficiency virus (HIV) type 1 concentration and protease genotype were evaluated in semen specimens from 22 HIV-positive men before and 6 months after the addition of indinavir to dual nucleoside therapy. Seminal HIV was detected by polymerase chain reaction analysis for DNA or RNA for 59% of men before combination treatment and persisted at 6 months for 31% of the men who initially had seminal HIV detected (P = .026). The maximum levels of cell-free RNA, cell-associated RNA, and proviral DNA in semen before treatment and at 6 months were 400,000 and 10,000 copies/mL, 70,000 and 27,000 copies/mL, and 80,000 and 3,000 copies/mL, respectively. Three of the four men with persistent seminal DNA had plasma viral loads of > 10,000 copies/mL before treatment. One patient who became intolerant to indinavir had seminal HIV RNA detected by PCR analysis after 6 months. Although none of the cultures of semen specimens from the four men with PCR analysis-detectable seminal DNA after 6 months yielded HIV, indinavir resistance mutations were identified in a seminal leukocyte DNA specimen from one patient, and a second patient whose therapy was switched to saquinavir had different protease inhibitor resistance mutations in seminal and blood leukocyte DNA specimens. HIV-1 protease inhibitor resistance mutants may emerge in the semen of patients receiving combination therapy.

Anti-HIV Agents↗
PubMed1999

Natural history of fetuses with cleft lip.

The prospect of fetal surgery for cleft lip is predicated on our ability to accurately identify fetuses with clefts and exclude those that have associated anomalies. Prenatal ultrasound is currently the most appropriate means with which to do this. We reviewed the ultrasonographic data from two large perinatal referral institutions to determine the natural history of fetuses with cleft lip who may be candidates for fetal surgery. Forty fetuses had a cleft lip diagnosed prenatally by ultrasound. In this group, severe associated anomalies were common (30 of the 40) and multiple (23 of the 40) in a majority of fetuses. Life-threatening anomalies, such as central nervous system and cardiac anomalies, were the most common defects. As a result, many fetuses were aborted therapeutically or died in the perinatal period. Out of 12 surviving fetuses, only six had isolated clefts, and two surviving fetuses, diagnosed with isolated cleft lip, had no defect identified postnatally. This information has important implications for the perinatal management of fetuses with cleft lip and the potential role of fetal intervention.

Abnormalities, Multiple↗