Nobel laureates' letter to President Bush.
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Biomedical subjects
Publications and source records attributed to S Cohen.
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OBJECTIVE: To explore how rigid and flexible bronchoscopy are used in pediatric otolaryngologic practice. DESIGN: Survey. PARTICIPANTS: Members of the American Society of Pediatric Otolaryngology who practice in the United States and Canada and were listed in the membership directory were eligible. Of the 206 members, 24 practicing outside the United States or Canada and 11 without an e-mail address or a fax machine were excluded. Hence, a questionnaire was e-mailed or faxed to 171 pediatric otolaryngologists. MAIN OUTCOME MEASURES: Questions concerned the practice setting, type and number of bronchoscopies, indications, complications, and medicolegal cases. RESULTS: Responses were received from 120 subjects (70.2%), with 3 retired and 2 practicing only otology, leaving 115 respondents who completed at least some of the questionnaire. Rigid and flexible bronchoscopy were performed by 72.7% (56/77) of those in academic settings and by 71.1% (27/38) of those in group or solo practices. In the last 12 months, approximately 10 454 total bronchoscopies were performed, with 2052 flexible and 9117 rigid bronchoscopies. Stridor, suspected foreign body inhalation, and laryngomalacia were the most common indications for bronchoscopy. Of the 83 respondents practicing rigid and flexible bronchoscopy, 25 (30.1%) used both instruments to manage complex or repeated foreign bodies, 25 (30.1%) used both to manage patients with cystic fibrosis, and 15 (18.1%) used both to manage simple foreign bodies. Complications were reported by 15.7% of the respondents, the most common being arrhythmia. Familiarity with a case resulting in medicolegal action was reported by 32.2% of the respondents. CONCLUSIONS: Rigid and flexible bronchoscopy have multiple uses in pediatric otolaryngologic practice. Also, flexible bronchoscopy appears to be emerging as a more frequently used diagnostic and therapeutic tool.
OBJECTIVE: Three 6-12-month, double-blind, randomized, controlled trials have shown leflunomide (LEF; 20 mg/day, loading dose 100 mg x 3 days) to be effective and safe for the treatment of rheumatoid arthritis (RA). This analysis of the North American trial assessed whether the clinical benefit evident at month 12 was sustained over 24 months of treatment with LEF as compared with the efficacy and safety of methotrexate (MTX), an equivalent disease-modifying antirheumatic drug, at 24 months. METHODS: The year-2 cohort, comprising patients continuing into the second year of treatment with > or = 1 dose of study medication and > or = 1 followup visit after week 52, consisted of 235 patients (LEF n = 98; placebo n = 36; MTX n = 101). The mean (+/- SD) maintenance dose of LEF was 19.6 +/- 1.99 mg/day in year 2 and that of MTX was 12.6 +/- 4.69 mg/week. Statistical analyses used an intent-to-treat (ITT) approach. Statistical comparisons of the active treatments only were prospectively defined in the protocol. RESULTS: In total, 85% and 79% of LEF and MTX patients, respectively, who entered year 2 completed 24 months of treatment. From month 12 to month 24, the American College of Rheumatology improvement response rates of > or = 20% (LEF 79% versus MTX 67%; P = 0.049), > or = 50% (LEF 56% versus MTX 43%; P = 0.053), and > or = 70% (LEF 26% versus MTX 20%; P = 0.361) were sustained in both of the active treatment groups. The mean change in total Sharp radiologic damage scores at year 2 compared with year 1 and baseline (LEF 1.6 versus MTX 1.2) showed statistically equivalent sustained retardation of radiographic progression in the active treatment groups. Maximal improvements evident at 6 months in the Health Assessment Questionnaire (HAQ) disability index (HAQ DI) and the physical component score of the Medical Outcomes Survey 36-item short form were sustained over 12 months and 24 months; improvement in the HAQ DI with LEF4(-0.60) was statistically significantly superior to that with MTX (-0.37) at 24 months (P = 0.005). Over 24 months in the ITT cohort, serious treatment-related adverse events were reported in 1.6% of the LEF-treated patients and 3.7% of the MTX-treated patients. Frequently reported adverse events included upper respiratory tract infections, diarrhea, nausea and vomiting, rash, reversible alopecia, and transient liver enzyme elevations. CONCLUSION: The safety and efficacy of LEF and MTX were maintained over the second year of this 2-year trial. Both active treatments retarded radiographic progression over 24 months. LEF was statistically significantly superior to MTX in improving physical function as measured by the HAQ DI over 24 months of treatment. Results indicate that LEF is a safe and effective initial treatment for active RA, with clinical benefit sustained over 2 years of treatment without evidence of new or increased toxicity.
Increased erythrocyte, leukocyte, and platelet adhesiveness and aggregation may contribute to the development of ischemic vascular conditions in diabetic patients. They have been described by using different diagnostic systems and following various ex vivo manipulations. We have adopted a simple slide test and image analysis to reveal the adhesiveness and aggregation of the three cellular elements in a picture that is obtained from one single citrated venous blood sample presented on a glass slide. A significant increment in the degree of adhesiveness/aggregation of erythrocytes, leukocytes and platelets was noted in 29 patients with diabetes mellitus as opposed to age- and gender-matched healthy controls. It is feasible to look at the increased state of adhesiveness/aggregation of erythrocytes, leukocytes and platelets present in their native milieu and following minimal manipulation by using an almost real time and low cost procedure.
The aim of this study was to determine whether chronic treatment with the selective MAO-B inhibitor rasagiline, N-propargyl-1-(R)-aminoindan (R-PAI), can prevent or delay stroke or improve its outcome in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). The S-enantiomer of rasagiline, S-PAI a much weaker MAO inhibitor was included in the study in order to expose a possible contribution from MAO inhibition to any beneficial effect by R-PAI. SHRSP were isolated, fed rat stroke prone diet and given 1% NaCl instead of water. Drugs were administered in the drinking fluid for 84 days. Rats were grouped as follows: (1) Untreated control; (2) R-PAI 1 mg/kg/day; (3) R-PAI 3 mg/kg/day; (4) S-PAI 3 mg/kg/day; (5) S-PAI 6 mg/kg/day. Survival, stroke frequency and neurological severity score following stroke were determined. R-PAI at 3 mg/kg/day significantly increased cumulative survival from 56.09 +/- 1.77 days in the untreated to 73.6 +/- 2.22 days in the R-PAI treated; S-PAI at 6 mg/kg/day to 78.61 +/- 2.05 (censored at 84 days). In these groups stroke was delayed, its incidence was decreased and its outcome was less severe than in the control group. Proteinurea observed in the untreated rats and in both lower dose groups of R-PAI and S-PAI was absent in the higher dose groups of both drugs. Histological examination of the brains and kidneys showed that the effects on stroke and survival were associated with decreased infarcts and hemorrhages in the brains and decreased tubular nephropathy and glomerulopathy. The time-dependent rise in systolic blood pressure in the untreated rats was significantly attenuated only in the R-PAI group at 3 mg/kg/day but not in the S-PAI group. There were no significant effects on heart rate. MAO-B activity in the brain was 95% blocked by both doses of R-PAI but only 62% by S-PAI at 6 mg/kg/day. In salt-loaded SHRSP chronic therapy with either R-PAI or S-PAI prevented stroke and severe vascular lesions in the kidney. When stroke did occur its neurological outcome was less severe. The drugs were equipotent when they were given at a ratio of 1:2. The mechanism has yet to be elucidated. The differential effects of the drugs on blood pressure and MAO inhibition rule out either effect as the sole explanation.
Polymyxin B (PMB) is a potent antibacterial lipopeptide composed of a positively charged cyclic peptide ring and a fatty acid containing tail. Polymyxin B nonapeptide (PMBN), the deacylated amino derivative of polymyxin B, is much less bactericidal but able to permeabilize the outer membrane of Gram-negative bacteria and to neutralize the toxic effects of lipopolysaccharide (LPS). In this study, we synthesized and evaluated the antibacterial and LPS neutralizing activities of four PMBN analogs modified at their N-terminal. Our results suggest that oligoalanyl substitutions of PMBN do not effect most of PMBN activities. However, a hydrophobic aromatic substitution generated a PMB-like molecule with high antibacterial activity and significant reduced toxicity.
Free cortisol measured in saliva has been shown to have the same diurnal rhythm as serum cortisol, one that typically declines rapidly throughout the waking day. A recent study showed that over 15% of a sample of community individuals who were monitored over two days did not show the typical diurnal rhythm. The present study specifically tested the hypothesis that there is significant between-subject variation (individual differences) in diurnal rhythms using multi-level, random regression models. Analyses of participants from four studies were conducted; studies varied in terms of the number of saliva samples taken per day, the number of days studied, and participants' demographic and health status. Significant individual differences of diurnal cycle in each of the four samples were found. In at least 10% of each sample no significant diurnal cycles was detected; however, the overall mean level of cortisol of those with flat cycles differed among the samples. These results suggest that some people do not have the expected diurnal rhythm of cortisol secretion. It is not clear what the determinants of this finding are or if there are any health consequences of having a flat cycle.
OBJECTIVE: The demand for organ transplantation exceeds organ donation in France and refusal to organ donation remains close to 30%. This study analysed risk factors associated with refusal of organ donation. STUDY DESIGN: Retrospective study. PATIENTS: All potential organ donors registered by the French transplantation agency between 1996 and 1999 were included, excepted those with a contraindication to organ procurement or a logistic problem: 5,911 donors were included. METHODS: Data analysed were those collected routinely on the French database. A logistic model was used to identify statistically significant factors and a stepwise procedure was performed to identify independent factors linked with refusal. RESULTS: In univariate analysis, age > 60 years and age < 13 years, stroke, lack of suicide, localisation in an university hospital and in others regions than the Centre-East of France were associated with a higher refusal rate. Year of harvesting, low level of organ procurement activity were not associated with refusal. In multivariate analysis, factors independently associated with refusal were age > 60 years [Odds-Ratio (OR) = 1.2)] or age < 13 years (OR = 1.5), stroke (OR = 1.2), meningitis and cranial tumour (OR = 1.4), suicide (OR = 0.5) and others French regions than Centre-East. CONCLUSION: The risk factors described should be taking into account when family's members are approached for donation. They represent the interactions between the history of the donors, harvesting organisation, and sociocultural factors.
This article reviews evidence for the hypothesis that psychological interventions can modulate the immune response in humans and presents a series of models depicting the psychobiological pathways through which this might occur. Although more than 85 trials have been conducted, meta-analyses reveal only modest evidence that interventions can reliably alter immune parameters. The most consistent evidence emerges from hypnosis and conditioning trials. Disclosure and stress management show scattered evidence of success. Relaxation demonstrates little capacity to elicit immune change. Although these data provide only modest evidence of successful immune modulation, it would be premature to conclude that the immune system is unresponsive to psychological interventions. This literature has important conceptual and methodological issues that need to be resolved before any definitive conclusions can be reached.
The authors report a 3-year follow-up of the effects of 8-week support group interventions on the quality of life of women with early stage breast cancer. Shortly after diagnosis, women were randomly assigned to 1 of 4 conditions: control, education, peer discussion, and education plus peer discussion. The education group intervention focused on providing information to enhance control over the illness experience, whereas the peer discussion group intervention focused on providing emotional support through the expression of feelings. Consistent with the results that emerged 6 months after the interventions (V. S. Helgeson, S. Cohen, R. Schulz, & J. Yasko, 1999), the authors found that the benefits of the education intervention were maintained over a 3-year period (N=252), although effects dissipated with time. The authors continued to find no benefits of the peer discussion intervention, either alone or in combination with education.
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The acute phase response is accompanied by the appearance of aggregated red blood cells in the peripheral blood. The Westergren erythrocyte sedimentation rate (ESR) is an indirect measurement of this enhanced aggregability. We adopted a simple slide test and image analysis to reveal the adhesiveness/aggregation of red blood cells. A significant correlation was found between the erythrocyte adhesiveness/aggregation test (EAAT) and the ESR. A predictive model for ESR based on EAAT and the age of the patients was created. This new approach will enable us to obtain within a few minutes a good estimate of whether a given individual has a mild moderate or significant acute phase response. With further development, we will be able to use a bedside small cartridge that will deliver the extrapolated ESR at low costs and within a couple of minutes.
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Adolescent women are at high risk of sexually transmitted diseases/human immunodeficiency virus (STDs/HIV) because of physiologic susceptibility and risky sexual behavior. The latter may be related to the "personal factors" of self-efficacy, sexual knowledge, self-esteem, and ability to communicate/negotiate. In the current study, near-peers attempted to have an impact on these factors by using the female condom as a negotiating tool for safer sex in a group of 100 urban adolescent women recruited from an adolescent health center waiting room. This pilot study consisted of a questionnaire, a workshop on how to use the female condom and negotiate its use, and follow-up interviews at 1 and 4 months. Demographics of the study sample define a multiethnic (40% black, 33% Hispanic) group in late adolescence (average age 18 years) completing high school. At baseline, 18% evidenced depression, 62% had moderate-to-low self-esteem, 91% had an internal locus of control. At baseline, male condom use in the prior 6 months was 28% always, 51% inconsistently, 21% never. When baseline and follow-up scores were compared, there was a statistically significant increase in sexual knowledge and self-efficacy, together with the suggestion of improved negotiating skills. At 1 month, 50% (20/40) had tried the female condom, and 17 of these women planned to use it in the future. Total percentage of protected sex acts increased significantly during the follow-up period through increased use of both the male and female condoms. The data suggest that adolescent women will accept the female condom and can be empowered to protect themselves from STDs/HIV through its application or through the using of it as a negotiating tool.
The objectives of our study were to assess the feasibility of using ground-penetrating radar (GPR) to study roots over a broad range of soil conditions in the southeastern United States. Study sites were located in the Southern Piedmont, Carolina Sandhills and Atlantic Coast Flatwoods. At each site, we tested for selection of the appropriate antenna (400 MHz versus 1.5 GHz), determined the ability of GPR to resolve roots and buried organic debris, assessed root size, estimated root biomass, and gauged the practicality of using GPR. Resolution of roots was best in sandy, excessively drained soils, whereas soils with high soil water and clay contents seriously degraded resolution and observation depth. In the Carolina Sandhills, 16 1 x 1-m plots were scanned with the 1.5 GHz antenna using overlapping grids. Plots were subsequently excavated, larger roots (> 0.5 cm diameter) sketched on graph paper before removal, and all roots oven-dried, classified by size and weighed. Roots as small as 0.5 cm in diameter were detected with GPR. We were able to size roots (0.5 to 6.5 cm in diameter) that were oriented perpendicular to the radar sweep (r(2) = 0.81, P = 0.0004). Use of image analysis software to relate the magnitude of radar parabolas to actual root biomass resulted in significant correlations (r(2) = 0.55, P = 0.0274). Orientation and geometry of the reflective surface seemed to have a greater influence on parabola dimensions than did root size. We conclude that the utility of current GPR technology for estimating root biomass is site-specific, and that GPR is ineffective in soils with high clay or water content and at sites with rough terrain (most forests). Under particular soil and site conditions, GPR appears to be useful for augmenting traditional biomass sampling.