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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 73 records · Page 4Linked to original sources
PubMed2001

Protective autoimmunity is a physiological response to CNS trauma.

Primary damage caused by injury to the CNS is often followed by delayed degeneration of initially spared neurons. Studies in our laboratory have shown that active or passive immunization with CNS myelin-associated self-antigens can reduce this secondary loss. Here we show, using four experimental paradigms in rodents, that CNS trauma spontaneously evokes a beneficial T cell-dependent immune response, which reduces neuronal loss. (1) Survival of retinal ganglion cells in rats was significantly higher when optic nerve injury was preceded by an unrelated CNS (spinal cord) injury. (2) Locomotor activity of rat hindlimbs (measured in an open field using a locomotor rating scale) after contusive injury of the spinal cord (T8) was significantly better (by three to four score grades) after passive transfer of myelin basic protein (MBP)-activated splenocytes derived from spinally injured rats than in untreated injured control rats or rats similarly treated with splenocytes from naive animals or with splenocytes from spinally injured rats activated ex vivo with ovalbumin or without any ex vivo activation. (3) Neuronal survival after optic nerve injury was 40% lower in adult rats devoid of mature T cells (caused by thymectomy at birth) than in normal rats. (4) Retinal ganglion cell survival after optic nerve injury was higher (119 +/- 3.7%) in transgenic mice overexpressing a T cell receptor (TcR) for MBP and lower (85 +/- 1.3%) in mice overexpressing a T cell receptor for the non-self antigen ovalbumin than in matched wild types. Taken together, the results imply that CNS injury evokes a T cell-dependent neuroprotective response.

Animals↗
PubMed2001

High-performance anion-exchange chromatography-electrospray mass spectrometry for investigation of the substituent distribution in hydroxypropylated potato amylopectin starch.

The use of high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) coupled on-line with electrospray mass spectrometry (ESI-MS) for analysis of the substitution pattern in chemically modified starch, has been investigated. In order to characterise the distribution of substitution groups along the polymer chain, hydroxypropylated potato amylopectin starch (HPPAP) was subjected to enzymic hydrolysis, followed by analysis of the degradation products by HPAEC-PAD-MS. When using conventional chromatographic techniques for characterisation of enzymic hydrolysates, standard compounds are required for identification of the hydrolysis products. However, the on-line coupling with ESI-MS allowed identification of all products obtained, substituted as well as unsubstituted, and also of those compounds that co-eluted, without the need for standards. Further, HPAEC-PAD-MS was shown to be useful for analysis of the substitution pattern in modified starch; from results obtained it was suggested that the hydroxypropyl groups were homogeneously distributed in the amylopectin molecule. It was also shown that the starch hydrolysing enzymes were hindered by the hydroxypropyl groups and preferentially cleaved glucosidic linkages between unsubstituted glucose units.

Amylopectin↗
PubMed2001

Regular outpatient medical and drug abuse care and subsequent hospitalization of persons who use illicit drugs.

CONTEXT: Patients and the public could benefit from identification of factors that prevent drug users' heavy reliance on inpatient care; however, optimal health care delivery models for illicit drug users remain ill-defined. OBJECTIVE: To evaluate associations of outpatient medical and drug abuse care with drug users' subsequent hospitalization rates. DESIGN AND SETTING: Retrospective cohort study of data from longitudinally linked claims for all ambulatory physician/clinic services and drug abuse services covered by the New York State Medicaid program. SUBJECTS: A total of 11 556 human immunodeficiency virus (HIV)-positive and 46 687 HIV-negative drug users. MAIN OUTCOME MEASURES: Hospitalization in federal fiscal year (FFY) 1997 compared by 4 patterns of care in FFY 1996: regular drug abuse care (>/=6 months in 1 program), regular medical care (>35% of care from 1 clinic, group practice, or individual physician), both, or neither. RESULTS: Hospitalization occurred in 55.6% of HIV-positive and 37.5% of HIV-negative drug users, with a mean of 27.5 and 24.5 inpatient days, respectively. In HIV-positive drug users, the adjusted odds ratio (AOR) for hospitalization was lowest among those with both regular medical and drug abuse care (AOR, 0.76; 95% confidence interval [CI], 0.67-0.85) followed by those with regular medical care alone (AOR, 0.82; 95% CI, 0.74-0.91) and regular drug abuse care alone (AOR, 0.85; 95% CI, 0.76-0.96) vs those with neither. In HIV-negative drug users, the AOR of hospitalization was lower for those with regular medical and drug abuse care (AOR, 0.73; 95% CI, 0.68-0.79), regular drug abuse care alone (AOR, 0.71; 95% CI, 0.66-0.76), and regular medical care (AOR, 0.91; 95% CI, 0.86-0.95) vs those with neither. Both types of care showed favorable effects for all but drug abuse-related hospitalizations. CONCLUSION: Our data indicate that regular drug abuse care with regular medical care for drug users is associated with less subsequent hospitalization.

Adult↗
PubMed2001

Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms.

OBJECTIVES: The aim of this study was to assess the diagnosis of myocarditis in patients presenting with acute myocardial infarction (MI) and normal coronary angiograms. BACKGROUND: Most often in these patients, the etiologic diagnosis remains unclear once they are found to have normal coronary arteries. The diagnosis of myocarditis mimicking MI is clinically relevant, because numerous arguments suggest a relation between myocarditis and dilated cardiomyopathy. Myocardial indium-111 (111In)-antimyosin antibody (AMA)/rest thallium-201 (201Tl) imaging allows noninvasive detection of myocarditis. METHODS: Forty-five patients admitted to three intensive care units for suspicion of acute MI, with normal coronary angiograms, were investigated. Indium-111-AMA planar images and then a dual-isotope rest AMA/201Tl tomographic study were performed. Six-month echocardiographic follow-up was obtained in 80% of the patients with initial left ventricular (LV) wall motion abnormalities. RESULTS: In eight patients, AMA and 201Tl scintigraphy were negative. In two patients, a matched 201Tl defect and focal AMA uptake suggested acute MI (due to prolonged vasospasm or spontaneously reperfused coronary occlusion). In 17 patients, diffuse AMA uptake over the whole LV suggested diffuse myocarditis. In 18 patients, focal AMA uptake with a normal 201Tl scan suggested diffuse but heterogeneous, or focal myocarditis. Complete functional recovery was observed in 81% of the patients with a pattern of myocarditis. CONCLUSIONS: Among 45 patients presenting with acute MI and normal coronary angiograms, 38% had diffuse myocarditis and 40% had a scintigraphic pattern of heterogeneous or focal myocarditis. Short-term follow-up showed complete LV functional recovery in 81% of these patients.

Adult↗
PubMed2001

Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.

A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m(2) daily for 5 days in combination with melphalan 180 mg/m(2) (n = 66) or 140 mg/m(2) (n = 12). Eight patients received cladribine 12 mg/m(2) continuous infusion for 5 days with melphalan 180 mg/m(2). The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Nonrelapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95% CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control can be achieved with reduced-intensity conditioning in this population.

Acute Disease↗
PubMed2001

Metabolic responses of fish following exposure to two different oil spill remediation techniques.

To assess the impacts of two oil spill remediation techniques on fish metabolism, change in aerobic and anaerobic enzyme activities in juvenile Australian Bass, Macquaria novemaculeata, was examined. Changes in cytochrome C oxidase (CCO) and lactate dehydrogenase (LDH) activities were investigated following exposure to the crude oil water accommodated fraction (WAF) and chemically dispersed crude oil WAF. There was a significant stimulation in CCO activity in the gills and livers of fish exposed to the WAF of Bass Strait crude oil and chemically dispersed crude oil, compared to the control treatment. In addition, LDH activity was significantly stimulated in the liver of fish exposed to dispersed crude oil WAF, compared to the crude oil WAF. Fish exposed to the dispersed crude oil WAF treatment had significantly higher oxygen consumption, as measured by oxygen depletion in a sealed chamber, than fish exposed to the crude oil WAF and control treatments.

Animals↗
PubMed2001

Recurrent stroke and vascular events in elderly patients with anticardiolipin antibodies: a prospective study.

The presence of anticardiolipin antibodies (aCL) is a recognized risk factor for ischaemic stroke and a predictor of recurrent ischaemic events in young patients, but the significance of positive aCL tests is uncertain in the elderly. We evaluated the frequency of aCL and the risk of recurrence of stroke and other vascular events in a series of 242 consecutive patients aged over 60 years, admitted for brain infarction. All underwent aCL immunoreactivity (ELISA; measured by IgG antiphospholipid, GPL, units) and transoesophageal echocardiography and were later examined or contacted by telephone (mean 2.33 +/- 1.25 years, max. 4). Fifty patients (21 %) had at least l0 GPL units aCL. There were no differences between these and the other patients in the results of transoesophageal echocardiography, including mitral or aortic valvular thickening, atrial thrombus, atrial spontaneous contrast, strands, and aortic plaques thickness. None had IgG higher than 80 GPL units or was positive for anti-beta2 glycoprotein I. Patients with at least 10 GPL units more often had a past history of cerebral infarction than patients lower aCL level. However, the incidence of recurrent stroke was 4.5 per 100 person-year in patients with more than 10 GPL units, and 2.7 per 100 person-year in those with more than 10 GPL units. Kaplan-Meier analysis for any vascular events showed no differences between the two groups. In contrast to young patients, elderly patients with 10 or more GPL units aCL and negative for anti-beta2 glycoprotein I do not seem to have a higher risk of vascular events.

Aged↗
PubMed2001

The evaluation of effects on driver behavior and accidents of concentrated general enforcement on interurban roads in Israel.

The study deals with the evaluation of the effects of a new deployment of the National Traffic Police in Israel--a concentrated general enforcement on 700 km of interurban roads, which contain 60% of all rural accidents and about half of the severe accident locations. The enforcement project began in April 1997 and lasted for 1 year, aiming at a 10% reduction of severe accidents on those roads. The evaluation study consisted of three main parts: (a) monitoring of everyday police operations on the project roads; (b) periodic evaluation of the project's influence on drivers' behavior and attitudes; and (c) the evaluation of accident changes within the project area, at the end of the project year. Speed measurements, performed before the police project launch, demonstrated that, depending on road type, up to 85% of drivers violated the rural road speed limits. Two rounds of field observations, before and during the project, took place at 32 sites throughout the project area and comprised eight behavior types: turning performance; signaling while turning; compliance with 'stop' and 'yield' signs; safety belt use by drivers and front-seat passengers, at the intersections; 'keeping to the right' on dual carriageway roads; and 'not-crossing of the white separating line' at single carriageway roads. A comparison revealed a general reduction in violation rates of most behaviors, during-the-project, except for compliance with 'stop' signs and signaling. Concurrently, two rounds of driver surveys were performed which examined the project's influence on the drivers' attitudes towards the police enforcement effectiveness and risk connected with traffic rule violations. An improvement was identified in perceived general level of police activity, during the project, whereas a lower or similar risk of apprehension was attributed by drivers to most specific violations of the traffic rules. Three groups of indices of police activity were estimated monthly during the study: inputs; outputs; and efficiency indices, which characterized the police presence on the project roads, the citations produced and the usage rates of the vehicle fleet and the enforcement tools. Analyzing these indices, two periods in the project performance were determined, and three criteria were proposed to subdivide the project roads into two groups, according to the level of enforcement intensity. Both periods and enforcement levels, as well as geographic zone, were accounted for in the analysis of accident trends on the project roads. For the accident analysis, a statistical model combining the odds ratio and longitudinal methods, was developed and applied to the severe accident counts, all injury accidents and severe casualties. A statistically significant reduction in severe accidents and severe casualties, as opposed to the comparison group, was found on the highly enforced roads in the center of the country. At the same time, since the police project began, an increase in accidents was observed on most interurban roads, including the northern parts of the project area. However, it was noted that in four of the five project road groups the mean value of the odds ratio was much less than one. Thus, although the enforcement project did not attain its full purpose, it seemed to be a deterrent factor for the increasing accident trend that appeared that year on the interurban roads. The findings pointed out that the National Traffic Police did not exhaust its potential in the project's performance and needs more flexible enforcement and deployment tactics.

Accidents, Traffic↗
PubMed2001

The role of oral contrast administration immediately prior to the computed tomographic evaluation of the blunt trauma victim.

BACKGROUND: It is unclear whether the administration of oral contrast followed by immediate computerised tomographic (CT) scanning presents a significant risk of aspiration and whether it is useful in the diagnosis of hollow viscus injury. OBJECTIVE: Determine the number of intestinal perforations diagnosed by oral contrast enhanced CT scans for blunt trauma and identify those who developed aspiration pneumonitis causally related to oral contrast administration. METHODS: We analysed a database of consecutive blunt trauma admissions over a 2-year period. The majority received oral contrast immediately prior to CT scanning. We determined the number of intestinal perforations identified by abdominal CT confirmed at laparatomy and the number of cases of aspiration pneumonia. RESULTS: Nine (1%) of the 1173 CT scans identified enteric perforations. Oral contrast enhanced CT scans demonstrated pneumoperitoneum (3), extraluminal contrast extravasation (2), and the presence of free fluid with small bowel wall thickening (8). In this same cohort, eight (0.7%) cases of aspiration pneumonia were diagnosed within 48 h of admission in patients with a mean GCS of 4.25; only one (0.1%) was temporally related to oral contrast administration. In a prospective study, none of the 65 consecutive patients who received oral contrast had witnessed aspiration. CONCLUSIONS: Oral contrast administration given immediately prior to CT scanning does not increase the risk of clinically significant aspiration and assists in the detection of enteric perforation.

Administration, Oral↗
PubMed2001

Interdelivery interval and risk of symptomatic uterine rupture.

OBJECTIVE: To relate interdelivery interval to risk of uterine rupture during a trial of labor after prior cesarean delivery. METHODS: We reviewed the medical records of all women who had a trial of labor after cesarean delivery over 12 years (July 1984 to June 1996). Analysis was limited to women with only one prior cesarean delivery and no prior vaginal deliveries who delivered term singletons and whose medical records included the month and year of the prior delivery. The time in months between the prior cesarean delivery and the index trial of labor was calculated, and the women were divided accordingly to permit comparison with respect to symptomatic uterine rupture. RESULTS: Two thousand four hundred nine women had trials of labor after one prior cesarean delivery and had complete data from the medical records. There were 29 uterine ruptures (1.2%) in the population. For interdelivery intervals up to 18 months, the uterine rupture rate was 2.25% (seven of 311) compared with 1.05% (22 of 2098) with intervals of 19 months or longer (P =.07). Multiple logistic regression was used to assess the risk of uterine rupture according to interdelivery interval while controlling for maternal age, public assistance, length of labor, gestational age at least 41 weeks, and oxytocin use. Women with interdelivery intervals of up to 18 months were three times as likely (95% confidence interval, 1.2, 7.2) to have symptomatic uterine rupture. CONCLUSION: Interdelivery intervals of up to 18 months were associated with increased risk of symptomatic uterine rupture during a trial of labor after cesarean delivery compared with that for longer interdelivery intervals.

Adult↗
PubMed2001

Oxytocin dose and the risk of uterine rupture in trial of labor after cesarean.

OBJECTIVE: To examine the association between uterine rupture and oxytocin use in trial of labor after cesarean. METHODS: A case-control study was performed. Cases were all women with uterine ruptures who received oxytocin during a trial of labor after a single cesarean delivery within a 12-year period (n = 24). Four controls undergoing trial of labor after a single cesarean delivery were matched to each case by 500 g birth weight category, year of birth, and by induction or augmentation (n = 96). The study had an 80% power to detect a 40% increase in oxytocin duration or a 65% increase in total oxytocin dose. RESULTS: No significant differences were seen in initial oxytocin dose, maximum dose, or time to maximum dose. Although women with uterine ruptures had higher exposure to oxytocin as measured by mean total oxytocin dose (544 mU higher) and oxytocin duration (54 minutes longer), these differences were not statistically significant. Women with uterine rupture who received oxytocin were more likely to have experienced an episode of uterine hyperstimulation (37.5% compared with 20.8%, P =.05). However, the positive predictive value of hyperstimulation for uterine rupture was only 2.8%. CONCLUSION: Although no significant differences in exposure to oxytocin were detected between cases of uterine rupture and controls, the rarity of uterine rupture limited our power to detect small differences in exposure. In women receiving oxytocin, uterine rupture is associated with an increase in uterine hyperstimulation, but the clinical value of hyperstimulation for predicting uterine rupture is limited.

Adult↗
PubMed2001

Trial of labor after 40 weeks' gestation in women with prior cesarean.

OBJECTIVE: To compare outcomes in women with prior cesareans delivering at or before 40 weeks' gestation with those delivering after 40 weeks. METHODS: We reviewed labor outcomes over 12 years at one institution for women with one prior cesarean and no other deliveries who had a trial of labor at term. We analyzed the rates of symptomatic uterine rupture and cesarean for term deliveries before or after 40 weeks and stratified for spontaneous and induced labor. Potential confounding by birth weight was controlled using logistic regression. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Of 2775 women with one prior scar and no other deliveries, 1504 delivered at or before 40 weeks and 1271 delivered after 40 weeks. For spontaneous labor, rupture rate at or before 40 weeks was 0.5% compared with 1.0% after 40 weeks (P =.2, adjusted OR 2.1, CI 0.7, 5.7). For induced labor, uterine rupture rates were 2.1% at or before 40 weeks and 2.6% after 40 weeks (P =.7, adjusted OR 1.1, CI 0.4, 3.4). For spontaneous labor, rate of cesareans during subsequent trials of labor at or before 40 weeks was 25% compared with 33.5% after 40 weeks (P =.001, adjusted OR 1.5, CI 1.2, 1.8). For induced labor, rate of cesareans during subsequent trials of labor at or before 40 weeks was 33.8% compared with 43% after 40 weeks (P =.03, adjusted OR 1.5, CI 1.1, 2.2). CONCLUSION: The risk of uterine rupture does not increase substantially after 40 weeks but is increased with induction of labor regardless of gestational age. Because spontaneous labor after 40 weeks is associated with a cesarean rate similar to that following induced labor before 40 weeks, awaiting spontaneous labor after 40 weeks does not decrease the likelihood of successful vaginal delivery.

Adult↗
PubMed2001

Long-Term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation.

Donor lymphocyte infusions (DLIs) are an effective treatment for relapsed Chronic myeloid leukemia (CML) after allogeneic transplantation but are limited by the occurrence of GVHD. CD8+ T lymphocytes are involved in the pathogenesis of GVHD but may not be essential for the graft-versus-leukemia (GVL) effect in CML. We have treated 26 CML patients with posttransplantation relapse with CD8-depleted DLI. Thirteen of 15 patients (87%) who relapsed in early-phase CML achieved complete cytogenetic response, but only 1 of 11 who relapsed in advanced-phase disease achieved complete response. Acute GVHD occurred in 2 patients (8%), and extensive chronic GVHD occurred in 2 patients (11%). Treatment-related mortality was 11.5%. Responses were durable; with a median follow-up of 4.2 years (1-7.5 years), only 1 responding patient relapsed (7%). CD8-depleted DLI was equally effective and safe after unrelated donor transplants and sibling transplants. Cytogenetic clonal evolution at the time of DLI was not predictive of treatment failure unless associated with hematologic criteria for disease acceleration. CD8 depletion is an effective method to separate GVL from GVHD for posttransplantation relapsed CML. This strategy is associated with durable complete remissions and a low rate of complications and therefore merits further investigation in larger-scale comparative trials.

Adult↗
PubMed2001

The search for meaning: eventfulness in the lives of homeless mentally ill persons in the Skid Row district of Los Angeles.

In the past two decades, the field of psychiatry has seen the once dominant psychoanalytic theories overtaken by biological explanations and approaches to severe mental illness. With this change in perspective, the significance of fantasies and delusions have been reduced to being merely symptoms of psychopathology rather than reflections of human needs and motivations. Using ethnographic evidence from a long-term research project. this paper explores one method by which mentally ill homeless individuals in the Skid Row district of Los Angeles attempted to wrest meaningful lives for themselves out of an environment that featured disaffiliation, violence, boredom, and extreme poverty.

Adaptation, Psychological↗
PubMed2001

Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient.

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive disease, which presents clinically as severe combined immunodeficiency (SCID). We report here two novel mutations in the PNP gene that result in SCID phenotype, in a single patient. The maternal-derived allele carries a C to T transition in exon 2 resulting in a premature stop codon at amino acid 57. The paternal-derived mutation is a G to A transition at position +1 in intron 3, causing a complete skipping of exon 3 and a reading frameshift at the exon 2-exon 4 junction. The predicted polypeptide encoded by the aberrantly spliced mRNA terminates prematurely after only 89 amino acids. Both mutations predict severely truncated proteins resulting in a complete deficiency of PNP enzymatic activity, yet the development of profound immunodeficiency in this patient is greatly delayed.

Amino Acid Sequence↗
PubMed2001

Statistical properties of the rWG(J) index of agreement.

L. R. James, R. G. Demaree, and G. Wolf (1984) introduced rWG(J) to estimate interrater agreement for a group. This index is calculated by comparing an observed group variance with an expected random variance. As researchers have gained experience using this index, several questions have arisen. What are the consequences of replacing values beyond the unit interval by 0? What is the dependence of rWG(J) on the group size? The authors' simulations show that a positive bias is caused by the truncation, but for large population values of rWG(J) it is negligible. Also, in this case, the group size has no effect on the expected value of rWG(J). For inference on rWG(J), researchers can exploit the availability of computers to simulate data from the hypothesized distribution and then compare the simulation results for rWG(J) with the actual values. In addition, it is shown how the bootstrap method can be used for comparing the indices of 2 groups.

Chi-Square Distribution↗
PubMed2001

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease.

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.

Chromosome Mapping↗