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Biomedical subjects

D J Cohen

Publications and source records attributed to D J Cohen.

At least 127 records · Page 7Linked to original sources

Neuropsychiatric disorders of childhood: Tourette's syndrome as a model.

Neuropsychiatric disorders of childhood include conditions such as autism, pervasive developmental disorder and attention deficit hyperactivity disorder. Tourette's syndrome (TS) of chronic, multiple, motor and vocal tics is a model neuropsychiatric disorder with a childhood onset and long-term, and sometimes life-long, course. Symptoms and signs change during the course of maturation, and include obsessions, compulsions, attentional difficulties and psychological responses to the disability. These clinical features reflect the interaction between genetic and environmental factors. The localization and cloning of the genetic substrate will allow for detailed study of the pathways from molecular vulnerability to clinical syndrome.

Adaptation, Psychological↗

Obsessive-compulsive disorder with and without tics in an epidemiological sample of adolescents.

OBJECTIVE: This study was undertaken to discriminate subtypes of obsessive-compulsive disorder in adolescents. METHOD: Forty individuals with obsessive-compulsive spectrum disorders were ascertained from an epidemiological sample of 861 adolescents. Interviews were conducted by child psychiatrists using semistructured diagnostic interviews, including a clinician-rated Yale-Brown Obsessive Compulsive Scale. Discriminant analysis was performed to compare the scores on the Yale-Brown scale of groups with and without comorbid tics and to compare boys and girls. RESULTS: Adolescents with tics were more prone to aggressive and sexual images and obsessions than were adolescents without tics; these differences could not be wholly attributed to sex differences. CONCLUSIONS: The subtypes among unreferred adolescents are similar to those of adult patients with obsessive-compulsive disorder with and without Gilles de la Tourette syndrome. Subtypes evident in adulthood may be established relatively early in the natural course of obsessive-compulsive disorder.

Adolescent↗

Symptoms of obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder encompasses a broad range of symptoms that represent multiple psychological domains, including perception, cognition, emotion, social relatedness, and diverse motor behaviors. The purpose of these analyses was to evaluate the correlational relationships of the symptoms of obsessive-compulsive disorder. METHOD: This study examined the 13 a priori categories used to group types of obsessions and compulsions in the Yale-Brown Obsessive Compulsive Scale symptom checklist in two independent groups of patients with obsessive-compulsive disorder (N = 208 and N = 98). A principal-components factor analysis with varimax rotation was performed, followed by a series of other exploratory analyses. RESULTS: The two data sets yielded nearly identical results. Four factors--obsessions and checking, symmetry and ordering, cleanliness and washing, and boarding--emerged in each data set, in total accounting for more than 60% of the variance. CONCLUSIONS: Obsessive-compulsive disorder is a multidimensional and etiologically heterogeneous condition. The four symptom dimensions identified in this study are largely congruent with those identified in earlier reports. These factors may be of value in future genetic, neurobiological, and treatment response studies.

Adult↗

Changes in substance use during times of stress: college students the week before exams.

A situational factor that is commonly thought to influence substance use is stress. The tension reduction theory posits that alcohol relieves stress-reactions and that most people drink alcohol in stressful situations in order to relieve stress-reactions. We conducted a naturalistic study in which we surveyed seventy-three college students' alcohol and drug use, behaviors, and emotions during a typical week and the week before final exams. As expected our subjects experienced an increase in aversive emotions during the week before exams. The simple tension reduction hypothesis predicts that these subjects' alcohol use should have increased during this time. Our data showed the opposite: subjects' alcohol use decreased during the week before exams. We hypothesized that this was due to the availability of effective alternatives for reducing anxiety. Implications for prevention were discussed.

Adolescent↗

Visual detection and perceptual independence: assessing color and form.

Visual stimuli are multidimensional. One important perceptual problem is to determine how the dimensions are combined. One important aspect of dimensional combination is whether the dimensions are perceptually independent or perceptually correlated. A new task is presented--the visual detection task--that directly assesses the degree of perceptual correlation between any two dimensions. Two experiments were conducted that assess the degree of perceptual correlation between form and color during the early stages of perceptual analysis. The results show that form and color are not perceptually independent. In addition, the pattern of perceptual correlation found indicates that form and color are not processed independently. The pattern of results constrains all models of early vision. A model of early vision based on active signal modulation is proposed.

Attention↗

Stent jail: a minimum-security prison.

Small but significant side branches (particularly those with baseline ostial narrowing) may be further compromised by stent placement within parent vessel segments. Despite the theoretical risks associated with dilating branches in stent jail, the procedure was successfully completed in 84%, with minimal complications (mostly balloon rupture and local dissection) and no cases of balloon entrapment or deterioration of the final result achieved in the parent vessel.

Angioplasty, Balloon, Coronary↗

Differential effects of costimulator signals and interleukin-2 on T cell receptor-mediated cell death of resting and activated CD4+ murine splenic T cells.

Postthymic T cell receptor (TCR)-mediated cell death offers the potential for creating antigen-specific transplant tolerance analogous to thymic clonal deletion. Murine specific CD4+ cell were rigorously purified by: (a) adherent cell depletion and (b) magnetic bead/monoclonal antibody (mAb) depletion of macrophages, Ia+ cells, mu-chain+ cells, NK cells, and CD8+ T cells. CD4+s were typically > 95% pure by flow cytometry. Resting CD4+s stimulated by plastic-immobilized anti-TCR/CD3 mAb wee shown to die in the absence of exogenous interleukin (IL)-2. Blasting CD4+s showed dose-dependent cell death upon religation of TCR/CD3 in the presence of IL-2; however, withdrawal of IL-2 from blasting CD4+s also resulted in cell death. Cell death was shown to be apoptotic by flow cytometry DNA content analysis. Anti-CD28 mAb, co-immobilized with anti-TCR/CD3 mAb, inhibited cell death of resting CD4+s in the absence of exogenous IL-2; however, anti-CD28 mAb showed minimal cell death inhibition of CD4+ blasts when TCR/CD3 was religated. In contrast, splenic adherent cells effectively inhibited cell death of blasting CD4+s induced by TCR/CD3 mAb religation. We conclude that TCR-mediated programmed cell death of highly purified splenic CD4+s is dependent upon activation state, availability of IL-2, and accessory cell or CD28 costimulator signals. Furthermore, IL-2 acts to protect against cell death in both resting and activated CD4+ T cells. IL-2 protection could be overcome by high concentrations of anti-TCR/CD3 mAb, which results in cell death of CD4+ blasts. In the effort to understand potential mechanisms of peripheral tolerance induction, these findings assist to distinguish and define conditions for antigen receptor-mediated programmed cell death of mature CD4+ T cells.

Animals↗

Israeli preschoolers under Scud missile attacks. A developmental perspective on risk-modifying factors.

BACKGROUND: The devastating effects of traumatic events on children are modulated by risk and protective factors. This study examines the differential effects of traumatic displacement of preschool children and their families following Scud missile attacks on Israel during the Persian Gulf War. METHODS: Three groups participated in the study: families displaced after their houses were damaged, undisplaced families from the same neighborhood (without home damage), and families from a distant city that was threatened but not directly attacked. Data concerning the traumatic event, the child (personality, internalizing, externalizing, and stress symptoms), the mother (Symptom Checklist-90-Revised), and the family (Family Adaptability and Cohesion Evaluation Scales) were gathered 6 months after the end of the war. RESULTS: Displaced children and mothers showed higher externalizing and stress symptom levels compared with undisplaced and threatened subjects. Destruction of the house and displacement, but not mere distance from the missile impact, explained symptomatic behavior. Inadequate family cohesion predicted symptomatic reaction for 3- and 4-year-old children but not for older ones. CONCLUSION: Both human and nonhuman factors contribute to the preschool child's adaptive mechanisms that regulate environmental stressful stimuli. These risk-modifying factors become more autonomous of caretakers with increasing age.

Adaptation, Psychological↗

Effects of tryptophan depletion in drug-free adults with autistic disorder.

BACKGROUND: The primary objective of this study was to investigate the behavioral and biochemical responses to acute tryptophan depletion in drug-free adult patients with autistic disorder. METHODS: Twenty drug-free adults with autistic disorder (16 men and 4 women) (mean [+/- SD] age, 30.5 +/- 8.5 years) underwent short-term tryptophan depletion in a double-blind, placebo-controlled, randomized crossover design. Patients received a 24-hour, low-tryptophan diet followed the next morning by an amino acid drink. Behavioral ratings were obtained on the morning of the amino acid drink (baseline) and 180, 300, and 420 minutes after the drink. Plasma free and total tryptophan levels were obtained at baseline and 5 hours after the drink. The active and sham testing sessions were separated by 7 days. RESULTS: Eleven (65%) of the 17 patients who completed both test days showed a significant global worsening of behavioral symptoms with short-term tryptophan depletion, but none of the 17 patients showed any significant change in clinical status from baseline after sham depletion (P = .001). Tryptophan depletion led to a significant increase in behaviors such as whirling, flapping, pacing, banging and hitting self, rocking, and toe walking (P < .05). In addition, patients were significantly less calm and happy and more anxious. No significant change was observed in social relatedness or repetitive thoughts and behavior. Plasma total and free tryptophan levels were reduced 86% and 69%, respectively, 5 hours after the tryptophan-deficient amino acid drink. Patients who had a significant global exacerbation of symptoms had significantly higher baseline plasma total tryptophan levels (P < .001) and Autism Behavior Checklist scores (P = .005) than did patients who showed no significant change in symptoms after tryptophan depletion. CONCLUSIONS: The results of this study are consistent with previous research that has implicated a dysregulation in serotonin function in some patients with autism. These data suggest that the short-term reduction of serotonin precursor availability may exacerbate some symptoms characteristic of autism in some patients. Continued investigation into the role of serotonin in the pathogenesis and treatment of autistic disorder is warranted.

Adult↗

A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder.

BACKGROUND: Autistic disorder is characterized by a fundamental disturbance in social interaction, impairments in communication, and a markedly restricted repertoire of activities and interests. Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism. No consistently effective and safe drugs have been developed for treating the symptoms of autism. METHODS: Thirty adults with autistic disorder completed a 12-week double-blind, placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate. Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Eight (53%) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group (P = .001). Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior (P < .001), maladaptive behavior (P < .001), and aggression (P < .03), and in improving some aspects of social relatedness (P < .04), especially language usage (P < .008). Treatment response was not correlated with age level of autistic behavior, or full-scale IQ. Other than mild sedation and nausea in a few patients, fluvoxamine was well tolerated. No dyskinesias, adverse cardiovascular events, or seizures occurred. CONCLUSIONS: Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.

Adolescent↗

Extravasation of thrombus into the aortic root: a complication following use of an infusion catheter for intragraft thrombolysis.

Overnight chronic urokinase infusion was used to successfully treat thrombotic occlusion of a saphenous vein graft. Following removal of the infusion catheter, a 3-cm linear thrombus was observed extending from the graft into the ascending aorta. This mobile thrombus was successfully treated with coumadinization for 9 wk. Potential preventive measures for this complication of indwelling catheters are discussed.

Aorta↗

Hyperglycemia augments macrophage growth responses to colony-stimulating factor-1.

Pathologic changes produced (or potentiated) by the diabetic state include diabetic retinopathy, nephropathy, and atherosclerosis. There is evidence that the macrophage is implicated in the pathogenesis of these lesions. One of the growth factors known to exert a profound influence on macrophage physiology is colony-stimulating factor-1 (CSF-1). CSF-1 has previously been shown to be produced by endothelial cells, mesangial cells, and vascular smooth muscle cells, and it is reasonable to suggest that the interaction of this factor on infiltrating macrophages is an event that may have pivotal importance in the formation of diabetic lesions. We report on the modulating influence of hyperglycemia on the proliferative response of mouse splenic macrophages to CSF-1. Our studies showed that hyperglycemia enhanced the growth response of such macrophages to CSF-1. The mechanism underlying this enhanced response was examined, and it was demonstrated that hyperglycemia induced a threefold increase in CSF-1 receptor (CSF-1r) mRNA expression as visualized by Northern blot analysis. These investigations provide insight into one of the molecular mechanisms potentially relevant to the genesis of diabetic lesions in the host.

Animals↗

Long-term (4- to 6-year) outcome of Palmaz-Schatz stenting: paucity of late clinical stent-related problems.

OBJECTIVES: The purpose of this prospective single-center study was to evaluate the longer-term outcome of Palmaz-Schatz stenting in the treatment of native coronary and saphenous vein bypass graft disease. BACKGROUND: The STRESS (Stent Restenosis Study) and BENESTENT (Belgian Netherlands Stent) trials have demonstrated a decrease in both angiographic restenosis and the need for repeat revascularization in the 1st year for vessels treated by stenting rather than balloon angioplasty. Longer-term (1 to 5 years) clinical results of Palmaz-Schatz stenting are not yet well established. Late migration of the stent, metal fatigue, endarteritis and late restenosis have all been proposed as potential late clinical complications of coronary stent implantation. METHODS: The study cohort consisted of 175 consecutive patients who underwent elective placement of 194 Palmaz-Schatz stents in 185 vessels. Clinical events (death, myocardial infarction, recurrent angina or any revascularization) were assessed at 6 weeks, 2, 4 and 6 months, 1 year and yearly thereafter. Clinical follow-up was available on all patients at a mean +/- SD of 54 +/- 17 months. RESULTS: Angiographic success was achieved in 173 patients (98.9%); angiographic restenosis was observed at 6 months in 26.1% of target sites. The survival rate was 86.7% at 5 years, with a 5-year event-free survival rate decreasing progressively to 50.7%, reflecting primarily repeat revascularization procedures (41.2% at 5 years). However, the rate of repeat revascularization of the treatment site (target site revascularization [TSR]) was 14.4%, 17.7% and 19.8% at 1, 3 and 5 years, respectively, with late (> 1 year) TSR driven by in-stent restenosis in only 3 patients (1.7%). Rates of both 5-year survival (70.5% vs. 93.4%) and event-free survival (21.1% vs. 63.3%) were lower for patients who underwent saphenous vein graft (SVG) stenting than for those with native coronary artery stenting. However, 5-year TSR rates were similar for SVGs (21.9%) and native vessels (19.2%), indicating that the higher incidence of repeat revascularization for SVGs was due to an increase in non-TSR, driven by progressive disease at other sites. CONCLUSIONS: The long-term outcome of stenting shows stability of the treated lesion, with only a slight increase in TSR between 2 and 5 years (17.1% to 19.8%). The progressive increase in repeat revascularization over that period (24% to 41%) and most ongoing late events can be attributed to the progression of coronary disease at other sites, rather than to late deterioration of the stent result itself. Such non-TSR events account for the majority of clinical events in the patients who underwent SVG stenting.

Aged↗

Demonstration of endothelial-activating properties of hypertensive sera.

Sera from patients with hypertension were examined for their ability to influence endothelial cell function. Sera from 10 patients with hypertension and from 11 age-matched controls were incubated with endothelial cells and their effect on cell growth assessed by endothelial cell 3H-thymidine uptake. Sera from patients with hypertension had a more pronounced stimulatory effect on endothelial cell proliferation than control sera. In addition, hypertensive sera were also examined for their capacity to stimulate endothelial cell production of the vasoactive peptide endothelin. Confluent monolayers of endothelial cells were incubated with sera and the amount of endothelin generated in the supernatant measured by an immunoassay. Amounts of endothelin produced by the endothelial cells in response to hypertensive sera were significantly higher compared with the amounts produced in response to normal sera. The results of the studies suggest that a serum factor(s) in hypertensive patients may be of importance in modulating endothelial cell function. Such a factor(s) may have a significant role in the pathogenesis of hypertension.

Aged↗

Prenatal diagnosis of type 2 Pfeiffer syndrome.

Pfeiffer syndrome is an autosomal dominantly inherited disorder consisting of craniosynostosis, a flattened midface with a beaked nose and ocular proptosis, and broad and medially deviated thumbs and great toes. Recently, based on clinical findings, the disorder has been divided into three subtypes: type 1, characterized by mild expression; type 2, in which clover leaf skull deformity and multiple congenital anomalies are present at birth; and type 3, which is similar to type 2, but lacks the presence of the clover leaf skull at birth. We describe a fetus in whom sonographic findings of clover leaf skull deformity, ocular hypertelorism, and varus deformity of the great toe led to the prenatal diagnosis of Pfeiffer syndrome type 2. We believe this is the second prenatal diagnosis of Pfeiffer syndrome, and the first time type 2 has been definitely identified in the second trimester of pregnancy.

Abortion, Induced↗