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Biomedical subjects

D J Cohen

Publications and source records attributed to D J Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Regional brain and ventricular volumes in Tourette syndrome.

BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve disturbances in cortico-striato-thalamo-cortical circuitry. The morphological characteristics of the cortical and associated white matter portions of these circuits have not been previously examined in TS subjects. METHODS: High-resolution anatomical magnetic resonance images were acquired in 155 TS and 131 healthy children and adults. The cerebrums and ventricles were isolated and then parcellated into subregions using standard anatomical landmarks. RESULTS: For analyses that included both children and adults, TS subjects were found to have larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital regions, and smaller inferior occipital volumes. Significant inverse associations of cerebral volumes with age were seen in TS subjects that were not seen in healthy controls. Sex differences in the parieto-occipital regions of healthy subjects were diminished in the TS group. The age-related findings were most prominent in TS children, whereas the diminished sex differences were most prominent in TS adults. Group differences in regional ventricular volumes were less prominent than in the cerebrum. Regional cerebral volumes were significantly associated with the severity of tic symptoms in orbitofrontal, midtemporal, and parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are involved in the pathophysiology of TS. Developmental processes, sexual dimorphisms, and compensatory responses in these cortical regions may help to modulate the course and severity of tic symptoms.

Adolescent↗
PubMed2001

Effect of glycoprotein IIb/IIIa receptor inhibition on angiographic complications during percutaneous coronary intervention in the ESPRIT trial.

OBJECTIVES: We sought to determine whether eptifibatide decreases the incidence of in-laboratory angiographic complications and to determine the relationship of angiographically evident complications to elevations of creatine kinase-MB (CK-MB) enzyme levels during percutaneous coronary intervention. BACKGROUND: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, eptifibatide during coronary intervention was associated with decreased ischemic complications at 48 h and 30 days. METHODS: Patients (n = 2,064) were randomized to placebo versus eptifibatide (two 180 microg/kg boluses 10 min apart and as a continuous infusion of 2 microg/kg per min) during percutaneous coronary stenting. Angiographic complications including major dissection, distal embolization, residual thrombus, abrupt closure, residual stenosis >50% and side-branch occlusion were prospectively recorded by the operator. Creatine kinase-MB levels were measured after the procedure and every 6 h thereafter. The incidence of angiographic complications and CK-MB elevation was determined for eptifibatide versus placebo groups. RESULTS: Eptifibatide-treated patients demonstrated nonsignificant trends toward fewer angiographic complications (10 vs. 12% for placebo patients, p = 0.13) and, for patients with angiographic complications, fewer subsequent CK-MB elevations (43 vs. 50% for placebo patients, p = 0.31). In patients without any angiographic complications, the incidence of CK-MB elevation >3 times the normal was 7% with placebo and 4% with eptifibatide (p = 0.003). CONCLUSIONS: Eptifibatide during nonurgent coronary stent intervention only minimally (and insignificantly) reduces the incidence of angiographic complications and subsequent CK-MB elevations in patients developing an angiographic complication. The greater effect is to reduce myocardial infarction in patients undergoing otherwise uneventful coronary stent implantation as well as in the overall study population.

Angioplasty, Balloon, Coronary↗
PubMed2001

Role of the serotonin transporter gene in the behavioral expression of autism.

The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC6A4) is of special interest in autism given the well-replicated platelet hyperserotonemia of autism, treatment effects of serotonin reuptake inhibitors, and the role of serotonin in limbic functioning and neurodevelopment. Parent-offspring transmission of the long (l) and short (s) alleles of the deletion/insertion polymorphism in the HTT promoter region was examined in families of 71 children with autism using the transmission test for linkage disequilibrium (TDT). Transmission of HTT promoter alleles did not differ between probands with autism and their unaffected siblings. However, allelic transmission in probands was dependent upon severity of impairments in the social and communication domains, with greater s allele transmission in severely impaired individuals and greater l transmission in mild/moderately impaired individuals. This relationship between HTT promoter alleles and severity of autistic impairment was also seen when ratings of social and communication behaviors were compared across genotypes. The data indicate that HTT promoter alleles by themselves do not convey risk for autism, but, rather, modify the severity of autistic behaviors in the social and communication domains. The results require replication and, given the size of the groups and subgroups examined, must be considered still preliminary. The results suggest that future research on the genetics of autism should carefully assess each of the major behavioral domains and seriously consider the possible role of modifying loci.

Adolescent↗
PubMed2001

Speech and prosody characteristics of adolescents and adults with high-functioning autism and Asperger syndrome.

Speech and prosody-voice profiles for 15 male speakers with High-Functioning Autism (HFA) and 15 male speakers with Asperger syndrome (AS) were compared to one another and to profiles for 53 typically developing male speakers in the same 10- to 50-years age range. Compared to the typically developing speakers, significantly more participants in both the HFA and AS groups had residual articulation distortion errors, uncodable utterances due to discourse constraints, and utterances coded as inappropriate in the domains of phrasing, stress, and resonance. Speakers with AS were significantly more voluble than speakers with HFA, but otherwise there were few statistically significant differences between the two groups of speakers with pervasive developmental disorders. Discussion focuses on perceptual-motor and social sources of differences in the prosody-voice findings for individuals with Pervasive Developmental Disorders as compared with findings for typical speakers, including comment on the grammatical, pragmatic, and affective aspects of prosody.

Adolescent↗
PubMed2001

Rheolytic thrombectomy during percutaneous revascularization for acute myocardial infarction: experience with the AngioJet catheter.

BACKGROUND: Although balloon angioplasty and stenting are effective in the treatment of acute myocardial infarction (MI), reduced coronary flow and distal embolization frequently complicate interventions when thrombus is present. Adjunctive treatment with mechanical thrombectomy devices may reduce these complications. METHODS AND RESULTS: We evaluated the angiographic and clinical outcomes of 70 patients with acute MI (16% with cardiogenic shock) and with angiographically evident thrombus who were treated with AngioJet rheolytic thrombectomy followed by immediate definitive treatment. Procedure success (residual diameter stenosis <50% and Thrombolysis in Myocardial Infarction [TIMI] flow > or =2 after final treatment) was achieved in 93.8%. Clinical success (procedure success without major in-hospital cardiac events) was achieved in 87.5%, with an in-hospital mortality rate of 7.1%. Final TIMI 3 flow was achieved in 87.7%. AngioJet treatment resulted in a mean thrombus area reduction from 73.2 +/- 64.6 mm(2) at baseline to 15.5 +/- 30.1 post-thrombectomy (P <.001). Subsequent definitive treatment included stenting in 67% and balloon angioplasty alone in 26% of patients. Procedural complications included distal embolization in six patients and perforation in two patients. There were no further major adverse events during 30-day follow-up. CONCLUSION: Rheolytic thrombectomy can be performed safely and effectively in patients with acute MI, allowing for immediate definitive treatment in thrombus-containing lesions.

Aged↗
PubMed2001

Economic assessment of rheolytic thrombectomy versus intracoronary urokinase for treatment of extensive intracoronary thrombus: Results from a randomized clinical trial.

BACKGROUND: Despite advances in mechanical and pharmacologic therapy, thrombus-containing lesions are at high risk for adverse events and remain a challenging subset for percutaneous coronary revascularization. Recently, rheolytic thrombectomy with the AngioJet device has been shown to safely remove intracoronary thrombus, but the overall cost-effectiveness of this technique is unknown. METHODS: We determined in-hospital and 1-year follow-up costs for 349 patients with overt intracoronary thrombus who were randomly assigned to treatment with intracoronary urokinase (6- to 30-hour infusion followed by definitive revascularization; n = 169) or immediate thrombectomy with the AngioJet device (n = 180) as part of the Vein Graft AngioJet Study (VeGAS) 2 trial. Catheterization laboratory costs were based on measured resource utilization and 1998 unit costs, whereas all other costs were estimated from hospital charges and cost center-specific cost-to-charge ratios. RESULTS: Compared with urokinase, rheolytic thrombectomy reduced the incidence of periprocedural myocardial infarction (12.8% vs 30.3%, P <.001) and major hemorrhagic complications (2.8% vs 11.2%, P <.001) and shortened length of stay by nearly 1 day (4.2 vs 4.9 days; P =.02). As a result, AngioJet treatment reduced procedural costs, hospital room/nursing costs, and ancillary costs with resulting hospital cost savings of approximately $3500 per patient during the initial hospitalization ($15,311 vs $18,841, P <.001). These cost savings were maintained at 1 year of follow-up ($24,389 vs $29,109, P <.001). CONCLUSIONS: Compared with standard treatment with intracoronary urokinase, rheolytic thrombectomy both improves clinical outcomes and reduces overall medical care costs for patients with extensive intracoronary thrombus.

Angioplasty, Balloon, Coronary↗
PubMed2001

Evidence that human epididymal protein ARP plays a role in gamete fusion through complementary sites on the surface of the human egg.

Human epididymal sperm protein ARP, a member of the cysteine-rich secretory proteins (CRISP) family, exhibits significant homology with rat epididymal protein DE, a candidate molecule for mediating sperm-egg fusion in rodents. The aim of this study was to investigate the involvement of ARP in human gamete fusion. Sequential extraction of proteins from ejaculated human sperm revealed the existence of a population of ARP that is tightly associated with the sperm surface and thus, potentially capable of participating in gamete interaction. Exposure of capacitated human sperm to a polyclonal antibody against recombinant ARP (anti-ARP) produced a significant and concentration-dependent inhibition in the ability of human sperm to penetrate zona-free hamster eggs. This inhibition was not due to a deleterious effect on the gametes because anti-ARP affected neither sperm viability or motility, nor egg penetrability. The antibody did not inhibit the occurrence of spontaneous or Ca(2+) ionophore-induced acrosome reaction, nor did it inhibit the ability of sperm to bind to the oolema, supporting a specific inhibition of the antibody at the sperm-egg fusion level. As a relevant evidence for a role of ARP in gamete fusion, the existence of complementary sites for this protein on the surface of human eggs was investigated. Experiments in which zona-free human oocytes discarded from in vitro fertilization programs were exposed to ARP, fixed, and subjected to indirect immunofluorescence revealed the presence of specific ARP-binding sites on the entire surface of the human egg, in agreement with the fusogenic properties of the human oolema. Together, these results strongly support the participation of ARP in the sperm-egg fusion process, suggesting that this protein would be the functional homologue of DE in humans.

Animals↗
PubMed2001

Mothers' functioning and children's symptoms 5 years after a SCUD missile attack.

OBJECTIVE: The authors assessed the long-term consequences of the SCUD missile attack in Israel on children as a function of their mothers' psychological functioning, family cohesion, and the event itself. METHOD: Five years after the Gulf War, the authors assessed the internalizing, externalizing, stress, and posttraumatic symptoms of 81 children aged 8-10 years whose homes were damaged in the SCUD missile attack, as well as general and posttraumatic symptoms, defensive style, and object relations in their mothers. RESULTS: There was a significant decrease in severity in most symptom domains and an increase in avoidant symptoms in the children. Greater severity of symptoms was associated with being displaced, living in a family with inadequate cohesion, and having a mother with poor psychological functioning. The association between the symptoms of children and mothers was stronger among the younger children. Posttraumatic symptoms increased in one-third of the children and decreased in one-third over the last 30 months of the study. Severe posttraumatic symptoms were reported in 8% of the children. CONCLUSIONS: Despite a continuous decrease in symptom severity, risk factors identified shortly after the Gulf War continued to exert their influence on children 5 years after the traumatic exposure.

Adaptation, Psychological↗
PubMed2001

A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

OBJECTIVE: This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). METHOD: Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. RESULTS: Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.

Adolescent↗
PubMed2001

Using magnitude estimation to investigate the perceptual components of signal detection theory.

Several experiments suggest that the relation between detection, signal energy, and perceived tone intensity is very different from the relation between detection, signal energy, and perceived tone duration. We propose a new task, the magnitude estimation and detection (MED) task, that allows one to assess the relation between the psychological dimensions of a stimulus and detection. In Experiment 1, we used the MED task to assess the relation between perceived tone intensity and detection in a yes/no task. The data show a strong relation between the two. In Experiment 2, we used the MED task to assess the relation between perceived tone duration and detection in a yes/no task. The data show a relatively weak relation between the two. Our data suggest that tone intensity is a less perceptually noisy dimension than tone duration. We present the advantages and disadvantages of the MED task with the hope that this task can aid researchers in better understanding the perceptual and decisional mechanisms underlying various cognitive processes.

Adult↗
PubMed2001

Plasmapheresis treatment of recurrent FSGS in adult renal transplant recipients.

Plasmapheresis (PP) is often employed in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the renal allograft, where it appears to be effective in the pediatric population. The efficacy of PP in adults and predictors of response are not well documented. We analyzed the records of 13 adult patients from three transplant centers who underwent PP for recurrent FSGS between 1993 and 1999. One patient (8%) had a complete response, one (8%) had a partial response, and 3 (23%) partially responded but remain PP-dependent. All 5 responders were started on PP within 30 days of recurrence, while 7 of the 8 non-responders initiated PP after a delay of at least 42 days (p = 0.0047). FSGS recurred within 30 days of transplantation in all 5 responders, while 4 of 8 non-responders had no evidence of recurrence until 42-150 days after transplantation (p = 0.098). Post-transplant biopsies were examined in 10 patients and revealed either cellular (6) or collapsing (4) variants of FSGS. We conclude PP is less effective in adults than in children as a treatment for recurrent FSGS in the renal allograft. Predictors of response to PP include early initiation of treatment after recurrence and possibly an early recurrence of disease.

Adult↗
PubMed2001

Tic disorders: when habit forming neural systems form habits of their own?

Tourette syndrome (TS), obsessive-compulsive disorder (OCD) and related conditions are prevalent disorders affecting as many as 0.3-3% of the population. They are frequently chronic and can be associated with marked impairment and disability. Although clinical care has improved over the past decade, a significant number of patients fail to respond adequately or experience intolerable side effects. The etiology of these disorders is unknown. Compelling evidence suggests that the vulnerability to develop TS and OCD is mediated by both genetic and environmental factors, and that neural systems located in the basal ganglia and functionally related brain structures are involved in their pathogenesis. Based on explicit models of pathogenesis for TS and OCD and building on work accomplished over the past two decades, an array of clinical, neuropsychological, genetic, neuroimaging, epidemiological neurobiological, and treatment studies have been completed or are underway at the Child Study Center at Yale University. A multidisciplinary team of investigators has joined forces to test specific hypotheses through the integration and translation of basic and clinical neuroscience research. All subjects have been studied using identical clinical, neuropsychological, genetic, neurobiological, and pharmacological techniques. Current conceptualizations of TS have been shaped by advances in clinical phenomenology, genetics, systems neuroscience and the emerging understanding of the role of the basal ganglia in implicit learning and habit formation, neuroimmunology and psychopharmacology. An appreciation of the premonitory urges that precede tics and temporal dynamics of tics have provided useful viewpoints from which to regard the natural history of TS. While the long-term outcome of TS can be relatively benign, the presence of comorbid conditions such as attention deficit/hyperactivity disorder (ADHD), OCD or a major affective disorder can have lasting untoward consequences. The identification of susceptibility genes in TS will doubtless point in new therapeutic directions for treatment, as will the characterization of the putative autoimmune mechanisms active in subgroup of patients. Continued success in functional in vivo neuroimaging studies will lead to the targeting of specific brain circuits for more intensive study. Although ideal anti-tic therapies are not available, recently completed clinical trials with alpha-adrenergic agents and atypical neuroleptics are encouraging. Given these developments, TS can be considered a model disorder to study the dynamic interplay of genetic vulnerabilities, epigenetic events, and neurobiological systems active during early brain development. It is likely that the research paradigms utilized in these studies and many of the empirical findings resulting from them, will be relevant to other disorders of childhood onset and to our understanding of normal development.

Animals↗
PubMed2000

Use of fractional myocardial flow reserve to assess the functional significance of intermediate coronary stenoses.

The goal of the present study was to compare the use of pressure-derived myocardial fractional flow reserve for detecting ischemia with nuclear stress imaging in patients undergoing stent placement for intermediate coronary lesions. We demonstrated that myocardial fractional flow reserve detects ischemia in intermediate coronary lesions accurately when compared with nuclear stress imaging.

Adult↗
PubMed2000

Selective protection and functionalization of morphine: synthesis and opioid receptor binding properties of 3-amino-3-desoxymorphine derivatives.

As part of an effort to identify novel opioid receptor interactive agents, we recently prepared a series of 8-(substituted)amino analogues of cyclazocine. We found the chiral 8-phenylamino (NHC(6)H(5)) cyclazocine derivative to have subnanomolar affinity for kappa opioid receptors and a 2-fold lower affinity for mu, opioid receptors. To determine if the benefits of (substituted)amino groups could be extended to the morphine core structure, we have made five novel 3-amino-3-desoxymorphine derivatives of general structure 5 where RR'N = H(2)N, CH(3)NH, (CH(3))(2)N, C(6)H(5)NH, and C(6)H(5)CH(2)NH. Relative to morphine, these derivatives had 38-273-fold, 11-41-fold, and 10-141-fold lower affinity for mu, delta, and kappa opioid receptors, respectively. Target compounds were made via Pd-catalyzed amination of a morphine 3-trifluoromethylsulfonate substrate where the 6-OH group was protected with a tert-butyldiphenylsilyl group. To make 6-tert-butyldiphenylsilyloxymorphine selectively, a new high-yield method was developed whereby morphine was bis-silylated using normal conditions followed by selective removal of the 3-tert-butyldiphenylsilyl group with catalytic tetrabutylammonium fluoride.

Adenylyl Cyclase Inhibitors↗