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Biomedical subjects

Jonathan Cohen

Publications and source records attributed to Jonathan Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2006

Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation.

Fragile X syndrome (FXS) is caused by a full mutation expansion (>200 CGG repeats) in the FMR1 gene that results in a deficiency of the fragile X mental retardation protein. Although most individuals with the premutation (55-200 CGG repeats) are considered unaffected by FXS, recent case studies have documented children with the premutation who have cognitive deficits, behavioral problems, and/or autism spectrum disorders. The objective of this study was to compare the prevalence of autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) symptoms in boys with the premutation who presented as probands, in brothers with the premutation who did not present as probands, and in normal brothers of premutation and/or full mutation carriers. Participants included 43 male children: 14 probands who presented to clinic, 13 nonprobands who were identified through cascade testing (routine genetic testing of family members after identification of a proband) and confirmed to have the premutation, and a control group of 16 male siblings of individuals with the fragile X premutation or full mutation who were negative for the FMR1 mutation. Participants came from 1 of 2 collaborative sites: University of California, Davis and La Trobe University in Australia. Parents completed the Conners' Global Index-Parent Version for assessing symptoms of ADHD and the Social Communication Questionnaire (SCQ) for identifying symptoms of ASD. Children who were in the ASD range on the SCQ (n = 13) underwent further evaluation with either the Autism Diagnostic Observation Schedule-Generic (n = 10) or the Autism Diagnostic Interview-Revised (n = 3). A final diagnosis of ASD included clinical assessment utilizing DSM-IV-TR criteria in addition to the standardized assessments. There was a higher rate of ASD in boys with the premutation presenting as probands (p < 0.001) or nonprobands (p < .04) compared with sibling controls without the premutation. In addition, probands had a significant increase in ADHD symptoms compared with controls (p < .0001). Of the probands, 93% had symptoms of ADHD and 79% had ASD. In the nonproband premutation group, 38% had symptoms of ADHD and 8% had ASD. Thirteen percent of sibling controls had symptoms of ADHD and none had ASD. IQ scores were similar in all 3 groups (p = .13), but the use of psychotropic medications was significantly higher in probands with the premutation compared with that in controls (p < .0001). Developmental problems have been observed in premutation carriers, particularly those who present clinically with behavioral difficulties. Although this study is based on a small sample size, it suggests that premutation carriers, even those who do not present clinically, may be at increased risk for an ASD and/or symptoms of ADHD. If the premutation is identified through cascade testing, then further assessment should be carried out for symptoms of ADHD, social deficits, or learning disabilities.

Adolescent↗
PubMed2006

Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury.

OBJECTIVE: To explore the effects of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants on the respiratory profile and outcome of patients with acute lung injury. DESIGN: Single-center, prospective, randomized, controlled, unblinded study. SETTING: General intensive care department of a tertiary-care, university-affiliated hospital. PATIENTS: A total of 100 patients with acute lung injury, diagnosed according to the American-European Consensus Conference on ARDS. INTERVENTIONS: Patients were randomized to receive the standard isonitrogenous, isocaloric enteral diet or the standard diet supplemented with EPA and GLA for 14 days. MEASUREMENTS AND MAIN RESULTS: Patient demographics, Acute Physiology and Chronic Health Evaluation II score, and type of admission were noted at admission. Compared with baseline oxygenation (EPA + GLA group vs. control group), by days 4 and 7, patients receiving the EPA + GLA diet showed significant improvement in oxygenation (PaO(2)/FIO(2), 317.3 +/- 99.5 vs. 214.3 +/- 56.4 and 296.5 +/- 165.3 vs. 236.3 +/- 79.8, respectively; p < .05). Compliance was significantly higher in the EPA + GLA group observed at day 7 (55.1 +/- 46.5 vs. 35.2 +/- 20.0 mL/mbar, p < .05). No significant difference was found in nutritional variables. Resting energy expenditure was significantly higher in patients in the EPA + GLA group, but their body mass index was also higher (p < .05). A significant difference was found in length of ventilation (p < .04) in favor of the EPA + GLA group. There was no between-group difference in survival. CONCLUSIONS: In patients with acute lung injury, a diet enriched with EPA + GLA may be beneficial for gas exchange, respiratory dynamics, and requirements for mechanical ventilation.

Adult↗
PubMed2006

Type 2 diabetes--the pharmacotherapy of glycaemic control and risk factor modification.

BACKGROUND: Patients with diabetes have a high cardiovascular risk. In addition to achieving good glycaemic control, cardiovascular risk reduction is a vital component of management. OBJECTIVE: This article summarises the pharmacotherapy of diabetes--both the achievement and maintenance of good glycaemic control, and the attenuation of co-existent cardiovascular risk factors. DISCUSSION: Metformin is the first line hypoglycaemic agent when diet and exercise fail to achieve optimal glycaemia. The thiazolindinediones (glitazones) are effective new adjunctive oral hypoglycaemic agents that can be used in combination with either oral hypoglycaemics or insulin. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are beneficial in reducing long term complications of diabetes, especially in patients with microalbuminuria, hypertension, heart failure, previous acute myocardial infarction, and retinopathy. Statins are well established in both primary and secondary prevention in people with diabetes. Aspirin should be considered for primary prevention in patients with diabetes and increased cardiovascular risk.

Blood Glucose↗
PubMed2005

Predictors of stress in mothers and fathers of children with fragile X syndrome.

This study examined parental and family stress and functioning where there is a child with fragile X syndrome. Mothers and fathers in 40 families were asked about their child with fragile X syndrome, family supports, their psychological stress, the marital relationship, and their family stress. Results indicate parents were well adjusted in terms of their levels of psychological stress and in their marital relationships, however, parents reported high levels of family stress. Mothers and fathers were found to experience similar levels of stress and to report similar levels of satisfaction with supports. Stress was predicted by different variables in mothers and fathers, suggesting that different processes underlie their experiences. The strongest predictor of maternal stress was the level of marital satisfaction while the strongest predictor of paternal stress was the level of the child's adaptive skills.

Adaptation, Psychological↗
PubMed2005

Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes.

Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an approximately 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils.

Amino Acid Sequence↗
PubMed2005

Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.

The low-density lipoprotein receptor (LDLR) prevents hypercholesterolemia and atherosclerosis by removing low-density lipoprotein (LDL) from circulation. Mutations in the genes encoding either LDLR or its ligand (APOB) cause severe hypercholesterolemia. Missense mutations in PCSK9, encoding a serine protease in the secretory pathway, also cause hypercholesterolemia. These mutations are probably gain-of-function mutations, as overexpression of PCSK9 in the liver of mice produces hypercholesterolemia by reducing LDLR number. To test whether loss-of-function mutations in PCSK9 have the opposite effect, we sequenced the coding region of PCSK9 in 128 subjects (50% African American) with low plasma levels of LDL and found two nonsense mutations (Y142X and C679X). These mutations were common in African Americans (combined frequency, 2%) but rare in European Americans (<0.1%) and were associated with a 40% reduction in plasma levels of LDL cholesterol. These data indicate that common sequence variations have large effects on plasma cholesterol levels in selected populations.

Adult↗
PubMed2005

Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project).

Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides (<25th and >75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). One thousand four hundred thirty-six (854 men/582 women) affected patients by our criteria were compared with 1,672 (737 men/935 women) unaffected persons. Affected patients had more hypertension, obesity, and hyperglycemia, and they met a higher number of ATP-III criteria (3.2 +/- 1.1 SD vs 1.3 +/- 1.1 SD, p <0.001). Overall, 76% of affected persons also qualified for the ATP-III definition (Cohen's kappa 0.61, 95% confidence interval 0.59 to 0.64), similar to a separate group of 464 sporadic, unrelated cases (75%). Concordance increased from 41% to 82% and 88% for ages < or =35, 36 to 55, and > or =55 years, respectively. Affected status was also independently associated with waist circumference (p <0.001) and fasting glucose (p <0.001) but not systolic blood pressure (p = 0.43). Thus, the lipid-based criteria used to define affection status in this study substantially parallels the ATP-III definition of metabolic syndrome in subjects aged >35 years. In subjects aged <35 years, atherogenic dyslipidemia frequently occurs in the absence of other metabolic syndrome risk factors.

Adolescent↗
PubMed2005

Efficacy and costs of a one-day hands-on EASIE endoscopy simulator train-the-trainer workshop.

BACKGROUND: The efficacy of an intensive hands-on training in endoscopic hemostasis on the compactEASIE simulator has been previously demonstrated in a randomized prospective trial. In the current study, we evaluated how quickly and effectively new tutors, without simulator training experience, are able to acquire teaching skills in endoscopic hemostasis. METHODS: Five tutors with prior Erlangen Active Simulator for Interventional Endoscopy (EASIE) teaching experience instructed 7 endoscopists without prior EASIE experience on how to teach when using the model. These new tutors then independently conducted a workshop for 8 fellows in 4 hemostasis techniques. Results were compared with a historical control trained similarly by experienced tutors. Two one-day workshops in endoscopic hemostasis on the compactEASIE ex vivo endoscopy simulator were conducted in a category A hospital in New York City, New York. Skill scores at the end of training were compared with baseline skills assessments, and qualitative ratings of the new tutors were obtained from both the trainees and the experienced tutors. RESULTS: Significant improvement was achieved by the fellows in all 4 skills areas. Both the expert tutors and the trainees consistently rated the teaching skill of the new tutors highly. Fellows' skill acquisition using new tutors was of similar magnitude to that achieved in the prior EASIE trial using experienced trainers teaching the fellows. CONCLUSIONS: It is feasible to conduct an effective EASIE train-the-trainer course in one day. Tutors trained in this manner are able to provide a similar educational experience with objective improvement in trainee skill to experts who have conducted many hands-on workshops.

Clinical Competence↗
PubMed2005

Training with the compactEASIE biologic endoscopy simulator significantly improves hemostatic technical skill of gastroenterology fellows: a randomized controlled comparison with clinical endoscopy training alone.

BACKGROUND: The Erlangen Active Simulator for Interventional Endoscopy (EASIE) was introduced in 1997 for interventional endoscopy training. compactEASIE developed in 1998 is a modified, light-weight version of the original model. Objective evidence of the benefits of training with these models is limited. A randomized controlled study, therefore, was conducted to compare the effects of intensive 7-month, hands-on training in hemostatic techniques by using the compactEASIE model (in addition to clinical endoscopic training) vs. pure clinical training in endoscopic hemostatic methods. METHODS: Thirty-seven fellows in gastroenterology in New York City area training programs were enrolled. Baseline skills were assessed on the simulator for the following techniques: manual skills, injection and electrocoagulation, hemoclip application, and variceal ligation. Twenty-eight fellows were then randomized into two comparable groups. Those randomized to Group A received purely clinical training in endoscopic hemostatic techniques at their hospitals. Those in Group B, in addition, were trained by experienced tutors in 3 full-day hemostasis workshops over 7 months. Both groups underwent a final evaluation on the compactEASIE simulator conducted by their tutors and additional evaluators who were blinded to the method of training. Initial and final evaluation scores were compared for each group and between groups. Outcomes of actual clinical hemostatic procedures performed during the study period also were analyzed. RESULTS: Ten of 14 fellows randomized to Group A (standard training) and 13 of 14 in Group B (intensive training) returned for the final evaluation. For Group B, scores for all techniques were significantly improved. In Group A, a significant improvement was noted for variceal ligation alone. CONCLUSIONS: compactEASIE simulator training (3 sessions over 7 months), together with clinical endoscopic training resulted in objective improvement in the performance by fellows of all 4 endoscopic hemostatic techniques, whereas significant improvement was noted for variceal ligation alone for fellows who had standard clinical training. In clinical practice, fellows who had intensive simulator/clinical training had a significantly higher success rate and a nonsignificant reduction in the frequency of occurrence of complications.

Animals↗
PubMed2005

Functional manipulations of acetylcholinesterase splice variants highlight alternative splicing contributions to murine neocortical development.

Proliferation and differentiation of mammalian central nervous system progenitor cells involve concertedly controlled transcriptional and alternative splicing modulations. Searching for the developmental implications of this programming, we manipulated specific acetylcholinesterase (AChE) splice variants in the embryonic mouse brain. In wild type mice, 'synaptic' AChE-S appeared in migrating neurons, whereas the C-terminus cleaved off the stress-induced AChE-R variant associated with migratory radial glial fibers. Antisense suppression of AChE-R reduced neuronal migration, allowing increased proliferation of progenitor cells. In contrast, transgenic overexpression of AChE-R was ineffective, whereas transgenic excess of enzymatically active AChE-S or inactive AChE-Sin suppressed progenitors proliferation alone or both proliferation and neuronal migration, respectively. Our findings attribute to alternative splicing events an interactive major role in neocortical development.

Acetylcholinesterase↗
PubMed2005

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study.

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.

APACHE↗
PubMed2005

The international sepsis forum consensus conference on definitions of infection in the intensive care unit.

OBJECTIVE: To develop definitions of infection that can be used in clinical trials in patients with sepsis. CONTEXT: Infection is a key component of the definition of sepsis, yet there is currently no agreement on the definitions that should be used to identify specific infections in patients with sepsis. Agreeing on a set of valid definitions that can be easily implemented as part of a clinical trial protocol would facilitate patient selection, help classify patients into prospectively defined infection categories, and therefore greatly reduce variability between treatment groups. DESIGN AND METHODS: Experts in infectious diseases, clinical microbiology, and critical care medicine were recruited and allocated specific infection sites. They carried out a systematic literature review and used this, and their own experience, to prepare a draft definition. At a subsequent consensus conference, rapporteurs presented the draft definitions, and these were then refined and improved during discussion. Modifications were circulated electronically and subsequently agreed upon as part of an iterative process until consensus was reached. RESULT: Consensus definitions of infection were developed for the six most frequent causes of infections in septic patients: pneumonia, bloodstream infections (including infective endocarditis), intravascular catheter-related sepsis, intra-abdominal infections, urosepsis, and surgical wound infections. CONCLUSIONS: We have described standardized definitions of the common sites of infection associated with sepsis in critically ill patients. Use of these definitions in clinical trials should help improve the quality of clinical research in this field.

Clinical Trials as Topic↗