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Biomedical subjects

David Cohen

Publications and source records attributed to David Cohen.

At least 19 recordsLinked to original sources
PubMed2007

Should the use of selective serotonin reuptake inhibitors in child and adolescent depression be banned?

BACKGROUND: European and US pharmaceutical agencies have recently warned against the use of selective serotonin reuptake inhibitors (SSRIs) in child and adolescent depression. This came as a surprise to many practitioners, who had made treatment decisions based on data from pharmaceutical trials using adult samples. METHOD: The author reviews the recent literature relevant to the use of SSRIs in youth depression, including psychiatricclinical trials, pharmacology and drug safety data. Recommendations and rationales for the use of SSRIs in this context are offered. RESULTS: Ten publications, comprising a total of 2,046 patients, evaluated the efficacy of four SSRIs (fluoxetine, paroxetine, sertraline and citalopram) in child and adolescent depression. It is noted that an additional 6 trials (with a total of 1,234 patients) were not reported by the industry because of a lack of efficacy or problematic side effects, including suicidal behaviors. Meta-analyses revealed no data supporting the use of SSRIs, except for fluoxetine. To formulate recommendations for clinical practice, it is necessary to examine specific issues such as (1) the link between SSRIs, depression and suicidal risk; (2) SSRI age-related specific effects, and (3) the high placebo response in child and adolescent depression. CONCLUSION: An SSRI prescription is still a second-line option in severe and resistant forms of youth depression. However, in children and adolescents only specialists well trained in child and adolescent psychiatry should prescribe SSRIs.

Adolescent↗
PubMed2006

Characterization of a carbohydrate transporter from symbiotic glomeromycotan fungi.

The symbiotic relationships between mycorrhizal fungi and plants have an enormous impact on terrestrial ecosystems. Most common are the arbuscular mycorrhizas, formed by fungi belonging to the phylum Glomeromycota. Arbuscular mycorrhizal fungi facilitate the uptake of soil nutrients by plants and in exchange obtain carbohydrates, thus representing a large sink for atmospheric plant-fixed CO(2). However, how carbohydrates are transported through the symbiotic interface is still unknown. Here we report the characterization of the first known glomeromycotan monosaccharide transporter, GpMST1, by exploiting the unique symbiosis of a glomeromycotan fungus (Geosiphon pyriformis) with cyanobacteria. The GpMST1 gene has a very low GC content and contains six introns with unusual boundaries. GpMST1 possesses twelve predicted transmembrane domains and functions as a proton co-transporter with highest affinity for glucose, then mannose, galactose and fructose. It belongs to an as yet uncharacterized phylogenetic monosaccharide transporter clade. This initial characterization of a new transporter family involved in fungal symbiosis will lead to a better understanding of carbon flows in terrestrial environments.

Biological Transport↗
PubMed2006

Animal models relevant to schizophrenia and autism: validity and limitations.

Development of animal models is a crucial issue in biological psychiatry. Animal models provide the opportunity to decipher the relationships between the nervous system and behavior and they are an obligatory step for drug tests. Mouse models or rat models to a lesser extent could help to test for the implication of a gene using gene targeting or transfecting technologies. One of the main problem for the development of animal models is to define a marker of the psychiatric disorder. Several markers have been suggested for schizophrenia and autism, but for the moment no markers or etiopathogenic mechanisms have been identified for these disorders. We examined here animal models related to schizophrenia and autism and discussed their validity and limitations after first defining these two disorders and considering their similarities and differences. Animal models reviewed in this article test mainly behavioral dimensions or biological mechanisms related to autistic disorder or schizophrenia rather than providing specific categorical models of autism or schizophrenia. Furthermore, most of these studies focus on a behavioral dimension associated with an underlying biological mechanism, which does not correspond to the complexity of mental disorders. It could be useful to develop animal models relevant to schizophrenia or autism to test a behavioral profile associated with a biological profile. A multi-trait approach seems necessary to better understand multidimensional disorders such as schizophrenia and autism and their biological and clinical heterogeneity. Finally, animal models can help us to clarify complex mechanisms and to study relationships between biological and behavioral variables and their interactions with environmental factors. The main interest of animal models is to generate new pertinent hypotheses relevant to humans opening the path to innovative research.

Animals↗
PubMed2006

Treatments in child and adolescent bipolar disorders.

The existence of bipolar disorder in adolescents is now clearly established. However, whether bipolarity exists in children is more controversial. We reviewed the literature on acute and prophylactic treatment of bipolar disorder in youths. The guidelines for the treatment of bipolar disorder in children and adolescents are generally similar to those applied in adult practice. But no evidence-based data support the use of mood stabilisers or antipsychotics since we only found two placebo-randomised controlled trials testing the efficacy of lithium in the paediatric literature. Therefore, we support the view that prescriptions should be limited to the most typical cases. In fact, the use of mood stabilisers or antipsychotics in the treatment of bipolar disorder in children and adolescents appears to be of limited use when a comorbid condition, such as attention deficit hyperactivity disorder, occurs unless aggressive behaviour is the target symptom.

Acute Disease↗
PubMed2006

Brief report: visual-spatial deficit in a 16-year-old girl with maternally derived duplication of proximal 15q.

Duplications of chromosome 15 may be one of the most common single genetic causes of autism spectrum disorders (ASD), aside from fragile X. Most of the cases are associated with maternally derived interstitial duplication involving 15q11-13. This case report describes a female proband with a maternally derived interstitial duplication of proximal 15q. She did not exhibit any symptoms of ASD apart from some developmental delay. By adolescence, she showed mild dysmorphism, a discrepant profile on the Wechsler Intelligence Scale for Children (Verbal IQ = 87; Performance IQ = 65) and a major deficit in visual-spatial abilities affecting fine motor skills, mathematical reasoning, visual memory and some global reading tasks. This is one of the first reports of a child with a maternal duplication who exhibits a visual-spatial deficit without ASD.

Abnormalities, Multiple↗
PubMed2006

Principles underlying the design of "The Number Race", an adaptive computer game for remediation of dyscalculia.

BACKGROUND: Adaptive game software has been successful in remediation of dyslexia. Here we describe the cognitive and algorithmic principles underlying the development of similar software for dyscalculia. Our software is based on current understanding of the cerebral representation of number and the hypotheses that dyscalculia is due to a "core deficit" in number sense or in the link between number sense and symbolic number representations. METHODS: "The Number Race" software trains children on an entertaining numerical comparison task, by presenting problems adapted to the performance level of the individual child. We report full mathematical specifications of the algorithm used, which relies on an internal model of the child's knowledge in a multidimensional "learning space" consisting of three difficulty dimensions: numerical distance, response deadline, and conceptual complexity (from non-symbolic numerosity processing to increasingly complex symbolic operations). RESULTS: The performance of the software was evaluated both by mathematical simulations and by five weeks of use by nine children with mathematical learning difficulties. The results indicate that the software adapts well to varying levels of initial knowledge and learning speeds. Feedback from children, parents and teachers was positive. A companion article describes the evolution of number sense and arithmetic scores before and after training. CONCLUSION: The software, open-source and freely available online, is designed for learning disabled children aged 5-8, and may also be useful for general instruction of normal preschool children. The learning algorithm reported is highly general, and may be applied in other domains.

Journal Article↗
PubMed2006

An open trial assessment of "The Number Race", an adaptive computer game for remediation of dyscalculia.

BACKGROUND: In a companion article, we described the development and evaluation of software designed to remediate dyscalculia. This software is based on the hypothesis that dyscalculia is due to a "core deficit" in number sense or in its access via symbolic information. Here we review the evidence for this hypothesis, and present results from an initial open-trial test of the software in a sample of nine 7-9 year old children with mathematical difficulties. METHODS: Children completed adaptive training on numerical comparison for half an hour a day, four days a week over a period of five-weeks. They were tested before and after intervention on their performance in core numerical tasks: counting, transcoding, base-10 comprehension, enumeration, addition, subtraction, and symbolic and non-symbolic numerical comparison. RESULTS: Children showed specific increases in performance on core number sense tasks. Speed of subitizing and numerical comparison increased by several hundred msec. Subtraction accuracy increased by an average of 23%. Performance on addition and base-10 comprehension tasks did not improve over the period of the study. CONCLUSION: Initial open-trial testing showed promising results, and suggested that the software was successful in increasing number sense over the short period of the study. However these results need to be followed up with larger, controlled studies. The issues of transfer to higher-level tasks, and of the best developmental time window for intervention also need to be addressed.

Journal Article↗
PubMed2006

PAR1b promotes cell-cell adhesion and inhibits dishevelled-mediated transformation of Madin-Darby canine kidney cells.

Mammalian Par1 is a family of serine/threonine kinases comprised of four homologous isoforms that have been associated with tumor suppression and differentiation of epithelial and neuronal cells, yet little is known about their cellular functions. In polarizing kidney epithelial (Madin-Darby canine kidney [MDCK]) cells, the Par1 isoform Par1b/MARK2/EMK1 promotes the E-cadherin-dependent compaction, columnarization, and cytoskeletal organization characteristic of differentiated columnar epithelia. Here, we identify two functions of Par1b that likely contribute to its role as a tumor suppressor in epithelial cells. 1) The kinase promotes cell-cell adhesion and resistance of E-cadherin to extraction by nonionic detergents, a measure for the association of the E-cadherin cytoplasmic domain with the actin cytoskeleton, which is critical for E-cadherin function. 2) Par1b attenuates the effect of Dishevelled (Dvl) expression, an inducer of wnt signaling that causes transformation of epithelial cells. Although Dvl is a known Par1 substrate in vitro, we determined, after mapping the PAR1b-phosphorylation sites in Dvl, that PAR1b did not antagonize Dvl signaling by phosphorylating the wnt-signaling molecule. Instead, our data suggest that both proteins function antagonistically to regulate the assembly of functional E-cadherin-dependent adhesion complexes.

Actins↗
PubMed2006

Idiopathic sudden sensorineural hearing loss in the only hearing ear: patient characteristics and hearing outcome.

OBJECTIVE: To determine the otological outcome in patients with idiopathic sudden sensorineural hearing loss (ISSHL) in their only hearing ear. DESIGN: Retrospective medical chart review study. SETTING: Tertiary care hospital. PATIENTS: Forty-five consecutive patients older than 18 years with sudden sensorineural hearing loss during a 10 year period (1985-1995), 9 of whom had ISSHL in their only hearing ear. INTERVENTION: Daily audiometric tests, oral prednisolone (full available dose), and bed rest for at least a week. MAIN OUTCOME MEASURE: The audiometric result 7 to 10 days following the start of treatment was used as the treatment outcome. RESULTS: Demographic characteristics were not significantly different between patients with ISSHL whose contralateral ear is deaf and those whose contralateral ear hears well. A tendency to seek help sooner (2.8 +/- 1.4 vs 7.1 +/- 5.2 days [mean +/- SD], respectively) was noted. The mean +/- SD improvement of hearing in the 3 more affected frequencies was 13 +/- 13.4 dB for the investigated group compared with 9 +/- 8.7dB for the rest of the patients (not statistically significant). Of the 9 patients who previously had sensorineural hearing loss in the opposite ear, 5 showed end results of speech reception thresholds of 35 dB or better, as did 13 of the 36 patients in the other group. CONCLUSIONS: Patients with ISSHL in their only hearing ear may be treated the same way as other patients because their outcome appears to be the same. About 50% of the patients will have a 10 dB or more hearing improvement, and about 60% of patients in the investigated group will regain useful hearing.

Administration, Oral↗
PubMed2006

Towards a valid nosography and psychopathology of catatonia in children and adolescents.

Paraphrasing Taylor and Fink (2003), catatonia needs "a home of its own" in child and adolescent psychiatry. Limited but expanding literature supports that catatonia in children and adolescent can be identified reliably among other childhood conditions, is sufficiently common, treatable with the same specific treatments as adult catatonia (e.g., sedative drugs and electroconvulsive therapy), and can be worsened by other treatments (e.g., antipsychotics). Other findings in child and adolescent catatonia suggest that sex ratio and associated disorders may differ, and the proposed classification of Taylor and Fink (2003) needs modification. Adopting a broader diagnostic schedule may accommodate both child, adolescent, and adult catatonia. A psychomotor automatism variant should be included as a diagnosis, as well as specifiers for associated disorders such as acute nonpsychotic anxious state and pervasive developmental disorder. Duration of illness should be specified as acute or chronic. Regardless of associated psychiatric disorders, this chapter describes a new psychopathological model. Three main modalities of movement dysfunction in catatonic subjects are listed: (1) adherence to delusional ideas leading to a psychomotor automatism (De Clérambault, 1927); (2) resistance to delusional thinking or conviction; and finally (3) hyperanxious states. Case-vignettes illustrate the model, and future research directions are identified.

Adolescent↗
PubMed2006

Scanning electron microscopy of thyroid cells under fully hydrated conditions--a novel technique for a seasoned procedure: a brief observation.

Technical information for handling fine-needle aspiration samples from thyroid lesions for WETSEM electron microscopy is presented. The use of wet SEM technology maintains cytological features of the thyroid cells, in the atmospheric electronic microscope chamber without the need for solidification. Images are presented from normal and pathological thyroid specimens showing subcellular elements unavailable to the cytopathologist by light microscopy. Of 24 samples, 18 were adequate for clinical evaluation. In 16 of these 18 specimens, we could find features compatible with the final histological or cytological diagnosis (post-hoc). In two cases, the cell features were too unique to be interpretable. Because this procedure is relatively simple, there is potential for the use of this technology as an adjunct to light microscopy in clinical and research settings.

Adult↗
PubMed2006

Cutaneous reactions to injectable corticosteroids.

Corticosteroids are used to treat a variety of medical conditions. While topical preparations are known to commonly cause allergic contact dermatits, systemic use of these drugs rarely causes cutaneous reactions. (This paper presents) Two cases of (systemic) injectable corticosteroid use resulting in delayed hypersensitivity reactions are presented.

Aged↗
PubMed2006

Mitral annuloplasty causing left circumflex injury and infarction: novel use of intravascular ultrasound to diagnose suture injury.

Suture injury of the left circumflex coronary artery and infarction may be an under-recognized complication of mitral valve annuloplasty. Our cases illustrate a potential role for early coronary angiography in patients who have persistent hemodynamic instability or ventricular irritability, which may be related to left circumflex artery injury. This potentially devastating complication of mitral annuloplasty can be diagnosed by use of intravascular ultrasound to distinguish suture injury from an atherosclerotic lesion.

Coronary Artery Disease↗
PubMed2006

Delayed diagnosis of incident type 2 diabetes mellitus in the ARIC study.

OBJECTIVES: To estimate delays to physician diagnosis of incident cases of type 2 diabetes mellitus (DM) and to identify predictors of delayed diagnosis. STUDY DESIGN: The Atherosclerosis Risk in Communities (ARIC) study, an ongoing population-based prospective study of 15 792 middle-aged adults. METHODS: The study population comprised 298 adults with incident DM. Exposures were demographic, socioeconomic, health behavior, and clinical risk factors before the onset of type 2 DM. The main outcome was the delay from onset of DM to physician diagnosis. RESULTS: Among 298 ARIC participants with incident type 2 DM at visit 2 of the study, the median delay from onset of DM to physician diagnosis was 2.4 years. More than 7% of incident cases remained undiagnosed for at least 7.5 years after the onset of disease. Compared with individuals with promptly diagnosed incident DM, those with delayed diagnosis were more likely to be obese before the onset of DM (P = .003), less likely to have heart disease at baseline (P = .02 for trend), less likely to have seen their physician in the past year (P = .005 for trend), and had a slower rise in fasting hyperglycemia (P = .04). Neither demographic characteristics nor study site predicted delayed diagnosis. CONCLUSIONS: Even with a de facto screening program, diagnosis of incident type 2 DM in the community is typically delayed for 2 years and sometimes as long as 7 years or more. The associated risk factors suggest deficiencies in organizational processes, physician actions, and patient access or acceptance of the diagnosis.

Atherosclerosis↗
PubMed2005

Individual cognitive training of reading disability improves word identification and sentence comprehension in adults with mild mental retardation.

Reading therapy has been shown to be effective in treating reading disabilities (RD) in dyslexic children, but little is known of its use in subjects with mild mental retardation (MR). Twenty adult volunteers, with both RD and mild MR, underwent 60 consecutive weeks in a cognitive remediation program, and were compared with 32 untreated control subjects. The experimental group showed a significant improvement in word identification, as measured by oral production (p=0.0004) or silent reading (p=0.023), and sentence comprehension (p=0.0002). Adults with MR appear to benefit from new approaches in the field of RD.

Adult↗