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Dan Cohen

Publications and source records attributed to Dan Cohen.

10 recordsLinked to original sources
PubMed2025

The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force.

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA's blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Clozapine↗
PubMed2006

Piezoresistive cantilever based nanoflow and viscosity sensor for microchannels.

Microfluidic channels are microreactors with a wide range of applications, including molecular separations based upon micro/nanoscale physicochemical properties, targeting and delivery of small amount of fluids and molecules, and patterned/directed growth. Their successful applications would require a detailed understanding of phenomena associated with the microscale flow of liquids through these channels, including velocity, viscosity and miscibility. Here we demonstrate a highly sensitive piezoresistive cantilever to measure flow properties in microfluidic channels. By milling down the legs of the piezoresistive cantilevers, we have achieved significantly higher mechanical sensitivity and a smaller spring constant, as determined by AFM. These cantilevers were used in microchannels to measure the viscosity and flow rate of ethylene glycol mixtures in water over a range of concentrations, as well as of low viscosity biologically relevant buffers with different serum levels. The sensor can be used alone or can be integrated in AFM systems for multidimensional study in micro and nanochannels.

Animals↗
PubMed2006

A high throughput Agrobacterium tumefaciens-mediated transformation method for functional genomics of perennial ryegrass (Lolium perenne L.).

A robust and high throughput Agrobacterium genetic transformation procedure has been developed for perennial ryegrass (Lolium perenne L.). Embryogenic callus lines were selected and maintained as plants in vitro. Embryogenic calli derived from meristematic regions of the vegetative tillers were co-cultivated with Agrobacterium tumefaciens strain EHA101 carrying the plasmid pCAMBIA 1305.1 in the presence of acetosyringone for 3-4 days. The calli were grown under 94.8 and 151.6 microM hygromycin selection, respectively for two cycles of 2-weeks each, followed by transfer to regeneration medium with 47.4 microM hygromycin. Regenerated plants were rooted and successfully transferred to soil. The transgenic nature of the regenerated plants was confirmed by DNA gel blot analysis and gene expression demonstrated by GUS histochemical assay and/or reverse transcription PCR. After development of the transformation procedure, we used Agrobacterium strain EHA101 carrying a modified binary plasmid pMH bearing genes of interest. In the past 2 years, we have produced more than 1,000 plants with constructs encoding different genes of interest from perennial ryegrass.

Agrobacterium tumefaciens↗
PubMed2006

Transformation of Actinidia eriantha: a potential species for functional genomics studies in Actinidia.

Protocols were developed for regeneration and Agrobacterium-mediated transformation of Actinidia eriantha Benth. A. eriantha has a number of features that make it a useful tool for functional genomics in Actinidia: the vines are relatively small and non-vigorous in nature, flowers form all over the vine including on lower axillary branches and the species flowers prolifically in greenhouse conditions. Flowering and fruiting of transgenic A. eriantha plants was obtained within 2 years of transformation in a containment greenhouse. GUS (beta-glucuronidase) activity indicating stable expression of the uidA gene was observed in leaf, stem, root, petal and fruit tissues. Molecular evidence for incorporation of transgenes into the A. eriantha genome was obtained by PCR and DNA gel blot analysis. Inheritance of transgenic phenotypes was demonstrated in seedling progeny. Functional genomic studies in kiwifruit have been initiated using transgenic A. eriantha plants.

Actinidia↗
PubMed2006

Hyperglycemia and diabetes in patients with schizophrenia or schizoaffective disorders.

OBJECTIVE: Pharmacoepidemiological studies have shown an increased prevalence of diabetes in patients with schizophrenia. To address this issue, we decided to assess glucose metabolism in a population of patients with schizophrenia or schizoaffective disorder. RESEARCH DESIGN AND METHODS: Oral glucose tolerance tests (OGTTs) were performed in 200 unselected in- and outpatients. Insulin sensitivity and beta-cell function were assessed using the homeostasis model assessment (HOMA) indexes and 30-min glucose and insulin levels. RESULTS: The mainly Western European (87.7%) study population had a mean age of 40.8 years, was 70% male, and had a mean fasting glucose of 5.1 mmol/l and a mean fasting insulin of 14.8 mU/l. Hyperglycemia was present in 7% of the population: 1.5% with impaired fasting glucose and 5.5% with impaired glucose tolerance. The prevalence of diabetes was 14.5%, of which 8% was previously known and 6.5% was newly diagnosed. Compared with a 1.5% prevalence of diabetes in the age-matched general Dutch population, the prevalence of identified cases was significantly increased in the study population. Comparable figures on the prevalence of hyperglycemia in the general population are not available. Insulin resistance was increased in the study population as a whole (HOMA of insulin resistance: 3.1-3.5), irrespective of the use of antipsychotic medication and, if used, irrespective of its type (typical or atypical). No indication of beta-cell defect was found, whereas a nonsignificant increased insulin resistance was found with antipsychotic medication. CONCLUSIONS: OGTTs in 200 mainly Caucasian patients with schizophrenia or schizoaffective disorder, mean age 41 years, showed that 7% suffered from hyperglycemia and 14.5% from diabetes. The prevalence of diabetes was significantly increased compared with the general population. No differential effect of antipsychotic monotherapy in diabetogenic effects was found. Therefore, a modification of the consensus statement on antipsychotic drugs, obesity, and diabetes is proposed, i.e., measurement of fasting glucose in all patients with schizophrenia, irrespective of prescribed antipsychotic drug.

Adult↗
PubMed2005

[Smallpox vaccination techniques: considerations and unresolved issues].

The smallpox vaccine is the oldest--and was, for 90 years, the only--vaccine known to man. Many vaccination techniques have been used over time, with no fewer than ten employed during the 20th century alone. In Israel, two main techniques were used prior to smallpox eradication in 1978--multiple punctures using a standard needle, and jet injection--while most other countries adopted the bifurcated needle as the method of choice. Despite the vaccination experience gained over time, doubt remains today as to the preferred vaccination technique. During 2002, when Israel became the first country to conduct large-scale smallpox vaccination in the 21st century, multiple standard needle puncture was adopted as the method of choice, while at the same time the bifurcated needle was readopted in the United States. The article reviews the various smallpox vaccination techniques, the supporting scientific data, and the current lacunae in knowledge related to the subject. Together, these factors will most likely influence the adoption of a preferred vaccination technique during a smallpox emergency.

Humans↗
PubMed2004

A high prevalence of organ-specific autoimmunity in patients with bipolar disorder.

BACKGROUND: In a previous study, we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in patients with bipolar disorder. Here we report the prevalence of other organ-specific autoantibodies: H/K adenosine triphosphatase (ATPA), glutamic acid decarboxylase-65 (GAD65A), and GAD-67 (GAD67A). METHODS: ATPA, GAD65A, and GAD67A were determined (via a commercially available enzyme linked immunosorbent assay for ATPA, and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder, in 74 patients with DSM-IV schizophrenia, and in 220 healthy control subjects. RESULTS: The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients compared with those in healthy control subjects (11.7 vs. 6.1% and 11.3 vs. 2.6% respectively; p <.05). Schizophrenia patients did not show such statistically higher prevalence. The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium. Interestingly, the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder. The level of TPOA was negatively correlated with the serum level of sIL-2R, a measure of T cell activation. CONCLUSION: Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO, H/K ATPase, and GAD65.

Autoantibodies↗
PubMed2004

Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus.

BACKGROUND: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. METHOD: In this cohort study, patients with newly diagnosed type 2 diabetes were selected from the PHARMO Record Linkage System, which comprises pharmacy records for all 320000 residents of 6 Dutch cities. In total, we identified 2585 patients with incident cases of type 2 diabetes who began treatment with oral hypoglycemic agents between 1991 and 1997 and had a medication history of at least 2 years after diagnosis of diabetes. A change in treatment from oral hypoglycemic agents alone to insulin therapy (with or without continuation of oral hypoglycemic agents) was considered a proxy for deterioration of beta-cell function. We compared the incidence of initiation of insulin therapy between users and nonusers of antipsychotic drugs by performing a Cox proportional hazards model analysis. RESULTS: We found an increased risk for initiation of insulin therapy at 2 years after diagnosis of diabetes in users of antipsychotics compared with nonusers; the relative hazard (hazard ratio) was 2.0 (95% CI = 1.2 to 3.3), which did not change after adjustment for potential confounders. The risk decreased in the years after diagnosis of diabetes. CONCLUSION: It seems that use of antipsychotics by patients with type 2 diabetes mellitus is associated with initiation of insulin therapy (i.e., "secondary failure"), especially in the first 2 years of the disease.

Antipsychotic Agents↗