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Biomedical subjects

H Cohen

Publications and source records attributed to H Cohen.

At least 73 records · Page 4Linked to original sources

[The risk of bloodborne infections in health care workers and their patients: possible preventive steps].

Hospital-based bloodborne infections are generally limited to viruses; hepatitis B virus, hepatitis C virus and the human immunodeficiency virus. The risk of infection by an infected patient to the health care worker is substantial. All preventable actions should be taken, including 3 injections of vaccine for hepatitis B, serological confirmation of protection, and further treatment if necessary. Since no preventable risk to a patient is acceptable, policies need to be set on the fitness-for-work of the infected surgeon. This article reviews the risks of bloodborne infections and preventive measures.

Communicable Disease Control↗

Autonomic nervous system derangement in fibromyalgia syndrome and related disorders.

Fibromyalgia syndrome is a chronic, painful musculoskeletal disorder of unknown etiology and/or pathophysiology. During the last decade many studies have suggested autonomic nervous system involvement in this syndrome, although contradictory results have been reported. This review focuses on studies of the autonomic nervous system in fibromyalgia syndrome and related disorders, such as chronic fatigue syndrome and irritable bowel syndrome on the one hand and anxiety disorder on the other, and highlights techniques of dynamic assessment of heart rate variability. It raises the potentially important prognostic implications of protracted autonomic dysfunction in patient populations with fibromyalgia and related disorders, especially for cardiovascular morbidity and mortality.

Adult↗

[Heart rate variability in schizophrenic patients treated with antipsychotic agents].

BACKGROUND: Antipsychotic medication causes a wide range of predictable adverse effects, and has long been associated with sudden unexplained and unexpected death in psychiatric patients, despite controversies surrounding the issue. In light of the evidence that sudden cardiovascular-related death is associated with neuroleptic medication, we are especially interested in examining whether measurements of the power spectral analysis (PSA) of heart rate variability (HRV) are differentially affected by various antipsychotic medications. We will also examine the cases in which PAS provides information regarding the relative safety of the various groups of drugs under investigation, in terms of their influence on the sympathetic-parasympathetic balance. AIM: The primary aim of this study is to utilize spectral analysis of heart rate variability as a tool to examine the differential arythmogenic effects of antipsychotic medications. The secondary aim was to examine the QT interval in schizophrenic patients receiving this treatment. METHOD: Standardized heart rate analysis was carried out in twenty-one schizophrenic patients receiving monotherapy with the following medications: treatment with 300-700 mg/day of clozapine, eighteen schizophrenic patients treated with 5-10 mg/day haloperidol, seventeen schizophrenic patients treated with 5-20 mg/day Olanzapine, and 53 healthy subjects. RESULTS: Our results show that schizophrenic patients treated with clozapine had significantly higher HR, lower HRV, lower high frequency (HF) and higher low frequency (LF) components compared to the patients treated with haloperidol, olanzapine, and the matched control subjects. Prolonged QTc intervals were more common in patients receiving treatment than in the control group, although the PR and QRS intervals did not differ significantly. CONCLUSIONS: The overall results showed that, patients treated with neuroleptic medication, especially clozapine, presented autonomic dysregulation and cardiac repolarization changes. Care should be taken in prescribing clozapine to patients prone to cardiovascular side effects.

Adult↗

Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome.

Interferon consensus sequence-binding protein (ICSBP) is a member of the interferon regulatory factors (IRF) that has a pivotal role in mediating resistance to pathogenic infections in mice and in promoting the differentiation of myeloid cells. ICSBP exerts some of its transcriptional activities via association with other factors that enable its binding to a variety of promoters containing DNA composite elements. These interactions are mediated through a specific COOH-terminal domain termed IAD (IRF association domain). To gain a broader insight of the capacity of ICSBP to interact with other factors, yeast two-hybrid screens were performed using ICSBP-IAD as a bait against a B-cell cDNA library. Trip15 was identified as a specific interacting factor with ICSBP in yeast cells, which was also confirmed by in vitro glutathione S-transferase pull-down assays and by coimmunoprecipitation studies in COS7 cells. Trip15 was recently identified as a component of the COP9/signalosome (CSN) complex composed of eight evolutionary conserved subunits and thus termed CSN2. This complex has a role in cell-signaling processes, which is manifested by its associated novel kinase activity and by the involvement of its subunits in regulating multiple cell-signaling pathways and cell-cycle progression. We show that in vitro association of ICSBP with the CSN leads to phosphorylation of ICSBP at a unique serine residue within its IAD. The phosphorylated residue is essential for efficient association with IRF-1 and thus for the repressor activity of ICSBP exerted on IRF-1. This suggests that the CSN has a role in integrating incoming signals that affect the transcriptional activity of ICSBP.

3T3 Cells↗

Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.

BACKGROUND: Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. METHODS AND RESULTS: Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997-1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985-1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985-1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years; P:<0.001) and more often female (32.1% versus 25.5%; P:<0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%; P:<0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction; P:<0.001), thrombotic (22.1% versus 11.3%; P:<0.001) or calcified (29.5% versus 10.8%; P:<0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985-1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%; P:<0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%; P:=0.001) than in the 1985-1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%; P:<0.001). CONCLUSIONS: Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985-1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Angioplasty, Balloon, Coronary↗

Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort.

Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome expressed along three domains: inattention, hyperactive-impulsive, and combined type. Both environmental and genetic factors contribute to the etiology of this complex disease. We previously reported an association in 48 ADHD triads (both parents and proband) between the catechol-O-methyl- transferase (COMT) polymorphism (especially the high enzyme activity val allele) and the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) combined category (excluding inattention) of ADHD (however, see erratum, Am. J. Med. Genet. [Neuropsychiatr. Genet.] 96:893). In the current report, we attempted to replicate this finding in an independently recruited group of 70 nuclear families using the haplotype relative risk design. In the current investigation, no evidence for association of the COMT polymorphism and ADHD (or any of the DSM IV subtypes) was observed in either the current cohort or the expanded cohort of 118 Israeli triads. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:858-860, 2000.

Attention Deficit Disorder with Hyperactivity↗

Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study.

A previous case control study by Vandenbergh et al. [1997: Am J Med Genet 74:439-442] showed an association between the high activity catechol O-methyltransferase (COMT) polymorphism and polysubstance abuse in a group of North American subjects. In the current study we confirm these results by genotyping 38 Israeli heroin addicts and both parents using a robust family-based haplotype relative risk (HRR) strategy. There is an excess of the val COMT allele (likelihood ratio = 4.48, P = 0.03) and a trend for an excess of the val/val COMT genotype (likelihood ratio = 4.97, P = 0.08, 2 df) in the heroin addicts compared to the HRR control group. We also genotyped an additional 101 nonrelated heroin addicts and 126 control subjects using a case control design and found no significant difference in COMT val allele frequency (25.4% vs. 29.7%, likelihood ratio = 1.04, P = 0.31). A significant difference is observed in COMT allele frequency among the three principal Israeli ethnic groups (Ashkenazi Jewish, non-Ashkenazi Jewish, and Palestinian Arab) in a large group of control subjects we have so far examined (chi-square = 7.9, P = 0.019, df = 2, n = 1,422 alleles) suggesting that population stratification is responsible for our failure to observe an excess of the COMT val allele when using the case-control design.

Alleles↗

A peptide prodrug approach for improving bisphosphonate oral absorption.

This work was aimed at improving the absorption of bisphosphonates by targeting carrier systems in the intestine and the intestinal peptide carrier system (hPEPT1), in particular. (14)C-Labeled pamidronate and alendronate as well as radiolabeled and "cold" peptidyl-bisphosphonates, Pro-[(3)H]Phe-[(14)C]pamidronate, and Pro-[(3)H]Phe-[(14)C]alendronate were synthesized. In situ single-pass perfusion studies revealed competitive inhibition of transport by Pro-Phe, suggesting peptide carrier-mediated transport. Prodrug transport in the Caco-2 cell line was significantly better than that of the parent drugs, and the prodrugs exhibited high affinity to the intestinal tissue. Oral administration of the dipeptidyl prodrugs resulted in a 3-fold increase in drug absorption following oral administration in rats, and the bioavailability of Pro-Phe-alendronate was 3.3 (F(TIBIA)) and 1.9 (F(URINE)) times higher than that of the parent drug. The results indicate that the oral absorption of bisphosphonates can be improved by peptidyl prodrugs via the hPEPT1; however, other transporters may also be involved.

Administration, Oral↗

Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks.

Power spectral analysis (PSA) of heart rate variability (HRV) offers reliable assessment of cardiovascular autonomic responses, providing a 'window' onto the interaction of peripheral sympathetic and parasympathetic tone. Alterations in HRV are associated with various physiological and pathophysiological processes, and may contribute to morbidity and mortality. Previous studies of posttraumatic stress disorder (PTSD) found lower resting HRV in patients compared to controls, suggesting increased sympathetic and decreased parasympathetic tone. This article describes the analysis of HRV at rest and after psychological stress in panic disorder (PD) patients, in an enlarged sample of PTSD patients, and in healthy control subjects. Standardized heart rate (HR) analysis was carried out in 14 PTSD patients, 11 PD patients and 25 matched controls. ECG recordings were made while subjects were resting ('rest 1'), while recalling the trauma implicated in PTSD, or the circumstances of a severe panic attack, as appropriate ('recall'), and again while resting ('rest 2'). Controls were asked to recall a stressful life event during recall. While both patient groups had elevated HR and low frequency (LF) components of HRV at baseline (suggesting increased sympathetic activity), PTSD patients, unlike PD patients and controls, failed to respond to the recall stress with increases in HR and LF. HRV analysis demonstrates significant differences in autonomic regulation of PTSD and PD patients compared to each other and to control subjects. HRV analysis may augment biochemical studies of peripheral measures in these disorders.

Adult↗

Controlled surface charging as a depth-profiling probe for mesoscopic layers

Probing the structure of material layers just a few nanometres thick requires analytical techniques with high depth sensitivity. X-ray photoelectron spectroscopy (XPS) provides one such method, but obtaining vertically resolved structural information from the raw data is not straightforward. There are several XPS depth-profiling methods, including ion etching, angle-resolved XPS (ref. 2) and Tougaard's approach, but all suffer various limitations. Here we report a simple, non-destructive XPS depth-profiling method that yields accurate depth information with nanometre resolution. We demonstrate the technique using self-assembled multilayers on gold surfaces; the former contain 'marker' monolayers that have been inserted at predetermined depths. A controllable potential gradient is established vertically through the sample by charging the surface of the dielectric overlayer with an electron flood gun. The local potential is probed by measuring XPS line shifts, which correlate directly with the vertical position of atoms. We term the method 'controlled surface charging' and expect it to be generally applicable to a large variety of mesoscopic heterostructures.

Journal Article↗

Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study.

The DRD4 exon III repeat polymorphism has been associated in adults with Novelty Seeking personality traits and in children with attention deficit hyperactivity disorder (ADHD) in some but not all studies. In a previous report we failed to observe preferential transmission of the long DRD4 repeat in ADHD compared to the haplotype relative risk (HRR) derived control group in a group of 49 triads (both parents and ADHD child) recruited in the Jerusalem area. In the current study we independently recruited an additional group of 49 triads from a different geographical location (Petak Tikvah) in Israel but having a similar ethnic background. In contrast to previous findings from a number of groups, in the current study an excess of the long DRD4 alleles was observed in the HRR control group compared to the ADHD subjects (Likelihood ratio = 5.50, P = 0. 02). In the expanded Israeli group of 98 triads so-far examined for the DRD4 repeat polymorphism there is an excess of the long alleles in the HRR control group (Likelihood ratio = 3.81, P = 0.05). These results attest to the complexity of ADHD inheritance and the likelihood that genetic heterogeneity characterizes this disorder especially across ethnic and cultural boundaries.

Adolescent↗

Oriented crystalline monolayers and bilayers of 2 x 2 silver(I) grid architectures at the air-solution interface: their assembly and crystal structure elucidation

Oriented crystalline monolayers, approximately 14 A thick, of a 2 x 2 Ag+ grid complex, self-assembled at the air-solution interface starting from an water-insoluble ligand 3,6-bis[2-(6-phenylpyridine)]pyridazine spread on silver-ion-containing solutions, were examined by grazing-incidence X-ray diffraction and specular X-ray reflectivity using synchrotron radiation. The monolayer structure was refined, including a determination of the positions of the counter-ions, with the SHELX-97 computer program. The monolayers were transferred from the interface onto various solid supports and visualized by scanning force microscopy, and characterized by X-ray photoelectron spectroscopy in terms of molecular structure. On surface compression, the initial self-assembled monolayer undergoes a transition to a crystalline bilayer in which the two layers, almost retaining the original arrangement, are in registry. Such a phase transition is of relevance to the understanding of crystal nucleation.

Journal Article↗

De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome.

Supravalvular aortic stenosis may present as an isolated finding or as part of Williams syndrome. Williams syndrome is a contiguous gene syndrome associated with neurodevelopmental and multisystemic manifestations caused by hemizygous deletion at 7q11.23. We report on the prenatal and histopathological findings in a patient with a chromosome translocation involving the Williams syndrome critical region. The initial abnormality on fetal ultrasound was hydrops fetalis detected at 30 weeks and echocardiography showed narrowing of the aorta and the pulmonary arteries. The baby died shortly after delivery and an autopsy revealed diffuse tubular thickening with luminal narrowing of the aorta, aortic branches, and the pulmonary arteries. Histopathology showed dysplasia of the media with reduced elastic content and "cartwheel" arrangement of collagen, elastic, and muscle fascicles. The karyotype was 46,XX,t(6;7)(q27;q11.23). Three signals were detected using the Oncor fluorescent in situ hybridization probe for elastin-Williams syndrome (WSCR) suggesting that the break in chromosome 7 is within the elastin-Williams gene. This patient is of special interest because of the prenatal presentation and the chromosomal translocation involving the elastin-Williams syndrome locus.

Aortic Valve Stenosis↗

Congenital diaphragmatic hernia in a family segregating a reciprocal translocation t(5;15)(p15.3;q24).

Congenital diaphragmatic hernia (CDH) is a relatively common malformation of unknown cause with high mortality due to hypoplasia of the lungs and pulmonary hypertension. We studied a family in which two fetuses had CDH, and two pregnancies resulted in first trimester missed abortions. Both fetuses with CDH had an apparently normal karyotype. In a subsequent pregnancy, fluorescent in situ hybridization analysis of amniocytes showed a balanced translocation 46,XY, t(5;15) (p15.3;q24) also present in the mother and in a normal child, suggesting that the diaphragmatic hernia in the first two fetuses was caused by a cryptic unbalanced translocation. This hypothesis is supported by a previous observation of CDH in a distal deletion of 15q as part of a multiple congenital anomalies syndrome. It is suggested that a gene distal to 15q21 is important for the normal development of the diaphragm.

Abortion, Induced↗

Expression of Von Willebrand factor, an endothelial cell marker, is up-regulated by angiogenesis factors: a potential method for objective assessment of tumor angiogenesis.

von Willebrand factor (vWF), a glycoprotein produced uniquely by endothelial cells and megakaryocytes, is routinely used to identify vessels in tissue sections. Vessel density in tumor specimens, as determined by immuno-histochemical staining for vWF or other endothelial cell markers, is a negative prognostic factor for many solid tumors. vWF is heterogeneously distributed throughout the vasculature, transcriptional control in response to the tissue microenvironment being responsible for local variations in endothelial cell levels of vWF. Here, we report that fibroblast growth factor-2 and vascular endothelial growth factor, potent angiogenesis inducers expressed in a variety of tumors, up-regulate expression of vWF mRNA and protein in cultured endothelial cells with a synergistic effect. Our data support the measurement of vWF mRNA in tumors to detect activated endothelium or angiogenesis. For this purpose, we developed a semi-quantitative RT-PCR for vWF mRNA. Preliminary results obtained with specimens from colon carcinoma and the corresponding normal colonic mucosa showed higher vWF mRNA levels in most tumors than in their normal counterparts. The differences in vWF mRNA levels were much larger than the differences in vessel counts between a tumor and the corresponding normal mucosa, indicating that high vWF mRNA levels in tumors may indeed be an early sign of activation of the endothelium. The rapidity, objectivity, sensitivity and specificity of this technique make it suitable for routine clinical application to identify aggressive, highly angiogenic tumors.

Base Sequence↗

High-resolution electron microscopy study of synthetic carbonate and aluminum containing apatites.

Aluminum (Al)-containing calcium-deficient carbonated hydroxyapatites were produced by a precipitation method from aqueous solution with carbonate (0-6.1%) and aluminum (0.1-0.5%) concentrations close to those found in biological materials. Two series of apatites were prepared: one at pH 7.0 and another at pH 9. 0. High-resolution electron microscopy has shown that many of them possess structural defects such as screw dislocations, grain boundaries, and central defects. Samples with high carbonate content and high water and high Al(3+) content had a high amount of structural defects. Accordingly, a sample (7Al1) with a relatively high carbonate content (6.1%) and a sample (7Al6) without carbonate but with a relatively high water (2.0 mol) and Al(3+) content (0. 39%) presented the highest amount of structural defects, 54% and 47%, respectively. A sample (7Al13) with a low level of crystalline water (1 mol) and low carbonate (2.5%) showed a small amount of defects. The presence of water associated with Al(3+) induced a high number of crystals having a central defect with a great similarity to the so-called water layer of octacalcium phosphate (OCP). Observed images of all these crystals have shown good correspondence with the computer-simulated image based on the crystal structure of hydroxyapatite, indicating that the addition of Al(3+) and carbonate does not perturb the apatitic structure.

Aluminum↗

The anxiolytic effect of chronic inositol depends on the baseline level of anxiety.

Inositol, a precursor for membrane phosphoinositides involved in signal transduction, has been found to be clinically effective in a number of psychiatric disorders and to reverse behavioural effects of lithium. To gain insight into the mechanism of action of inositol, it is critical to establish its efficacy in animal models. Following the initial report by Cohen et al. (1997b) that inositol was anxiolytic in the elevated plus maze model of anxiety, the effect of chronic intraperitoneal and chronic dietary inositol administration in rats was tested in four experiments. There was a significant increase in closed arm and total arm entries following chronic injection of inositol, but no effect of inositol when it was given chronically in rat chow. Because the first 2 experiments suggested that the mode of drug administration affected the control levels of anxiety (open arm entries and time in open arms) in control groups, the effect of chronic dietary inositol was tested in rats that were exposed to a mild and a more severe form of stress. Chronic saline injections elevated anxiety in the plus maze, which was only marginally affected by chronic dietary inositol. Following 3 weeks administration of 5% dietary inositol rats were pre-exposed to a cat. There was a clear increase in number of entries into open arms, suggesting an anxiolytic effect of inositol.

Animals↗