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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 55 records · Page 3Linked to original sources

[Deterioration of schizoaffective disorder due to an interaction between haloperidol and carbamazepine].

A 40-year-old woman with a schizoaffective disorder was initially treated with lithium carbonate and haloperidol decanoate, but after three years the lithium was replaced with carbamazepine. Following this, her performance deteriorated over several years despite increasing dosages of haloperidol. After withdrawal of the carbamazepine a remarkable recovery occurred. A pharmacokinetic interaction between haloperidol and carbamazepine, which results in decreased haloperidol blood levels, provides a good explanation of this clinical picture. This clinically relevant interaction should be incorporated into pharmacovigilance systems.

Adult↗

Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: This randomised trial compared three chemotherapy regimens in the first-line treatment of advanced colorectal cancer, in terms of their effect on overall and progression-free survival; other endpoints included toxicity, symptom palliation, and quality of life. METHODS: 905 patients were randomly assigned the de Gramont regimen (n=303; folinic acid 200 mg/m(2), fluorouracil bolus 400 mg/m(2), and infusion 600 mg/m(2) on days 1 and 2, repeated every 14 days), the Lokich regimen (n=301; protracted venous infusion of fluorouracil 300 mg/m(2) daily), or raltitrexed (n=301; 3 mg/m(2) intravenously every 21 days). Analyses were by intention to treat. FINDINGS: Median follow-up of survivors was 67 weeks. For the de Gramont, Lokich, and raltitrexed groups, respectively, median survival was 294, 302, and 266 days. The hazard ratios for overall survival were 0.88 (95% CI 0.70-1.12, p=0.17) for de Gramont versus Lokich, and 0.99 (0.79-1.25, p=0.94) for de Gramont versus raltitrexed. An increase in treatment-related deaths was seen on raltitrexed (de Gramont one, Lokich two, raltitrexed 18) due to combined gastrointestinal and haematological toxicity. Patients' assessment of quality of life showed that raltitrexed was inferior to the fluorouracil-based regimens, especially in terms of palliation and functioning. INTERPRETATION: The deGramont and Lokich regimens were similar in terms of survival, quality of life, and response rates. The Lokich regimen was associated with more central line complications and hand-foot syndrome. Raltitrexed showed similar response rates and overall survival to the de Gramont regimen and was easier to administer, but resulted in greater toxicity and inferior quality of life.

Adenocarcinoma↗

Norwalk virus gastroenteritis among Israeli soldiers: lack of evidence for flyborne transmission.

BACKGROUND: Paired sera collected from subjects before and after a fly-control intervention trial conducted in the Israel Defense Force (IDF) were tested for seroconversion to Norwalk virus (NV) to examine the role of NV as a cause of diarrhea in this population and to ascertain whether flies might also be implicated in transmission. MATERIALS AND METHODS: An enzyme-linked immunosorbent assay (ELISA), using recombinant NV capsid proteins (rNV) as antigen was employed to determine the seroconversion rate in a sample of 444 subjects. RESULTS: During 11-week field training cycles, 18% of IDF soldiers who were tested had an NV infection defined as a > or = 4-fold rise in antibody, yielding a cumulative incidence of nearly one infection (0.95) per soldier per year. The rate of seroconversion was nearly twice as high among soldiers who recalled having diarrhea as among those who did not, but the rates did not differ significantly between soldiers in the fly intervention areas and those in the control areas. CONCLUSION: NV is a common cause of enteric infections and diarrhea among Israeli soldiers who serve under field conditions, but unlike infections with Shigella and enterotoxigenic Escherichia coli, transmission of NV cannot be interrupted with an aggressive program of fly-control.

Adolescent↗

Clinical relevance of electroconvulsive therapy (ECT) in adolescents with severe mood disorder: evidence from a follow-up study.

Given the limited knowledge on the long-term outcome of adolescents who receive electroconvulsive therapy (ECT), the study aimed to follow-up adolescents treated with ECT for severe mood disorder. Eleven subjects treated during adolescence with bilateral ECT for psychotic depression (n = 6) or mania (n = 5), and ten psychiatric controls matched for sex, age, school level, and clinical diagnosis, completed at least 1 year after treatment a clinical and social evaluation. Mean duration between time of index episode and time of follow-up evaluation was 5.2 years (range 2-9 years). At follow-up: (1) all patients except two in the control group received a diagnosis of bipolar disorder. (2) Fifteen patients had had more than one episode of mood disorder. (3) The two groups did not differ in social functioning nor school achievement. (4) Impact on school achievement was related to the severity of the mood disorder rather than ECT treatment. The results suggest that adolescents given ECT for bipolar disorder, depressed or manic, do not differ in subsequent school and social functioning from carefully matched controls.

Achievement↗

[Juvenile aponeurotic fibroma. A case report with a review of the literature].

Juvenile aponeurotic fibroma is a rare benign tumour which occurs mainly in young patients under 20 years of age and especially during childhood. Clinical presentation is a unique, hard and painless tumour of the palm or sole. The treatment commonly accepted for this locally recurrent tumour is complete excision with function preservation. In this paper, we report on a case of juvenile aponeurotic fibroma of the thenar area with a thickening of the first metacarpal bone shaft. Bone involvement in juvenile aponeurotic fibroma is a very rare condition. We only found one report of a comparable case in literature.

Adolescent↗

Prevalence of the genes for shigella enterotoxins 1 and 2 among clinical isolates of shigella in Israel.

Two enterotoxins, shigella enterotoxin 1 (SHET1) and shigella enterotoxin 2 (SHET2) have been recently characterized and are believed to play a role in the clinical manifestation of shigellosis. One hundred and twenty-one isolates of Shigella spp. of 13 different serotypes and variants and 10 isolates of enteroinvasive Escherichia coli (EIEC) isolated in Israel, were examined by polymerase chain reaction for the presence of SHET1 and SHET2 genes. SHET1 was only prevalent among isolates of S. flexneri 2a while SHET2 was found in all the serotypes that were tested except for several isolates of S. flexneri 1b that lost their virulence plasmid during storage. In addition, we found that the S. flexneri 2a vaccine strain T-32 Istrati contains the gene encoding for SHET1 but not that encoding for SHET2, suggesting that the latter is located within a large deletion occurring in the 140 Mda plasmid of this S. flexneri 2a non-invasive vaccine strain.

Base Sequence↗

The development of a new site-specific measure of quality of life for breast problems: the Cardiff breast scales.

The management of women presenting to primary care with symptoms of breast disease is of increasing interest given recent organisational changes aimed at improving accuracy and speed of referrals. As part of a randomised controlled trial, 1063 women were recruited following a primary care consultation for a variety of breast-related problems. In the absence of a suitable outcome measure for such women, a site-specific instrument was developed to complement a generic quality of life scale (SF-36). Items were generated using key informant interviews with health professionals. Draft scale items were piloted using a postal questionnaire and subsequent patient debrief interviews. A sample of respondents were also sent the same questionnaire I month later to assess test-retest reliability. Across the whole sample (n = 848), three factors were identified: 'general well-being', 'concerns' and 'relationships'. These factors accounted for 60% of total variance. Evidence of scale validity, reliability and responsiveness are reported for this new outcome measure for use in women presenting with breast problems.

Breast Diseases↗

Structure of the (110) antiphase boundary in gallium phosphide.

The morphology of antiphase boundaries in GaP films grown by molecular beam epitaxy on Si (001) has been studied by transmission electron microscopy. The inversion of the crystal polarity between antiphase domains was confirmed by convergent-beam electron diffraction. The APBs were often found to facet parallel to [110] planes. Strong-beam alpha-fringe contrast observed along the (110) facets indicates that adjacent antiphase domains are related by an additional rigid-body lattice translation. Diffraction-contrast analysis shows that this R corresponds to a shear parallel to the [001] direction and a small expansion. The magnitude of the translation was inferred, quantitatively, through a comparison between energy-filtered zero-loss images of the alpha-fringe contrast with numerical calculations. The components of the rigid-body lattice translation were determined to be 0.023 +/- 0.0033 nm in the [001] direction and 0.005 +/- 0.002 nm in the 0 direction. Based upon a geometric model of the [110] antiphase boundary, the lengths of the Ga and P antisite bonds were calculated to be 254 +/- 2 pm and 227 +/- 4 pm, respectively.

Journal Article↗

Prescribing on a single rubric.

Homeopathic prescribing depends on accurate case taking and correlation of information. This can be difficult if there is a paucity of symptoms. These cases illustrate one possible technique in such situations. Two elements seem to be of use in these circumstances. The first is the need to select the 'more striking singular uncommon and peculiar symptoms'. The second is the reliability of the information in the homeopathic literature. At times there is only one outstanding feature in the case and nothing else to confirm the prescription.

Adult↗

The olivocerebellar system as a generator of temporal patterns.

The large number of diverse functions attributed to the cerebellum appears to be inconsistent with its simple, homogeneous and evolutionary preserved structure. A homogeneous structure that participates in a variety of functions implies that a common denominator underlies all of them. Since the concept of precise timing can be recognized in almost all cerebellar functions, it is likely, therefore, that the basic cerebellar circuit is capable of generating temporal patterns. Of the different mechanisms that can generate temporal patterns, two are suggested by the functional anatomy of the cerbellum: transmission lines or oscillators. Our recent experimental observations indicate that the olivary oscillatory property is more likely to serve this function. We propose that interactions between the cerebellum and the inferior olive endow the system with the ability to generate complex temporal patterns. These temporal patterns can be used for fine adjustment of motor output, sensory expectation, or shifting attentions.

Animals↗

Failure of random matrix theory to correctly describe quantum dynamics.

Consider a classically chaotic system that is described by a Hamiltonian H(0). At t=0 the Hamiltonian undergoes a sudden change (H)0-->H. We consider the quantum-mechanical spreading of the evolving energy distribution, and argue that it cannot be analyzed using a conventional random-matrix theory (RMT) approach. Conventional RMT can be trusted only to the extent that it gives trivial results that are implied by first-order perturbation theory. Nonperturbative effects are sensitive to the underlying classical dynamics, and therefore the Planck's over 2 pi-->0 behavior for effective RMT models is strikingly different from the correct semiclassical limit.

Journal Article↗

Electroconvulsive therapy in adolescents with mood disorder: patients' and parents' attitudes.

The aim of the study was to assess retrospectively patients' and parents' experiences and attitudes towards the use of electroconvulsive therapy (ECT) in adolescence. The experiences of subjects (n=10) who were administered ECT in adolescence for a severe mood disorder and their parents (n=18) were assessed using a semi-structured interview after a mean of 4.5 years (range, 19 months to 9 years). Their attitudes were mostly positive and ECT was considered a helpful treatment. Concerns were frequently expressed, probably because ECT was not fully understood by the patients and their families. Most complaints were of transitory memory impairment. The parents were satisfied with the consent procedure, while all but one patient did not remember the consent procedure. We concluded that, despite negative views about ECT in public opinion, adolescent recipients and their parents shared overall positive attitudes towards the use of ECT in this age range.

Adolescent↗

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Biopsy, Needle↗

Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors.

Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding regions have been reported in cancer. The mechanisms that generate such mutations and the importance of mtDNA mutations in tumor development are still not clear. Here we present the identification of a specific and highly polymorphic homopolymeric C stretch (D310), located within the displacement (D) loop, as a mutational hotspot in primary tumors. Twenty-two % of the 247 primary tumors analyzed harbored somatic deletions/insertions at this mononucleotide repeat. Moreover, these alterations were also present in head and neck preneoplastic lesions. We further characterized the D310 variants that appeared in the lung and head and neck tumors. Most of the somatic alterations found in tumors showed deletion/insertions of 1- or 2-bp generating D310 variants identical to constitutive polymorphisms described previously. Sequencing analysis of individual clones from lymphocytes revealed that patients with D310 mutations in the tumors had statistically significant higher levels of D310 heteroplasmy (more than one length variant) in the lymphocyte mtDNA as compared with the patients without D310 mutations in the tumor mtDNA. On the basis of our observations, we propose a model in which D310 alterations are already present in normal cells and achieve homoplasmy in the tumor through a restriction/amplification event attributable to random genetic drift and clonal expansion.

Carcinoma, Squamous Cell↗

Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis.

Large scale gene expression profiling was carried out on laser capture microdissected (LCM) tumor and normal oral epithelial cells and analysed on high-density oligonucleotide microarrays. About 600 genes were found to be oral cancer associated. These oral cancer associated genes include oncogenes, tumor suppressors, transcription factors, xenobiotic enzymes, metastatic proteins, differentiation markers, and genes that have not been implicated in oral cancer. The database created provides a verifiable global profile of gene expression during oral carcinogenesis, revealing the potential role of known genes as well as genes that have not been previously implicated in oral cancer.

Aged↗

Mammalian histone deacetylase 1 protein is posttranslationally modified by phosphorylation.

HDAC1, a member of the histone deacetylase family, is involved in transcription regulation through the modification of chromatin structure. Several studies also implicated HDAC1 in tumorigenesis. Much attention has been concentrated on protein-protein interactions involving HDAC1 and the possibility that posttranslational modifications may occur in mammalian HDAC1 proteins has not been carefully and systematically investigated. In this study, we utilized in vivo labeling assays to demonstrate that both human and murine HDAC1 proteins are phosphorylated in cells. Assays using HDAC1 deletion mutants indicated that phosphorylation occurs in its C-terminal domain. cAMP-dependent kinase and casein kinase II, but not protein kinase C, cdc2, or MAP kinase, could phosphorylate HDAC1 in vitro, although HDAC1 contains several protein kinase C consensus sites. We also found that phosphorylation did not influence HDAC1 enzymatic activity using a human histone H4 N-terminal peptide as the substrate. Interestingly, HDAC1-FLAG fusion protein immunoprecipitated from transfected cells was found to be in association with a kinase activity, providing an in vitro assay for further studies of this posttranslational modification.

Amino Acid Sequence↗

cdc42 regulates the exit of apical and basolateral proteins from the trans-Golgi network.

It is well established that Rho-GTPases regulate vesicle fusion and fission events at the plasma membrane through their modulatory role on the cortical actin cytoskeleton. In contrast, their effects on intracellular transport processes and actin pools are less clear. It was recently shown that cdc42 associates with the Golgi apparatus in an ARF-dependent manner, similarly to coat proteins involved in vesicle formation and to several actin-binding proteins. We report here that mutants of cdc42 inhibited the exit of basolateral proteins from the trans-Golgi network (TGN), while stimulating the exit of an apical marker, in two different transport assays. This regulation may result from modulation of the actin cytoskeleton, as GTPase-deficient cdc42 depleted a perinuclear actin pool that rapidly exchanges with exogenous fluorescent actin.

Actin Cytoskeleton↗