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Biomedical subjects

Y Cohen

Publications and source records attributed to Y Cohen.

At least 91 records · Page 5Linked to original sources

[Adjuvant therapy of colon cancer stage C MAC. Adverse effects and efficacy in the Department of Oncology, Soroka Medical Center in the years 1991-1994].

The National Institutes of Health (NIH) held a consensus conference which recommended 5-FU and levamisole as adjuvant chemotherapy for colon cancer MAC (Modified Astler Coller) stage C. From 1991-1994, 37 such patients diagnosed here were treated with 5-FU (intravenous dose of 450/mg/m2/d for 5 days and from day 29, once a week for 48 weeks) and oral levamisole (50 mg 3 times/d. for 3 days, every 2 weeks for a year), as suggested by NIH guidelines. 16 patients were males and 21 were females, mean age was 62 years and median 64. Cancer locations were: right colon (in 16, 43%), left colon (19, 51%), multiple colon primaries (2, 1%). 25 (68%) had 1-3 positive lymph nodes and 12 (32%) had 4 or more positive lymph nodes. Only 20 (54%) finished treatment as prescribed. In the others, 1 or both drugs caused side-effects for which the drugs had to be stopped. 6 patients relapsed while on treatment. The most common side-effects were diarrhea, stomatitis and bone marrow suppression. 3 were hospitalized due to neutropenic fever. 5-year actuarial survival of all patients was 61%; 5-year relapse-free survival was 61%; 5-year relapse-free survival of right versus left colon was 41% and 82%, respectively (p < 0.01). There was no significant difference in 5-year survival of those with 1-3 positive lymph nodes as compared to those with 4 or more (62% and 56%, respectively). 5-year survival in those who finished or did not finish treatment (excluding those who stopped treatment because of progressive disease) was 83% and 70%, respectively (NS). The 5-year survival of our series was similar to that of patients treated similarly elsewhere. The 5-FU and levamisole treatment was not tolerated well by our study population. It has recently been replaced in our service by a 5-FU and leucovorin regimen given for 6 months.

Adenocarcinoma↗

Comparison of the prognostic value of qualitative versus quantitative stress tomographic perfusion imaging.

This study compared qualitative assessment of exercise thallium imaging to quantitative assessment in predicting outcome in 713 patients with 78% prevalence of coronary artery disease by coronary angiography; during a mean follow-up of 52 months, there were 106 hard cardiac events (death or nonfatal myocardial infarction). The qualitative method provided important prognostic information; however, unlike the quantitative technique, less patients were assigned to either the low- or high-risk group and proportionally more patients into the intermediate-risk group, which may limit the clinical usefulness of the technique.

Coronary Angiography↗

[Self-limited lymphadenopathy mimicking lymphoma or lupus (Kikuchi-Fujimoto disease)].

Kikuchi-Fujimoto disease in a self-limited lymphadenopathy that can be confused histologically and clinically with lymphoma or systemic lupus erythematosus. It was diagnosed in a 37-year-old woman presenting with fever, cervical, submandibular and axillary lymphadenopathy, weight loss and recurrent urinary tract infections. Lymph node biopsy was consistent with the diagnosis of a histiocytic necrotizing lymphadenitis. Early diagnosis of Kikuchi-Fujimoto disease can prevent harmful treatment.

Adult↗

Structural information in neuronal tissue as revealed by q-space diffusion NMR spectroscopy of metabolites in bovine optic nerve.

1H NMR diffusion experiments performed on the signal of the metabolites in bovine optic nerve showed that the signal decay due to diffusion is bi-exponential with a slow and a fast diffusing component. Diffusion was measured as a function of the diffusion time, and the data were analyzed as a function of b and q values. Bi-exponential fit was used to analyze the data, and the results were compared with the displacement distribution profiles obtained from the q-space analysis of the data. This q-space analysis showed that the fast diffusing component has a broad displacement distribution and appears not to be restricted. On the other hand, the slow diffusing component appears to be highly restricted to milieu in the order of 1-2 microm. The orientation of the sample with respect to the axis for which diffusion was measured affected mainly the relative sizes of the populations of each component, but had only a small effect on the extracted apparent diffusion coefficients. These results from both the b and the q value analyses suggest that the slow diffusing component is related to restricted diffusion of these metabolites in the axonal fibers, while the fast diffusing component represents diffusion of metabolites in cells and along the long axis of the nerve fibers. It is concluded that q-space analysis of metabolite diffusion enables extraction of structural information about the sample, and that the diffusion of the metabolites in optic nerve is dictated mainly by the cellular medium and microstructure of the tissue.

Animals↗

Is uterine serous papillary carcinoma a BRCA1-related disease? Case report and review of the literature.

OBJECTIVES: Type II endometrial carcinomas are estrogen-independent and have adverse histologic features and a substantially poorer prognosis. No risk factors have been identified. Interestingly, there is a striking clinical and histopathological similarity between serous papillary carcinomas of the ovary (OSPC), endometrium, and peritoneal cavity, suggesting a common oncogenic mechanism. Several common molecular alterations were found using molecular comparative analysis of OSPC and uterine serous papillary carcinoma (USPC). Germline mutations in the BRCA1 tumor suppressor gene predispose to breast and ovarian cancer but no association with sporadic endometrial cancer has been found. A family of Ashkenazi Jewish origin, in which one sister was first diagnosed with USPC and the second diagnosed with OSPC, led to the hypothesis that a BRCA mutation may contribute to USPC. METHODS: Genomic DNA from both patients as well as two unaffected siblings was analyzed for the three mutations common in Ashkenazi Jews. Loss of heterozygosity (LOH) analysis was performed on DNA extracted from USPC tumor tissue. RESULTS: Both affected sisters tested positive for BRCA1 5382insC germline mutation. LOH analysis confirmed the results. CONCLUSIONS: We present a breast-ovarian cancer family including two sisters with advanced serous papillary carcinomas of endometrial and ovarian origins, carrying the same BRCA1 mutation (5382insC). LOH analysis on USPC tumor DNA showed loss of the wild-type allele, suggesting a causal relationship between the germline BRCA1 mutation and USPC. We believe a study examining BRCA1 mutations in a large cohort of women with this high-risk endometrial carcinoma is warranted. A positive finding may have implications for surveillance and prophylactic surgery in carriers of BRCA1 mutations.

Cystadenocarcinoma, Papillary↗

Dermatomyositis and peritoneal papillary serous carcinoma.

We describe an unusual case of peritoneal papillary serous carcinoma (PPSC) arising in a female patient with dermatomyositis (DM). Despite periodic extensive searches for an underlying malignancy, no malignancy had been detected in this patient during the first 2.5 years after the diagnosis of DM. It was only when the patient presented with pleural effusion and ascites that the underlying intra-abdominal malignancy was detected by laparoscopy. Treatment with four cycles of pre-operative chemotherapy (taxol and cisplatin) resulted in tumor regression with amelioration in the muscular manifestation of the DM, but without parallelic amelioration in the skin manifestations of the DM. Explorative laparotomy confirmed the presence of papillary serous carcinoma in the omentum, surface of the left ovary and the retroperitoneal lymph nodes, and established the diagnosis of PPSC. Following two cycles of postoperative chemotherapy, the patient is alive with no evidence of internal malignancy. However, although muscle strength and enzymes have remained normal, no effect on the skin manifestation of DM has been observed. This case illustrates that, alongside the more frequently occurring ovarian carcinoma, PPSC should also be considered in the differential diagnosis of the underlying malignancy that may occur in the female patient with DM.

Aged↗

Diffusion and perfusion magnetic resonance imaging following closed head injury in rats.

Diffusion-, perfusion-, T1-, and T2-weighted magnetic resonance imaging (MRI) were performed at 1-2 h, 24 h, and 1 week following closed head injury (CHI) in rats, and data was compared with hematoxylin and eosin histology. At 1-2 h, large areas of low perfusion in the damaged hemisphere overestimate the histological damage. In the first 2 h, the histological damage seems to be a superposition of abnormalities in the T1- and diffusion-weighted images. In areas with more than 10% reduction in the apparent diffusion coefficients (ADCs), reduced regional cerebral blood volume (r-CBV) was also observed. The decrease in ADCs and rCBV correlated with r = 0.78. Changes in the MRI parameters revealed the following: (a) Further reduction in ADC occurred from 83+/-15% at 1-2 h after trauma to 69+/-9% at 24 h, and 1 week later a marked elevation in the ADC values is observed. (b) Blood perfusion measurements performed 1-2 h posttrauma revealed a pronounced reduction in r-CBV (53+/-18%) in the damaged hemisphere in all rats. At 24 h postimpact, areas of hyper- and hypoperfusion were observed. One week later, similar perfusion was found in both hemispheres of all rats. (c) T2 hyperintensity at 24 h overestimated the histological damage found at 1 week. At one week following the trauma, the T2 hyperintensity underestimated the histological damage. It is concluded that CHI, which is a heterogeneous insult, should be studied by a combination of MRI techniques. The superposition of the abnormalities seen on T1 and on the diffusion-weighted MR images at early time point represents best the histological damage. Both T2 and rCBV images are less informative in terms of actual histological damage.

Animals↗

Unexpected population distribution in a microbial mat community: sulfate-reducing bacteria localized to the highly oxic chemocline in contrast to a eukaryotic preference for anoxia.

The distribution and abundance of sulfate-reducing bacteria (SRB) and eukaryotes within the upper 4 mm of a hypersaline cyanobacterial mat community were characterized at high resolution with group-specific hybridization probes to quantify 16S rRNA extracted from 100-microm depth intervals. This revealed a preferential localization of SRB within the region defined by the oxygen chemocline. Among the different groups of SRB quantified, including members of the provisional families "Desulfovibrionaceae" and "Desulfobacteriaceae," Desulfonema-like populations dominated and accounted for up to 30% of total rRNA extracted from certain depth intervals of the chemocline. These data suggest that recognized genera of SRB are not necessarily restricted by high levels of oxygen in this mat community and the possibility of significant sulfur cycling within the chemocline. In marked contrast, eukaryotic populations in this community demonstrated a preference for regions of anoxia.

Anaerobiosis↗

Diversity of sulfate-reducing bacteria in oxic and anoxic regions of a microbial mat characterized by comparative analysis of dissimilatory sulfite reductase genes.

Sequence analysis of genes encoding dissimilatory sulfite reductase (DSR) was used to identify sulfate-reducing bacteria in a hypersaline microbial mat and to evaluate their distribution in relation to levels of oxygen. The most highly diverse DSR sequences, most related to those of the Desulfonema-like organisms within the delta-proteobacteria, were recovered from oxic regions of the mat. This observation extends those of previous studies by us and others associating Desulfonema-like organisms with oxic habitats.

Anaerobiosis↗

Haemodynamic measurements (continuous cardiac output and systemic vascular resistance) in critically ill patients: transoesophageal Doppler versus continuous thermodilution.

Ten critically ill patients underwent this prospective study to assess the reliability of the continuous thermodilution versus transoesophageal Doppler techniques in the determination of continuous cardiac output (CO) and systemic vascular resistance (SVR). A total of 145 pairs of CO and SVR measurements were obtained by both a pulmonary artery catheter with a heated filament and a transoesophageal Doppler apparatus (ODM II). Total CO ranged from 2.4 and 13 l.min-1; the bias of all measurements was 0.01 +/- 0.48 l.min-1, and the 95% confidence limits (mean difference +/- 2 SD) were 0.97/0.96 l.min-1. Total SVR ranged from 309 and 2643 dyn.s.cm-5; the bias of all measurements was 18 +/- 127 dyn.s.cm-5, and the 95%, confidence limits were 272/236 dyn.s.cm-5. Transoesophageal Doppler accurately measures continuous CO and SVR in critically ill patients. It should be viewed as complementary to pulmonary catheterization.

Aged↗

Increase in PDX-1 levels suppresses insulin gene expression in RIN 1046-38 cells.

RIN1046-38 cells (RIN-38) exhibit a passage-dependent reduction in both basal and glucose-regulated insulin secretion, accompanied by decreased insulin content. In an attempt to explain the mechanism of the gradual decrease in insulin production in cultured cells, we analyzed the insulin promoter activity and the levels of an important trans-activator of the insulin gene, PDX-1, as a function of aging in culture. We demonstrate that the decrease in insulin content and secretion is reflected in decreased promoter activity and is associated with a decrease in E47 and BETA2 nuclear factors, but with a paradoxical 3-fold increase in PDX-1 protein levels. To dissect the effect of increased PDX-1 from the decrease in the additional transcription factors on insulin promoter activity, we overexpressed PDX-1 protein in low passage RIN-38 cells by recombinant adenovirus technology. PDX-1 overexpression did not reduce E47 and BETA2 levels, but was sufficient to suppress rat insulin promoter activity in a dose-dependent manner. The fact that PDX-1 levels participate in trans-activation of insulin promoter activity was demonstrated in HIT-T15 cells. Treating HIT-T15 cells with 1-2 multiplicity of infection of AdCMV-PDX-1 increased rat insulin promoter activity, whereas higher doses repressed insulin promoter activity in these cells as in RIN-38 cells. Our data demonstrate that PDX-1 regulates transcription of the insulin gene in a dose-dependent manner. Depending on its nuclear dosage and the levels of additional cooperating transcription factors, PDX-1 may act as an activator or a repressor of insulin gene expression, such that low as well as high doses may be deleterious to insulin production.

Adenoviridae↗

Factors associated with health indicators in patients undergoing coronary artery bypass surgery.

BACKGROUND: The main goals of coronary artery bypass graft (CABG) surgery for most patients are to relieve angina, to improve functional capacity, to return to work, and to improve health. A limited amount of information is available regarding the various attributes that are associated with achieving these goals. STUDY OBJECTIVES: To investigate different patient attributes affecting these outcomes. DESIGN: Prospective data collection. SETTING: Fourteen medical centers that perform CABG surgery in Israel. PATIENTS: The 4,012 patients who underwent CABG surgery during 1994. MEASUREMENTS: Trained nurses collected data using structured questionnaires prior to and 4 to 5 months after the operation. Using logistic regression, four risk models were created to the following health indicators: recurrence of angina, functional capacity, return to work, and perception of health. Candidate variables were sociodemographic details, major comorbidities, risk factors for cardiac disease, and severity of cardiac disease. RESULTS: The mean age of the patients was 63.8 years old, 79.3% were men, 59.9% were elective operations, and left main disease was found in 17.3%. Multivariate logistic regression revealed that the variables that significantly contributed to three or more of the models were Sephardic Jewish origin, female gender, left ventricular dysfunction, and diabetes mellitus. CONCLUSIONS: There is a similarity between risk factors of various health indicators in CABG surgery patients. Thus, it is possible to define a population at high risk that may not benefit from the procedure.

Adult↗

Cytokine-inducible SH2 protein (CIS3) and JAK2 binding protein (JAB) abolish prolactin receptor-mediated STAT5 signaling.

The ability of five members of the cytokine-inducible SH2 protein family (CIS1-4) and JAK2 binding (JAB) protein to affect prolactin receptor (PRLR)-mediated activity was tested in human 293 embryonic kidney fibroblasts transiently transfected with rat PRLR, five concentrations of CIS/JAB Myc-tagged cDNAs and a STAT5-responsive reporter gene encoding luciferase. The protein expressions of CIS1, CIS2, CIS3 and JAB were comparable, whereas the level of CIS4 was slightly lower. PRLR-mediated luciferase activity was abolished in a dose-dependent manner in cells transfected with cDNA of CIS3 or JAB, even at concentrations below the level of protein detection by anti-Myc antibody. In contrast, CIS1, CIS2 and CIS4 had little or no effect, despite similar levels of expression. CIS1 expression in postpartum mouse mammary glands was high and changed little in the course of 3 days. CIS2 and CIS3 expression was also high and increased further, whereas JAB expression was very low. These results hint that at least in mammary gland CIS3 is likely the main physiological negative regulator of the PRLR-mediated JAK2/STAT5 pathway.

Animals↗

Sex pheromones and amino acids evoke distinctly different spatial patterns of electrical activity in the goldfish olfactory bulb.

Until now, electrophysiological studies of the vertebrate olfactory bulb have tested only 'generalist' cues. These studies suggest that odorants are discriminated by a broadly distributed spatial map. In this study, we tested for the first time in a vertebrate the hypothesis that 'specialist' cues (pheromones) are discriminated by a more restricted component of the olfactory bulb. Our model is the male goldfish, Carassius auratus, for which five sex pheromones with both behavioral and physiological activity have now been identified. Electrical activity (electroencephalography: EEG) was recorded over a 12-point grid from the surface of the olfactory bulb, while fish were exposed to one of ten stimuli including: five sex pheromones, two amino acids, two bile steroids and a control. Evoked activity was evaluated by time series analysis. Power ratios were calculated by dividing the power of the dominant frequency in the power spectrum before stimulation by the power of the dominant frequency during stimulation. Next, the average magnitudes of odorant responses were compared using analysis of variance (ANOVA). The spatial patterning of these responses was also described using cluster analysis, which grouped odorants based on the similarity of their spatial patterns of activity. Although all odorants elicited EEG responses with similar dominant frequencies, odorant-specific differences were evident in the size and distribution of these responses. Sex pheromones and bile steroids elicited relatively small responses that were spatially restricted in distinctive manners, although some overlap was evident. In contrast, amino acids consistently produced large responses at all positions. These results are consistent with the hypothesis that vertebrate pheromones are discriminated by a distinctive subcomponent of the vertebrate olfactory system comprised of a relatively small number of olfactory neurons.

Animal Communication↗

Effect of Interparticle Electrostatic Double Layer Interactions on Permeate Flux Decline in Crossflow Membrane Filtration of Colloidal Suspensions: An Experimental Investigation.

A systematic study on the effect of electrostatic double layer interaction on permeate flux decline and deposit cake formation in crossflow membrane filtration of colloidal suspensions is reported. Three monodisperse silica suspensions with diameters of 47, 110, and 310 nm were used as model colloids, and a tubular zirconia membrane with an average pore diameter of 20 nm was used as a model membrane. The magnitude and range of the electrostatic double layer interactions were controlled via changes in solution ionic strength and pH. The coupling between colloidal interactions and hydrodynamic forces was investigated by changing the transmembrane pressure and particle size. The results indicate that the rate of flux decline is strongly dependent on solution ionic strength and, to a much lesser degree, on solution pH (for the investigated pH range 6.1-10.0). Variations in flux decline rate with solution ionic strength are especially significant as the particle size decreases. Particle cake thickness, permeability, and porosity generally increased with a decrease in solution ionic strength for a given particle size. For given physical and chemical conditions, the cake layer porosity increased with decreasing particle size, while cake permeability decreased with decreasing particle size. These trends are consistent with the increased importance of double layer repulsive forces in controlling the cake layer structure as the solution ionic strength and particle size decrease. Pressure relaxation experiments indicated that the particle cake layer is reversible, implying no irreversible deposition (attachment) of silica colloids onto the zirconia membrane surface. Copyright 1998 Academic Press.

Journal Article↗

Comparison of factors associated with 30-day mortality after coronary artery bypass grafting in patients with versus without diabetes mellitus. Israeli Coronary Artery Bypass (ISCAB) Study Consortium.

The purpose of this study was to identify factors associated with 30-day mortality after coronary artery bypass graft surgery (CABG) among diabetic patients, and to compare them with risk factors among nondiabetics. A subanalysis of a prospective national cohort study was performed which included patients who underwent CABG in 14 medical centers in Israel during 1994. Data including patient demographic and historical information, comorbidity, and cardiac catheterization results were collected by trained nurses. Data were derived from direct patient interviews, charts, catheterization reports, surgical reports, and national vital records. Multivariate logistic regression analysis was used to identify factors associated with a 30-day mortality in diabetic and nondiabetic patient populations. The results showed that crude mortality was 5.0% among diabetic patients (n = 1,034) and 2.5% among nondiabetics (n = 3,350; p < 0.001). The risk profile in diabetics was found to be worse. Multivariate logistic regression analysis identified female gender, 3-vessel disease, and left main disease as independent risk factors for 30-day, past-CABG mortality unique to diabetic patients. Left ventricular dysfunction was found to effect a greater risk among diabetic patients, whereas chronic renal failure was associated with greater risk among nondiabetics. In conclusion, we found differences in patterns of risk factors for post-CABG mortality between diabetics and nondiabetics. These findings may help physicians to identify patients at high risk for CABG mortality.

Aged↗

Squamous cell carcinoma of the vulva in the south of Israel: a study of 50 cases.

BACKGROUND AND OBJECTIVES: Vulvar carcinoma accounts for 4.9% of all female genital tract malignancies in the south of Israel. The most common histologic type is squamous cell carcinoma (82%). The purpose of this study was to investigate the clinical findings, treatment, and outcome of patients with vulvar squamous cell carcinoma in the south of Israel. METHODS: Data from the files of 50 patients with vulvar squamous cell carcinoma who were managed at the Soroka Medical Center between January 1961 and December 1996 were evaluated. RESULTS: Mean age at diagnosis was 67.1 years. The most prevailing presenting symptoms were vulvar lump, ulcer, and itching. Mean patient delay in seeking medical help was 48.2 months. Clinical palpation as a test for detecting groin lymph node metastases had a sensitivity and specificity of 57.1% and 61.5%, respectively. The 5-year survival rate was 60.3% overall. By means of univariate analysis, a significant worsening in survival was demonstrated with advancing stage of disease (P < 0.001), tumor >4 cm (P < 0.001), and positivity of surgical margins (P < 0.0001). In a multivariate analysis (Cox proportional hazards model) in a group of 45 patients, stage of disease was the strongest and the only significant predictor of survival (P = 0.0098). CONCLUSIONS: Vulvar squamous cell carcinoma predominantly affects older women. Stage of disease, tumor size, and status of surgical margins are sensitive predictors of survival. The treatment of choice for most patients is surgery consisting of radical vulvectomy and bilateral groin lymphadenectomy.

Adult↗