Biomedical subjects

Ehud Klein

Publications and source records attributed to Ehud Klein.

23 records · Page 2Linked to original sources

PubMed2002

The role of extended-release benzodiazepines in the treatment of anxiety: a risk-benefit evaluation with a focus on extended-release alprazolam.

Immediate-release (IR) benzodiazepines have a short duration of therapeutic effect and are generally less effective for anxiety than selective serotonin reuptake inhibitors in reducing concomitant depressive symptomatology. Common criticisms of benzodiazepines also include the patient's tendency to develop a tolerance to the anxiolytic effect and a dependence on the drug itself. The newer extended-release (XR) benzodiazepine formulation was designed to increase efficacy, duration of therapeutic effect, tolerance, compliance, and ease of discontinuation. The XR benzodiazepine alprazolam has shown efficacy in panic disorder and generalized anxiety disorder comparable to the older benzodiazepine formulations. Pharmacokinetic data show that the XR formulation has a longer therapeutic effect compared with IR formulations, which reduces the potential for breakthrough anxiety symptoms. Data also indicate that the XR formulation has less abuse liability than the IR formulation. This article reviews the efficacy, safety, and discontinuation data from clinical trials of IR and XR benzodiazepines in the treatment of anxiety disorders and provides guidelines to minimize the risk of withdrawal syndrome during benzodiazepine discontinuation.

Alprazolam↗

PubMed1999

Increased mitochondrial complex I activity in platelets of schizophrenic patients.

It is believed that dopamine and alterations of energy metabolism in cortical and subcortical structures are involved in the pathophysiology of schizophrenia. Recently, we and others have shown that dopamine may affect energy metabolism by interacting with mitochondrial complex I activity in rats both in vivo and in vitro. In this study activity of complexes I and IV was assessed in mitochondria isolated from blood platelet of schizophrenic patients and compared to patients with affective disorders and healthy control subjects. Seventy-seven in-patients who met DSM-IV criteria for schizophrenia (in acute exacerbation), bipolar disorder depressed type (BP), or recurrent major depressive disorder (MDD) and 24 control subjects participated in the study. A highly significant increase (240%, p < 0.001) in complex I activity but not in complex IV, was detected in medicated and unmedicated schizophrenic patients compared to controls. No such change was observed in patients with affective disorders. The data demonstrate a specific and selective, alteration in platelet complex I activity in schizophrenic patients, which is not related to medication. If this abnormality in platelet mitochondria reflects brain alterations, it may further support the relevance of alterations in energy metabolism to the pathophysiology of schizophrenia. Finally in the lack of any clinically relevant biological marker for schizophrenia, complex I activity in platelets might become a useful peripheral marker for this disorder.

Journal Article↗

PubMedDate not supplied

Risk factors for early postpartum depressive symptoms.

OBJECTIVE: Postpartum depressive disorders are common and symptoms may appear as early as the first 2 weeks postpartum. Data regarding hormone-related risk factors for depressive symptoms occurring in the very early postpartum period are scarce and may be of importance in identifying serious postpartum illness. We examined the association between the reported history of psychiatric symptoms of possible hormonal etiology and very early postpartum depressive symptoms. METHODS: All women (n= 1,800) in a general hospital maternity ward were assessed during the first 3 days after parturition for potential risk factors for postpartum depressive disorders by a self-reported questionnaire and for present mood symptoms (Edinburgh Postnatal Depression Scale, EPDS). The associations between potential risk factors and postpartum depressive symptoms were analysed. RESULTS: The incidence of women with an EPDS >or=10 was 6.8% (88/1,286). Significant risk factors for early postpartum depressive symptoms were a history of mental illness including past postpartum depression (PPD), premenstrual dysphoric disorder (PMDD), and mood symptoms during the third trimester. CONCLUSION: In accordance with other studies, a history of depression was found to be a risk factor for early postpartum mood symptoms. An association was also found between some risk factors of possible hormone-related etiology such as PMDD and third trimester mood symptoms and early postpartum mood symptoms. As such, early postpartum symptoms may indicate vulnerability to subsequent PPD; it may be of importance to assess these risk factors and mood immediately after parturition. A prospective study is needed to determine which of these risk factors is associated with progression to PPD and which resolves as the blues.

Adult↗

PubMedDate not supplied

Angiogenic switch in earliest stages of human colonic tumorigenesis.

BACKGROUND: Angiogenesis is activated in numerous physiological and pathological conditions. We examined whether new vessel formation exists in the earliest stages of colonic tumorigenesis. MATERIALS AND METHODS: Microvascular density (MVD) was examined in 176 formalin-fixed and paraffin-embedded aberrant crypt foci (ACF) dissected from macroscopically-normal mucosa obtained from patients with colorectal cancer. ACF were classified as non-hyperplastic, non-dysplastic (NH-ACF, n = 80), hyperplastic (H-ACF, n = 72) and dysplastic (D-ACF, n = 24). Mucosal strips were stained with methylene blue solution and screened under x 40 magnification for ACF. The identified ACF were microdissected and stained with an anti-CD-34 monoclonal antibody. MVD in ACF were compared to that of normal corresponding mucosa. RESULTS: The mean MVD for normal mucosa and ACF were 13.7 +/- 7.7 and 23 +/- 13, respectively. Microvessel counts increased in NH-ACF versus normal mucosa (18.7 +/- 10 vs. 13.7 +/- 7.7, p = 0.05), in H-ACF versus NH-ACF (24.8 +/- 14 vs. 18.7 +/- 10, p = 0.002) and in D-ACF versus H-ACF (31.7 +/- 10 vs. 24.8 +/- 14, p = 0.014). We further evaluated the effect of low-dose aspirin on MVD in ACF. No effect of aspirin on microvessel counts could be detected. CONCLUSION: Our data suggest that angiogenesis occurs in ACF which are the earliest morphologically identifiable preneoplastic and early neoplastic lesions in colonic mucosa. With progression from NH-ACF to D-ACF there is a progressive, statistically significant increase in MVD, suggesting active angiogenesis during the earliest steps of colorectal tumorigenesis.

Aspirin↗

PubMedDate not supplied

Predominance of younger age, advanced stage, poorly-differentiated and mucinous histology in Israeli Arab patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence in the Israeli population is higher in the Jewish population than among Arabs. MATERIALS AND METHODS: To determine the differences in demographic, clinical, histopathological and molecular characteristics of CRC between these two ethnic groups, 125 Arab patients treated at 3 community hospitals over a 20-year period were compared to a group of 208 consecutive Jewish patients. The mutator (replication error-positive [RER]) phenotype was detected by immunohistochemical evaluation of hMLH1 and hMSH2 protein expression in tumor tissue. RESULTS: The Arab patients were younger than the Jewish patients with a higher percentage of poorly-differentiated and mucinous cancers and a higher percentage of advanced stage cancers (Dukes' C+D) at presentation. The mutator phenotype was detected at similar rates in both ethnic groups. CONCLUSION: Our study demonstrated that CRC patients from two major ethnic populations in Israel, Arabs and Jews, differed in terms of the prevalence of the disease, pathological features and age at presentation, but not in frequency of mismatch-repair-positive cancers.

Adaptor Proteins, Signal Transducing↗