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Biomedical subjects

R Durst

Publications and source records attributed to R Durst.

At least 19 recordsLinked to original sources

The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients.

BACKGROUND AND AIM: Hypercholesterolaemia is a major risk factor for atherosclerosis. Cholesterol is modulated by genetic and environmental factors. An important regulatory pathway is controlled by the sterol-regulatory element-binding proteins (SREBPs) and the SREBP cleavage-activating protein (SCAP). Both SREBP-2 and SCAP are candidates to contribute to the development of atherosclerosis. We investigated the possible effects of the variability of proteins involved in this regulatory pathway on plasma lipids among familial hypercholesterolaemia patients. METHODS AND RESULTS: Single nucleotide polymorphisms (SNPs) in the genes encoding SREBP-2 and SCAP causing amino acid changes at positions 595 (595G/A) and 796 (796I/V), respectively, were genotyped in 801 FH individuals originating from Israel, The Netherlands, and Switzerland. A linear regression model to examine the associations between SREBP-2 and SCAP isoforms and lipid and lipoprotein levels was used. In females, homozygosity either for the SREBP-2-595A or for the SCAP-796I isoform was associated with higher LDL-cholesterol plasma concentrations (14.7 mg/dl and 20.3 mg/dl, respectively). Surprisingly, heterozygosity for the combination SREBP-2-595A/SCAP-796I was associated with a decrease of 30.28 mg/dl in LDL-C (p-value for gene-gene interaction=0.09). No such effect was observed among FH males. Subgroup analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2, ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender-dependent effects of the SCAP mutations on LDL-cholesterol concentrations (p=0.0345). These effects were, however, not present when less frequent LDL receptor mutations were investigated. CONCLUSIONS: These results suggest a possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that modulate plasma lipids in a strictly gender-specific fashion. Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration.

Atherosclerosis↗

Post-partum hypocalcemia: idiopatic hypoparathyroidism manifested early in lactation.

Hypocalcemia associated with labor and lactation is a rare condition reported previously in patients with hypovitaminosis D. We here describe a case of a young woman in whom symptomatic severe hypocalcemia appeared after her second delivery, early in lactation. At the end of lactation the condition worsened. We review all previously reported cases and suggest a possible physiologic explanation for the association between pregnancy, lactation and the appearance of symptomatic hypocalcemia.

Adult↗

The generation of psychosis: a pragmatic approach.

The paper discusses the role of speech in the generation of psychosis. The traditional phenomenological approach describes schizophrenic speech as desocialized, autistic and destructive. Based on 'Speech Act Theory', we argue that patients in an acute psychotic state assign maximal illocutionary force to their utterances and mark these speech acts as felicitous. We hypothesize that the pragmatic approach can serve a special role in bilingual patients, the mother tongue being more pronounced in the generation of the psychosis. This view gains support from clinical experience and case studies and can be used as a treatment strategy for bilingual patients.

Humans↗

Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews.

G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 +/- 7 generations (the 95% confidence interval is 15-26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious hypothesis explaining the spread of G197del-LDLR-linked FH in AJ individuals.

Adolescent↗

Psychiatric aspects of jet lag: review and hypothesis.

Jet lag is a travel-induced circadian rhythm phenomenon that afflicts healthy individuals following long- distance flights through several time zones. The typical jet-lag manifestations - insomnia during local sleep time, day fatigue, reduced concentration, irritability, and exhaustion with mild depression - are attributed to transient desynchronization in the circadian rhythm until the internal biological clock is rephased to the new environmental conditions. There is strong evidence relating affective disorders with circadian rhythm abnormalities. Less convincing suggestions relate jet lag to psychosis. It can be hypothesized that in predisposed individuals jet lag may play a role in triggering exacerbation or even de novo affective disorders. Furthermore, we propose the possibility that psychosis and even schizophrenia can be elicited by jet lag. This outlook gains its support from case studies and some common underlying phase-advanced biological denominators involved in both jet lag sufferers and psychotic patients.

Humans↗

Kleptomania: diagnosis and treatment options.

Kleptomania--the inability to resist the impulse to steal objects, not for personal use or monetary gain--is currently classified in psychiatric nomenclature as an impulse control disorder. However, some of the principle features of the disorder, which include repetitive intrusion thoughts, inability to resist the compulsion to perform the thievery and the relief of tension following the act, suggest that kleptomania may constitute an obsessive-compulsive spectrum disorder. Kleptomania is commonly under-diagnosed and is often accompanied by other psychiatric conditions, most notably affective, anxiety and eating disorders, and alcohol and substance abuse. Individuals with the disorder are usually referred for treatment due to the comorbid psychiatric complaints rather than kleptomanic behaviour per se. Over the past century there has been a shift from psychotherapeutic to psychopharmacological interventions for kleptomania. Pharmacological management using selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) and other antidepressants, mood stabilisers and opioid receptor antagonists, as adjuvants to cognitive-behavioural therapy, has produced promising results.

Antidepressive Agents↗

[Drug abuse among patients requiring psychiatric hospitalization].

We assessed the incidence of drug abuse among patients requiring psychiatric hospitalization, and characterized the population at risk. The data on drug abuse were obtained from self-reports and urine tests in 103 patients, aged 18-65, hospitalized in the Kfar Shaul Psychiatric Hospital (autumn 1998). There was close correspondence between the self-reports and the results obtained from urine tests. 1/3 admitted to having used illegal drugs and signs of drug abuse were found in about 1/4 of the urine tests. The most prevalent drugs were cannabis products (hashish and/or marijuana) and in 15 patients opiates. Drug users were younger than non-users. With regard to psychiatric symptomatology, fewer negative symptoms were recorded among cannabis abusers with schizophrenia, compared to schizophrenic patients with no history, past or present, of cannabis abuse. The present findings confirm the clinical impression that there has been an increase in drug abuse among mental patients, parallel to that found in society at large. Confirmatory surveys are necessary. Our findings clearly suggest that a change in attitude has occurred in Israel to what has been considered a marginal problem. Hospitalized mentally-ill patients, the younger in particular, should be considered at risk for drug abuse.

Adolescent↗

[Jet lag causing or exacerbating psychiatric disorders].

Desynchronization of circadian rhythmicity resulting from rapid travel through at least 4 time zones leads to symptoms of jet lag syndrome. The most commonly experienced symptoms in normal individuals are sleep disorders, difficulties with concentrating, irritability, mild depression, fatigue, and gastrointestinal disturbances. There is strong evidence relating affective disorders to circadian rhythm abnormalities, such as occur in jet lag. Less convincing suggestions relate jet lag to psychosis. We presume, relying on the literature and our accumulated experience, that in predisposed individuals jet lag may play a role in triggering exacerbation of, or de novo affective disorders, as well as, though less convincing, schizophreniform psychosis or even schizophrenia. An illustrative case vignette exemplifies the possible relationship between jet lag following eastbound flight and psychotic manifestations.

Antipsychotic Agents↗

Risperidone in treating behavioural disturbances of Prader-Willi syndrome.

OBJECTIVE: This paper reports the results of risperidone treatment in seven patients (six adults and one adolescent) diagnosed as suffering from Prader-Willi syndrome (PWS) accompanied by severe behavioural disturbances. Risperidone was chosen following the failure of these patients to respond to other acknowledged modes of treatment for the psychiatric manifestations of PWS. METHOD: This was a prospective open-label study. Measures of Clinical Global Impression Scale (CGIS), Retrospective Overt Aggression Scale (ROAS), Aggression Score (AS) and weight were obtained during two baseline visits and again following 37 weeks of treatment with risperidone. RESULTS: Low dosages (1-3 mg/day; 1.6 mg/day on average) of risperidone brought about notable clinical improvement with no apparent adverse side effects. All measures evaluated--general behaviour, CGIS, OAS and weight--reacted favourably to the treatment protocol. CONCLUSION: The preliminary results presented here suggest that risperidone is useful in treating PWS due to its positive effect on the disruptive behavioural symptoms that accompany it.

Adolescent↗

Olanzapine and sulpiride: a preliminary study of combination/augmentation in patients with treatment-resistant schizophrenia.

Coadministration of olanzapine, an atypical neuroleptic, with sulpiride, a selective D2 antagonist, is suggested as an efficient strategy for treating patients with resistant unremitting schizophrenia. The psychopharmacologic rationale that may account for the enhanced clinical efficacy of combining sulpiride with olanzapine and vice versa is the difference in affinity of the two drugs to brain receptors. Olanzapine affinity is related more to serotonin 5-HT2 than to dopamine-2, whereas sulpiride is considered a selective D2 blocker. The adjunction of a selective D2 antagonist to olanzapine may act as the olanzapine's augmentor by enhancing D2 blockage. This mode of treatment was introduced to six patients with chronic schizophrenia who showed noteworthy and rapid clinical improvement, supported by a decrease in their scores on the Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale. No bothersome side effects were noticed. This clinical approach is in accordance with the findings of previous reports assessing the efficacy of the combined treatment of clozapine and sulpiride. The grounds for this treatment regimen using olanzapine rather than clozapine are discussed, calling for further studies to affirm the hypothesis and clinical results.

Adult↗

Jerusalem syndrome.

BACKGROUND: Jerusalem's psychiatrists expect to encounter, as the millennium approaches, an ever-increasing number of tourists who, upon arriving in Jerusalem, may suffer psychotic decompensation. AIMS: To describe the Jerusalem syndrome as a unique acute psychotic state. METHOD: This analysis is based on accumulated clinical experience and phenomenological data consisting of cultural and religious perspectives. RESULTS: Three main categories of the syndrome are identified and described, with special focus on the category pertaining to spontaneous manifestations, unconfounded by previous psychotic history or psychopathology. CONCLUSIONS: The discrete form of the Jerusalem syndrome is related to religious excitement induced by proximity to the holy places of Jerusalem, and is indicated by seven characteristic sequential stages.

Adult↗

Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation.

OBJECTIVE: Clozapine and risperidone were the first two antipsychotic drugs of a new class of agents for the pharmacotherapy of schizophrenia. It has been suggested that refractory schizophrenic patients who fail to respond to neither clozapine nor risperidone may respond to a combination/augmentation strategy of both medicaments. METHOD: Three cases of individuals with unremittent schizophrenia treated via this combination are presented. Response was evaluated by clinical follow-up and PANSS rating scale. RESULTS: Good clinical results with no noticeable adverse side effects, ascertained by a reduction from baseline scores of the Positive and Negative Syndrome Scale (PANSS) were obtained in all three patients. CONCLUSION: The findings from this pilot study suggest this combination as a possible therapeutic approach for treating resistant schizophrenic patients.

Adult↗

Adaptation of immigrant psychiatrists from the former Soviet Union in the Department of Mental Health of the Israel Defense Forces.

Psychiatrists from the former Soviet Union serve in the Department of Mental Health of the Israel Defense Forces. The new immigrant psychiatrists confront a wide range of difficulties during the process of integration to the military system and adaptation to the specifically military aspects of psychiatry. These include unfamiliarity with the military system, cultural clashes with the different groups of soldiers representing the various subgroups of the absorbing society, the psychopathology of soldiers, which is different from that seen in civil psychiatry, and the change in focus in the military mental health service, which emphasizes the importance of evaluating ego strength. Arbitrarily, one can describe four stages of adaptation that the immigrant psychiatrist has to pass through before recruitment and during service until adaptation and integration in the new role take place. Individual and group supervision are the main means by which the assimilation process is eased. The military service smooth the acculturation process and has an important role in helping the immigrant's adaptation to Israeli society and in building his or her professional identity.

Acculturation↗