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Biomedical subjects

A Shahar

Publications and source records attributed to A Shahar.

At least 37 records · Page 2Linked to original sources

Molecular epidemiology of hematological neoplasms--present status and future directions.

The field of molecular epidemiology, using modern epidemiological approaches and taking the advantage of the advances in molecular biology can provide new tools for the exploration of etiological determinants, either environmental or hereditary, in the development of hematological neoplasms. It is now possible to identify some host susceptibility characteristics, to measure the effective dose of exposure, and to identify early, pre-clinical biological effects, using sensitive and specific biomarkers. The significant variation in the incidence of hematological neoplasms in different geographical areas, races, and age groups, the high rates of familial aggregation in certain populations, the involvement of protooncogenes and tumor suppressor genes in the development of hematological neoplasms, as well as of many environmental agents such as chemicals, radiation, and viruses, support the important role of molecular epidemiology in the investigation of the development of hematological neoplasms.

Animals↗

The dynamics of patient visits to a public hospital ED: a statistical model.

Using a public hospital's computerized database, we formulated a statistical model to explain emergency department (ED) patient volume for better staffing and resource allocation. All patients visiting the ED over a 3-year period were included in this retrospective study. Each observation described the total daily number of referrals and was defined by the following variables: day of the week, month of the year, holiday/ weekday, relative order in a 3-year sequence, and number of visits to the ED on that day. The statistical method used to build the model was analysis of covariance. Periodicity in average number of daily visits existed for each of the seasonal factors that were examined, repeating every year during the study period. Based on a graphic analysis, the model was defined and explained 65% of the variance during the 3-year study, with a relatively low standard deviation of error. A statistically significant correlation existed between time-related factors and the number of visits to the ED. This statistical model may prove to be of value for planning emergency services, which operate under stressful, unpredictable situations.

Analysis of Variance↗

The next stage: molecular epidemiology.

The traditional approach in epidemiology of relating exposure to an environmental agent such as a drug or infective agent has been to measure an overall risk (i.e., average and then "adjust risk for demographic variables and other confounders"). An attempt is sometimes made to define a "susceptible" subgroup. The analyses are usually based on good statistical methodology rather than an understanding of the interaction of body of host and agent. A twofold risk for 1000 exposed versus nonexposed people could be an average twofold risk for all 1000 exposed or a 20-fold risk for 100 exposed individuals (i.e., a drug-host interaction). Clearly, finding the 100 individuals with a 20-fold risk has much greater clinical importance than a twofold risk for 1000 people. The world of epidemiology may be changing-we may soon be able to define risk based on genetic susceptibility, at least sometimes.

Apolipoproteins E↗

Control-relevant intervention in the treatment of minor and major depression in a long-term care facility.

The authors assessed the effect of a control-relevant psychosocial intervention in 31 nursing home residents with either major depressive episode or minor depression. An initial group of 22 residents were randomized to either active treatment or waiting list. Four of 11 residents randomized to active treatment were deemed Responders, compared with 0 of 11 on the waiting list (P < 0.05). Of the total of 31 residents who participated in the intervention, 14 (45%) were deemed Responders during the intervention period. For these Responders, the Hamilton Rating Scale for Depression (Ham-D) and Geriatric Depression Scale scores improved significantly during the intervention. The improvement in the Ham-D was not sustained 2 months after intervention was terminated. These findings suggest that a psychosocial intervention enhancing socialization according to each resident's choice had a positive therapeutic impact on almost half of the nursing home residents with major or minor depression. However this effect could not be sustained by the residents without the support of the structured program.

Aged↗

A new organotypic culture method to study the actions of steroid hormones on the nervous system.

A new organotypic culture method for growing slices of nervous system tissue, based on the use of hyaluronic acid as a growth supporting milieu, is described. This method allows cultures derived from either fetuses or newborns to grow and develop with markedly reduced amounts of added serum. Organotypic cultures from fetal rat hypothalamus were exposed to 17 beta estradiol and compared to control cultures exposed to the ethanol vehicle. When exposed to estradiol, cultures showed an outgrowth of thick nerve fibers that was accompanied by an elevation in the number of microtubules present in the neuronal processes, an increment in the number of synapses, and an increased morphological differentiation of synaptic terminals. Freeze-fracture analysis of neuronal membranes from estradiol-treated cultures revealed a significant increase in the number of exoendocytotic images and a decrease in the number of intramembranous particles. Estradiol's effects parallel those found in in vivo studies, indicating that hyaluronic acid-based organotypic cultures represent an appropriate model to study hormonal influences on the developing nervous system.

Animals↗

Action of steroid hormones on growth and differentiation of CNS and spinal cord organotypic cultures.

During the prenatal period, gonadal steroid environment induces dramatic sexually dimorphic changes in the nervous system. We have used in vitro methods to study the mechanism and timing of hormonal influences on neuronal sprouting and myelination during the prenatal period. Organotypic cultures of hypothalamus and lumbar spinal cord (SC) slices from rat fetuses were grown on plasma clot or in hyaluronic acid and exposed to estrogen (17 beta estradiol) and testosterone (T) during cultivation. Both steroid hormones were active: 17 beta estradiol enhanced sprouting of hypothalamic neuronal fibers and increased the amount of synapses. In SC cultures T induced regeneration of thick nerve processes and an early onset of myelination, mainly of peripheral myelin.

Animals↗

Factors influencing mossy fiber collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus.

Collateral sprouting of dentate granule cell axons, the mossy fibers, occurs in response to denervation, kindling, or excitotoxic damage to the hippocampus. Organotypic slice culture of rodent hippocampal tissue is a model system for the controlled study of collateral sprouting in vitro. Organotypic roller-tube cultures were prepared from hippocampal slices derived from postnatal day 7 mice. The Timm heavy metal stain and densitometry were used to assay the degree of mossy fiber collateral sprouting in the molecular layer of the hippocampal dentate gyrus. Factors influencing mossy fiber collateral sprouting were time in culture, positional origin of the slice culture along the septotemporal axis of the hippocampus, and presence of attached subicular-entorhinal cortical tissues. Collateral sprouting in the molecular layer was first detected after 6 days in culture and increased steadily thereafter. By 2 weeks considerable sprouting was apparent, and at 3 weeks intense sprouting was observed within the molecular layer. An intrinsic septal-to-temporal gradient of collateral sprouting was apparent at 14 days in culture. To determine whether differential damage to the mossy fibers was the basis for the differences in collateral sprouting along the septotemporal axis, we made complete transections of the mossy fiber projection as it exited the dentate hilus at various levels along the septotemporal axis; no differences were found on subsequent collateral sprouting in the dentate molecular layer. Timm-stained hippocampal cultures with an attached entorhinal cortex, a major source of afferent innervation to the dentate granule cells, displayed significantly less collateral sprouting at 10 days in culture compared to that in cultures from adjacent sections without attached subicular-entorhinal tissues present. Thus, time in culture, position along the septotemporal axis, and presence of afferent cortical tissues influence aberrant neurite collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus.

Animals↗

[Mediastinitis secondary to esophageal ulceration after doxycillin].

Doxycillin is a tetracycline antibiotic widely used in outpatients, particularly for treating pelvic inflammatory disease, acne, and Rickettsial infections. Among the more common side effects is acute esophageal inflammation leading to ulceration and occasionally to perforation. We describe the clinical course of a 35-year-old woman with esophageal perforation secondary to the use of Doxycillin.

Adult↗

Early T wave inversion after thrombolytic therapy predicts better coronary perfusion: clinical and angiographic study.

OBJECTIVES: This study was undertaken to test the hypothesis that early inversion of T waves after thrombolytic therapy for acute myocardial infarction predicts patency of the infarct-related artery with high Thrombolysis in Myocardial Infarction (TIMI) perfusion flow and better in-hospital outcome. BACKGROUND: Although numerous studies have demonstrated a strong association between early resolution of ST segment elevation after acute myocardial infarction and successful thrombolysis, little is known about early changes in T waves after thrombolytic therapy. METHODS: Ninety-four consecutive patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) were studied with admission and predischarge radionuclide ventriculography and with coronary angiography within 72 h of admission. Patient stratification was based on the presence or absence of early (within 24 h) T wave inversion. RESULTS: Early T wave inversion was associated with a higher patency rate of the infarct-related artery (90% vs. 65%, p < 0.02) and less severe residual stenosis ([mean +/- SD] 73 +/- 27 vs. 83 +/- 22, p = 0.06), and when only TIMI perfusion grade 3 was considered, the difference was even greater (77% vs. 41%, p < 0.001). Patients with early inversion of T waves had a lower peak creatine kinase value ([mean +/- SD] 678 +/- 480 vs. 1,076 +/- 620, p < 0.01), and although a similar percent of patients with and without early T wave inversion had a normal ejection fraction (> or = 55%) on admission, a higher percent of patients with early inversion had a normal ejection fraction at hospital discharge (71% vs. 44%, p < 0.03). Early T wave inversion anticipated a more benign in-hospital clinical course with a lower incidence of adverse cardiac events (10% vs. 33%, p < 0.02). CONCLUSIONS: Early inversion of T waves in patients with acute myocardial infarction treated with thrombolytic therapy suggests patency of the infarct-related artery, better perfusion grade and left ventricular function and a more benign in-hospital course.

Coronary Angiography↗

Disappearance of a syndrome: Dressler's syndrome in the era of thrombolysis.

The incidence of the post-myocardial infarction syndrome (Dressler's syndrome) among thrombolized patients has not been established yet. To clarify this issue we prospectively studied 201 consecutive patients with acute myocardial infarction who had undergone recombinant tissue-type plasminogen activator therapy followed by 5 days of heparin administration. All patients were followed for at least 3 months for clinical signs of Dressler's syndrome. None of the 148 patients (76%) who showed clinical signs of early reperfusion had Dressler's syndrome. The sole patient in the group who manifested the syndrome developed it 3 weeks following extensive anterior myocardial infarction with no evidence of reperfusion. Although 4 patients manifested signs of early pericarditis, none developed the syndrome. We conclude that Dressler's syndrome has in fact been rendered a rare phenomenon among patients who benefit from thrombolytic therapy.

Adult↗

Differentiation of myoblasts and CNS cells grown either separately or as co-cultures on microcarriers.

Dispersed neuronal and muscular elements from fetal or neonatal origin, can organize and mature in culture when grown on positively charged cylindrical microcarriers (MCS), to a stage which simulate in vivo maturation. Cells arrange themselves on the MCS to form aggregates which remain floating in the nutrient medium. In such a tridimensional organization, the neuronal tissue is capable of regenerating a network of nerve fibers which establish synapse interconnections and undergo myelination. Oligodendrocytes organize on MCS in a tridimensional pattern and produce extensive myelin-like membranes. Myoblasts in MC-cultures fuse into polynucleated myotubes which become striated and contract spontaneously. Creatine kinase and acetylcholine receptor (AChR) are formed during myogenesis in similar quantities in MC-cultures and in monolayers. When both neuronal and muscle tissues are prepared from the same fetus (autologous nerve-muscle co-cultures) and are cultured on MCS, they interconnect to form neuro-muscular junctions. Cells from both tissues, exhibit better differentiation, for longer periods in MC-cultures than they do in monolayers. The floating functional entities are easy to sample and can be harvested for ultrastructural, immunocytochemical and biochemical analysis. In addition, MC-cultures can be used as a good tool for the study of acute and chronic exposures to toxicological agents, as well as for implantation into demyelinated, injured or dystrophic tissues. In this case the MCS in the implanted entities will serve as identifiable markers.

Animals↗

Vocal attrition related to idiosyncratic dysphonia: re-analysis of survey data.

In a recent survey study it was found that female army instructors were significantly more likely to suffer from symptoms of vocal attrition than new female recruits, supporting the clinical impression that those who are engaged in a vocally taxing vocation are at higher risk for vocal attrition than those who are not. In the present study we found that instructors who reported having rapid, excessive or loud speech, or a combination of these, were significantly more likely to report symptoms of vocal attrition than instructors who reported not having these speech habits. Difference in prevalence of vocal attrition symptoms among recruits with and without these speech habits was statistically non-significant. The present findings confirm the clinical impression that idiosyncratic dysphonia can increase the risk of vocal attrition, especially in people who are engaged in a vocally demanding profession or vocation.

Adolescent↗

Neuronal cell cultures as a model for assessing neurotoxicity induced by encephalitic viruses.

Primary dispersed and organotypic cultures were prepared from selected brain areas and spinal cords of rat (Sprague-Dawley) and mouse (SJL/OLA(F) Ness-Ziona) fetuses and neonates. Following fiber regeneration, synapse formation and myelination, cultures were infected with one of the following viruses: Rabies CVS-21 strain, Sindbis Alphavirus, West-Nile Flavivirus and Theiler Murine Encephalomyelitis virus. Light and electron microscopical studies showed clear differences in the target cells for virus infection; time of viral replication and in the intensity and specificity of the cytopathic effects induced by these viruses. Thus, Sindbis and Theiler viruses induced severe cytotoxicity and demyelination due to rapid viral replication in both neurons and all glial cell types. Rabies and West-Nile viruses, on the other hand, replicated mainly in neurons and at a much slower rate, causing only mild damage to the cells and the myelin sheath. A very specific alignment of West-Nile virions was observed along the interperiod lines of the myelin sheath in several myelinated axons. This peculiar arrangement of the virions, entrapped between the myelin lamellae may lead to a novel concept in the understanding of viral infection.

Animals↗

Irradiation neurotoxicity assessed in organotypic cultures of rat hippocampus.

The neurotoxic effects of irradiation on the developing nervous system were studied in organotypic cultures of hippocampus prepared from newborn Sprague-Dawley rats. Hippocampus slices of 7-day-old rats were irradiated at the day of explantation at doses of 1, 2 and 4 Gy, and cultured in a roller drum for a fortnight. Light and electron microscopy showed remarkable damage to neuronal cells following irradiation, oligodendrocytes and myelogenesis being also affected. In contrast to alterations in neuronal perikarya, no morphological changes in synapses were obvious, though their number seemed to be reduced after irradiation with 4 Gy. These results confirm that low dose radiation produces damage to the central nervous system not only pre-natally, but even in post-natal periods of differentiation and development.

Animals↗