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Biomedical subjects

L Goldstein

Publications and source records attributed to L Goldstein.

At least 19 recordsLinked to original sources

Factors associated with self-evaluated severity of illness and quality of life in male Israeli asthmatic soldiers.

OBJECTIVE: To evaluate whether the asthmatic condition and quality of life of male asthmatic Israeli soldiers deteriorate during army service. METHOD: We retrospectively assessed 178 asthmatic soldiers during service using an adapted version of the Mini Asthma Quality of Life Questionnaire, and compared it to their condition before service. The participants responded additionally to questionnaires assessing psychosocial resources and adjustment to illness. RESULTS: The self-evaluated degree of asthma disease severity (SEDOAD) of the participants deteriorated in the army compared to before service. Soldiers with mild SEDOAD during service, compared to soldiers with severe (and in most cases also moderate) SEDOAD, had less severe medically evaluated and self-evaluated asthma before service. Mild SEDOAD participants showed, additionally, lower inclination towards active seeking of asthma-related information, more favorable health care-related attitudes, less unfavorable effects of their illness on military and extra-military functioning, greater reported pre-enlistment optimism, and a greater belief in their ability to cope successfully with their asthma during service. CONCLUSION: SEDOAD and the quality of life during service are associated not only with pre-enlistment asthma severity, but also with the manner in which the soldier perceives the influence of the illness on his health condition, and the manner in which he copes with this influence.

Adult↗

Facial nerve palsy after acute exposure to dichloromethane.

BACKGROUND: Dichloromethane poisoning affects predominantly the central nervous and the cardiovascular systems, and results from both carboxyhemoglobin formation and direct solvent-related narcosis. Exposure is frequently occupational and related to paint-stripping. Several reports have described severe adverse effects as well as fatalities. Conflicting reports regarding peripheral nerve toxicity have been found with no reports of clinical acute toxicity heretofore. METHODS: We present a case report of a patient who developed a facial nerve palsy after acute occupational exposure to Dichloromethane. The patient was part of a paint removing crew who have worked without proper protecting measures and were thus exposed to high levels of Dichoromethane. RESULTS: The patient was involved in paint stripping with Dichloromethane, and developed facial nerve palsy. Other known causes of facial palsy were excluded, and although idiopathic palsy cannot be ruled out, there were no corroborating findings. Carboxyhemoglobin levels taken after a significant delay were normal. CONCLUSION: This is the first article that describes a case of Facial Nerve Palsy related to acute dichloromethane exposure, indicating a possible peripheral neurotoxic effect of this solvent.

Acute Disease↗

The prevalence of obesity and associated morbidity among 17-year-old Israeli conscripts.

BACKGROUND: There has been a significant increase in the prevalence of obesity among children and adolescents over the last few decades. Obesity is associated with significant psychosocial and physical morbidity. OBJECTIVE: The aim of this study was to define the prevalence of obesity and associated morbidity, including type 2 diabetes and hypertension, among 17-year-old adolescents. A comparison between the morbidity patterns of females and males was also performed. DESIGN: All 17-year-old Israeli nationals are obliged by law to present at the Israel Defence Forces recruiting office for a medical examination, with the exception of orthodox religious and Arabic adolescents. Height and weight are measured and classified, and a trained specialist evaluates those with suspected associated diseases. The level of education is also recorded. RESULTS: Our survey included 76,732 adolescents, 32,402(42.2%) females and 44,330(57.8%) males. The prevalence of obesity and morbid obesity among 17-year-old Israeli conscripts was 4.1% in males and 3.3% in females. The prevalence of borderline overweight was 12.4% in males and 11.4% in females. The prevalence of hypertension and type 2 diabetes was significantly higher among conscripts with BMI>30 kg/m2 in both genders. There was also a significantly higher prevalence of hypertension and type 2 diabetes in males compared with females(P<0.001, 0.015). A significantly higher prevalence of conscripts without high-school education(<10 years of education) was found among females with BMI>30 kg/m2. There was no significant difference among the male conscripts. CONCLUSIONS: This study found a relatively low prevalence of obesity among 17-year-old Israeli conscripts, but an alarmingly high prevalence of borderline overweight. Obesity was correlated with a higher prevalence of hypertension and type 2 diabetes, and a lower level of education. There was a significant difference between genders in the prevalence of hypertension and type 2 diabetes, and this should be further investigated. These data call for the creation of new education programmes on the prevention of overweight among children and adolescents.

Adolescent↗

How much acetaminophen do paediatricians prescribe? A survey among Israeli paediatricians.

OBJECTIVE: To describe the current practice of Israeli paediatricians regarding acetaminophen dosing. METHODS: A cross-sectional survey among 200 paediatricians. The paediatricians were questioned of the recommended dose of acetaminophen, and whether they give prescriptions for acetaminophen and instruct their patients how to use it. RESULTS: The response rate was 36%. When asked on the recommended dose of acetaminophen, 30 (42%) physicians gave doses different from the dose recommended by the Israeli formulary. Thirty (42%) of the paediatricians answered that they usually or always give prescriptions for antipyretics. CONCLUSIONS: A large percentage of Israeli paediatricians do not provide parents proper instructions regarding the correct dosing of acetaminophen.

Acetaminophen↗

Expression of the skate (Raja erinacea) AE1 osmolyte channel in Xenopus laevis oocytes: monovalent cation permeability.

The aim of this study was to express the cloned skate anion exchanger 1 (skAE1) in Xenopus oocytes and determine whether the differences in monovalent cation permeabilities in hypotonically stimulated skate and trout erythrocytes could be due to differences in the presence or absence of intracellular channel regulators between the two species or in the intrinsic permeability properties of the channels themselves. The expressed protein (skAE1) was inserted into the oocyte cell membrane and facilitated both Cl- exchange and taurine transport. Expression of skAE1 in oocytes showed similar monovalent cation permeabilities as previously reported for skate erythrocytes and different from both trout erythrocytes and trAE1 expressed in Xenopus oocytes. These results show that the skAE1 expressed in oocytes functions in a manner similar to that of the osmolyte channel in hypotonically activated skate erythrocytes and supports the hypothesis that differences in the monovalent cation permeabilities of the osmolyte channels in skate and trout RBCs resides in the differences in permeability properties of the channels between the two species.

Animals↗

Evidence for the presence of three different anion exchangers in a red cell. Functional expression studies in Xenopus oocytes.

Anion exchangers (AE) are transmembrane proteins catalyzing electroneutral exchange of Cl(-) for HCO3-. To date, three different genes coding for this protein, AE1, AE2 and AE3, have been identified in many species. AE1 is considered to be the unique anion exchanger expressed in erythrocytes. In this paper we propose the presence of three different AEs in skate erythrocytes, a skAE1, a skAE2 and a skAE3, cloned by RT-PCR (reverse-transcriptase polymerase chain reaction). These three skAE have a similar predicted secondary structure. All three skAE are divided in two main domains: a hydrophilic cytoplasmic N-terminal domain and a C-terminal domain crossing the lipid bilayer at least 12 times. The greatest similarity is found in the membrane-spanning domain of the three skAE. The size as well as the amino-acid sequence of the cytoplasmic domain differ significantly among three anion exchangers. Functional expression studies in Xenopus oocytes led to the conclusion that skAE-1 and -2 share some functional features (Cl-dependence and DIDS sensitivity). The skAE3 could not be expressed in Xenopus oocytes. These data are in agreement with expression data obtained with AEs of different species utilizing the oocyte system. It is highly probable that these three new AE sequences come from three different genes, thus suggesting for the first time the presence of the three AE genes in Chondrichthyes.

Amino Acid Sequence↗

Comparison of the osmolyte transport properties induced by trAE1 versus IClswell in Xenopus oocytes.

During cell swelling, cells release organic osmolytes via a volume-activated channel as part of the regulatory volume decrease. The erythrocyte membrane protein AE1 (band 3), has been shown to be involved in regulatory volume responses of fish erythrocytes. Previous studies showed that the expression of trout AE1 in Xenopus laevis oocytes induces band 3 anion exchange activity and organic osmolyte channel activity. However, an endogenous swelling-activated anion channel, IClswell, is present in Xenopus oocyte membranes. Therefore, it is not yet known whether a new organic osmolyte channel is formed or whether the endogenous channel, IClswell, is activated when trout AE1 is expressed in the oocytes. The purpose of this study was to determine whether the expression of trout AE1 in Xenopus oocytes leads to the formation and membrane insertion of a new organic osmolyte channel or activates IClswell. To differentiate between the two possibilities, we compared the time courses, pH profiles and inhibitor sensitivities of both trout AE1 and IClswell. The results of taurine-uptake experiments show that the time courses and pH levels for optimum expression of trout AE1 and IClswell differ significantly. The inhibitor sensitivities of the organic osmolyte channel mediated by trout AE1 and IClswell are also significantly different, strongly suggesting that the expression of trout AE1 in Xenopus oocytes does not activate IClswell, but rather forms a new organic osmolyte channel.

Animals↗

Modulation of erythrocyte band 4.1 binding by volume expansion.

Erythrocyte band 4.1 is an important protein in the control and maintenance of the cytoskeleton. Skate erythrocyte band 3, the anion exchanger, appears to play a pivotal role in the regulation of volume-stimulated solute efflux during volume expansion. Because band 4.1 interacts with band 3, we tested whether their interaction might change during volume expansion. Skate red blood cells were volume-expanded in either hypotonic media (one-half osmolarity) or were swollen under isoosmotic conditions by inclusion of ethylene glycol or ammonium chloride in the medium. Microsomal membranes isolated from red cells under volume expanded conditions demonstrated a significant decrease in the amount of band 4.1 bound to band 3. In unstimulated cells, approximately one third of the binding of band 4.1 occurred to band 3. This binding was characterized as being sensitive to competition by the peptide IRRRY. The majority of band 4.1 is bound to glycophorin (as demonstrated in other species), and this binding does not change during volume expansion. The alteration in band 4.1:band 3 interaction occurs within 5 min after volume expansion and is transient, returning to near normal interaction within 60 min. Two drugs that promote band 3 oligomerization, pyridoxal-5'-phosphate and DIDS, also decreased band 4.1 interaction with band 3. Band 4.1 and ankyrin binding to band 3 may be reciprocally related as high-affinity ankyrin binding sites to band 3 observed under volume-expanded conditions are decreased by inclusion of band 4.1 in the binding reactions. J. Exp. Zool. 289:177-183, 2001.

Animals↗

Psychological treatments for epilepsy.

BACKGROUND: Psychological interventions such as relaxation therapy, cognitive behaviour therapy, EEG bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. OBJECTIVES: To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE using OVID (1966 - May 2001) and cross references from identified publications. SELECTION CRITERIA: Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for patients with epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency, and quality of life. MAIN RESULTS: We found three small trials (50 patients) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and two of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in subjects with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, improving compliance to medication and improving social competencies. REVIEWER'S CONCLUSIONS: In view of methodological deficiencies and limited number of patients studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.

Biofeedback, Psychology↗

Gram-Negative anaerobic endocarditis: two case reports and review of the literature.

The rarity of anaerobic gram-negative endocarditis limits the ability of physicians to define its prognosis. Two cases of endocarditis due to Bacteroidesfragilis are described, and a review of the English literature for all cases of anaerobic gram-negative endocarditis reported since 1940 is presented. The disease predominantly affects males. Clinical features are similar to those of endocarditis due to nonanaerobic organisms, but underlying heart disease is less common and the rate of thromboembolic complications is high. All deaths reported were due to Bacteroides spp.; no deaths due to Fusobacterium spp. have been reported. Treatment with metronidazole has dramatically improved the prognosis of patients with endocarditis due to anaerobic gram-negative bacilli.

Aged↗

Enhanced peripheral T-cell apoptosis in chronic hepatitis C virus infection: association with liver disease severity.

BACKGROUND/AIMS: It has been suggested that enhanced T-cell apoptosis in hepatitis C virus (HCV) infection may lead to down-regulation of their cellular immune response, thus contributing to the persistency of HCV infection. In the present study we have investigated the role of bcl-2 and nuclear factor kappa B (NFkappaB) in dexamethasone-induced apoptosis of peripheral T cells in chronic HCV infection. METHODS: The expression of bcl-2 and NFkappaB in peripheral T cells as well as spontaneous and dexamethasone-induced T-cell apoptosis were studied in HCV-infected patients (n=21), hepatitis B virus (HBV)-infected patients (n=14) and healthy individuals (n=19). These parameters were correlated with markers of autoimmunity and disease severity. RESULTS: NFkappaB, but not bcl-2 expression, was significantly decreased in the HCV-infected patients. This decrease was associated with the presence of mixed cryoglobulins (MC) and rheumatoid factor and was positively correlated with alanine aminotransferase (ALT) levels and histological activity index (HAI). Both spontaneous and dexamethasone-induced T-cell apoptosis were enhanced in HCV-infected patients; however, only the latter was correlated with the presence of MC, ALT levels and HAI. CONCLUSIONS: We confirm previous reports that enhanced T-cell apoptosis in HCV infection may play an important role in disease severity. Decreased expression of NFkappaB is important in the development of peripheral T-cell apoptosis, thus contributing to viral persistence and autoimmunity in these patients.

Adult↗

Conditional logistic analysis of case-control studies with complex sampling.

Methods for the analysis of unmatched case-control data based on a finite population sampling model are developed. Under this model, and the prospective logistic model for disease probabilities, a likelihood for case-control data that accommodates very general sampling of controls is derived. This likelihood has the form of a weighted conditional logistic likelihood. The flexibility of the methods is illustrated by providing a number of control sampling designs and a general scheme for their analyses. These include frequency matching, counter-matching, case-base, randomized recruitment, and quota sampling. A study of risk factors for childhood asthma illustrates an application of the counter-matching design. Some asymptotic efficiency results are presented and computational methods discussed. Further, it is shown that a 'marginal' likelihood provides a link to unconditional logistic methods. The methods are examined in a simulation study that compares frequency and counter-matching using conditional and unconditional logistic analyses and indicate that the conditional logistic likelihood has superior efficiency. Extensions that accommodate sampling of cases and multistage designs are presented. Finally, we compare the analysis methods presented here to other approaches, compare counter-matching and two-stage designs, and suggest areas for further research.To whom correspondence should be addressed.

Journal Article↗

Overexpression of the HER-2/neu oncogene in pancreatic adenocarcinoma.

Novel systemic treatments are needed in pancreatic cancer. The authors sought to establish the frequency of overexpression of the HER-2/neu oncogene in patients with pancreatic adenocarcinoma to determine the potential role of trastuzumab (Herceptin) as a therapeutic agent in this disease. Tumor specimens from patients with pancreatic adenocarcinoma were analyzed by staining for p185HER2 protein using the DAKO immunohistochemical assay. Patients with and without HER-2/neu overexpression by immunohistochemistry were compared with respect to clinical and pathologic characteristics. HER-2/neu gene amplification was also evaluated by fluorescence in situ hybridization (FISH). Thirty-two of 154 patients (21%) had pancreatic adenocarcinoma that demonstrated HER-2/neu overexpression by immunohistochemistry. At initial diagnosis, 16% of resectable cancers, 17% of locally advanced cancers, and 26% of metastatic cancers were determined to have HER-2/neu overexpression. Three of 11 (27%) patients with HER-2/neu overexpression by immunohistochemistry had gene amplification by FISH. HER-2/neu overexpression occurs in a subset of pancreatic cancer. Evaluation of the efficacy of trastuzumab for patients with pancreatic cancer who overexpress HER-2/neu appears indicated.

Aged↗

Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias).

The aims of this study were to determine the pathway of swelling-activated trimethylamine oxide (TMAO) efflux and its regulation in spiny dogfish (Squalus acanthias) red blood cells and compare the characteristics of this efflux pathway with the volume-activated osmolyte (taurine) channel present in erythrocytes of fishes. The characteristics of the TMAO efflux pathway were similar to those of the taurine efflux pathway. The swelling-activated effluxes of both TMAO and taurine were significantly inhibited by known anion transport inhibitors (DIDS and niflumic acid) and by the general channel inhibitor quinine. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea activated both TMAO and taurine effluxes similarly. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea also stimulated the activity of tyrosine kinases p72syk and p56lyn, although the stimulations by the latter two treatments were less than by hypotonicity. The volume activations of both TMAO and taurine effluxes were inhibited by tyrosine kinase inhibitors, suggesting that activation of tyrosine kinases may play a role in activating the osmolyte effluxes. These results indicate that the volume-activated TMAO efflux occurs via the organic osmolyte (taurine) channel and may be regulated by the volume activation of tyrosine kinases.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer.

PURPOSE: To compare outcome for ipsilateral breast tumor recurrence (IBTR), or regional node recurrence, initial and subsequent distant metastases, and overall and cause-specific survival in women treated with conservative surgery and radiation based on whether or not radiation was targeted to the internal mammary nodes (IMN). METHODS AND MATERIALS: From 1979-1994, 1383 women with Stage I-II breast cancer underwent wide excision, axillary node dissection with >/=10 nodes removed, and radiation. Median follow-up was 6 years; median age was 55 years. A total of 114 women had radiation targeted to the IMN with deep tangents and 1269 did not. Women who received IMN treatment were more often axillary node-positive (40% vs. 25%, p = 0. 002), had central or inner quadrant tumors (61% vs. 40%, p = 0.001), and had T2 tumors (47% vs. 31%, p = 0.001). All axillary node-positive women received adjuvant chemotherapy and/or tamoxifen. For axillary node-negative women, 13% of the IMN treatment group received adjuvant systemic therapy compared to 37% of the no treatment group (p = 0.001). Radiation was directed to the breast only in 97% of the axillary node-negative women who had IMN treatment and 99% of the no IMN treatment group. For axillary node-positive women, 98% of the IMN-treated group had radiation to the breast and supraclavicular nodes +/- a posterior axillary field compared to 77% of the no IMN treatment group (p = 0.001). There were no significant differences between the two groups for median age, menopausal status, histology, final surgical margin, estrogen and progesterone receptor status, or the number of positive nodes. RESULTS: There were no significant differences in the 5- and 10-year cumulative incidence of an IBTR, regional node recurrence, initial or total distant metastases for the two groups. Similarly 5- and 10-year actuarial overall and cause-specific survival were not significantly different. However, subset analysis revealed a statistically significant increase in initial (29% vs. 15% at 10 yr, p = 0.002) and total (30% vs. 17% at 10 yr, p = 0.01) distant metastases and a significant decrease in cause-specific survival (76% vs. 89% at 10 yr, p = 0.02) for postmenopausal women who received IMN treatment. These findings could not be attributed to differences in the use of systemic therapy or the number of positive nodes. Axillary node-positive patients did not experience a significant decrease in initial (36% vs. 22% at 10 yr, p = 0.21) or total distant metastases (37% vs. 28% at 10 yr, p = 0.62) or a significant improvement in cause-specific survival (72% vs. 76% at 10 yr, p = 0.76) with IMN treatment regardless of whether the tumor was lateral or medial/central in location. IMN treatment was not associated with an increase in non-breast cancer deaths during this period of observation. CONCLUSIONS: This retrospective series was unable to identify a significant benefit for IMN irradiation in terms of distant metastases or cause-specific survival for the entire patient population, and in particular, for patients with positive axillary nodes and medially located lesions. The results of the proposed or ongoing prospective randomized trials will further address this controversial issue.

Adult↗

Inhibition of volume-stimulated taurine efflux and tyrosine kinase activity in the skate red blood cell.

Phosphorylation of the band 3 anion exchange protein by the tyrosine kinases p72syk and p56lyn is thought to play a role in the pathway that regulates swelling-activated taurine efflux from the skate red blood cell. In this study, the protein tyrosine kinase (PTK) inhibitors piceatannol and tyrphostin A23 both inhibited taurine efflux and the activities of the tyrosine kinases p72syk and p56lyn in the skate erythrocyte. However, the PTK inhibitors genistein and tyrphostin A46 had only small effects on taurine efflux and PTK activities. In general, a strong correlation between the extent of inhibition of taurine efflux and of tyrosine kinase activity was observed. PTK inhibitors showed a similar pattern of inhibition of band 3 phosphorylation, with the greatest inhibition observed in cells treated with piceatannol. The protein kinase C inhibitors staurosporine and bisindolylmaleimide tested alone or in combination with piceatannol had little or no significant effect on swelling-activated taurine efflux. Overall the results support the hypothesis that phosphorylation of the skate band 3 protein by p72syk and p56lyn contributes to the regulation of volume-activated taurine efflux in skate red cells, and suggest that protein kinase C may not be involved in this regulation.

Animals↗