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Biomedical subjects

A Barzilai

Publications and source records attributed to A Barzilai.

At least 73 records · Page 4Linked to original sources
PubMed1998

Severe acute asthma in a community hospital pediatric intensive care unit: a ten years' experience.

BACKGROUND: The clinical literature on the incidence and subsequent mortality of asthma has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of asthma in smaller, community-based intensive care units. OBJECTIVES: The purpose of this study was to explore the course and outcome of children with acute severe asthma treated within a community hospital PICU compared with those described in the literature from larger tertiary referral centers. DESIGN: A retrospective analysis of 49 asthmatic children admitted to the Pediatric Intensive Care Unit (PICU) over a 10-year period was performed. MEASUREMENTS AND RESULTS: The mean age was 5.2 years (range 2 months to 16 years), and the male:female ratio was 3:1. Duration of symptoms prior to admission to hospital was less than 24 hours in 60.4% of the patients. The majority of patients was not treated with either inhaled or oral steroids before admission. Drugs used in the PICU included nebulized beta2-agonists, theophylline, steroids, intravenous salbutamol, and intravenous isoproterenol. Although a pharmacologic approach was successful in the majority of patients, intubation and mechanical ventilation were necessary for progressive hypercapnea, exhaustion, and cardiorespiratory arrest in 11/49 of these patients. The average stay in the ICU for our patient group was 2.4 days. Intubated patients had a mean average stay of 3.5 days. Two patients had pneumothorax related to positive pressure ventilation, requiring chest tube insertion for drainage. There were no deaths among the 49 patients admitted to our PICU. CONCLUSIONS: These data show that for acute severe asthma, outcome is comparable in a community PICU to a tertiary referral institution. We conclude that early ICU admission along with close monitoring is important in reducing morbidity and mortality in children with severe asthma.

Acute Disease↗
PubMed1998

Expression of cell cycle-related genes during neuronal apoptosis: is there a distinct pattern?

An emerging hypothesis considers the process of neuronal apoptosis as a consequence of unscheduled and unsynchronized induction of cell cycle mediators. Induction of several cell cycle genes precedes neuronal apoptosis and may be involved in determination of cell fate. We have now characterized changes in expression of cell cycle genes during apoptosis induced by oxidative stress in chick post-mitotic sympathetic neurons. Induction of cyclin B occurred prior to the commitment of neurons to both dopamine- and peroxide-triggered apoptosis. Both the neuronal death and the rise in cyclin B were inhibited by antioxidant treatment, suggesting a functional role for cyclin B induction during neuronal apoptosis. Induction of the cyclin dependent kinase CDK5 protein coincided with the time point when neurons were irreversibly committed to die. Expression of other cell cycle mediators such as cyclin D1 and the cyclin dependent kinases CDC2 and CDK2 was undetected and not induced by exposure to oxidative stress. Comparative analysis of the profile of cell cycle mediators induced during neuronal apoptosis of different neuronal cell populations revealed no distinct pattern of events. There are no cell cycle stage-specific mediators that are ultimately stimulated during neuronal apoptosis, suggesting that multiple pathways of re-activating the dormant cell-cycle, converge to determine entry into apoptosis. Nevertheless, the existence of some cell cycle mediators, that were not reported so far to be induced in post mitotic neurons during oxidative stress, substantiate them as part of the strong differentiating forces.

Animals↗
PubMed1998

Cone and platelet analyser (CPA): a new test for the prediction of bleeding among thrombocytopenic patients.

The risk of bleeding among thrombocytopenic patients was evaluated using our new cone and platelet analyser (CPA) test. Using this test, adherence of platelets was quantitated on extracellular matrix and expressed as percent of surface coverage (SC) and the average size (AS) of aggregates. 42 thrombocytopenic patients with ITP (n=23), post chemotherapy (n= 12) and others (n= 7) were tested over a total of 82 visits. On each visit, complete blood count and CPA tests were performed and patients were evaluated for evidence of bleeding (found in 40 visits). Bleeding patients had significantly lower platelet counts (27.4 +/- 22.0 v 47.1 +/- 21.0 x 10(9)/l), lower haematocrit values (30.2 +/- 8.1 v 35.2 +/- 6.6%), lower MPV (6.83 +/-1.89 v 8.98 +/- 1.13 fl), and lower SC (4.87 +/- 3.95 v 10.33 +/-5.48%) and AS (33.99 +/- 14.94 v 52.9 +/- 24.34 microm2). Univariate analysis yielded platelet count < or =20.0 x 10(9)/l, MPV < or =8 fl, haematocrit <35%, SC <5%, AS< or =40 microm2 as significantly associated with bleeding, whereas only MPV and SC were associated with bleeding (OR 6.95, CI 2.25-21.46 and OR 4.27, CI 1.29-14.16, respectively) by multivariate analysis. When taken together, 21/22 of patients (95%) with both low SC (<5%) and low MPV (<8.0 fl) had bleeding symptoms, whereas only 9/43 (21%) patients with both these parameters above these values experienced bleeding symptoms. We conclude that the CPA test and the parameter SC (<5%) together with MPV (< or =8 fl) might be used as independent predictors of bleeding in the management of thrombocytopenic patients.

Adolescent↗
PubMed1998

Primary cutaneous mucormycosis in a premature infant: case report and review of the literature.

Mucormycosis is an uncommon infection caused by fungi of the order Mucorales, family Mucoraceae, and almost always occurs in individuals with predisposing factors such as diabetes mellitus, metabolic acidosis, or immunodeficiency states. Although mucormycosis is a rare infection in childhood, sporadic cases of skin infections have been described in young infants and older children; primary skin infection has been associated with multiple nosocomial outbreaks caused by contaminated elastic bandages. In all reported cases involving premature infants, the elimination of the infection involved surgical debridement. We report for the first time successful conservative treatment with intravenous amphotericin B in a premature infant with primary cutaneous infection caused by Rhizopus oryzae.

Amphotericin B↗
PubMed1998

Successful treatment of disseminated Mycobacterium simiae infection in AIDS patients.

Mycobacterium simiae is rarely isolated in clinical settings of non-HIV-infected patients. Isolation of M. simiae from clinical specimens in clusters has been limited to some parts of the world that include Israel, Cuba and the southern USA, mainly Texas. Only 8 patients with HIV and disseminated M. simiae infection have been previously described in the English literature. Successful treatment of disseminated M. simiae infection has never been reported and 6 of the cases have died within 8 months of diagnosis. We reviewed retrospectively the medical records of HIV-infected patients who had positive blood or bone marrow cultures for M. simiae at the Sheba Medical Center, Tel-Hashomer, Israel, between January 1992 and December 1996. A case of disseminated M. simiae infection was defined as isolation of M. simiae in blood or bone marrow culture in an HIV-infected patient with a compatible, otherwise unexplained, systemic disease. Mycobacterium simiae was isolated in blood and/or bone marrow cultures from 3 HIV-infected patients during the last 5 y. We describe the first successful treatment in AIDS patients with disseminated M. simiae infection. The patients are alive and well 20 months after instituting a combination of 3 antimycobacterial agents, clarithromycin, ethambutol and ciprofloxacin and intensive antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

Local application of honey for treatment of neonatal postoperative wound infection.

Honey has been described in ancient and modern medicine as being effective in the healing of various infected wounds. In this report we present our experience in nine infants with large, open, infected wounds that failed to heal with conventional treatment. Conventional treatment was defined as having failed if after > or = 14 d of intravenous antibiotic and cleaning the wound with chlorhexidine 0.05% W/V in aqueous solution and fusidic acid ointment the wound was still open, oozing pus, and swab cultures were positive. All infants showed marked clinical improvement after 5 d of treatment with topical application of 5-10 ml of fresh unprocessed honey twice daily. The wounds were closed, clean and sterile in all infants after 21 d of honey application. There were no adverse reactions to the treatment. We conclude that honey is useful in the treatment of post-surgical wounds that are infected and do not respond to conventional systemic and local antibiotic treatment.

Honey↗
PubMed1998

Pseudotumour cerebri complicating varicella in a child.

Pseudotumour cerebri is a clinical syndrome characterized by increased intracranial pressure in the absence of intracranial pathology. The possible association between this condition and infections has already been mention in a few case series. This paper describes a 6-y-old girl with a classical picture of pseudotumour cerebri: which developed 1 week following varicella. To the authors' knowledge, this is the first description suggesting this association. Additional reports are required to support the possible relationship between the two conditions.

Chickenpox↗
PubMed1998

Gunshot wounds in brains of children: prognostic variables in mortality, course, and outcome.

A retrospective study of 51 children presenting with craniocerebral gunshot lesions was carried out to identify predictors of outcome. The patients ranged in age from 2 months to 17 years, with a mean of 14.5 years. The outcome was good in 20 patients, and seven and four were moderately and severely disabled, respectively. Twenty patients died. Statistical analysis showed prognostic significance of the admission Glasgow Coma Score (GCS), computerized tomographic findings of intraventricular hemorrhage and midline shift, and metabolic abnormalities, including hypokalemia and hyperglycemia. These prognostic factors may have implications regarding counseling of families, utilization of resources, and organ transplantation.

Adolescent↗
PubMed1998

Silver-stained nucleolar organizer regions (AgNORs) as a prognostic value in malignant melanoma.

The nucleolar organizer regions (NORs) are chromosomal loops of DNA and proteins involved in ribosomal synthesis. By silver staining, they can be identified as black dots (AgNORs) in the nuclei. Their size and number reflect cell and nuclear activity. Therefore, AgNOR count may correlate with the proliferative activity of tumors. In malignant melanoma, correlation between AgNOR count and the growth phase was found. However, the value of AgNORs in determining prognosis is disputable. Our purpose was to evaluate the role of AgNORs in predicting the biological behavior of melanoma. Paraffin-embedded sections of 30 cases of primary melanoma, 0.4-5 mm thick (mean, 1.6 mm) were stained with silver. Follow-up of all patients was at least 5 years. For each tumor, at least 50 cells were randomly selected for AgNOR count at a final magnification of 500, and the mean of AgNOR content was calculated. Sample parameters corresponded well to the epidemiology and the natural history of melanoma. AgNOR counts (0.78-4.26; mean, 1.42+/-0.72) correlated with tumor thickness (p = 0.01); thus, most superficial tumors had low AgNOR counts, whereas most deep tumors (> or = 1.5 mm) showed high counts. Patients who had tumors with AgNOR counts lower than the median had longer disease-free interval (DFI) than did patients who had tumors with higher counts (p = 0.02). Furthermore, in a multivariate Cox analysis, AgNOR count was independent of tumor thickness in determining DFI (p = 0.05). Therefore, AgNORs may serve as a parameter to predict more accurately the progression of melanomas (mainly thin ones). Larger studies are needed in order to consolidate these preliminary results and to characterize AgNOR value further as a prognostic factor in melanoma.

Adolescent↗
PubMed1998

Effect of cholera toxin on intestinal elimination of ciprofloxacin in rabbits.

The transepithelial intestinal elimination of ciprofloxacin (CPX) was studied in cholera toxin (CT)-challenged and control intestinal loops in the rabbit. CPX concentrations were similar in CT-challenged and control jejunal and ileal loops, while cecal elimination was negligible. The quantities of eliminated CPX per square centimeter of bowel wall were significantly higher in the small intestine CT-challenged loops. The mechanism of elimination of CPX in the small intestine is therefore mainly passive diffusion.

Animals↗
PubMed1997

Levodopa induces apoptosis in cultured neuronal cells--a possible accelerator of nigrostriatal degeneration in Parkinson's disease?

Apoptosis is an active, intrinsic cell suicide program. We recently suggested that it may have a role in the death of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). We now report that levodopa, the current major therapy for PD, is a potent inducer of apoptosis in cultured postmitotic chick sympathetic neurons. Levodopa, in a concentration range of 0.01-0.3 mM, caused the characteristic apoptotic cascade of cell shrinkage, massive membrane blebbing, and nuclear fragmentation, as evident by nuclear flow cytometry and fluorescence microscopy. Levodopa-induced apoptosis was inhibited by antioxidants, indicating that it may be mediated by autooxidation-reactive species. Levodopa treatment for PD may therefore constitute an additional challenge for the defective apoptosis-inhibiting systems in the nigrostriatal neurons. Despite reassuring data from some, but not all, previous studies, these findings suggest that the possible in vivo toxic effects of levodopa on the survival of the remaining nigral neurons should be further explored.

Animals↗
PubMed1997

Induction of mitosis-related genes during dopamine-triggered apoptosis in sympathetic neurons.

It was suggested that neuronal degeneration in Parkinson's Disease (PD) is linked to dopamine (DA) toxicity. Dopamine has been shown to induce programmed cell death in both neuronal and non-neuronal cell types. We examined the molecular changes associated with dopamine-triggered apoptosis in sympathetic neurons using the differential display approach, and isolated 14 different DA responsive genes whose expression is altered during the early stages of the apoptotic process. Nine of these genes are upregulated and five are downregulated in response to DA exposure. Two of the upregulated genes were identified as cyclin B2 and a chicken homologue of chaperonin, a member of the heat shock protein family. Total increase in mRNA expression of both genes after 12 hours of exposure to DA was 40%. These two genes participate in cell cycle control and are specifically involved in determining entry of dividing cells into mitosis. Upregulation of mitosis-related genes in postmitotic sympathetic neurons undergoing apoptosis, may be indicative of an abortive attempt of these neurons to re-enter the cell cycle prior to their death. Possible implications to neuronal degeneration in PD are discussed.

Animals↗
PubMed1997

Modulation of control mechanisms of dopamine-induced apoptosis--a future approach to the treatment of Parkinson's disease?

The cause for the progressive and selective degeneration of the dopaminergic (DA) nigrostriatal neurons in Parkinson's disease (PD) is still unknown. We suggest a novel approach, that links this neuronal degenerative process to inappropriate triggering of apoptosis, an active, controlled program of cellular self destruction, by excess oxidative stress mediated by DA metabolism. In support of this concept, we found that DA, the endogenous neurotransmitter, is capable of initiating apoptosis in cultured, postmitotic chick sympathetic neurons, an observation further extended to other cellular systems (PC-12 cells, cerebellar granular cells, thymocytes, splenocytes). In comparing the relative apoptosis-triggering potency of other mononamine neurotransmitters, DA was found to be the most active, whereas norepinephrine and serotonin had a moderate and a mild effects, respectively. This grading can be correlated with the relative involvement of the relevant neuronal systems (i.e., substantia nigra, locus ceruleus and raphe nuclei) in PD. We therefore hypothesize that neuronal degeneration in PD may be caused, at least in part, by a failure, either inherited or acquired, in cellular control systems of apoptosis, that may normally restrain the lethal potential of these endogenous neuro-transmitters and their potentially-toxic oxidation products. We therefore point at apoptosis-control systems as a critical scene of events, where the fate of nigrostriatal neurons is ultimately determined, and whose modulation may yield attenuation of the neuronal degenerative process. In support of this concept, we found that vector-driven stable expression of the proto-oncogene bcl-2, an inhibitor of apoptosis, can exert powerful cellular protection against DA toxicity in rat pheochromocytoma PC-12 cells. Furthermore, cell extracts from bcl-2-expressing cells were found to markedly inhibit in vitro oxidation of DA and production of DA-melanin. We also found that expression of bcl-2 can inhibit the decrease in intracellular reduced thiol (-SH) groups which we observed following exposure to DA. Research of the bcl-2 system and associated control mechanisms of apoptosis, possibly acting in association with intra-cellular anti-oxidant pathways, may therefore lead to novel therapeutic approaches for neuroprotection in PD.

Animals↗
PubMed1997

Nigrostriatal neuronal death in Parkinson's disease--a passive or an active genetically-controlled process?

The cause for the rather selective degeneration of the nigrostriatal dopaminergic (DA) neurons in Parkinson's disease (PD) is still enigmatic. The major current hypothesis suggests that nigral neuronal death in PD is due to excessive oxidant stress generated by auto- and enzymatic oxidation of DA, formation of neuromelanin and presence of high concentrations of iron. Such cell death is generally regarded as a passive, necrotic process, mainly resulting from membrane lipid peroxidation, leading to its dysfunction and rupture and then to neuronal disintegration. We suggest a novel approach, that views neuronal degeneration in PD as an active process that occurs mainly the nuclear level. Our concept is based on the following observations: (1) Nigral histopathology in PD is characterized by a slow, protracted degeneration of individual neurons. We propose that it may be due to apoptosis [programmed cell-death (PCD), an active, genetically-controlled, intrinsic program of cell "suicide"] rather than to necrotic cell death. (2) DA exerts antitumor effect on melanoma and neuroblastoma cells. (3) Many anticancer drugs, trigger PCD by causing DNA damage. (4) DA has been shown to be genotoxic. (5) We recently first showed that DA, the endogenous neurotransmitter in the nigra, can trigger apoptosis in cultured, postmitotic sympathetic neurons. (6) We have also shown that PC-12 cells, transfected with the bcl-2 gene (a proto-oncogene that inhibits PCD) are relatively resistant to DA-apoptotic effect. Degeneration of nigrostriatal neurons in PD may therefore be linked to dysregulation of the control mechanisms that normally restrain the PCD-triggering-potential of their own neurotransmitter.

Animals↗
PubMed1997

Dopamine-melanin induces apoptosis in PC12 cells; possible implications for the etiology of Parkinson's disease.

The function of neuromelanin (NM), the oxidized dopamine (DA) polymer, within the DA-producing cells in the human and primate substantia nigra (SN), is still an enigma. Some studies show that the vulnerability of nigral neurons in Parkinson's disease is correlated to their toxic NM content, while others suggest that it contributes to cellular protection. We showed recently that DA, the endogenous nigral neurotransmitter, triggers apoptosis, an active program of cellular self-destruction, in neuronal cultures. In the present study, we exposed cells to synthetic dopamine-melanin (DA-M) and analysed the cellular and genetic changes. We found that exposure of PC12 cells to DA-M (0.5 mg/ml for 24 h) caused 50% cell death, as indicated by trypan blue exclusion assay and 3H-thymidine incorporation. Gel electrophoresis DNA analysis of PC12 cells treated with DA-M showed the typical apoptotic DNA ladder, indicating inter-nucleosomal DNA degradation. The DNA fragmentation also was visualized histochemically in situ by DNA end-labeling staining (the TUNEL method). The FeCl2 (0.05 mM) significantly increased DA-M toxicity, while desferrioxamine, an iron chelator, totally abolished the additive toxicity of iron. The contribution of oxidative stress in this model of DA-M-induced cell death was examined using various antioxidants. In contrast to DA, inhibition of DA-M toxicity antioxidants by reduced glutathione (GSH), N-acetyl cysteine, catalase and Zn/Cu superoxide dismutase (SOD) was very limited. In conclusion, we found that DA-M may induce typical apoptotic death in PC12 cells. Our findings support a possible role of NM in the vulnerability of the dopaminergic neural degeneration in Parkinson's disease. The differential protective effect by antioxidants against toxicity of DA and DA-M may have implications for future neuroprotective therapeutic approaches for this common neurological disorder.

Animals↗
PubMed1997

Monoamine-induced apoptotic neuronal cell death.

1. The monoamines dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT) serve as endogenous neurotransmitters in the nervous system. We recently reported that the neurotransmitter DA can trigger apoptosis (programmed cell death; PCD) in cultured, postmitotic chick embryo sympathetic neurons, suggesting a role for apoptosis in degenerative processes such as Parkinson's disease (PD). However, PD is also associated with involvement of other monoaminergic (MA) neuronal systems (noradrenergic and serotoninergic), though to a lesser extent. 2. We therefore tested the apoptosis-triggering potential of NE, E, and 5-HT in comparison to the DA effect, in cultured postmitotic nerve growth factor (NGF)-dependent chick embryo sympathetic neurons and mouse cerebellar granule cells. 3. In both model systems MA induced neuronal attrition characteristic of apoptosis. MA caused marked morphological alterations: severe neuronal soma shrinkage, membrane blebbing, nuclear condensation and fragmentation, and axonal disintegration. Flow-cytometric analysis of propidium iodide-stained cell nuclei revealed characteristic apoptotic nuclear fragmentation. MA-induced apoptosis could be blocked by SH-group containing antioxidants but not by inhibitors of transcription and translation. 4. Comparison between the two model systems revealed that the cerebellar granule neurons were distinctly more sensitive to the neurotoxic potential of the MA than sympathetic neuronal cells. Significant differences in the dose dependencies and time course of the apoptotic effect were observed among the examined MA, graded as DA > NE approximately E > 5-HT. 5. We conclude that the apoptosis triggering potential, probably mediated by oxidative metabolites, is shared by all MA tested, but with differential time course and dose dependencies. A correlation can be drawn between the effects of DA vs NE vs 5-HT and the relative involvement of dopaminergic/noradrenergic/serotoninergic pathways in PD, which may suggest a common multisystem underlying abnormality in neuronal apoptosis-control mechanisms.

Animals↗
PubMed1997

Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2.

1. Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic substrate of Parkinson's disease (PD). It is assumed that the lethal trigger is the accumulation of oxidative reactive species generated during metabolism of the natural neurotransmitter dopamine. 2. We have recently shown that dopamine is capable of inducing programmed cell death (PCD) or apoptosis in cultured postmitotic chick sympathetic neurons and rat PC12 pheochromocytoma cells. 3. The bcl-2 gene encodes a protein which blocks physiological PCD in many mammalian cells. In an attempt to elucidate further the mechanism of dopamine toxicity, we examined the potential protective effect of bcl-2 in PC12 cells which were transfected with the protooncogene. 4. In our experiments, Bcl-2 producing cells showed a marked resistance to dopamine toxicity. The percentage of nuclear condensation and DNA fragmentation visualized by the end-labeling method following dopamine treatment was significantly lower in bcl-2 expressing cells. Bcl-2 did not protect PC12 cells against toxicity induced by exposure to dopamine-melanin. Extracts of PC12 cells containing Bcl-2 inhibited dopamine autooxidation and formation of dopamine-melanin. Furthermore, the presence of Bcl-2 protected cells from thiol imbalance and prevented thiol loss following exposure to dopamine. 5. The protective effects of Bcl-2 against dopamine toxicity may be explained, in part, by its action as an antioxidant and by its interference in the production of toxic agents. The possible protection by Bcl-2 against neuronal degeneration caused by dopamine may play a role in the pathogenesis of PD and may provide a new direction for the development of neuroprotective therapies.

Animals↗