Biomedical subjects

A Levine

Publications and source records attributed to A Levine.

At least 19 recordsLinked to original sources

PubMed2005

Discovery of the short gamma-ray burst GRB 050709.

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Journal Article↗

PubMed2004

Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole.

BACKGROUND: The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. AIM: To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. METHODS: Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. RESULTS: One hundred and seventy-nine patients, mean age 45.8 +/- 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). CONCLUSIONS: Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

The fetal esophagus: anatomical and physiological ultrasonographic characterization using a high-resolution linear transducer.

OBJECTIVE: To study the sonographic anatomy and physiology of the human fetal esophagus during the mid-trimester of pregnancy using a high-resolution linear transducer. METHODS: This was a prospective observational study of the fetal esophagus between 19 and 25 weeks' gestation. The study was performed in 60 consecutive fetuses, after a normal anatomy scan, using a 5-13-MHz matrix array wide-band transducer. During the examination the collapsed esophagus was first visualized, and followed by a 5-min video recording in order to demonstrate luminal patency and peristaltic waves. RESULTS: Complete anatomical visualization of the esophagus was possible in 52 (86.7%) patients and at least partial visualization in 58 (96.7%) patients. Three different patterns of esophageal motility were observed: a simultaneous and short opening of the whole esophagus was found in 35 (58.3%) fetuses; a segmental, peristalsis-like movement from the pharynx, through the mediastinum, and into the stomach was found in 18 (30%) fetuses; and in one fetus reflux-like passage of solid contents from the stomach was observed. The mean time required for demonstration of esophageal patency was 96.1 (range, 10-300) s. CONCLUSIONS: Demonstration of normal anatomy and physiological activity of the fetal esophagus is feasible using appropriate transducers. The most commonly observed pattern of esophageal motility in the mid-trimester of pregnancy is the simultaneous relaxation of the upper and lower esophageal sphincters with concurrent opening of the esophageal lumen from the upper thorax to the stomach. Demonstration of a patent esophagus may be helpful in fetuses with suspected esophageal atresia.

Esophagus↗

PubMed2004

Comparison of invasive and non-invasive tests diagnosis and monitoring of Helicobacter pylori infection in children.

BACKGROUND: There are few reports which the tests used for diagnosing Helicobacter pylori infection and monitoring its eradication in children. STUDY AIMS: Prospective evaluation of invasive (gastric histology, rapid urease test [RUT]) and non-invasive (stool antigen [FemtoLab H. pylori], urea breath test [UBT]) tests in the diagnosis of H. pylori infection and post-treatment eradication in children and adolescents. METHODS: Ninety-two patients (50 male, 42 female) referred for upper gastrointestinal endoscopy were prospectively enrolled. UBT was performed and stool specimens collected for monoclonal enzyme immunoassay for H. pylori antigen (FemtoLab) 1 to 4 days before endoscopy. H. pylori in gastric biopsies was evaluated by RUT and staining with hematoxylin-eosin and giemsa. Eradication therapy was given to children with abdominal pain and H. pylori gastritis. FemtoLab H. pylori and UBT were repeated 6 weeks after the end of triple therapy. RESULTS: Histology identified H. pylori in 49 of 92 (53%) subjects. Concordance between histology and RUT was found in 78 of 92 children. FemtoLab H. pylori was positive in 41 of 78 (52.6%) children with sensitivity, specificity, positive and negative predictive values of 97.5%, 94.7%, 95.1% and 97.3%, respectively. For UBT, these values were 100%, 96.9%, 97.5% and 100%, respectively. Twenty-six of 36 patients who received triple therapy returned for eradication evaluation. Tests for H. pylori antigen in stool were positive in 10 of 26 and for UBT in 11 of 26. CONCLUSION: Stool antigen (FemtoLab) and UBT were equally effective in diagnosing and confirming eradication of H. pylori infection in children.

Antigens, Bacterial↗

PubMed2004

Hepatic haemangiomas: possible association with female sex hormones.

BACKGROUND AND AIMS: The association of hepatic haemangiomas with female sex hormones is not entirely clear. We prospectively evaluated the impact of female sex hormones on the natural history of liver haemangiomas. METHODS: We followed 94 women with 181 haemangiomas diagnosed by ultrasound for a period of1-17 years (mean 7.3 (5.5) years). The location, number, size, and ultrasonographic pattern of the lesions were evaluated. Patients were also evaluated by questionnaire for gynaecological and reproductive history. We compared the change in number and size of haemangiomas in patients who received or did not receive exogenous hormonal treatment. RESULTS: Age at first period was inversely associated with the size of haemangiomas (r = 0.181, p = 0.015) while age at menopause was positively correlated with the number of haemangiomas detected at first ultrasound (r = 0.542, p<0.0001). During follow up, no change in the ultrasonographic pattern or number of haemangiomas was observed. An increase in the size of the lesions was demonstrated in 5/22 (22.7%) hormone therapy exposed patients compared with 7/72 (9.7%) controls. Three variables (ultrasonographic pattern, number of haemangiomas, and hormone therapy) predicted whether or not a given haemangioma would increase in size. A hypoechoic pattern increased the risk of progression while a hyperechoic pattern decreases that risk (p = 0.003). The number of haemangiomas was inversely associated with the likelihood of progression (p = 0.006) and hormone therapy increased the risk of haemangioma enlargement (p = 0.05). CONCLUSIONS: Hepatic haemangiomas seem to be influenced by both endogenous and exogenous female sex hormones although significant enlargement occurs only in a minority of patients. Consequently, routine liver ultrasound follow up in women with hepatic haemangiomas receiving hormone therapy appears appropriate.

Adult↗

PubMed2003

Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

Biopsy↗

PubMed2002

Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols.

BACKGROUND: We conducted a 3-year follow-up study of long-term antibody persistence following vaccination of low-risk preterm infants with recombinant hepatitis B vaccine (HBV). Two three-dose protocols were compared: vaccination beginning within 24 h of birth to initial vaccination delayed until a weight of 2,000 g was reached. SUBJECTS AND METHODS: The study population included 136 children, divided into three groups: children born prematurely (< or = 35 weeks, n = 57), children born at term (> or = 37 weeks, n = 39), both groups receiving the first dose of HBV within 24 h of birth, and children born prematurely (< or = 35 weeks, n = 40), who received the first dose of HBV when a weight of 2,000 g was reached. All infants received the second hepatitis vaccination 1 month after the first, and the third dose 6 months after the first. Hepatitis B surface antibody (AntiHBs) was measured at an age of 3-3.5 years (at least 2.5 years after completion of the three-dose HBV series). An AntiHBs level of > or = 10 IU/l was considered positive. RESULTS: At 3-3.5 years of age, a higher percentage of the premature-delayed vaccination group had a positive AntiHBs level (92.5%) compared to both the premature (54.4%, p < 0.001) and full-term groups (71.8%, p < 0.05) vaccinated soon after birth. The premature-delayed vaccination group also had a significantly higher geometric mean concentration (GMC) (119 vs 14.2 IU/l, p < 0.001 and 119 vs 32.7 IU/l, p < 0.005, respectively). CONCLUSION: Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3-3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

Age Factors↗

PubMed2002

Reversible fulminant lactic acidosis and liver failure in an infant with hepatic cytochrome-c oxidase deficiency.

Cytochrome-c oxidase (COX) is the most common respiratory chain complex involved in liver failure, either as a single enzyme deficiency or as part of multiple enzyme deficiencies. We describe an infant who presented with fulminant lactic acidosis in the neonatal period. The lactic acidosis resolved spontaneously but liver and pancreatic insufficiency ensued. Isolated cytochrome-c oxidase deficiency was found in liver but not in muscle and fibroblasts. mtDNA rearrangements or depletion were ruled out. By the age of one year, liver and pancreatic functions have normalized completely and neurodevelopment is normal.

Acidosis, Lactic↗

PubMed2002

Food allergy is a matter of geography after all: sesame as a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel.

OBJECTIVE: To determine the prevalence, importance, and the order of frequency of IgE-mediated food allergens among infants and young children in Israel. STUDY DESIGN AND PATIENTS: In a cross-sectional study, the prevalence of IgE-mediated food allergy was investigated in 9070 infants and young children (0-2 years) who were followed-up at 23 Family Health Centers (FHCs) in central Israel. Patients with suspected IgE-mediated food allergic reactions, were recruited for further evaluation (detailed questionnaire and skin-prick test (SPT)). RESULTS: We identified 150 out of 9070 (1.7%) patients with suspected IgE-mediated food allergy. Among them, 102/150 (67%) [59 males, 43 females; mean age 10.3 months] completed a detailed questionnaire and underwent SPT. Evaluation revealed 131 positive SPTs in 78/102 (76.5%) patients. Twenty-seven positive SPTs in 18 patients were considered clinically irrelevant based on previous consumption of the relevant foods without clinical symptoms. Thus, there were 104 relevant positive SPTs in 78 patients. The overall prevalence of clinically relevant IgE-mediated food allergic reactions among these patients is estimated to be 1.2% (104/9070). The most common food allergens were egg, cow's milk, and sesame. Anaphylaxis was the presenting symptom in 14/78 (18%) including six sesame-induced cases. A history of other atopic diseases was reported in 27 (35%) patients. In addition, 22 (28%) had a history of atopy in first-degree family members. CONCLUSIONS: We found sesame to be a major cause of IgE-mediated food allergy in Israel. In fact, it is second only to cow's milk as a cause of anaphylaxis. We recommend that testing for food allergens be tailored to each community based on local experience and should include sesame in appropriate populations.

Child Welfare↗

PubMed2001

Determinants of HIV-1 shedding in the genital tract of women.

BACKGROUND: Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission. However, direct contact with HIV-1 present locally in the genital tract might be necessary for transmission. We aimed to assess the relation between HIV-1 shedding (RNA or culturable virus) in female genital secretions and other factors that might affect HIV-1 shedding. METHODS: This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-infected women. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assessments, cultured HIV-1, and measured RNA in peripheral blood mononuclear cells (PBMC) and genital secretions. We compared the results with univariate and multivariate analyses. Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding. FINDINGS: HIV-1 RNA was present in genital secretions of 57% (152/268) of women whereas infectious virus was detected only in 6% (17/271). Genital tract HIV-1 shedding was found in 80% (130/163) of women with detectable plasma RNA and 78% (116/148) of women with positive PBMC cultures. 33% (27/83) of women with less than 500 copies/mL plasma RNA and 39% (35/90) of those with negative PBMC cultures also had genital tract shedding. INTERPRETATION: Plasma RNA concentration, both qualitatively and quantitatively, was the most important factor in predicting genital HIV-1 shedding, even among women receiving potent antiretroviral therapy. However, HIV-1 shedding did occur in women with less than 500 copies/mL plasma HIV-1 RNA. This finding suggests that a separate reservoir of HIV-1 replication may exist in some women.

Adult↗

PubMed2001

A computational scan for U12-dependent introns in the human genome sequence.

U12-dependent introns are found in small numbers in most eukaryotic genomes, but their scarcity makes accurate characterisation of their properties challenging. A computational search for U12-dependent introns was performed using the draft version of the human genome sequence. Human expressed sequences confirmed 404 U12-dependent introns within the human genome, a 6-fold increase over the total number of non-redundant U12-dependent introns previously identified in all genomes. Although most of these introns had AT-AC or GT-AG terminal dinucleotides, small numbers of introns with a surprising diversity of termini were found, suggesting that many of the non-canonical introns found in the human genome may be variants of U12-dependent introns and, thus, spliced by the minor spliceosome. Comparisons with U2-dependent introns revealed that the U12-dependent intron set lacks the 'short intron' peak characteristic of U2-dependent introns. Analysis of this U12-dependent intron set confirmed reports of a biased distribution of U12-dependent introns in the genome and allowed the identification of several alternative splicing events as well as a surprising number of apparent splicing errors. This new larger reference set of U12-dependent introns will serve as a resource for future studies of both the properties and evolution of the U12 spliceosome.

Alternative Splicing↗

PubMed2001

Vesicle-associated membrane protein of Arabidopsis suppresses Bax-induced apoptosis in yeast downstream of oxidative burst.

Programmed cell death (PCD) in many systems is controlled by relative amounts of the apoptosis-regulating proteins Bax and Bcl-2 through homo- or heterodimerization. Here we show that Bax-induced PCD of yeast was suppressed by transformation with a vesicle-associated membrane protein from Arabidopsis (AtVAMP), which was isolated by screening a cDNA expression library against sugar-induced cell death in yeast. AtVAMP expression blocked Bax-induced PCD downstream of oxidative burst. AtVAMP also prevented H(2)O(2)-induced apoptosis in yeast and in Arabidopsis cells. Reduced oxidation of lipids and plasma membrane proteins was detected in the AtVAMP-transformed yeast, suggesting improved membrane repair. Inhibition of intracellular vesicle trafficking by brefeldin A induced apoptosis from a sublethal concentration of H(2)O(2). No protection occurred by overexpression of the yeast homolog SCN2. However, efficient suppression of yeast PCD occurred by expression of a chimeric gene, composed of the conserved domains from yeast, fused to the variable N-terminal domain from Arabidopsis, resulting in exchange of the proline-rich N-terminal domain of SCN2 with a proline-poor Arabidopsis sequence. Our results suggest that intracellular vesicle traffic can regulate execution of apoptosis by affecting the rate of membrane recycling and that the proline-rich N-terminal domain of VAMP inhibited this process.

Apoptosis↗

PubMed2001

Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.

PURPOSE: This study investigated the efficacy, toxicity, and pharmacokinetic interactions resulting from simultaneous combination chemotherapy and highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on viral load, CD4 counts, and opportunistic infections were examined with the use of combination chemotherapy combined with HAART. PATIENTS AND METHODS: Sixty-five patients with previously untreated and measurable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 patients entered onto the study received reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered onto the study received full doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and indinavir. RESULTS: The complete response rates were 30% and 48% among patients who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%), constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectively. Doxorubicin clearance and indinavir concentration curves were similar among patients on this study and historical controls, whereas cyclophosphamide clearance was 1.5-fold reduced as compared with control values. Human immunodeficiency virus (HIV) load declined from a median baseline value of 29,000 copies/mL to a median minimum value on therapy of 500 copies/mL. CONCLUSION: Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.

Adult↗

PubMed2001

Induction of cell death in arabidopsis by superoxide in combination with salicylic acid or with protein synthesis inhibitors.

Induction of programmed cell death (PCD) by oxidative stress is a widespread phenomenon in all living organisms. The degree of cell death depends on the concentration of oxidants and on environmental and physiological conditions. In plants, generation of reactive oxygen intermediates (ROI) occurs during many biotic and abiotic stresses. Recently, a number of spontaneous cell death mutants have been isolated in Arabidopsis. In one of the mutants (lsd1) induction of PCD has been attributed to superoxide (O(2)(*)(-)). Here we show that while in wild type plants generation of superoxide is symptomless, combination of O(2)(*)(-) with salicylic acid or with inhibitors of protein synthesis induced PCD. Cell death induced by these treatments was suppressed by protease inhibitors, indicating an active response. PCD induced by both treatments was preceded by nuclear condensation, which is a hallmark of apoptosis in plants and animals. These results may explain increased sensitivity to oxidative stress under certain physiological conditions, associated with high levels of salicylic acid or decrease in protein synthesis.

Apoptosis↗

PubMed2001

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

AIDS-Related Opportunistic Infections↗

PubMed2001

Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein.

The aryl hydrocarbon receptor (AhR) belongs to the basic helix-loop-helix/periodicity/AhR nuclear translocator/simple-minded (Per-Arnt-Sim) family of transcription factors that regulate critical functions during development and tissue homeostasis. Within this family, the AhR is the only member conditionally activated in response to ligand binding, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We recently demonstrated that the AhR interacts with the retinoblastoma protein (pRb). This report presents evidence that a LXCXE motif in the AhR protein confers pRb binding, which is necessary for maximal TCDD induced G(1) arrest in rat 5L hepatoma cells. The data support a mechanism whereby pRb seems to regulate G(1) cell cycle progression distinct from the direct repression of E2F-mediated transcription. Furthermore, the results indicate that the AhR-pRb interaction regulates TCDD induction of CYP1A1, suggesting that pRb may be a general AhR coactivator.

Amino Acid Motifs↗

PubMed2001

Benign intracranial hypertension associated with budesonide treatment in children with Crohn's disease.

Oral budesonide in adult studies is a potent corticosteroid with decreased systemic bioavailability and an improved adverse effect profile in comparison with prednisone. It has recently been introduced for the treatment of inflammatory bowel disease in Europe, Canada, and Israel. Benign intracranial hypertension has rarely been associated with corticosteroid therapy but has not been reported in association with budesonide therapy. Three adolescents with Crohn's disease and poor nutritional status developed benign intracranial hypertension while receiving oral budesonide. All three patients had previously received multiple courses of prednisone during the course of their disease, without developing intracranial hypertension. Benign intracranial hypertension resolved after medication withdrawal and did not recur with subsequent use of prednisone. Evaluation for benign intracranial hypertension should be considered in patients with inflammatory bowel disease who develop headache while receiving oral budesonide. This side effect may be associated with poor nutritional status.

Adolescent↗

PubMed2001

Carnitine-deficient myopathy as a presentation of tyrosinemia type I.

Carnitine deficiency secondary to renal Fanconi's tubulopathy has been described in only a few inborn errors of metabolism: cystinosis, galactosemia, and Fanconi-Bieckel syndrome. We report a 27-month-old infant who presented with a sudden change in gait owing to proximal muscle weakness. The laboratory evaluation showed carnitine deficiency associated with Fanconi's tubulopathy. Eventually, tyrosinemia type I was diagnosed. Carnitine deficiency can contribute to the clinical picture of hepatorenal tyrosinemia and should therefore be evaluated and treated.

Carnitine↗