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Biomedical subjects

A Regev

Publications and source records attributed to A Regev.

At least 19 recordsLinked to original sources
PubMed2006

The impact of nonalcoholic fatty liver disease and the metabolic syndrome on progression of fibrosis in patients with recurrent HCV after liver transplantation.

Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have been shown to play a role in disease progression and response to therapy in patients with chronic hepatitis C virus (HCV) infection. The primary objective of this study was to evaluate the impact of coexisting NAFLD and MS on the progression of fibrosis in patients with recurrent HCV treated with interferon (IFN)/ribavirin after orthotopic liver transplantation (OLT). From 1998 to 2004, a total of 418 patients underwent OLT in our center for HCV-related cirrhosis. Thirty-five patients with recurrent HCV on IFN/ribavirin treatment, who had at least 2 posttransplant liver biopsies at least 6 months apart, were included in the study. Patients who had MS at the time of their first posttransplant biopsy were identified. The first and last posttransplant biopsies were assessed for the presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The fibrosis progression rate (FPR) was calculated and expressed in fibrosis units per month (FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first posttransplant biopsy. The mean FPR was 0.05+/-0.16 FU/mo in the presence of NAFLD compared to 0.07+/-0.10 FU/mo in its absence (P=.68) and 0.03+/-0.06 FU/mo in the presence of MS versus 0.10+/-0.15 FU/mo in its absence (P=.06). When FPR values were divided into two categories of <0.16 FU/mo or >or=0.16 FU/mo (below/above the 25% upper quartile) or <0.08 FU/mo or >or=0.08 FU/mo (below/above the 50% upper quartile), there was no correlation between FPR categories and the presence of NAFLD with or without MS, only MS, or the absence of both in the first liver transplant biopsy (P=.13). Coexisting NAFLD or MS had no significant effect on the progression of fibrosis after OLT in patients with treated hepatitis C after OLT.

Adult↗
PubMed2006

Very late recurrence of hepatocellular carcinoma after liver transplantation: case report and literature review.

Hepatocellular carcinoma (HCC) recurs in 10% to 60% of the patients after liver transplantation (OLT) and is associated with increased mortality. The average time to recurrence ranges from 1 to 2 years following OLT, and the median survival from the time of diagnosis is about 1 year. We report a case of a 69-year-old man who underwent OLT for hepatitis C virus-related cirrhosis with HCC, and was diagnosed with recurrent HCC 6.5 years after OLT. Biopsies from the initial and recurrent tumors showed a well-differentiated HCC with foci of clear cell pattern. The patient was still alive and asymptomatic 32 months after the diagnosis despite extensive tumor burden. He expired 9 years, 9 months after OLT and 3 years, 2 months after the detection of recurrence. In conclusion, HCC may recur more than 6 years after OLT and may exhibit an indolent course. This case illustrates the highly variable rate of tumor growth and progression post-OLT. The impact of this information on the need for long-term surveillance for recurrent HCC post-OLT remains to be determined.

Aged↗
PubMed2005

The impact of Campath 1H induction in adult liver allotransplantation.

BACKGROUND: We report our experience with Campath 1H in adult liver allotransplantation. METHODS: Between December 2001 and February 2004, 77 patients underwent liver transplantation using Campath 1H induction and low-dose maintenance tacrolimus immunosuppression. The control group consisted of 50 patients with similar baseline characteristics and the same eligibility criteria, transplanted under our standard Tacrolimus/steroids regimen. Hepatitis C patients were excluded from the study. RESULTS: Patient and graft survival were similar for both groups. The incidence of rejection was significantly lower in the Campath vs the control group (51% vs 65% at 12 months, P = .009). Tacrolimus trough levels and conversion from Tacrolimus or the addition of other immunosuppressive drugs due to nephrotoxicity were also significantly lower in the Campath 1H group. CONCLUSION: Campath 1H induction with low-dose Tacrolimus maintenance immunosuppression is an effective regimen in reducing acute rejection in adult liver transplantation, while maintaining lower tacrolimus levels and less nephrotoxicity than our conventional immunosuppressive regimen.

Adult↗
PubMed2005

Liver enzymes elevation after HAART in HIV-HCV co-infection.

Hepatitis C virus (HCV) co-infection is common among human immunodeficiency virus (HIV) patients. The incidence and risk factors associated with hepatotoxicity in this population after high active antiretroviral therapy (HAART) is initiated are still not well-understood. We argued to evaluate the incidence and risk factors associated with liver enzyme elevation (LEE) and their clinical significance. A retrospective chart review of patients who started HAART and had follow up at our centre for at least 1 year was undertaken. The frequency and severity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation after treatment initiation were investigated and searched for clinical manifestations. Between January 1996 and March 2002, 85 HIV-HCV co-infected patients began HAART and continued follow up for at least 1 year. The incidence of severe toxicity [grades 3 + 4 LEE: >5 and >10 times the upper limit of normal (ULN) of ALT or AST] was calculated at 4% per person-years. There were no clinical manifestations of liver toxicity, and patients continued their treatment with a trend towards a decrease of their enzymes. No statistical differences in opportunistic infections or mortality were evident. The variables associated with severe hepatotoxicity were a higher baseline AST, higher international normalized ratio (INR) and lower albumin. A baseline AST < 2.1 ULN had a negative predictive value of 92% of leading to severe hepatotoxicity. In HIV-HCV co-infected patients therefore, the group at a higher risk of developing higher transaminase elevations is the one with a higher baseline AST, higher INR and lower albumin.

Adult↗
PubMed2004

Inferring quantitative models of regulatory networks from expression data.

MOTIVATION: Genetic networks regulate key processes in living cells. Various methods have been suggested to reconstruct network architecture from gene expression data. However, most approaches are based on qualitative models that provide only rough approximations of the underlying events, and lack the quantitative aspects that are critical for understanding the proper function of biomolecular systems. RESULTS: We present fine-grained dynamical models of gene transcription and develop methods for reconstructing them from gene expression data within the framework of a generative probabilistic model. Unlike previous works, we employ quantitative transcription rates, and simultaneously estimate both the kinetic parameters that govern these rates, and the activity levels of unobserved regulators that control them. We apply our approach to expression datasets from yeast and show that we can learn the unknown regulator activity profiles, as well as the binding affinity parameters. We also introduce a novel structure learning algorithm, and demonstrate its power to accurately reconstruct the regulatory network from those datasets.

Binding Sites↗
PubMed2001

Liver disease in the elderly.

Despite several morphologic and functional changes that have been described in the aging liver, most relevant studies fail to identify a significant age-related deficit in liver function in humans. One of the important age-related changes is a decrease in regenerative capacity, which may partly explain the impaired recovery after severe viral and toxic injury in the elderly. Nevertheless, livers from older subjects are used successfully for transplantation. Substantial morbidity and mortality in the elderly is attributable to liver diseases, and the number of patients older than 65 years of age with chronic liver disease is increasing rapidly. Although there are no liver diseases specific to advanced age, the presentation, clinical course and management of liver diseases in the elderly may differ in important respects from those of younger individuals.

Aged↗
PubMed2001

Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center.

BACKGROUND: Cystic lesions of the liver consist of a heterogeneous group of disorders and may present a diagnostic and therapeutic challenge. Large hepatic cysts tend to be symptomatic and can cause complications more often than smaller ones. STUDY DESIGN: We performed a retrospective review of adults diagnosed with large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15 years. Polycystic disease and abscesses were not included. RESULTS: Seventy-eight patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary cystadenocarcinoma. In four patients, the precise diagnosis could not be ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection (one patient) were rare manifestations. Percutaneous aspiration of 28 simple cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months (mean 4(1/2) months). Forty-eight patients were treated surgically by wide unroofing or resection (laparoscopically in 18), which resulted in low recurrence rates (11% for laparoscopy and 13% for open unroofing). Four of the eight patients with echinococcal cysts were symptomatic. All were treated by open resection after irrigation of the cavity with hypertonic saline. There was no recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe (left:right, 8:0). Seven were multiloculated. All were treated by open resection, with no recurrence, and none had malignant changes. Cystadenocarcinoma was diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy. CONCLUSIONS: Large symptomatic simple cysts invariably recur after percutaneous aspiration. Laparoscopic unroofing can be successfully undertaken, with a low recurrence rate. Open resection after irrigation with hypertonic saline is a safe and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have predilection for women and for the left hepatic lobe. Malignant transformation is an uncommon but real risk. Open resection is a safe and effective treatment for hepatobiliary cystadenoma, and is associated with a low recurrence rate.

Adenoma, Bile Duct↗
PubMed2001

Transient hepatopulmonary syndrome in a patient with acute hepatitis A.

The hepatopulmonary syndrome is defined as the triad of liver disease, hypoxaemia and intrapulmonary vascular dilatation. This syndrome has been described in patients with liver cirrhosis, noncirrhotic portal hypertension, and fulminant hepatic failure, however, there are no previous descriptions of hepatopulmonary syndrome in patients with acute nonfulminant viral hepatitis. We report a 47-year-old, previously healthy man that presented with acute hepatitis A, and developed progressive dyspnoea, platypnoea and orthodeoxia with no evidence of parenchymal or thromboembolic lung disease. PaO2 on room air was 58 mmHg, O2 saturation was 88% and alveolar-arterial O2 gradient was 62%. During his hospitalization serum albumin level decreased to 3.1 g/dl and prothrombin time was prolonged to 16.8 s, however, he remained alert with no signs of hepatic encephalopathy. Contrast echocardiography revealed left heart chamber opacification 3-4 cardiac cycles after the opacification of the right heart chamber, consistent with hepatopulmonary syndrome. During the following days there was a gradual improvement in the patient's condition, with resolution of his dyspnoea and gradual increase of PaO2. Repeat contrast echocardiography and PaO2 determinations, 3 weeks later, were normal. On long-term follow-up the patient remained asymptomatic with normal liver function tests and normal O2 saturation. This report indicates that hepatopulmonary syndrome may be a transient manifestation of acute hepatitis A in the absence of fulminant liver failure.

Acute Disease↗
PubMed2001

Inferring subnetworks from perturbed expression profiles.

Genome-wide expression profiles of genetic mutants provide a wide variety of measurements of cellular responses to perturbations. Typical analysis of such data identifies genes affected by perturbation and uses clustering to group genes of similar function. In this paper we discover a finer structure of interactions between genes, such as causality, mediation, activation, and inhibition by using a Bayesian network framework. We extend this framework to correctly handle perturbations, and to identify significant subnetworks of interacting genes. We apply this method to expression data of S. cerevisiae mutants and uncover a variety of structured metabolic, signaling and regulatory pathways.

Bayes Theorem↗
PubMed2001

Representation and simulation of biochemical processes using the pi-calculus process algebra.

Despite the rapidly accumulating body of knowledge about protein networks, there is currently no convenient way of sharing and manipulation of such information. We suggest that a formal computer language for describing the biomolecular processes underlying protein networks is essential for rapid advancement in this field. We propose to model biomolecular processes by using the pi-Calculus, a process algebra, originally developed for describing computer processes. Our model for biochemical processes is mathematically well-defined, while remaining biologically faithful and transparent. It is amenable to computer simulation, analysis and formal verification. We have developed a computer simulation system, the PiFCP, for execution and analysis of pi-calculus programs. The system allows us to trace, debug and monitor the behavior of biochemical networks under various manipulations. We present a pi-calculus model for the RTK-MAPK signal transduction pathway, formally represent detailed molecular and biochemical information, and study it by various PiFCP simulations.

Biochemistry↗
PubMed2001

Drug therapy for hepatitis B.

Until recently, IFN has been the only available therapy for chronic HBV infection; however, many new and exciting therapeutic strategies have emerged during the last decade. Recent advances in our understanding of the replicative mechanism of HBV and the development of potent nucleoside analogues have opened a new era in the treatment of HBV. Lamivudine has been introduced as an alternative to IFN, showing at least similar efficacy, but with a wider spectrum of indications and without the adverse effects. Therapeutic vaccination and molecular or gene therapy are being investigated as potential approaches, and aggressive combination therapy is emerging as a promising strategy. Based on the experience with HIV, the future of drug therapy against HBV likely includes combination therapy with 1 or more nucleoside/nucleotide analogues and an immune-modulating agent, such as IFN or a therapeutic vaccine. This combination may act synergistically against HBV and delay or prevent the development of drug-resistant mutants.

Adenine↗
PubMed2001

Abolition of pentagastrin-stimulated alkaline tide using the carbonic anhydrase inhibitor acetazolamide.

BACKGROUND: Alkaline tide is the transient increase in blood and urine pH following stimulation of gastric acid secretion. It is attributed to HCO3- release from parietal cells in parallel with H+ secretion. The enzyme carbonic anhydrase is thought to be responsible for HCO3- production from CO2 and OH- in the parietal cell. OBJECTIVE: To examine the effect of pretreatment with the carbonic anhydrase inhibitor, acetazolamide, on the alkaline tide phenomenon. METHODS: Ten patients with dyspepsia and demonstrable alkaline tide were tested on three separate days. The pH and base excess were determined in arterialized venous blood before and 45 minutes after an intramuscular injection of pentagastrin. The pH of the urine was measured before and 120 min after pentagastrin injection. Measurements were performed after pentagastrin alone on day 1, following pretreatment with acetazolamide 60 min before pentagastrin on day 2, and after the administration of acetazolamide alone on day 3. RESULTS: Following the administration of pentagastrin alone, the blood base excess increased by 1.61 +/- 0.2 mEq/L (mean +/- standard deviation) and the calculated alkaline tide at 45 min was 33.99 +/- 4.49 mEq. On day 2 with prior administration of acetazolamide, base excess decreased by 0.21 +/- 0.39 mEq/L, and the calculated alkaline tide was -3.28 +/- 7.57 mEq, which was significantly lower than on day 1 (P = 0.0001). On day 3, following acetazolamide alone, the base excess values decreased by 0.53 +/- 0.2 mEq/L and the alkaline tide was -10.05 +/- 3.33 mEq; there was no significant difference compared with day 2 (P = 0.44). CONCLUSION: Pretreatment with acetazolamide abolished the alkaline tide induced by pentagastrin. This finding supports the view that carbonic anhydrase has a major role in the alkaline tide phenomenon.

Acetazolamide↗
PubMed2000

Viral hepatitis A, B, and C.

Mankind probably has known viral hepatitis for many centuries; however, the major and most dramatic developments in our knowledge of these diseases have taken place during the second half of the 20th century. During this relatively short period of time, the infectious nature of hepatitis A, B, and C has been proven, leading to their identification and description. The advent of serologic markers has provided the means for establishing the diagnosis. Epidemiologic studies have provided important information that led to exciting achievements in detection and prevention of transmission. Molecular biology studies and cell culture techniques have established our knowledge of the viral genomes, and led to the development of specific vaccines for hepatitis A and B. Anti-viral therapy has been developed and aggressive combination therapy has emerged as a promising strategy for chronic hepatitis B and C. This article reviews some of the main fields of progress and achievement related to viral hepatitis A, B, and C in the 20th century.

Communicable Disease Control↗
PubMed1999

Seroprevalence of Helicobacter pylori and length of stay in a nursing home.

BACKGROUND: Helicobacter pylori infection appears to be contracted mainly in childhood, and it is associated with disadvantaged socioeconomic conditions, overcrowding, and living in institutions. In this study we determined the seroprevalence of H. pylori among elderly patients (age > or = 70 years) admitted to a major medical center in Israel, and studied the relationship between seroprevalence of H. pylori and the duration of stay in a nursing home prior to the admission. PATIENTS AND METHODS: Whole blood from 182 consecutive patients hospitalized at the Rabin Medical Center was tested for the presence of anti-H. pylori IgG using Helisal Rapid Blood Test kit (Cortecs Diagnostics). Multivariate logistic regression analysis was used to study the relation between H. pylori seropositivity and possible predictive factors such as age, gender and duration of stay in a nursing home. RESULTS: Of the 182 patients included in the study, 80 (44%) were living in nursing homes (NH) and 102 (56%) were living in their own homes (H) prior to admission. Subjects that stayed in nursing homes for more than 15 months were significantly more likely to be seropositive than subjects with a shorter duration of stay (84% and 63% respectively, p = 0.03). Using a multivariate logistic regression analysis on both the NH group and the whole group, seropositivity was found to be significantly associated with duration of stay in a nursing home (p = 0.03 and p = 0.01 respectively). Seropositivity was not associated with age in either group. CONCLUSIONS: Living in a nursing home is associated with increased risk for H. pylori infection in the elderly. There is a strong correlation between the duration of stay in a nursing home and the prevalence of H. pylori infection.

Age Factors↗
PubMed1999

Viral hepatitis.

Viral hepatitis is still one of the most common causes of acute and chronic liver disease worldwide. Major advances have been made in our knowledge of these diseases, many during the past year. Molecular biology and clinical studies have improved our understanding of the mechanisms of antiviral drugs, as well as viral resistance to therapy. The risks of hepatitis A in patients with chronic liver disease have been confirmed, and the efficacy of hepatitis A vaccines in these patients has been proven. Aggressive combination therapy has emerged as a promising strategy for chronic hepatitis B and C, and techniques for immune prophylaxis for hepatitis B are being improved. Liver transplantation has become routine for end-stage hepatitis B virus liver disease, and new strategies to prevent and treat recurrence are being explored. This review discusses the recent advances in our knowledge of hepatitis viruses A through G, focusing on the literature of the past year.

Journal Article↗
PubMed1999

Hepatitis C and alcohol.

BACKGROUND: Alcohol abuse and hepatitis C virus (HCV) infection frequently coexist in patients with chronic liver disease. It is widely believed that alcohol and HCV act synergistically in these patients to promote the development and progression of liver damage. METHODS: A review of the relevant medical literature, identified by computer assisted literature search, was conducted. RESULTS: It has been established that alcohol consumption is associated with the accelerated progression of liver injury, higher frequency of cirrhosis, and higher incidence of hepatocellular carcinoma. Alcohol abuse is also associated with decreased response to interferon treatment, and there are reports to suggest that patients with HCV cirrhosis, who abuse alcohol, have higher mortality than those who do not. Abstinence may reverse some of these deleterious effects of alcohol, and may even improve the ultimate response to treatment. The mechanism for the synergistic effect of alcohol and HCV is not fully understood, but has been attributed to alcohol's effect on viral replication, or to its effect on the immune system, hepatic iron content, or hepatic regeneration. CONCLUSIONS: Alcohol has a deleterious effect on HCV associated liver disease. It is recommended that patients with HCV infection abstain from alcohol consumption.

Alcoholism↗
PubMed1998

Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability.

Small polydisperse circular DNA (spcDNA) is a heterogeneous population of extrachromosomal circular molecules present in a large variety of eukaryotic cells. Elevated amounts of total spcDNA are related to endogenous and induced genomic instability in rodent and human cells. We suggested spcDNA as a novel marker for genomic instability, and speculated that spcDNA might serve as a mutator. In this study, we examine the presence of telomeric sequences on spcDNA. We report for the first time the appearance of telomeric repeats in spcDNA molecules (tel-spcDNA) in rodent and human cells. Restriction enzyme analysis indicates that tel-spcDNA molecules harbor mostly, if not exclusively, telomeric repeats. In rodent cells, tel-spcDNA levels are higher in transformed than in normal cells and are enhanced by treatment with carcinogen. Tel-spcDNA is also detected in some human tumors and cell lines, but not in others. We suggest, that its levels in human cells may be primarily related to the amount of the chromosomal telomeric sequences. Tel-spcDNA may serve as a unique mutator, through specific mechanisms related to the telomeric repeats, which distinguish it from the total heterogeneous spcDNA population. It may affect telomere dynamics and genomic instability by clastogenic events, alterations of telomere size and sequestration of telomeric proteins.

Animals↗