PubMed Health⌕ Search

Biomedical subjects

A I Sharara

Publications and source records attributed to A I Sharara.

At least 19 recordsLinked to original sources
PubMed2003

Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study.

BACKGROUND: The measurement of the hepatic venous pressure gradient may identify a suboptimal response to beta-blockers in patients with varices at risk for bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide primary prophylaxis has not been examined. METHODS: We used decision analysis to evaluate two hepatic venous pressure gradient measurement strategies relative to standard beta-blocker therapy in a hypothetical cohort of patients with high-risk varices: (i) hepatic venous pressure gradient measurement 4 weeks after the initiation of beta-blocker therapy; and (ii) hepatic venous pressure gradient measurement prior to and 4 weeks after the initiation of beta-blocker therapy. The total expected costs, variceal bleeding episodes and deaths were calculated over a 1-year time horizon. RESULTS: Beta-blocker therapy was associated with total costs of $1464, seven variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. One hepatic venous pressure gradient measurement was associated with total costs of $5015, four variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. Two hepatic venous pressure gradient measurements were associated with total costs of $8657, four episodes of variceal bleeding, one variceal bleeding episode-related death and 15 deaths. Compared with beta-blocker therapy alone, the incremental costs per variceal bleeding episode prevented and death averted were, respectively, $108 185 and $355 100 (one hepatic venous pressure gradient measurement) and $202 796 and $719 300 (two hepatic venous pressure gradient measurements). The results were sensitive to the time horizon of the analysis, the probability of bleeding whilst on beta-blockers and the cost of hepatic venous pressure gradient measurement. CONCLUSION: Hepatic venous pressure gradient measurement to guide primary prophylaxis is an expensive strategy for reducing variceal bleeding or death, especially in patients with limited life expectancy, such as those with advanced, decompensated cirrhosis.

Adrenergic beta-Antagonists↗
PubMed2001

Ultrashort regimen of lansoprazole-amoxicillin-azithromycin for eradicating Helicobacter pylori.

The efficacy and safety of two ultrashort azithromycin-containing regimens for Helicobacter pylori infection were studied. Patients positive for H. pylori infection were assigned to receive either a three-day drug regimen (group A) or a five-day regimen (group B). In both groups, patients received lansoprazole 30 mg p.o. twice daily on day 1 and, on days 2 and 3, lansoprazole 30 mg p.o. twice daily, amoxicillin 1 g (of anhydrous amoxicillin) p.o. twice daily, and azithromycin 500 mg (of anhydrous azithromycin) p.o. twice daily. Group B patients received lansoprazole 30 mg p.o. twice daily and amoxicillin 1 g p.o. twice daily for two additional days. Gastric biopsy specimens were subjected to culture and susceptibility testing. A minimum of four weeks after the completion of therapy, the patients underwent a 14C-urea breath test to determine whether H. pylori had been eradicated. A total of 28 patients were enrolled (15 in group A and 13 in group B). Treatment was well tolerated. H. pylori was eradicated in 4 (36%) of 11 patients in group A and 2 (22%) of 9 group B patients (26.6% and 15.4%, respectively, in intention-to-treat analysis). None of the isolates of H. pylori showed resistance to amoxicillin or clarithromycin. Regimens consisting of lansoprazole plus two or four days of azithromycin and amoxicillin therapy eradicated H. pylori in 36% and 22% of patients, respectively.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Effect of aggressive therapy on laryngeal symptoms and voice characteristics in patients with gastroesophageal reflux.

Gastroesophageal reflux (GER) is associated with a variety of laryngopharyngeal signs and symptoms. Injury of the laryngopharynx as a result of GER can be refractory to conventional antireflux therapy. This prospective study was undertaken to evaluate the prevalence of laryngopharyngeal signs and symptoms in patients with documented GER and to assess the response to a high-dose combination antireflux therapy consisting of cisapride and pantoprazole. Twenty-two patients with symptoms of GER were enrolled. After baseline evaluation using a history questionnaire for symptoms, laryngeal endoscopy and vocal acoustic analysis, patients were started on treatment consisting of pantoprazole 40 mg b.d. and cisapride 20 mg twice daily. Repeat history and otolaryngologic evaluation was performed at 4 weeks. Laryngopharyngeal symptoms were frequent in most patients, with throat clearing and globus being the most prevalent symptoms followed by vocal fatigue and excess mucus production. Almost 90% of the patients had abnormal endoscopic laryngeal findings but the acoustic parameters did not show any abnormal results except for mild elevation in the shimmer. After treatment, all symptoms and endoscopic abnormalities improved significantly except for intermittent dysphonia and laryngeal mucosal redness. Acoustic abnormalities did not change significantly following therapy. Laryngeal symptoms and voice abnormalities are highly prevalent in patients with GER. Combination antireflux therapy with a proton pump inhibitor and a prokinetic agent results in rapid symptomatic and endoscopic response in the majority of patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Acute granulomatous schistosomal cholecystitis.

Schistosomal cholecystitis is a rare entity with less than 10 cases described in the medical literature [1-3]. It is unclear whether schistosomal eggs deposited in the wall of the gallbladder trigger a clinically manifest acute cholecystitis, since most of the cases described were also found to have concomitant gallstones. Herein, we report a patient who developed acute schistosomal granulomatous acalculous cholecystitis. The clinical presentation, chronology of events and pathological findings strongly support the association between cholecystitis and schistosomal infection.

Acute Disease↗
PubMed1999

Liver disease in pregnancy.

Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy.

Cholelithiasis↗
PubMed1997

Interferon (IFN)-alpha activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: possible relationship of induced NOS2 to the anti-hepatitis C effects of IFN-alpha in vivo.

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) gamma and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-alpha serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-alpha caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-alpha also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-alpha therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-alpha treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-alpha-treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-alpha-enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-alpha treatment of cells in vitro or administration of IFN-alpha to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-alpha in hepatitis C infection.

Adult↗
PubMed1997

Hepatitis C in pregnancy.

OBJECTIVE: To review the epidemiology and clinical course of hepatitis C virus (HCV) infection, to examine current data on the vertical transmission of HCV to neonates, and to develop recommendations for intrapartum and postpartum follow-up of neonates born to HCV-infected mothers. DATA SOURCES: The English-language medical literature from 1988 to 1996 was reviewed through MEDLINE. METHODS OF STUDY SELECTION: Case series evaluating vertical transmission of HCV infection in neonates, determined by HCV RNA testing, after delivery and breast-feeding were reviewed and summarized. TABULATION, INTEGRATION, AND RESULTS: Vertical transmission of HCV infection was examined with respect to maternal human immunodeficiency virus (HIV) status (as heterosexual transmission of HCV is enhanced in HIV-positive patients) and chronicity of HCV infection. Vertical transmission of HCV from HIV-negative mothers with chronic hepatitis C ranged from 0 to 18%. The risk of HCV vertical transmission from HIV-negative mothers with acute hepatitis C may be higher than that from mothers with chronic HCV infection. Vertical transmission of HCV was proportional to maternal HCV RNA levels; no transmission was noted in women without HCV RNA, whereas the greatest transmission was noted in women with HCV RNA greater than 1 million copies/mL. Vertical transmission of HCV from HIV-positive mothers with chronic hepatitis C ranged from 6 to 36%. In colostrum, HCV RNA was found to be present in low titers. No studies have documented transmission of HCV infection to infants via breast-feeding. CONCLUSION: Vertical transmission of HCV complicates up to 18% of pregnancies in HCV-positive, HIV-negative women and 6-36% in HCV-positive, HIV-positive women. The highest rates of vertical transmission of HCV were noted in women with high HCV RNA or concurrent HIV infection. Breast-feeding has not been associated with vertical transmission of HCV infection.

Breast Feeding↗
PubMed1997

Chronic hepatitis C.

BACKGROUND: Infection with the hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Epidemiologic and natural history studies have helped to define the clinical impact of HCV infection, and molecular diagnostic assays have established clinical endpoints against which therapeutic regimens are currently tested. The absence of definitive therapy has generated controversy regarding indications and optimal candidacy for currently approved treatment. This paper reviews the epidemiology, natural history, clinical manifestations, diagnostic modalities, and current treatment of chronic HCV infection. METHODS: Search of the MEDLINE database for English-language articles and abstracts on chronic HCV infection yielded data from more than 500 original papers, reviews, and abstracts. RESULTS AND CONCLUSIONS: Hepatitis C virus is transmitted primarily through contaminated blood and less effectively by human body secretions, but a large proportion of patients have no clearly identifiable parenteral risk factors for viral acquisition. Infection with HCV results in subclinical chronic hepatitis in the majority of patients and may progress, usually over decades, to cirrhosis and hepatocellular carcinoma. Extrahepatic manifestations of HCV infection include porphyria cutanea tarda, mixed essential cryoglobulinemia, and membranoproliferative glomerulonephritis. Diagnostic modalities are accurate in estimating viral load and genotype and may be helpful in predicting and assessing response to treatment. Current therapy is limited to interferon alfa and is effective at viral eradication in only a small number of patients. The adjuvant use of drugs, such as ribavirin, in combination with interferon may hold promise at enhancing viral eradication. Understanding the mechanisms behind viral persistence and immune escape of HCV will be essential in developing effective future therapeutic and preventive strategies.

Antiviral Agents↗
PubMed1997

Regulation of biliary secretion through apical purinergic receptors in cultured rat cholangiocytes.

To evaluate whether ATP in bile serves as a signaling factor regulating ductular secretion, voltage-clamp studies were performed using a novel normal rat cholangiocyte (NRC) model. In the presence of amiloride (100 microM) to block Na+ channels, exposure of the apical membrane to ATP significantly increased the short-circuit current (Isc) from 18.2 +/- 5.9 to 52.8 +/- 12.7 microA (n = 18). The response to ATP is mediated by basolateral-to-apical Cl- transport because it is inhibited by 1) the Cl- channel blockers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (1 mM), diphenylanthranilic acid (1.5 mM), or 5-nitro-2-(3-phenylpropylamino)benzoic acid (50 or 100 microM) in the apical chamber, 2) the K+ channel blocker Ba2+ (5 mM), or 3) the Na(+)-K(+)-2Cl- cotransport inhibitor bumetanide (200 microM) in the basolateral chamber. Other nucleotides stimulated an increase in Isc with a rank order potency of UTP = ATP = adenosine 5'-O-(3)-thiotriphosphate, consistent with P2u purinergic receptors. ADP, AMP, 2-methylthioadenosine 5'-triphosphate, and adenosine had no effect. A cDNA encoding a rat P2u receptor (rP2uR) was isolated from a liver cDNA library, and functional expression of the corresponding mRNA in Xenopus laevis oocytes resulted in the appearance of ATP-stimulated currents with a similar pharmacological profile. Northern analysis identified hybridizing mRNA transcripts in NRC as well as other cell types in rat liver. These findings indicate that exposure of polarized cholangiocytes to ATP results in luminal Cl- secretion through activation of P2u receptors in the apical membrane. Release of ATP into bile may serve as an autocrine or paracrine signal regulating cholangiocyte secretory function.

Adenosine Triphosphate↗
PubMed1996

Hepatitis C.

OBJECTIVES: To review the virology, epidemiology, pathogenesis, natural history, clinical manifestations, and current treatment of hepatitis C virus (HCV) infection. DATA SOURCES: The MEDLINE database (1966 to 1996) was searched for English-language articles and abstracts on HCV and non-A, non-B hepatitis. Papers cited in relevant primary articles were also reviewed. STUDY SELECTION: More than 500 original and review articles were evaluated, and the most relevant were selected. DATA EXTRACTION: Data were extracted and reviewed by all authors. DATA SYNTHESIS: In most patients, HCV infection results in chronic hepatitis. The disease is insidious and subclinical but may progress over decades into end-stage liver disease and hepatocellular carcinoma, which makes HCV cirrhosis a leading indication for orthotopic liver transplantation. Current diagnostic methods are highly sensitive and specific, and quantitative assessment of viral load may help to predict and monitor response to treatment. The only available therapeutic option is interferon, and this agent is effective in only a small subset of patients. CONCLUSIONS: Infection with HCV is a significant public health problem that has important clinical and financial consequences. The tailoring of specific therapy according to viral load or genotype, better patient selection, and use of combination drug regimens may improve the chance of viral clearance and sustained biochemical and histologic response. Further understanding of the basic virology of HCV and the exact mechanisms of viral persistence and tissue injury is needed to help define future therapeutic and preventive strategies.

Carcinoma, Hepatocellular↗
PubMed1996

Cytomegalovirus infection following liver transplantation: review of the literature.

Cytomegalovirus (CMV) remains a major cause of problems following solid organ transplantation, accounting for a significant increase in morbidity and affiliated costs. Infection with CMV following orthotopic liver transplantation (OLT) is commonly seen as a result of marked cell-mediated immunosuppression and is an independent risk factor for opportunistic and fungal infections. The role of CMV infection in acute cellular or chronic rejection remains unclear. Recent advances in diagnostic modalities, particularly the use of the antigenemia assay and the polymerase chain reaction, have provided ways to quantitate viral load during infection or disease, as well as providing a useful marker of response to therapy. Ganciclovir remains the best antiviral agent for the treatment of CMV disease, but the use of combination therapy with other antivirals or CMV immunoglobulin may improve outcome for patients with severe disease. The ideal prophylactic therapy for patients undergoing OLT remains to be identified, as tested regimens have shown variable efficacy when analyzed with regard to defined risk groups. The use of risk group-specific prophylaxis may prove to be most successful, however, in terms of efficacy and cost savings. Future advances in basic CMV virology and transplant immunology will be essential in defining rational approaches to control and prevention of CMV infection and disease following liver transplantation.

Animals↗
PubMed1996

Evidence that ursodeoxycholic acid prevents steroid-resistant rejection in adult liver transplantation.

Steroid-resistant rejection continues to be a serious problem in liver transplantation. Since ursodeoxycholic acid (UDCA) is beneficial in several cholestatic disorders and possesses in vitro immunomodulatory and immunosuppressive effects, we have tested in a pilot study the effects of adjuvant UDCA in the prevention of steroid-resistant rejection. Fifty consecutive liver transplant patients were treated with a standard cyclosporine immunosuppressive regimen. Treatment with UDCA (10 mg/kg/d) was initiated in each patient who developed biopsy-proven rejection or biochemical evidence of cholestasis. Clinical and laboratory features were monitored for evidence of rejection. Data were analyzed after at least a 10-month follow-up period was available in each patient. Seven patients died during the study period, all within 4 wk of surgery. No evidence of rejection was documented in these patients. Twenty three of the 43 survivors 53% (23/43) developed an episode of rejection, and UDCA was initiated in each of them. Only one patient had a second episode of rejection, which responded to intravenous methylprednisolone therapy; no patient required antilymphocyte therapy. There was no evidence of toxicity for UDCA. These data suggest that UDCA can be given safely following OLT and may contribute to prevention of steroid-resistant rejection in liver transplant recipients.

Adolescent↗