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Biomedical subjects

K Rajender Reddy

Publications and source records attributed to K Rajender Reddy.

At least 19 recordsLinked to original sources
PubMed2003

Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine.

BACKGROUND: The increasing demand for transplantation has resulted in a trend toward using virologically compromised donors. We reviewed our experience with liver grafts from hepatitis-B surface antigen (HBsAg)(-), antibody to core antigen (anti-HBc)(+) donors. METHODS: Sixty-two liver transplants using HBsAg(-), anti-HBc(+) donors were studied. The decision to use prophylaxis was based on the presence or absence of donor and recipient risk factors for posttransplant hepatitis-B virus (HBV) transmission or reinfection. If the donor or recipient showed positive HBVDNA, hepatitis-B immunoglobulin (HBIg) and lamivudine were used. If both donor and recipient HBVDNA were negative, a choice between lamivudine and no prophylaxis was made on the basis of presence or absence of HBsAg and antibody to the surface antigen (anti-HBs) in the recipient. RESULTS: No death or graft loss could be ascribed to HBV. Mild HBV infection occurred in two patients who were not taking the recommended prophylaxis. Among the other 60 patients, 1 showed positive e antigen (HBeAg) early after transplantation, and 2 (1 with recurrent cancer, 1 with HIV infection) showed HBsAg(+). None of the three patients had any other evidence of HBV infection. Forty-seven patients underwent liver biopsies. Changes consistent with hepatitis were observed in 26, and 24 had HCV infection; immunostains for HBV antigens were negative in all cases, and 7 showed positive HBVDNA. CONCLUSIONS: A selective protocol based on donor and recipient risk factors for post-liver transplant HBV infection can prevent hepatitis-B infection and avoid unnecessary administration of antiviral prophylaxis in recipients of HBsAg(-), anti-HBc(+) liver allografts.

Adult↗
PubMed2003

Synthesis, structure, and magnetic properties of [MnIII(salpn)NCS]n, a helical polymer, and the dimer [MnIII(salpn)NCS]2. Weak ferromagnetism in [MnIII(salpn)NCS]n related to the strong magnetic anisotropy in Jahn-Teller MnIII (salpnH2 = N,N'-bis(salicylidene)-1,3-diaminopropane).

Dimeric [Mn(salpn)NCS](2)(1) and polymeric [Mn(salpn)NCS](n)(2) are formed by the reaction of Mn(CH(3)CO(2))(2).4H(2)O, the schiff base, and thiocyanate. The formation of the two polymorphic forms is solvent and temperature dependent. 1: orthorhombic, space group Pbca, with a = 12.573(2) A, b = 13.970(7) A, c = 18.891(9) A, and Z = 8. 2: orthorhombic, space group Pna2(1), with a = 12.5277(14) A, b = 11.576(2) A, c = 11.513(2) A, and Z = 4. The dimers in 1 are held together by weak noncovalent S...pi (phenyl) interactions leading to a chain along the a-axis. Each monomeric unit of the polymer in 2 is related to its adjacent ones by a 2-fold screw axis leading to a helix along the c-axis. The exchange coupling is nondetectable in the dimer. The magnetic susceptibility of the helical chain fits a classical chain law with J = -3.2 cm(-1) and shows a weak ferromagnetic ordering below 7 K due to spin canting effects.

Journal Article↗
PubMed2003

Pegylated interferons.

In summary, pegylated IFNs have a longer half-life, reduced immunogenicity, better pharmacokinetics, and enhanced biological activity when compared with standard IFN. Better adherence rates are feasible because of the once weekly administration of pegylated IFN. The adverse event profile is largely comparable. The improved pharmacokinetics of pegylated IFNs, compared with standard IFN, has translated into greater efficacy with at least similar tolerability. Pegylated IFNs with ribavirin are the standard of care for treating patients with chronic HCV who have not been treated previously.

Animals↗
PubMed2003

Hepatotoxicity of hypolipidemic drugs.

Dyslipidemic conditions and their cardiovascular related complications are common. Effective primary and secondary prevention strategies include therapies to lower LDL and total cholesterol and to increase HDL. Further, it seems that there is a need for therapeutic reduction in triglycerides as it emerges as an independent risk factor for CVD. Many clinical trials have been designed to evaluate pharmacologic compounds in the treatment of the dyslipidemias and they seem to have shown a safe profile, both in the experiment phases and in post-marketing observation studies. Nevertheless, sporadic reports of hepatotoxicity with statins and niacin still arise (Table 2). Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness is questionable because often these reactions are idiosyncratic and may not be identified by this routine screening. The risk/benefit ratio is in favor of using these medications in individuals at risk. There is no evidence to suggest intrinsic hepatotoxic activity as such. Drugs that lower triglycerides such as fibrates, have been observed to improve hepatic biochemical tests, although in small series. This leads to speculation whether treatment with fibrates would be beneficial for non-alcoholic fatty liver disease (NAFLD), a condition that is emerging as one of enormous magnitude.

Anticholesteremic Agents↗
PubMed2003

Factors that influence the severity of recurrent hepatitis C virus following liver transplantation.

Poor outcomes following OLT for HCV disease have been associated with several host, viral, and non-host/non-viral factors. As is evident from the literature, there is confounding data in favor of and against these factors in the pathogenesis of severe recurrent HCV. Nevertheless, from a viral perspective, the patient most likely to achieve a good outcome following OLT is someone with low-level (< or = 10(9) copies/mL) HCV RNA viremia both pre- and post-OLT and a genotype other than lb. In terms of host factors, the patients with best outcomes are: whites, men, less than 49 years of age, receiving a donor liver less than 40 years of age, not coinfected with CMV, and have low HAI or histologic activity indices during the early stage of follow-up. Host recipient immune homology may or may not be a major factor in outcomes. A non-host, non-viral factor favoring less severe recurrence of HCV is a shorter warm ischemia time. Finally, features that may influence outcomes over which there is no control include: recipient age, recipient gender, and donor age (in the case of cadaveric donors). Unfortunately, the best-case scenario is uncommon.

Age Factors↗
PubMed2003

Rising incidence of hepatocellular carcinoma: the role of hepatitis B and C; the impact on transplantation and outcomes.

Hepatocellular carcinoma caused by hepatitis B and hepatitis C are global scourges but are likely to peak in incidence in the next 2 decades and then decline. Universal vaccination has been effective in stemming the incidence of chronic hepatitis B and early-onset HCC in regions of high endemicity where implemented, but preventive measures in HCV are not yet available. After the attrition of older affected generations, the incidence of HCC will likely decline rapidly. While no vaccine is currently available for hepatitis C, cases are projected to peak and decline because of a marked reduction in transmission as a result of behavioral modification and safeguarding of blood supplies. Until these epidemiologic projections come to pass, management of hepatocellular carcinoma will continue to become a progressively more frequently encountered clinical challenge. Therapy for chronic hepatitis may ameliorate but will not eliminate the development of tumors. The demand for orthotopic liver transplantation will continue to climb, and palliative therapies for non-resectable cases will require studies aimed at optimization of benefit. LDLT may remain an option for high-risk patients affording tumor-free survival for some otherwise terminal patients.

Carcinoma, Hepatocellular↗
PubMed2003

The North American Study for the Treatment of Refractory Ascites.

BACKGROUND AND AIMS: The clinical utility of transjugular intrahepatic portosystemic shunts (TIPS) vis-à-vis total paracentesis in the management of refractory ascites is unclear. METHODS: A multicenter, prospective, randomized clinical trial was performed in which 109 subjects with refractory ascites were randomized to either medical therapy (sodium restriction, diuretics, and total paracentesis) (n = 57) or medical therapy plus TIPS (n = 52). The principal end points were recurrence of tense symptomatic ascites and mortality. RESULTS: A technically adequate shunt was created in 49 of 52 subjects. TIPS plus medical therapy was significantly superior to medical therapy alone in preventing recurrence of ascites (P < 0.001). The total number of deaths in the 2 groups was identical (TIPS vs. medical therapy alone: 21 vs. 21). There were no significant differences in the 2 arms with respect to overall and transplant-free survival. There was a higher incidence of moderate to severe encephalopathy in the TIPS group (20 of 52 vs. 12 of 57; P = 0.058). There were no significant differences in the number of subjects who developed liver failure (7 vs. 3), variceal hemorrhage (5 vs. 8), or acute renal failure (3 vs. 2). There were also no significant differences between the 2 groups in the frequency of emergency-department visits, medically indicated hospitalizations, or quality of life. CONCLUSIONS: Although TIPS plus medical therapy is superior to medical therapy alone for the control of ascites, it does not improve survival, affect hospitalization rates, or improve quality of life.

Ascites↗
PubMed2003

Comparison of three commercially available assays for HCV RNA using the international unit standard: implications for management of patients with chronic hepatitis C virus infection in clinical practice.

OBJECTIVES: The present study was performed to evaluate the impact of the international unit standard for measuring HCV RNA in the management of patients with chronic hepatitis C virus (HCV) infection. METHODS: The three assays used were Amplicor Monitor PCR, the National Genetics Institute PCR assay, and branched chain DNA. HCV RNA was measured at four time points (baseline, 3 months after the start of therapy, at the end of treatment, and 6 months after discontinuation of therapy) in 106 consecutive patients who received interferon and ribavirin for chronic HCV. RESULTS: The mean age of the patients was 44 yr. Of the patients, 62% were male, 24% were African American, 38% had bridging fibrosis or cirrhosis, and 75% were HCV genotype 1. Of the 424 samples analyzed, 82-89% of values were within 1 log unit and 85-92% were within 2 log units by the various assays. This variability was not dependent upon HCV genotype. HCV RNA was undetectable in 1.4-6.8% of samples when virus was detected by another assay. The mean HCV RNA in these discordant samples was 1.47-6.33 log IU/ml (30-2,100,000 IU/ml). CONCLUSIONS: These data demonstrate that approximately 90% of serum values for HCV RNA were within 1 log unit by the international unit standard regardless of which virological assay was used. However, false positive and false negative results as well as variations in the HCV RNA level of more than 1 to 2 log units can occur with any of the assays, and these results may have an impact upon the management of patients receiving interferon therapy. It is therefore unwise in clinical practice to base important treatment decisions upon a single HCV RNA determination.

Adult↗
PubMed2002

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

BACKGROUND: Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS: A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS: A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P<0.001) or peginterferon alfa-2a alone (56 percent vs. 29 percent, P<0.001). The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent, 36 percent, and 21 percent, respectively, for the three regimens. Among patients with HCV genotype 1 and high base-line levels of HCV RNA, the proportions of those with sustained virologic responses were 41 percent, 33 percent, and 13 percent, respectively. The overall safety profiles of the three treatment regimens were similar; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin. CONCLUSIONS: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.

Adult↗
PubMed2002

Use of peginterferon alfa-2a (40 KD) (Pegasys) for the treatment of hepatitis C.

Thrice-weekly interferon alfa-2b plus ribavirin has been the standard of care for chronic hepatitis C; however, a majority of patients fail to achieve a sustained virological response with this treatment. Peginterferon alfa-2a (40 KD), interferon alfa-2a conjugated to a 40 kDa branched polyethylene glycol moiety, exhibits sustained absorption and reduced renal clearance, resulting in antiviral pressure throughout a once-weekly dosing schedule. Peginterferon alfa-2a (40 KD) has superior virological efficacy to interferon alfa-2a, and elicits histological improvements in patients with and without sustained virological response. Peginterferon alfa-2a (40 KD) is effective in patients infected with viral genotype 1 and those with liver cirrhosis. Viral RNA measurements at 12 weeks can be used to predict the probability of achieving sustained virological response to peginterferon alfa-2a (40 KD) therapy. Peginterferon alfa-2a (40 KD) has comparable safety to interferon alfa-2a. The addition of ribavirin to peginterferon alfa-2a (40 KD) further enhances the therapeutic benefit for patients with hepatitis C.

Antiviral Agents↗
PubMed2002

Prognostic factors and early predictability of sustained viral response with peginterferon alfa-2a (40KD).

BACKGROUND/AIMS: Baseline factors and early decline in serum hepatitis C virus RNA are predictive of sustained virological response to interferon therapy in patients with chronic hepatitis C. We evaluated the prognostic value of baseline factors and early viral RNA among patients treated with peginterferon alfa-2a (40KD). METHODS: Data were pooled from three randomized trials involving 814 patients treated with peginterferon alfa-2a (40KD) (90, 135, or 180 mirog). Stepwise and multiple logistic regression identified independent baseline factors associated with response. Receiver operating characteristic curves for both absolute values and log(10) decline in viral RNA at 4, 8, 12 and 24 weeks of therapy were created. RESULTS: Independent prognostic factors for sustained virological response included viral genotype non-1, low pretreatment viral load, age (<40 years), no cirrhosis and body weight (<85 kg). In addition, alanine aminotransferase quotient (>3) and histological activity index score (>10) were also independently prognostic. Receiver operating characteristic curves showed that detectable or less than 2-log(10) decline in viral RNA at week 12 predicted sustained virological non-response (negative predictive value is 98%) . CONCLUSIONS: In patients with chronic hepatitis C treated with peginterferon alfa-2a (40KD), the decision to continue or stop treatment can be made as early as week 12.

Adult↗
PubMed2002

Induction therapy with consensus interferon (CIFN) does not improve sustained virologic response in chronic hepatitis C.

In patients infected with hepatitis C virus (HCV) genotype 1, sustained viral response (SVR) averages 10-40% depending on treatment regime. It has been proposed that high dose daily interferon (IFN) therapy early in therapy (induction dosing) may enhance SVR. In the present study we examined this issue and also assessed whether one could predict SVR and non-SVR, based on viral kinetics during the first month of induction therapy. End of treatment response and SVR was determined in 173 HCV infected patients who were treated with different induction doses of consensus interferon (CIFN) for one month followed by 11 months of standard 9 microg of CIFN thrice weekly (TIW). The second phase decline slope was calculated by log-linear regression on weekly measurements of serum HCV RNA during the first 7-28 days of treatment; rapid viral response (RVR) during the first month of induction dosing was defined as a decline of > 0.3 log copies/mL/week. Overall, SVR occurred in 11% of genotype 1 infected patients and 41% of patients with nongenotype 1. High dose induction therapy did not increase the rate of SVR, in either genotype 1 or genotype 2/3 infected patients. No patient without a RVR during the first month had SVR, while SVR occurred in 55% of the patients with RVR. RVR was the best predictor of SVR using multivariate analysis. These results indicate that induction dosing with CIFN does not improve SVR rates. They also suggest that early viral kinetics during the first month of therapy can predict non-SVR and thus save a patient a year long treatment which is fraught with side-effects and significant cost.

Adult↗
PubMed2002

First phase viral kinetic parameters as predictors of treatment response and their influence on the second phase viral decline.

It has recently been shown that upon initiation of interferon (IFN) treatment there is a biphasic decline in hepatitis C virus (HCV) RNA levels. In preliminary results, the rate of second phase viral decline has been shown to be an excellent predictor of treatment response. In this analysis, we determined whether the first phase viral kinetic parameters affected the rate of second phase viral decline. We also assessed whether first phase viral kinetic parameters could be used to predict treatment response within 24 h of initiating treatment. This study is a retrospective analysis of two completed studies from which detailed kinetic data were obtained in patients infected with genotype 1 HCV. In both studies, viral levels were measured frequently over the first 24 h, allowing the determination of IFNs effectiveness in blocking viral production and the viral load at the end of the first phase (v1). The second phase decline slope was calculated by log-linear regression on measurements of serum HCV RNA during days 2, 7 and 14. In study one, sustained viral response (SVR) rates were obtained, allowing the determination of the first phase's predictive power for SVR. Logistic regression and fisher exact tests were used to analyse data. In study one, no patient achieved SVR without an IFN effectiveness greater than 98% and a V1 less than 250 000 copies/mL. When V1 and IFN effectiveness were combined to predict SVR, a negative predictive value= 100%, positive predictive value=71% and accuracy of 95% was obtained after only 24 h of IFN treatment. Both studies illustrated strong correlations for both IFN effectiveness and V1 with the rate of 2nd phase slope (P < 0.001). V1 also correlated significantly with a calculation of infected cell loss (delta), which is a major determinant of the second phase viral decline. These results suggest that early viral kinetics may predict lack of response after only 24 h of treatment initiation and indicate a strong link between the degree of viral load reduction during the first phase, and the subsequent 2nd phase decline slope. This might be explained by a viral dynamics model assuming a jump-start of the immune response when viral loads are reduced below a threshold, subsequently giving rise to a faster 2nd phase decline slope.

Antiviral Agents↗
PubMed2002

Portal vein thrombosis: a concise review.

Portal vein thrombosis (PVT) is an uncommon cause for presinusoidal portal hypertension. Although several predisposing conditions are known to exist in the background of PVT, there still remains a proportion of patients in whom the etiology is not known and the pathogenesis is unclear. In this review we summarize the literature on PVT and present the current knowledge about the precipitating factors of PVT. Further, we discuss the advances in the radiological diagnosis that have improved diagnostic accuracy and are noninvasive. Finally, we discuss the treatment options for patients who have varying extents of thrombosis in the portal vein and specifically focus on PVT that is encountered before and after liver transplantation.

Humans↗
PubMed2002

Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease.

Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus.

Adult↗