Subcutaneously administered recombinant human β-interferon in the treatment of chronic hepatitis B virus infection

Background: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. β-Interferon treatment has been less well studied than α-interferon. Methods: The efficacy and tolerability of a 6-month course of subcutaneously administered human recombinant β-interferon (rINF-β_ser) was studied and the results of a low-dose regime compared with a high-dose regime. Twenty patients (17 men and three women), aged 24–54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen-positive with detectable HBV-DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low-dose group received 6×10⁶ U/dose and the high-dose group received 30×10⁶ U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months. Results: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side-effects. HBV-DNA decreased in all patients during treatment, demonstrating the anti-viral efficacy of rINF-β_ser, and was undetectable in 20 and 40% of patients receiving low-dose and high-dose regimes, respectively, at the end of 6 months treatment (P=N.S.). One year after completion of treatment, HBV-DNA was undetectable in 50 and 30% of patients in the low-dose and high-dose groups, respectively (P=N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an anti-hepatitis B ‘e’ antigen at the end of 18 months. Conclusion: This study shows that subcutaneously administered rINF-β_ser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.     

The pattern of functional and organic disorders in an Asian gastroenterological clinic

Abstract The aim of the present study was to determine the pattern of structural and functional disorders encountered in an Asian gastroenterological clinic and to compare this pattern with findings from Western centres. Consecutive new patients (totalling 2384) attending the clinics of two consultant gastroenterologists were studied. Of these, 2141 suffered from gastroenterological problems. One thousand and sixty-three (49.6%) had structural diseases, the commoner ones being liver disease, peptic ulcer, malignancy, haemorrhoids and gallstones. The remainder who were found to have no structural disease ( n = 1078; 50.4%) were deemed to have functional disorders including non-ulcer dyspepsia, irritable bowel, simple constipation and functional diarrhoea. The proportions of functional and structural disease were similar to those in the West. Major differences included a higher frequency of hepatoma and a lower frequency of inflammatory bowel disease and gastro-oesophgeal reflux in the present series.     

Clinically relevant drug interactions between anticancer drugs and psychotropic agents

YAP K.Y.‐L., TAY W.L., CHUI W.K. & CHAN A. (2011) European Journal of Cancer Care 20 , 6–32
Clinically relevant drug interactions between anticancer drugs and psychotropic agents Drug interactions are commonly seen in the treatment of cancer patients. Psychotropics are often indicated for these patients since they may also suffer from pre‐existing psychological disorders or experience insomnia and anxiety associated with cancer therapy. Thus, the risk of anticancer drug (ACD)‐psychotropic drug–drug interactions (DDIs) is high. Drug interactions were compiled from the British National Formulary (53rd edn), Lexi‐Comp's Drug Information Handbook (15th edn), Micromedex® (v5.1), Hansten & Horn's Drug Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of the individual drugs, as well as documented literature on ACD‐psychotropic interactions from PubMed and other databases was also incorporated. This paper identifies clinically important ACD‐psychotropic DDIs that are frequently observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors, corticosteroids and antimicrotubule agents due to their inhibitory or inductive effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for thalidomide with central nervous system depressants, procarbazine with antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT‐prolonging psychotropics. Clinicians should be vigilant when psychotropics are prescribed concurrently with ACDs. Close monitoring of plasma drug levels should be carried out to avoid toxicity in the patient, as well as to ensure adequate chemotherapeutic and psychotropic coverage.     

Study on the comparative immunogenicity of a recombinant DNA hepatitis B vaccine containing pre-S components of the HBV coat protein with non pre-S containing vaccines

Abstract A new recombinant hepatitis B vaccine (SCI-B-VAC), derived from Chinese hamster ovary (CHO) cells and consisting of both the major S protein and the minor pre-S₁ and pre-S₂ proteins of the viral coat were compared with two yeast-derived vaccines containing only S proteins (B-Hepavac II and Engerix-B) for immunogenicity in human volunteers in a randomized controlled study. Two hundred and ninety-five healthy subjects completed the 12 month follow up. There was no difference in the mean age and sex distribution among the three study groups. Seroconversion rates for all the three groups were similar at months 6, 9 and 12. However, hepatitis B surface antibody (anti-HBs) geometric mean titres (GMT) were significantly higher with 10 μg SCI-B-VAC and 20 μg Engerix-B than with 10 μg B-Hepavac-II at months 6, 9 and 12. SCI-B-VAC at month 6 also showed a significantly higher anti-HBs GMT than Engerix-B (295 vs 143 miu/mL, P < 0.02).     

Eighteen years experience in pediatric acute dialysis: analysis of predictors of outcome

This study reviewed the 18-year experience of acute dialysis in the pediatric intensive care unit, in order to identify factors that could predict outcome, and to determine whether newer modalities of acute dialysis have influenced this outcome. Sixty-six children (ages 1 day to 19 years) received acute dialysis from May 1980 to April 1998. Factors predicting outcome were analyzed using univariate and Cox regression analysis. Modality of dialysis in the first 15 years was exclusively peritoneal dialysis, with a mortality of 63.9%. However, in the last 3 years, with increasing patient numbers, continuous hemodiafiltration (CHDF) was the modality of choice (56.7%), with a mortality of 73.3%. Univariate analysis showed that age <1 year, coma, acute tubular necrosis, disseminated intravascular coagulopathy, assisted ventilation, and hypotension were associated significantly with poor outcome (P<0.05). Cox regression analysis revealed that mortality was significantly higher in patients on mechanical ventilation (RR 5.96, 95% CI 1.82–19.50), or with age <1 year (RR 2.00, 95% CI 1.08–3.73). In conclusion, despite the increasing use of CHDF over the last 3 years, there was no significant improvement in mortality, probably related to the fact that more critically ill patients were dialyzed. Received: 21 March 2000 / Revised: 12 October 2000 / Accepted: 19 October 2000     

Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease. METHODS: Seventy-two Singapore Chinese children with MCNS and 78 normal controls were screened for single nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele and genotype frequencies of these SNPs were determined and their relationship with different clinical courses was analysed. RESULTS: Six SNPs were identified in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype frequencies between MCNS children and normal controls. However, there was a significantly lower frequency of allele 4738G in those MCNS children who were still relapsing after 5 years of follow-up (G = 0.52), compared with those in complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05). Haplotype analysis showed a significantly higher frequency of the GCC haplotype in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while the frequency of AAT haplotype was higher in those MCNS children still relapsing after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was significantly higher than in those with haplotype GCC. CONCLUSIONS: These results suggest that genetic polymorphisms in the 3'UTR of the IL-13 gene correlate with long-term outcome of MCNS, rather than disease susceptibility, in Singapore Chinese children.     

Dengue Hemorrhagic Fever after Living Donor Renal Transplantation

Nephrol Dial Transplant 2005 20(2): 447–8 Due     

Evaluation of Intracardiac and Pericardial Tumours with Computed Tomography

Though echocardiography is the standard method in the diagnosis of cardiac tumours computed tomography may demonstrate the presence, location and size of intracardiac tumours and the relationship of the mass to the cardiac chambers and extracardiac extension.     

Comparative Reproducibility of QT, QT Peak, and T Peak-T End Intervals and Dispersion in Normal Subjects, Patients with Myocardial Infarction, and Patients with Hypertrophic Cardiomyopathy

Abnormal repolarizaiion is associated with arrhythmogenesis. Because of controversies in existing methodology, new computerized methods may provide more reliable tools for the noninvasive assessment of myocardial repolarization from the surface electrocardiogram (ECC). Measurement of the interval between the peak and the end of the T wave (TpTe interval) has been suggested for the detection of repolarization abnormalities, but its clinical value has not been fully studied. The intrasubject reproducibility and reliability of automatic measurements of QT, QT peak, and TpTe interval and dispersion were assessed in 70 normal subjects, 49 patients with acute myocardial infarction (5th day; MI), and 37 patients with hypertrophic cardiomyopathy (HC). Measurements were performed automatically in a set of 10 ECCs obtained from each subject using a commercial software package (Marquette Medical Systems, Milwaukee, WI, U.S.A.). Compared to normal subjects, all intervals were significantly longer in HC patients (P < 0.001 for QT and QTp; p < 0.05 for TpTe); in MI patients, this difference was only significant for the maximum QT and QTp intervals (P < 0.05). In both patient groups, the QT and QTp dispersion was significantly greater compared to normal subjects (P < 0.05) but no consistent difference was observed in the TpTe dispersion among all three groups. In all subjects, the reproducibility of automatic measurement of QT and QTp intervals was high (coefficient of variation, CV, 1%-2%) and slightly lower for that of TpTe interval (2%–5%; p < 0.05). The reproducibility of QT, QTp, and TpTe dispersion was lower (12%–24%, 18%–28%, 16%–23% in normal subjects, MI and HC patients, respectively). The reliability of automatic measurement of QT, QTp, and TpTe intervals is high but the reproducibility of the repeated measurements of QT, QTp and TpTe dispersion is comparatively low.