New one-week, low-dose triple therapy for the treatment of duodenal ulcer with Helicobacter pylori infection

BACKGROUND: Antimicrobial therapy is the recommended treatment for duodenal ulcer associated with Helicobacter pylori infection. The eradication of bismuth-based triple therapy with bismuth subcitrate, metronidazole and amoxicillin is limited by low compliance, drug resistance and side-effects. Two-week proton pump inhibitor (PPI)-based triple therapy has a higher eradication rate but is costly. This study was designed to compare the efficacy, patient compliance and cost of short-term PPI-based triple therapy with those of bismuth-based triple therapy. METHODS: Ninety patients with active duodenal ulcer disease and H pylori infection, proven with the 13C-urea breath test and CLO test (Campylobacter-like organism test) were treated randomly in three therapeutic groups: Group A, DeNol 120 mg, amoxicillin 500 mg and metronidazole 250 mg four times a day orally for 14 days; Group B, omeprazole 20 mg plus clarithromycin 500 mg twice a day and amoxicillin 500 mg four times a day for 14 days; Group C, omeprazole 20 mg, clarithromycin 250 mg and metronidazole 500 mg twice a day for seven days. Nizatidine 150 mg twice a day was given continuously following the end of anti-H pylori therapy for each group. Two months later, endoscopy, the CLO test and 13C-urea breath test were repeated to assess the eradication rate of H pylori and the ulcer-healing rate. Drug tolerance was evaluated by patients themselves by daily recording of any side-effects. RESULTS: Eighty-four patients completed the entire course of therapy and evaluation for H pylori infection. The H pylori eradication rates in Groups A, B and C were 75% (21/28), 93% (26/28) and 89% (25/28), respectively (p = 0.466). The ulcer healing rate was 86% (24/28) in Group A and 89% (25/28) in Groups B and C (p = 0.764). A total of 74 patients (88%) were free from symptoms at the end of the triple therapy. Symptom relief was faster in patients with PPI-based triple therapy (Groups B and C) (days 3 and 4) than for patients with bismuth-based triple therapy (day 5). The cost of Group C therapy was lower than that for Groups A and B. There were no major side-effects in any of the patients. CONCLUSIONS: One-week triple therapy with omeprazole, clarithromycin and metronidazole is highly effected for the eradication of H pylori. A therapeutic regime of one week's duration with lower cost, good compliance and mild side-effects may offer a good choice for treatment of duodenal ulcer associated with H pylori infection in clinical practice.     

Predictors of GBV-C infection among patients referred for renal transplantation

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Radical radiotherapy for squamous cell carcinoma of the larynx, oropharynx and hypopharynx: patterns of recurrence, treatment and survival

The present study investigates 1085 previously untreated patients with squamous cell carcinoma of the head and neck for factors that influence recurrence following treatment with definitive radiotherapy. In the second part of this study, those diagnosed with recurrence were studied with regard to treatment and were further analysed with regard to identification of prognostic factors which may affect outcome in the patient who actually develops a recurrence.     

A new class of tobacco chitinases homologous to bacterial exo-chitinases displays antifungal activity

A novel chitinase gene of tobacco was isolated and characterized by DNA sequence analysis of a genomic clone and a cDNA clone. Comparative sequence analysis of both clones showed an identity of 94%. The proteins encoded by these sequences do not correspond to any of the previously characterized plant chitinases of classes I-IV and are designated as class V chitinases. Comparison of the chitinase class V peptide sequence with sequences in the Swiss Protein databank revealed significant sequence similarity with bacterial exo-chitinases from Bacillus circulans, Serratia marcescens and Streptomyces plicatus. It was demonstrated that class V chitinase gene expression is induced after treatment of tobacco with different forms of stress, like TMV-infection, ethylene treatment, wounding or ultraviolet irradiation. Two related chitinase class V proteins of 41 and 43 kDa were purified from Samsun NN tobacco leaves inoculated with tobacco mosaic virus. The proteins were purified by Chelating Superose chromatography and gel filtration. In vitro assays demonstrated that class V chitinases have endo-chitinase activity and exhibit antifungal activity toward Trichoderma viride and Alternaria radicina. In addition, it was shown that class V chitinase acts synergistically with tobacco class I beta-1,3-glucanase against Fusarium solani germlings.     

Description and evaluation of a new 3-D computerized treatment planning dose compensator system

Evaluation has been performed of compensators generated by means of a computerized three-dimensional treatment planning system that can utilize either digitized slice profiles or CT scans. Two methods of calculating compensator thickness are used: the modified Batho power law (dSAR) method for digitized profiles and the equivalent TAR (eqTAR) method for CT scans. This system not only compensates for patient surface contours but also compensates for internal inhomogeneities. In addition, any required wedging will be incorporated in the compensator generation. This system has been tested for a number of extreme cases with inhomogeneities and sloping contours. Good agreement was obtained between the measured and computer calculated dose profiles especially along the central axis of the beam. A "Profile Uniformity Index" was defined to quantify the goodness of dose compensation in three dimensions. Compensation using this system can achieve good dose uniformity within the target volume in all clinical cases and is definitely an improvement over systems based solely on tissue deficit.     

Using the Nutrition Screening Initiative to survey the nutritional status of clients participating in a home delivered meals program

A large percentage of older Americans are at risk for malnutrition. This puts them at risk for premature institutionalization, creating a financial burden. The objective of this survey was to determine the nutritional health of clients receiving home delivered meals in Lake County, Indiana and the impact that home delivered meals had on them. Nutrition Screening Initiative (NSI) Determine Your Nutritional Health Checklists were mailed to recipients of meals; 58.3% were returned. Twenty-eight percent were found to be at no nutritional risk, 39% at moderate nutritional risk and 33% at high nutritional risk. One-hundred-thirty clients that scored three or more on the "Checklist" were visited by a Registered Dietitian for further screening using the NSI Level I Screen. This screen found many nutritional problems but the fact that the clients did receive home delivered meals decreased the risk. It was determined by the author that 68% of these clients could not function in their own homes without home delivered meals.     

Differentiation of promonocytic U937 subclones into macrophagelike phenotypes regulates a cellular factor(s) which modulates fusion/entry of macrophagetropic human immunodeficiency virus type 1

Monocytes/macrophages (M/M) and CD4+ T cells are two important targets of human immunodeficiency virus (HIV) infection. Different strains of HIV-1 vary markedly in their abilities to infect cells belonging to the M/M lineage. Macrophagetropic (M-tropic) HIV-1 strains replicate well in primary lymphocytes as well as in primary macrophages; however, they generally infect T-cell lines poorly, if at all. Although promonocytic cell lines such as U937 have been used as in vitro models of HIV-1 infection of M/M, these cell lines are susceptible to certain T-cell-tropic (T-tropic) HIV-1 strains but are resistant to M-tropic HIV-1. In this study, we demonstrate that (i) certain U937 clones ("plus" clones), which are susceptible only to T-tropic HIV-1, become highly susceptible to M-tropic HIV-1 upon differentiation with retinoic acid (RA); (ii) other U937 clones ("minus" clones), which are resistant to both T- and M-tropic HIV-1, remain resistant to both viruses; and (iii) RA treatment induces expression of CCR5, a fusion/entry cofactor for M-tropic HIV-1 in both types of U937 clones, and yet enhances the fusogenicity of the plus clones, but not the minus clones, with M-tropic Env's. These results indicate that the major restriction of M-tropic HIV-1 infection in promonocytic cells occurs at the fusion/entry level, that differentiation into macrophage-like phenotypes renders some of these cells highly susceptible to infection with M-tropic HIV-1, and that CD4 and CCR5 may not be the only determinants of fusion/entry of M-tropic HIV-1 in these cells.     

Refining the level for anticipated hepatotoxicity in acetaminophen poisoning

Treatment of an acetaminophen overdose with N-acetyl cysteine usually is based on the position of the 4-h acetaminophen (APAP) level on the Rumack-Matthew nomogram; however, there is disagreement on the level at which clinically relevant hepatotoxicity occurs. A retrospective review of all acute adult formulation APAP exposures reported to our poison center between 1986 and 1993 was performed and cases corresponding to the "possible risk or toxicity" range on the nomogram were identified. Our current poison center protocol for APAP poisoning does not recommend treatment with N-acetylcysteine (NAC) in low-risk patients if the 4-h serum APAP level or the extrapolated equivalent falls within the possible toxicity range on the nomogram. Seventeen cases met the inclusion criteria for the study and received no NAC; six additional patients met inclusion criteria but received one or two doses of NAC before therapy was discontinued. No patients in either group demonstrated clinical evidence of hepatotoxicity. This pilot study suggests that patients with no risk factors and APAP levels in the "possible risk" range may not require NAC therapy.