Effect of nitrous acid on lung function in asthmatics: a chamber study.

Nitrous acid, a component of photochemical smog and a common indoor air pollutant, may reach levels of 100 ppb where gas stoves and unvented portable kerosene heaters are used. Nitrous acid is a primary product of combustion and may also be a secondary product by reaction of nitrogen dioxide with water. Because the usual assays for nitrogen dioxide measure several oxides of nitrogen (including nitrous acid) together, previous studies of indoor nitrogen dioxide may have included exposure to and health effects of nitrous acid. To assess the respiratory effects of nitrous acid exposure alone, we carried out a double-blinded crossover chamber exposure study with 11 mildly asthmatic adult subjects. Each underwent 3-hr exposures to 650 ppb nitrous acid and to filtered room air with three 20-min periods of moderate cycle exercise. Symptoms, respiratory parameters during exercise, and spirometry after exercise were measured. A statistically significant decrease in forced vital capacity was seen on days when subjects were exposed to nitrous acid. This effect was most marked at 25 min and 85 min after exposure began. Aggregate respiratory and mucous membrane symptoms were also significantly higher with nitrous acid. We conclude that this concentration and duration of exposure to nitrous acid alters lung mechanics slightly, does not induce significant airflow obstruction, and produces mild irritant symptoms in asthmatics.     

Isolation,Replication and Polyhedrin Gene Sequence of an Israeli Helicoverpa Armigera Single Nucleopolyhedrovirus

A local strain of Helicoverpa armigera baculovirus was isolated from infected H. armigera larvae. Infectivity to Helicoverpa cells, restriction enzyme analysis and electron microscopy allowed its identification as a single embedded nucleopolyhedrovirus, designated HaSNPV-IS. Analysis of DNA replication, protein synthesis and polyhedrin expression in HaSNPV-infected cells located the late and very late phases of the viral cycle at 24 and 48 h after infection, respectively. The viral polyhedrin gene was isolated and characterized. It encoded for a polypeptide of 246 amino acid residues. A 32 kDa polypeptide was identified by immunoblot analysis using anti-polyhedrin antiserum. The HaSNPV-IS polyhedrin DNA sequence revealed 99.4% of homology to the HzSNPV polyhedrin. The availability of this efficient replication system and the above knowledge paves the way to future genetic engineering of the HaSNPV. This revised version was published online in July 2006 with corrections to the Cover Date.     

Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer.

PURPOSE: To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study. PATIENTS AND METHODS: Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR). RESULTS: One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P =.71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation. CONCLUSION: Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment.     

Tegaserod maleate in the treatment of irritable bowel syndrome: a clinical review

BACKGROUND: Approved in July 2002, tegaserod maleate is a partial 5-hydroxytryptamine 4-receptor agonist used to improve symptoms of constipation-predominant irritable bowel syndrome (IBS). The physiologic actions of tegaserod relate to its ability to stimulate gastric and intestinal motility. OBJECTIVE: This article reviews available data on the pharmacokinetic and pharmacodynamic properties and clinical efficacy of tegaserod. METHODS: Searches of MEDLINE and PubMed from 1966 to the present were conducted using the search terms tegaserod, tegaserod maleate, irritable bowel syndrome, and Rome criteria. Abstracts presented at national meetings between 1997 and 2002 were reviewed and included if perceived to be reliable and relevant. RESULTS: In clinical trials, tegaserod was associated with significantly better scores on the subject's global assessment of relief compared with placebo (P < 0.05). The absolute efficacy of tegaserod compared with placebo varied between trials and averaged 10% to 12%. Tegaserod had a good safety profile; diarrhea was the only adverse effect that occurred more often in tegaserod recipients than in placebo recipients. No electrocardiographic changes were observed at therapeutic concentrations of tegaserod. Long-term (1-year) treatment with tegaserod appeared to be well tolerated. The recommended dosage for patients aged >18 years with constipation-predominant IBS is 6 mg PO BID before meals for 4 to 6 weeks, with an additional 4 to 6 weeks of treatment if initial therapy is partially effective. CONCLUSIONS: The addition of tegaserod to the arsenal of moderately effective medication currently used in the treatment of IBS may be helpful in patients with constipation-predominant IBS. Continuous postmarketing surveillance and reporting of adverse reactions are essential to further characterize the safety profile of this new agent.     

Selection of a gene for apolipoprotein a1 using autoantibodies from a patient with systemic lupus erythematosus

Objective. To investigate immunoreactivity of systemic lupus erythematosus (SLE) sera with apolipoprotein A1, (Apo A1), the major lipid-binding protein of high-density lipoprotein (HDL). Methods. Since early attempts to identify Apo A1 autoantibodies using standard enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques had been unsuccessful, a mouse complementary DNA lambda phage expression library was screened. Results. A selected clone (MA1) was found to have 82% DNA sequence homology to a segment of human Apo A1. Since there were nonconservative substitutions in the MA1 protein and lack of a complete sequence, it was possible that the SLE patient'S antibodies were binding MA1 epitopes that were shared by the complete human protein but had not been conformationally accessible using the earlier techniques. Thus, gamma-irradiated ELISA plates were used as an alternative antigen-binding surface for intact human Apo A1, and high-titer anti-human Apo A1 autoantibodies were then identified in the sera of 5 more SLE patients. Conclusion. These findings show that Apo A1 is immunogenic. Apo A1 antibodies may play a role in the decreased HDL levels and Apo A1:Apo B ratios previously reported to occur in subgroups of SLE patients.     

Adenoma Recurrences After Resection of Colorectal Carcinoma: Results From the Southwest Oncology Group 9041 Calcium Chemoprevention Pilot Study

Background: Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC).Methods: A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates.Results: Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P = .01). Lower stage was associated with higher adenoma recurrence rates (P = .04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates.Conclusions: The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.