Vascular architecture and hypoxic profiles in human head and neck squamous cell carcinomas.
(25/721)
Tumour oxygenation and vasculature are determinants for radiation treatment outcome and prognosis in patients with squamous cell carcinomas of the head and neck. In this study we visualized and quantified these factors which may provide a predictive tool for new treatments. Twenty-one patients with stage III-IV squamous cell carcinomas of the head and neck were intravenously injected with pimonidazole, a bioreductive hypoxic marker. Tumour biopsies were taken 2 h later. Frozen tissue sections were stained for vessels and hypoxia by fluorescent immunohistochemistry. Twenty-two sections of biopsies of different head and neck sites were scanned and analysed with a computerized image analysis system. The hypoxic fractions varied from 0.02 to 0.29 and were independent from T- and N-classification, localization and differentiation grade. No significant correlation between hypoxic fraction and vascular density was observed. As a first attempt to categorize tumours based on their hypoxic profile, three different hypoxia patterns are described. The first category comprised tumours with large hypoxic, but viable, areas at distances even greater than 200 micrometer from the vessels. The second category showed a typical band-like distribution of hypoxia at an intermediate distance (50-200 micrometer) from the vessels with necrosis at greater distances. The third category demonstrated hypoxia already within 50 micrometer from the vessels, suggestive for acute hypoxia. This method of multiparameter analysis proved to be clinically feasible. The information on architectural patterns and the differences that exist between tumours can improve our understanding of the tumour micro-environment and may in the future be of assistance with the selection of (oxygenation modifying) treatment strategies. (+info)
PCR-restriction fragment length polymorphism analysis for identification of Bacteroides spp. and characterization of nitroimidazole resistance genes.
(26/721)
Bacteroides spp. are opportunist pathogens that cause blood and soft tissue infections and are often resistant to antimicrobial agents. We have developed a combined PCR-restriction fragment length polymorphism (RFLP) technique to characterize the 16S rRNA gene for identification purposes and the nitroimidazole resistance (nim) gene for detection of resistance to the major antimicrobial agent used to treat Bacteroides infections: metronidazole (MTZ). PCR-RFLP analysis of 16S ribosomal (rDNA) with HpaII and TaqI produced profiles that enabled discrimination of type strains and identification of 70 test strains to the species level. The 16S rDNA PCR-RFLP identification results agreed with routine phenotypic testing for 62 of the strains. The discrepancies between phenotypic and PCR-RFLP methods for eight strains were resolved by 16S rDNA sequencing in three cases, but five strains remain unidentified. The presence of nim genes was indicated by PCR in 25 of 28 strains that exhibited reduced sensitivity to MTZ. PCR-RFLP of the nim gene products identified the four reported genes (nimA, -B, -C, and -D) and indicated the presence of a previously unreported nim gene in 5 strains. This novel nim gene exhibited 75% DNA sequence similarity with nimB. These rapid, accurate, and inexpensive methods should enable improved identification of Bacteroides spp. and the detection of MTZ resistance determinants. (+info)
Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics for 1 week-a meta-analysis of efficacy.
(27/721)
OBJECTIVE: To compare the efficacy of proton pump inhibitor vs. ranitidine bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori eradication. METHODS: Randomized trials comparing 1-week regimens with (i) proton pump inhibitor plus two antibiotics [clarithromycin (C) and amoxycillin (A) or a nitroimidazole (N)]; or (ii) RBC plus the same antibiotics. Eradication was confirmed by histology or 13C-urea breath test at least 4 weeks after therapy. Data sources included PubMed database and abstracts from congresses until October 1999. Statistical analysis was by meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). RESULTS: Twelve studies met the selection criteria. Nine compared proton pump inhibitor vs. RBC plus C and A, and five compared proton pump inhibitor vs. RBC plus C and N. With RBC, C and A, mean H. pylori eradication efficacy by intention-to-treat analysis (pooled data) was 76.6% (95% CI: 72-81%) and 73.7% (95% CI: 69-78%) with proton pump inhibitor, C and A. The OR for the effect of RBC vs. proton pump inhibitor (plus C and A) on H. pylori eradication was 1.15 (95% CI: 0.8-1.64%). Mean H. pylori eradication with RBC, C and N was 87. 2% (95% CI: 83-91%), and 74.9% (95% CI: 74-84%) with proton pump inhibitor plus these two antibiotics. The OR for the effect of RBC vs. proton pump inhibitor (plus C and N) on H. pylori eradication was 1.76 (95% CI: 1.08-2.85%). CONCLUSION: RBC and proton pump inhibitor have similar efficacy for H. pylori eradication when given with C and A for 1 week, but RBC seems to have a higher efficacy than proton pump inhibitor when C and N are the co-prescribed antibiotics. (+info)
Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole.
(28/721)
The effectiveness of metronidazole (Flagyl) and nimorazole (Naxogin) has been compared by using these drugs in the recommended dosage in alternate patients in a series of 218 consecutive cases of vaginal trichomoniasis. Follow-up tests in 100 patients treated with metronidazole and 97 treated with nimorazole indicated cure-rates of 95 and 82 per cent. respectively. Male consorts were examined and given treatment on epidemiological grounds in about 70 per cent. of both treatment groups. Both drugs were free from significant side-effects. The causes of treatment failure in trichomoniasis are discussed and the desirability of relating dosage to the patient's body-weight is suggested. This factor may be especially important in deciding the dosage given on epidemiological grounds to the male consorts. It may also be an important advantage in the current trend of treating trichomoniasis in both sexes with larger doses over a much shorter time. (+info)
Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori.
(29/721)
AIM: To perform a meta-analysis of studies comparing twice daily, one-week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication. REVIEW METHODS: SELECTION CRITERIA: Comparative randomized trials of PCA vs. PCN were included. DATA SOURCES: PubMed database and abstracts from congresses until September 1999. STATISTICS: Meta-analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention-to-treat (ITT) and on a per protocol (PP) basis. RESULTS: Twenty-two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79-83%) ITT, and 84% (82-86%) PP with PCA, and 81% (78-83%) ITT and 84% (82-86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83-1.22) on an ITT, and 0.98 (0.8-1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78-85%) ITT, vs. 86% (83-89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48-0.98). Finally, when comparing PC(500 b.d. )A against PC(250 b.d.)N ITT cure rates were 77% (74-80%), and 75% (72-78%) with an odds ratio of 1.18 (0.93-1.5). CONCLUSION: Overall, one-week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.). (+info)
Cytotoxicity and probable mechanism of action of sulphimidazole.
(30/721)
Sulphimidazole (1-methyl-2((4-aminophenyl)-sulphonyl)-amino-5-nitroimidazole) is a new compound in which a p-aminobenzenesulphonamide radical has been attached at position 2 of the 5-nitroimidazole ring. It possesses a useful spectrum of activity in vitro against various anaerobic microorganisms and its action against aerobic and facultative bacteria is synergically enhanced in association with trimethoprim. In the present study, we determined the cytotoxicity in vitro of sulphimidazole and trimethoprim, both alone and in combination, and analysed the viability of Vero cells and the protein content of their cell lysate in the presence of increasing concentrations of these drugs. Also, in order to verify the hypothesis that the action of sulphimidazole against aerobic and facultative bacteria is mediated by the sulphonamide component of the molecule, while that against anaerobic bacteria depends on the action of the nitro group of the 5-nitroimidazole ring, we studied the mechanism of action of the new compound both indirectly, by means of microbiological techniques, and directly, by determining its oxidoreduction potential with respect to that of metronidazole. The results show that sulphimidazole is only slightly toxic in vitro for Vero cells, either alone or in association with trimethoprim, and that the combination of the two functional groups in a single molecule not only maintains its structure-activity relationship intact but also broadens its antibacterial spectrum. (+info)
Mutagenicity of nitrofurans, nitrothiophenes, nitropyrroles, nitroimidazole, aminothiophenes, and aminothiazoles in Salmonella typhimurium.
(31/721)
Thirty-two heterocyclic compounds, including 24 nitroheterocycles, 7 aminoheterocycles and derivatives, and 1 thiophene lacking a nitro group, were tested for mutagenic activity in Salmonella typhimurium TA 98 and TA 100. All the nitroheterocycles (11 new), including nitrofurans, nitrothiophenes, nitropyrroles, and 1 nitroimidazole, were mutagenic in TA 100; 13 were also mutagenic in TA 98. 5-Nitro-2-furoic acid, a noncarcinogen, was mutagenic in TA 100. Seven carcinogenic nitroheterocycles were mutagenic in both strains. Seven aminoheterocycles (4 new), aminothiophenes and aminothiazole derivatives, and 1 thiophene without a nitro group were not mutagenic. Both TA 98 and TA 100 were uvrB and lacked the ability of excision repair of DNA. Among the 24 mutagenic nitroheterocycles, only 13 compounds exhibited bacterial killing effects, suggesting that more than 1 mechanism may be involved in the interaction of nitroheterocycles with bacterial DNA. (+info)
Comparison between the comet assay and pimonidazole binding for measuring tumour hypoxia.
(32/721)
Pimonidazole is finding increasing use in histochemical analyses of hypoxia in tumours. Whether it can identify every hypoxic cell in a tumour, and whether the usual subjective criteria used to define 'positive' cells are optimal, are less certain. Therefore, our aim was to develop an objective flow cytometry procedure for quantifying pimonidazole binding in tumours, and to validate this method by using a more direct indicator of radiobiologic hypoxia, the comet assay. SCCVII tumours in C3H mice were analysed for pimonidazole binding using flow cytometry and an iterative curve-fitting procedure, and the results were compared to the comet assay for the same cell suspensions. On average, cells defined as anoxic by flow analysis (n = 43 tumours) bound 10.8 +/- 0.95 times more antibody than aerobic cells. In samples containing known mixtures of aerobic and anoxic cells, hypoxic fractions as low as 0.5% could easily be detected. To assess the flow cytometry assay under a wider range of tumour oxygen contents, mice were injected with hydralazine to reduce tumour blood flow, or allowed to breathe various gas mixtures during the 90 min exposure to pimonidazole. Hypoxic fraction estimated by the pimonidazole binding method agreed well with the hypoxic fraction measured using the comet assay in SCCVII tumours (r2 = 0.87, slope = 0.98), with similar results in human U87 glioma cells and SiHa cervical carcinoma xenografts. We therefore conclude that this objective analysis of pimonidazole labelling by flow cytometry gives a convenient and accurate estimate of radiobiological hypoxia. Preliminary analyses of biopsies from 3 patients given 0.5 g m-2 pimonidazole also suggest the suitability of this approach for human tumours. (+info)