Detection of hypoxia by measurement of DNA damage and repair in human lymphocytes (comet assay): a predictive variable for tumor response during chemotherapy in patients with head and neck squamous cell carcinoma

BACKGROUND: Only few studies have tried to identify parameters at the time of diagnosis or during treatment that can assist the clinician in predicting the response to Cisplatin, 5-Fluorouracil +/- Folinic acid therapy in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The alkaline comet assay was used to measure both cellular hypoxia and DNA single-strand break (ssb) kinetics in individual lymphocytes of HNSCC patients undergoing combined therapy. The intracellular level of FdUMP, dUMP and mTHF were also measured during treatment. RESULTS: Two distinct types of cell populations were detected, from the less damaged population representing the hypoxic cells to the most damaged cells population representing the aerobic cells. We also described a direct relationship between DNA damage and repair and drug metabolism in lymphocytes and treatment efficacy. CONCLUSION: The response of tumors to chemotherapy is thought to be a function of the drug's pharmacological properties (the intracellular level of FdUMP and mTHF). In addition, a relationship between platinum DNA adduct levels in lymphocytes DNA (comet assay) and tumor response has been observed, suggesting that clinical resistance to platinum drugs is attributable to DNA repair functions of the host, and thus the degree of cytotoxicity is similar across all cell types.     

A systematic review of Helicobacter pylori eradication therapy—the impact of antimicrobial resistance on eradication rates

BACKGROUND: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates. METHODS: A comprehensive search of all published trials on H. pylori eradication therapy was carried out via an electronic database search, hand-searching and checking reference lists of pharmaceutical companies and other reviews. Full papers and abstracts in the English language which study currently advised eradication regimes were included. RESULTS: 770 study-arms were analysed. Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92%. In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth-based triple and proton pump inhibitor-based triple therapies. For quadruple therapy, a significant difference in efficacy was found in the equal-effects analysis; however, this could not be confirmed in the random-effects analysis. In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one- and two-week clarithromycin containing proton pump inhibitor-triple therapies and of 58% for two-week ranitidine bismuth citrate combined with clarithromycin therapies. For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce. CONCLUSIONS: The cure rate with most regimens dropped significantly, in case of nitroimidazole-resistant strains, compared to nitroimidazole-susceptible strains. In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce. These data should allow physicians to make a better choice of an appropriate therapy for their patients.     

Review article: cardiac adverse effects of gastrointestinal prokinetics

Gastrointestinal prokinetics, such as metoclopramide, cisapride and levosulpiride, are widely used for the management of functional gut disorders. Recently, several studies have shown that cisapride (a partial 5-HT4 receptor agonist) can induce dose-dependent cardiac adverse effects, including lengthening of the electrocardiographic QT interval, syncopal episodes and ventricular dysrhythmias. Until recently, it was not clear whether these effects were dependent on 5-HT4 receptor activation or related to peculiar characteristics in the molecular structure of single agents within the benzamide class. Experimental evidence now favours the second hypothesis: cisapride possesses Class III antiarrhythmic properties and prolongs the action potential duration through blockade of distinct voltage-dependent K+ channels, thus delaying cardiac repolarization and prolonging the QT interval. Patients at risk of cardiac adverse effects are children, subjects with idiopathic, congenital or acquired long QT syndrome and, in particular, those receiving concomitant medication with Class III antiarrhythmic agents, some H1-receptor antagonists (e.g. terfenadine), or drugs such as azole antifungals (e.g. ketoconazole, itraconazole, miconazole and fluconazole) and macrolide antibacterials (e.g. erythromycin, clarithrod-mycin and troleandomycin), which can inhibit cisapride metabolism by interfering with the CYP3A4 isoenzyme.     

Port malaria caused by Plasmodium falciparum a case report

A case of unusual transmission by Plasmodium falciparum malaria is reported. The patient, had not been travelling outside North-West of Italy for the previous 6 months, he was not drug abuser. He had spent the last two months prior his admission, partly in his home town, an urban area in the region of Piemonte, and partly in a resort area on the Ligurian sea. Neither place has ever been associated with unusual malaria transmission. The possible transmission way is through a live vector imported from endemic area in a port terminal near a resort area.     

Histamine H2-receptor antagonists stimulate proliferation but not migration of human gastric mucosal cellsin vitro

Gastric mucosal cell migration and proliferation are crucial events in the repair of gastric mucosal erosions. This study was designed to test the hypothesis that the H₂ blockers roxatidine and ranitidine might stimulate migration and proliferation of gastric mucous cells derived from a human well-differentiated gastric adenocarcinoma cell line (MKN 28 cells)in vitro, in conditions independent of systemic factors and of acid inhibition. Confluent monolayers of MKN 28 cells were wounded with a razor blade and were then incubated with roxatidine or ranitidine. The number of cells migrating to the damaged area was determined 24 hr later. Cell proliferation was assessed by means of [³H]thymidine uptake and cell counts after incubation with roxatidine or ranitidine. Neither H₂ antagonist significantly stimulated cell migration. On the other hand, cell proliferation was dose-dependently and significantly enhanced by incubation with roxatidine and ranitidine. Exogenous administration of TGF- significantly stimulated MKN 28 cell division. However, incubation with roxatidine or ranitidine did not increase the steady-state mRNA expression of TGF- or EGFR as assessed by northern blot analysis. Based on thesein vitro findings, we postulate that the ulcer healing effect of these H₂ antagonistsin vivo might be due in part to stimulation of gastric mucosal cell proliferation.Data from this paper have been presented in part at the 1995 meeting of the American Gastroenterological Association and published in abstract form in Gastroenterology 108:A72, 1995.     

Outbreak of Escherichia coli O157 in Sweden

The Swedish Institute for Infectious Disease Control (Smittskyddsinstitutet - SMI) received no more than three reports of enterohaemorrhagic E. coli O157 infections (EHEC) each year from 1988 to 1994. About half of these were due to E. coli O157. In July     

The World Bank's perspective on global health

Over the next 25 years, as populations age and tobacco consumption increases, most developing regions will likely see noncommunicable diseases become the leading causes of disability and premature mortality. The already existing problems of malnutrition and infectious diseases will remain. In this context, the World Bank is examining its role and contribution to global health. From a small start approximately 25 years ago, the Bank has greatly expanded its role in international health, population, and nutrition to become the largest single external financier of health activities in low- and middle-income countries. Many other Bank-supported activities affect health, including poverty reduction, housing, water and sanitation, and the education of girls. The Bank is also increasingly active in health policy debates, publishing numerous studies annually. Most of these studies focus upon specific countries, but some address key issues of concern to many developing countries. This article explains why the Bank continues to expand its resources devoted to health and the rationale for the changing emphasis of its activities in the field.     

Variability of Clinical and Pressure-Flow Study Variables After 6 Months of Watchful Waiting in Patients with Lower Urinary Tract Symptoms and Benign Prostatic Enlargement

Purpose

We quantified the physiological variability of clinical and pressure-flow study variables in patients with symptomatic benign prostatic enlargement.

Materials and Methods

Symptom scores were measured, and advanced urodynamic studies with pressure-flow analysis were performed in 178 patients before and 6 months after a period of watchful waiting.

Results

Patients without bladder outlet obstruction experienced significant symptomatic improvement. Symptoms in patients with obvious bladder outlet obstruction did not improve significantly. The reproducibility of mean pressure-flow variables was evident. However, there was an important intra-individual variability. Patients with obvious bladder outlet obstruction showed a significant decrease in detrusor pressure at maximal flow of 14 cm. water, a significant decrease in the urethral resistance factor of 7 cm. water and a significant decrease of 1 obstruction class on the linear passive urethral resistance relation nomogram, indicating less severe bladder outlet obstruction.

Conclusions

Mean differences among therapy groups must be regarded critically, especially when the differences are slight and possibly within physiological variability.     

Sonographic findings in haemodialysis — related chronic arthropathy

In 33 subjects receiving long-term haemodialysis sonographic examination of shoulders, hips and knees was performed. Changes of both joints and periarticular soft tissues were found in 60 shoulders, 16 hips and 42 knees. In the shoulder besides the presence of tenosynovitis and bursitis, even significant thickening of rotator cuff and increased distance between capsule and bone in transascellar scan were found. Also, in the hip the distance between capsule and bone was significantly increased. In the knee effusion was present in 14 cases and synovial hypertrophy in 20. Articular femoral cartilage was significantly thinned. Results obtained suggest the hypothesis of the presence of an important inflammatory component in the pathogenesis of arthropathy related to haemodialytic treatment. The production of cytokines by mononuclear cells stimulated by -2 microglobulin may cause the inflammatory response. Sonographic findings of alterations in 42 symptomless joints show the importance of this diagnostic method to begin an early therapy.Correspondence to: G. Coari