Fleroxacin pharmacokinetics in patients with liver cirrhosis.

In this open-label study, the disposition of fleroxacin in liver disease in 12 healthy male volunteers, 6 male cirrhotics without ascites (group A), and 6 male cirrhotics with ascites (group B) was evaluated. Fleroxacin (400 mg) was administered orally and intravenously to each subject in a random crossover fashion. Fleroxacin was completely absorbed and achieved similar peak concentrations in plasma in all three study groups (P greater than 0.05). The volume of distribution exceeded 1 liter/kg in healthy controls and was not affected by liver impairment (P greater than 0.05). Only group B demonstrated differences in the pharmacokinetic parameters evaluated: the systemic and renal clearances of fleroxacin and the renal clearances and clearances of the two major metabolites of fleroxacin formed, N-demethyl fleroxacin and fleroxacin N-oxide, were significantly lower and the half-lives of the parent drug and its metabolites were significantly longer in group B than in healthy controls and group A (P less than 0.05). The elimination of the two metabolites appeared to be formation rate limited in all three study groups. It was concluded from this study that a 50% reduction in the fleroxacin maintenance dose in patients with liver disease appears justified only in patients with ascites. However, no change in the fleroxacin loading dose is needed in patients with compromised liver function.     

TP53 status and gene amplification in human colorectal carcinomas

Gene amplification is one of the characteristics of cancer cells. In vitro studies suggested that alterations of the TP53 gene might be responsible for gene amplification. We have examined the presence of TP53 mutations and looked for cytogenetic evidence of gene amplification in a series of 79 primary colorectal carcinomas. Other parameters such as the pattern of cytogenetic alterations, microsatellite instability, tumor site, and histological staging were also considered. A multiparametric study supported by statistical analyses suggests the existence of two major pathways of colorectal carcinogenesis. No relationships could be established between the presence of TP53 alterations and gene amplification.     

Characterization of the viral-type nucleotide sequences detected in the RNA of human leukaemic cells by probes of murine and simian origins (author's transl)]

Molecular hybridization techniques were used for searching nucleic acid sequences homologous to murine and simian oncornaviral genomes in the RNA of various categories of human leukaemic cells. We report attempts to characterize the sequences that were detected in defined categories of leukemias. It is shown that: i) although there is some correlation between the two probes used in our study with regard to the positivity or the negativity of the tests for the same leukaemic cases, there are also some discrepancies since some of the cases are positive with one probe and negative with the other; ii) the common sequences of the two probes when isolated, were ineffective to detect any complementary sequences in leukemic cases which were scored as positive when the entire probes were used; iii) the complementary sequences detected in three positive cases of acute myelogenous leukemias by a recycled probe are additive and therefore most probably distributed along the viral genome.     

Residual nitrite and nitrate content in French cooked hams and shoulders]

The test laboratory of the "Centre technique de la salaison, de la charcuterie et des conserves de viandes" has evaluated the nitrite and nitrate salts contents of 1 468 cooked hams and shoulders. 90,5 p. 100 of sample have a sodium nitrite content of less than 150 mg/kg. 81,5 p. 100 have a potassium nitrate content of less than 500 mg/kg. The measured contents show a wide scattering. The nitrite mean content is of 61 mg/kg with a standard deviation of 95. The nitrate mean content is of 292 mg/kg with a standard deviation of 382. There were no significant variations between the various categories of cooked hams and shoulders.     

Analysis of the p21 gene in gliomas

The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.     

Association between depressive symptoms,CD4 count and HIV viral suppression among HIV-HCV co-infected people

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security &; HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300–665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4?=?0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.     

Anti‐LG3 Antibodies Aggravate Renal Ischemia–Reperfusion Injury and Long‐Term Renal Allograft Dysfunction

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia–reperfusion injury (IRI) can modify self‐antigenic targets. We hypothesized that ischemia–reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti‐LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti‐LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti‐AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti‐LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti‐LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti‐LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long‐term outcomes.     

Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety

OBJECTIVE: Esomeprazole, the S-isomer of omeprazole, achieves a significantly greater healing rate and symptom resolution of erosive esophagitis than that achieved by omeprazole. The objective of this study is to assess the efficacy of the new proton pump inhibitor esomeprazole in preventing relapse over a prolonged period in patients with healed erosive esophagitis. METHODS: A total of 318 gastroesophageal reflux patients whose erosive esophagitis was healed in a comparative study of esomeprazole 40 mg, 20 mg, or omeprazole 20 mg, were randomized to maintenance therapy with once daily esomeprazole 40 mg, 20 mg, or 10 mg, or placebo in a U.S., double-blind multicenter trial. RESULTS: After 6 months, healing was maintained (cumulative life table rates) in 93.6% (95% CI 87.4-99.7) of patients treated with esomeprazole 40 mg, 93.2% (95% CI 87.4-99.0) treated with esomeprazole 20 mg, and 57.1% (95% CI 45.2-69) treated with esomeprazole 10 mg; p < 0.001 vs placebo (29.1%; 95% CI 17.7-40.3). Of patients relapsing, mean time to first recurrence of esophagitis increased with dose, from 34 days (placebo) to 78 days (10 mg), 115 days (20 mg), and 163 days (40 mg). Patients treated with esomeprazole had less frequent and less severe heartburn than those treated with placebo. At month 6, more than 70% of patients being treated with esomeprazole remained symptom-free. CONCLUSIONS: Esomeprazole is effective and well tolerated in the maintenance of a healing erosive esophagitis. Esomeprazole 40 mg and 20 mg maintain healing in over 90% of patients while providing effective control of heartburn symptoms.