Potential therapeutic role of melatonin in hepatobiliary diseases: current evidence and clinical observations.

Melatonin (MEL) is produced and secreted by the pineal gland as well as the small intestine, liver, retina, lymphocytes, and melanocytes in the skin in both experimental animals as well as in humans. While pineal and retinas MEL is closely related to the light/dark cycle, the production of MEL by other so called extrapineal tissues is independent of such circadian rhythm. Among the primary mechanisms of action of MEL in humans, the most important are interaction of MEL with specific receptors (M1, M2, M3) and the MEL 'scavenging' activity against the formation of free oxygen metabolites as a result of MEL's ability to transfer free electrons and stimulation of the expression of redox reaction enzymes. In addition, MEL binds to intracellular proteins such as calmodulin, thereby affecting the course of cell cycle, and it has been shown to activate of nuclear receptors belonging to the retinoid orphan receptors/retinoid Z receptors (ROR/RZR) subfamily. MEL exerts regulatory effects on the master clock regulating diurnal rhythms. This updated review presents current view on the synthesis and metabolism of MEL and the growing body of experimental evidence transferable to the practical medicine supporting a pleiotropic molecule beneficial effects on the health including protection against various organ abnormalities, including internal organs such as the liver. Although the beneficial effects of MEL in various types of liver damage have been well documented in experimental studies, there are relatively few studies on liver dysfunction in humans. Considering the worldwide obesity pandemic often associated with the occurrence of steatohepatitis and cirrhosis, the beneficial effects of MEL in liver pathology should be proven in randomized trials involving patients presenting with hepatic disorders.

[Cause of non-pertinent hospital stays: interobserver concordance using the French version of the Appropriateness Evaluation Protocol]. / Etude de la concordance inter-observateurs des raisons de non-pertinence des journées d'hospitalisation identifiée par la version française de l'Appropriateness Evaluation Protocol (2e partie).

BACKGROUND: The modified French version of the Appropriateness Evaluation Protocol (AEPf) has been validated. Inappropriate days according to simple medical and technical criteria are identified with this tool. The aim of this study is to highlight the interest of investigating the reasons for inappropriate days and to assess the inter-observers reliability of the questionnaire developed for this purpose. METHODS: This questionnaire collects on one hand the needs of patients - distinguishing health care and accommodation needs - and on the other hand the reasons for inappropriate hospital days. The data were collected from January to September 1998 in nine voluntary medical and surgical departments. For each day of study randomly selected, each inappropriate hospital day according to AEPf has been included. Data were collected by two health professionals (a nurse and a physician), using a concurrent design. RESULTS: The reliability of the over-ride option of the appropriateness assessment of the 345 hospital days was good (overall Kappa coefficient: 0.66; 95% CI: 0.55-0.78). The comparison of the two expert judgments on health care needs fulfilled during the hospital day was acceptable; the Kappa coefficient was 0.62 (95% CI: 0.52-0.72). The reliability of expert assessment on patient accommodation needs (home, housing facilities or hospital) was good (Kappa coefficient: 0.67; 95% CI: 0.60-0.75). When hospital was not the accommodation the most adapted for patient, the reliability of the reasons for inappropriate days was high (Kappa coefficient: 0.75; 95% CI: 0.61-0.80). Kappa coefficients were different between hospitals, indicating a center effect. CONCLUSION: This instrument has been found to be reliable and should be used in complement of the first part of the AEPf which assess the prevalence of inappropriate days. It might help to detect dysfunctions within or outside the hospital and thus be used for evaluation or planning of health care.

Human papillomavirus genotype as a major determinant of the course of cervical cancer.

PURPOSE: To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS: Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS: HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION: The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.

[Urinary stress incontinence. Comparison of the Raz technique and the Bologna technique. Analysis of a series of 188 patients]. / Incontinence urinaire d'effort féminine. Comparaison de la technique de Raz et de la technique de Bologna. Analyse d'une série de 188 patientes.

OBJECTIVE: Our purpose was to evaluate and compare the perioperative morbidity and the long-term results of the Raz colposuspension and the Bologna operation for the treatment of stress urinary incontinence in women. STUDY DESIGN: Data of 188 women who underwent either a Bologna operation (group 1) or a Raz colposuspension (group 2) for the treatment of stress urinary incontinence between January 1, 1987 and December 1, 1995 were analysed retrospectively regarding history, preoperative evaluation, associated surgical procedures, complications and cure and failure rate. POPULATION AND METHODS: 80 patients were treated with the Bologna operation and 108 with the Raz colposuspension. Patients with prior anti-incontinence surgery, and patients with a preoperative diagnosis of urge incontinence were excluded from the study. Success was defined both subjectively (complete absence of complaint of stress urinary incontinence) and objectively (no evidence of loss of urine on cough provocation during physical examination). Survival curves were generated in each group for time to event data: "time to recurrent stress incontinence" and compared by the logrank test. A multivariate analysis using a Cox proportional hazards regression model was performed to indentify possible outcome predictors. RESULTS: The success rate of group 1 was significantly higher than that of group 2 (p = 0.00001). The median of success was 51 months in group 1 and 21 months in group 2 (p = 0.00001). The incidence of intraoperative complications in each group (inadvertent cystostomy, hemorrhage) did not differ. The multivariate analyses using the Cox regression model showed that the most highly correlated variable with the surgical cure rate was the type of surgical anti-incontinence procedure adopted: Bologna or Raz (p = 0.00001) CONCLUSION: In our hands, the Bologna operation has a higher cure rate than the Raz colposuspension. For us, when treating patients with stress urinary incontinence by the vaginal route, the Bologna operation is indicated when sufficient anterior vaginal tissue is available to create vaginal bands.

The Bologna bladder neck suspension procedure for treatment of stress urinary incontinence associated with cystocele.

The object was to study retrospectively the perioperative complications and results of the Bologna procedure for the treatment of stress urinary incontinence associated with cystocele grade 2 or more. In the study, 80 patients underwent a repair of all defects of pelvic support plus the Bologna procedure. Mean duration of follow-up was 40.2 months (range 3-127). The incidence of operative complications was 2.5% for inadvertent cystostomy and for hemorrhage. Mean hospital stay was 7.2 days (range 2-17). At 2-year follow-up 85% of the patients were completely free of incontinence symptoms (95% CI: 75-92) and 76% at 3-year follow-up (95% CI: 66-86). None of the parameters tested in a univariate analysis was independently linked with surgical failure. Further studies are needed to establish the place of this technique in the surgical management of urinary incontinence associated with genital prolapse.