S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results

S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.     

Incisional surgical infection in heart transplantation

Background. Incisional surgical site infections (ISSIs) are common bacterial infections in heart transplantation (HT). The purpose of this study was to determine the incidence, etiology, timing, and risk factors for ISSIs.
Methods. A prospective study was performed, which included all heart transplants carried out in the participating hospitals (pertaining to the Spanish National Hospital Network RESITRA) between August 2003 and February 2005. A population of 292 consecutive patients was included (84.9% males). The definition of ISSI used in the study was based on the Centers for Disease Control criteria.
Results. Seventeen episodes of ISSIs were recorded in 14 patients (4.8%; confidence interval [CI] 95% 2.7–7.7%). The median time from transplant to ISSI was 14 days (range 3–75). Two patients (14%) died; fatality was related to ISSI (mediastinitis) in 1 patient (7%). Coagulase-negative staphylococci (7 cases), methicillin-resistant Staphylococcus aureus (3 cases), Proteus mirabilis , extended-spectrum β-lactamase-producing Escherichia coli , Candida albicans , and Candida glabrata , 1 case each, were the isolated pathogens. The duration of extracorporeal circulation was longer in patients with ISSI, although the difference did not reach statistical significance. Antibiotic prophylaxis with ciprofloxacin alone (odds ratio, 15.8; 95% CI, 1.2–216.9) was independently associated with the development of ISSI.
Conclusions. ISSIs in HT are frequently caused by resistant bacteria and Candida , but are associated with good prognosis.     

Optimism predicts resilience in repatriated prisoners of war: a 37-year longitudinal study

Resilience, exhibiting intact psychological functioning despite exposure to trauma, is one perspective as to why some people who are exposed to trauma do not develop symptoms. This study examines the prisoner of war experience to expand our understanding of this phenomenon in extreme cases of trauma such as prolonged captivity, malnourishment, and physical and psychological torture. The study examined the United States' longest detained American prisoners of war, those held in Vietnam in the 1960s through early 1970s. A logistic regression analysis using resilience, defined as never receiving any psychiatric diagnosis over a 37-year follow-up period, as the outcome was performed (n = 224 with complete data). Six variables showing at least small effects emerged: officer/enlisted status, age at time of capture, length of solitary confinement, low antisocial/psychopathic personality traits, low posttraumatic stress symptoms following repatriation, and optimism. Odds ratios (ORs) and confidence intervals (CIs) confirmed the significance and relative strength of these variables, with a range from OR = 0.54, 95% CI [0.13, 2.29] to OR = 1.11, 95% CI [1.04, 1.17]. When all variables were examined continuously and categorically, dispositional optimism was the strongest variable, accounting for 17%, continuously, and 14%, categorically. We discuss optimism as a protective factor for confronting trauma and the possibility of training to increase it.     

Health status and health practices--Alameda and beyond

Using the population of St John's, Newfoundland, we did a constructive replication of previous studies testing the association between health practices and health status. A telephone questionnaire was applied to all adults in a probabilistic sample of households (3300 subjects, 85% response rate). Several health practices and preventive behaviours indexes were developed and tested. An additive index of six practices (breakfast, sleeping, drinking, smoking, weight and exercise) using the Alameda County definitions, and an additive score of five practices (excluding breakfast and with revised definitions for smoking, drinking and exercise) were analysed using log-linear models; there was association between the indexes and self-assessed health status when controlling for sex, age and education, with the exception of the six-practice index in males. The association between these two indexes and several variables and constructs of health status showed that the best relationships were with self-assessed health status and with a construct including variables measuring subjective health.     

Age-dependent changes in nitric oxide synthase activity and protein expression in striata of mice transgenic for the Huntington’s disease mutation

Huntington’s disease (HD) is an autosomal hereditary neurodegenerative disorder caused by an abnormal expansion of the CAG repeats that code for a polyglutamine tract in a novel protein called huntingtin (htt). Both patients and experimental animals exhibit oxidative damage in specific areas of the brain, particularly the striatum. Nitric oxide (NO) is involved in many different physiological processes, and under pathological conditions it may promote oxidative damage through the formation of the highly reactive metabolite peroxynitrite; however, it may also play a role protecting cells from oxidative damage. We previously showed a correlation between the progression of the neurological phenotype and striatal oxidative damage in a line of transgenic mice, R6/1, which expresses a human mutated htt exon 1 with 116 CAG repeats. The purpose of the present work was to explore the participation of NO in the progressive oxidative damage that occurs in the striata of R6/1 mice. We analyzed the role of NO by measuring the activity of nitric oxide synthase (NOS) in the striata of transgenic and control mice at different ages. There was no difference in NOS activity between transgenic and wild-type mice at 11 weeks of age. In contrast, 19-week-old transgenic mice showed a significant increase in NOS activity, compared with same age controls. By 35 weeks of age, there was a decrease in NOS activity in transgenic mice when compared with wild-type controls. NOS protein expression was also determined in 11-, 19- and 35-week-old transgenic mice and wild-type littermates. Our results show increased neuronal NOS expression in 19-week-old transgenic mice, followed by a decreased level in 35-week-old mice, compared with controls, a phenomenon that parallels the changes in NOS enzyme activity. The present results suggest that NO is involved in the process leading to striatal oxidative damage and that it is associated with the onset of the progressive neurological phenotype in mice transgenic for the HD mutation.     

Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1.

We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2(Delta27/Delta27) mutation). In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2(Delta27/Delta27) mice, either young or adult. Additionally, a high incidence of spontaneous chromosomal instability was observed in Brca2(Delta27/Delta27) bone marrow (BM) cells, but not in Brca2(+/Delta27) or Fanca(-/-) BM cells. Although Brca2(Delta27/Delta27) CFCs were not hypersensitive to ionizing radiation, a very severe hematopoietic syndrome was observed in irradiated Brca2(Delta27/Delta27) mice. Conventional BM competition experiments showed a marked repopulation defect in Brca2(Delta27/Delta27) hematopoietic stem cells (HSCs), compared to wild-type HSCs. Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2(Delta27/Delta27) HSCs maintained in their natural physiological environment. The progressive repopulation of wild-type HSCs transplanted into unconditioned Brca2(Delta27/Delta27) recipients is reminiscent of the somatic mosaicism phenomenon observed in a number of genetic diseases, including FA. The hematopoietic phenotype associated with the Brca2(Delta27/Delta27) mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy.     

Assessment of multiple coagulase-negative staphylococci isolated in blood cultures using pulsed-field gel electrophoresis

One of the criteria used to determine the clinical importance of coagulase-negative staphylococci (CMS) is the isolation of the bacteria from sequential blood cultures. Sequential isolates of CNS obtained from five immunocompromised patients over three months were genetically characterized by pulsed-field gel electrophoresis (PFGE). This typing method was compared to two first-line typing methods: determination of the species and of antibiotic susceptibility. In four patients the initial clinical evaluation changed because of the PFGE results; several episodes of bacteremia would have been wrongly assessed if only the biotype and the antibiotype had been determined. Pulsed-field gel electrophoresis should therefore be used for CNS strains from immunocompromised patients or those suffering from chronic diseases with non-concordant biotype and antibiotype.