Formaldehyde exposure and lower respiratory infections in infants: findings from the PARIS cohort study

Background: Certain chemical pollutants can exacerbate lower respiratory tract infections (LRIs), a common childhood ailment. Although formaldehyde (FA) is one of the most common air pollutants found in indoor environments, its impact on infant health is uncertain.Objective: Our aim was to determine the impact of FA exposure on the LRI incidence during the first year of life of infants from the Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort.Methods: FA was measured in a random sample of 196 infants’ dwellings, and exposure to this pollutant was estimated for 2,940 infants using predictive models based on measurements and data about potential determinants of FA levels. Health data were collected from parents by regular self-administered questionnaires. We used multivariate logistic regressions to estimate associations between FA exposure and the occurrence of LRI and wheezy LRI (wLRI), adjusting for potential confounders/risk factors.Results: During the first year of life, 45.8% of infants had at least one LRI, and LRI occurred simultaneously with wheezing in 48.7% of cases. The FA predictive models correctly classified 70% of dwellings as having high or low exposure, and we estimated that 43.3% of infants were exposed throughout the first year to levels of FA > 19.5 µg/m³. FA exposure was significantly associated with LRI and wLRI before and after adjustment for known LRI risk factors/confounders. For an interquartile increase in FA levels (12.4 μg/m³), we estimated a 32% [95% confidence interval (CI): 11, 55] and 41% (95% CI: 14, 74) increase in the incidence of LRI and wLRI, respectively.Conclusion: The findings of this study suggest that infants exposed to FA at an early age have an increased incidence of LRI.     

Competition in liver transport between chenodeoxycholic acid and ursodeoxycholic acid as a mechanism for ursodeoxycholic acid and its amidates'' protection of liver damage induced by chenodeoxycholic acid

BACKGROUND: Ursodeoxycholic acid has been widely used as a therapeutic agent in cholesterol gallstones and liver disease patients, but its mechanism of action is still under investigation. AIMS: The protective effect of ursodeoxycholic acid, both free, taurine and glycine conjugated, against hepatotoxic bile acids such as chenodeoxycholic acid and its taurine amidate was studied in bile fistula rats and compared with the cholic and taurocholic acid effect. METHODS: Tauroursodeoxycholic acid, glycine ursodeoxycholic acid, ursodeoxycholic acid, taurocholic acid and cholic acid were infused iv over 1 hour (8 micromol/min/kg) together with an equimolar dose of either taurochenodeoxycholic acid or chenodeoxycholc acid. Bile flow, total and individual bile acid and biliary lactate dehydrogenase and alkaline phosphatase enzymes were measured. RESULTS: Taurochenodeoxycholic acid and chenodeoxycholc acid caused cholestasis and liver damage associated with a decreased bile flow, total and individual bile acids secretion accompanied by a biliary leakage of lactate dehydrogenase and alkaline phosphatase enzymes. Tauroursodeoxycholic acid, glycine ursodeoxycholic acid, ursodeoxycholic acid and taurocholic acid, on the contrary, were choleretic, inducing an opposite effect on biliary parameters. Simultaneous infusion of taurochenodeoxycholic acid and the protective bile acid resulted in a functional and morphological improvement of the above parameters in the following order: glycine ursodeoxycholic acid > tauroursodeoxycholic acid > ursodeoxycholic acid followed by taurocholic acid; cholic acid was ineffective. CONCLUSIONS: The results show the protective effect of glycine ursodeoxycholic acid, ursodeoxycholic acid and tauroursodeoxycholic acid. This may be due to a facilitated transport of the toxic bile acid into bile; conjugation with taurine is less effective than glycine. Finally, the better protective effect of ursodeoxycholic acid and its amidates with respect to cholic acid and its taurine conjugated form seems to be related to their different lipophilicity and micellar forming capacity.     

Women Versus Men: Is There Equal Benefit and Safety from Statins?

Coronary heart disease (CHD) is the leading cause of death in the United States. CHD risk differs between genders, with coronary events lagging behind ten years for women in comparison to men. Low-density lipoprotein cholesterol lowering with statin therapy is a major target for cardiovascular risk reduction. The benefit of statin therapy has been well established in men, for both primary and secondary prevention. However, the same has not been shown for women. While studies have demonstrated benefit in women for secondary prevention, their role in primary prevention of cardiovascular disease remains controversial. Data released over the past several years regarding statin efficacy and safety in men and women has been inconsistent, given that these studies had small sample sizes with numerous study limitations. A recent large scale meta-analysis of both primary and secondary statin prevention trials with sex-specific outcomes demonstrated a similar benefit in both men and women. Statins demonstrated a decrease in cardiovascular events and all-cause mortality in both sexes. In regards to statin safety, additional trials investigating the difference in adverse events of statins in men versus women, particularly new onset of diabetes, myalgias, and liver dysfunction, are warranted. Increased awareness and monitoring of female patients for myalgias and hyperglycemia should be considered as a precaution. Overall, women need to be better represented in prospective clinical trials powered to evaluate gender-specific differences in statin safety and efficacy in the management of cardiovascular disease.     

Efficacy and safety of three 7-day Helicobacter pylori eradication regimens containing ranitidine bismuth citrate

Background:

This multicentre, randomized study was designed to assess the clinical efficacy, safety and tolerability of three novel 7-day triple therapies containing ranitidine bismuth citrate (RBC) and two antibiotics.

Methods:

We studied patients with non-ulcer dyspepsia and gastritis who were randomly assigned to one of three treatment regimens given for 7 days in a b.d. dosing schedule: RBC 400 mg plus clarithromycin 250 mg and tinidazole 500 mg (RBCCT); RBC 400 mg plus clarithromycin 500 mg and amoxycillin 1 g (RBCCA); RBC 400 mg plus tinidazole 500 mg and amoxycillin 1 g (RBCTA). H. pylori status was determined by CLO-test, histology and ¹³C-urea breath test. A repeat breath test was performed at least 28 days after completion of therapy to assess eradication.

Results:

One hundred and fifty-seven patients were eligible for intention-to-treat analysis (ITT) and 140 patients completed the study and returned for assessment of eradication. Intention-to-treat cure rates were 78% with RBCCT, 71% with RBCCA and 61% with RBCTA. An all-patients-treated analysis (APT), performed on evaluable patients, demonstrated eradication rates of 85% with RBCCT, 81% with RBCCA and 70% with RBCTA. No statistically significant difference was found between treatment groups. Twenty-four patients experienced side-effects, but in only seven cases was treatment discontinued due to adverse events.

Conclusions:

A 7-day course of RBC, clarithromycin and either tinidazole or amoxycillin provides a good rate of H. pylori eradication. Three novel RBC-based triple therapies proved to be safe and well tolerated, with discontinuations due to side-effects occurring in less than 5% of cases.

     

Living donor liver transplantation for neonatal fulminant hepatitis due to herpes simplex virus infection

Although rare, ALF caused by disseminated HSV infection is associated with high mortality in the neonatal population. This condition is often diagnosed relatively late due to the absence of specific signs. We present a case involving a neonate with ALF submitted to living donor liver transplantation without a prior diagnosis. The patient had no skin or mucosal lesions, and IgM serology was negative for HSV‐1 and HSV‐2. Immunohistochemical staining of the liver explant was positive for herpes virus infection, and the patient subsequently received antiviral drug treatment, with a good outcome. Due to organ shortages and the rarity of the aforementioned condition, LT has seldom been reported for the treatment of ALF caused by herpes virus infection; however, LT may be the only option for neonates with fulminant hepatitis. The use of living donors in an urgent scenario is well established in Eastern countries and safely applicable for pediatric patients with ALF.     

Endosonography in gastric lymphoma and large gastric folds.

To establish a correct preoperative differential diagnosis between gastric lymphoma and cancer is essential but can be difficult as endoscopic biopsies can sometimes provide a low diagnostic yield. By EUS, infiltrative carcinoma tends to show a vertical growth in the gastric wall, while lymphoma tends to show mainly a horizontal extension. EUS provides an accurate staging of gastric lymphoma, showing the exact level of infiltration and the presence of perigastric lymph nodes, thus the physician can obtain an accurate prognosis for each patient and select the best form of treatment accordingly. The response to chemoradiotherapy can also be investigated very accurately by EUS. Large gastric folds are seen in a great number of benign and malignant conditions. Diagnosis represents a clinical challenge because etiology may be extremely varied and standard biopsies are often inconclusive. Different diseases show different levels of infiltration of the gastric wall, thus a characteristic echo-pattern helps for the differential diagnosis. Endosonography, used always in combination with biopsy, allows to rule out malignancies and to select the most appropriate treatment for each patient (medical or surgical).     

Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression.

Fifty percent of individuals infected with human immunodeficiency virus type 1 (HIV-1) progress to AIDS in the presence of only non-syncytium-inducing (NSI) variants. These rapidly replicating NSI isolates are associated with a high viral load. The question of whether disease progression in the absence of syncytium-inducing (SI) HIV-1 variants is associated with an expansion of the coreceptor repertoire of NSI HIV-1 variants was studied. Biological HIV-1 clones were isolated both early and late in infection from progressors and long-term survivors with wild-type or mutant CCR5 or CCR2b genotypes and analyzed for their capacity to use CCR1, CCR2b, CCR3, CCR5, and CXCR4 on U87 cells coexpressing CD4. All HIV-1 clones were restricted to the use of CCR5. Absent replication of all HIV-1 clones in peripheral blood mononuclear cells from a CCR5 Delta32 homozygous blood donor confirmed this result. These findings indicate that an expanded coreceptor repertoire of HIV-1 is not a prerequisite for a progressive clinical course of HIV-1 infection.     

Hippocampal cell loss in transient global cerebral ischemia in rats: a critical assessment.

The induction of transient global cerebral ischemia by permanent vertebral occlusion and temporary carotid ligation (four-vessel occlusion) is widely accepted as a valid tool for the study of pathogenesis and treatment of ischemia. The neural damage inflicted by this intervention is often assessed by measuring pyramidal cell loss in the CA1 hippocampal field. Nevertheless studies using this model in rats often fail to control variables that are relevant to the outcome, and/or apply biased methods to quantitate histological damage. We have applied unbiased stereological methods to estimate absolute numbers of surviving neurons in CA1 in Wistar rats subjected to either 10 or 20 min global ischemia using the Sugio et al. variant of the original four-vessel occlusion model. Animal mortality was high at both times, with neuron losses averaging 39% and 31%, respectively. Post-operative mortality was reduced substantially by using decompressive craniectomies and, even more effectively, by pre-treating the rats with low doses of phenytoin. Both maneuvers led to a severely increased CA1 neuron loss, which reached 50%, after an ischemia of 10 min. This finding strongly supports that mortality biases the sample. Other noteworthy findings that emerged from this study were a linear relationship between per-ischemic blood pressure increments and animal survival, and a negative correlation between cell survival and preferentially left-sided damage.