Suppression of alcohol delirium tremens by baclofen administration: a case report

Delirium tremens (DT) is a clinical condition that appears in some patients affected by severe alcohol withdrawal syndrome (AWS). DT represents a serious complication, being characterized by elevated morbidity and mortality. Benzodiazepines are presently the drug of choice; however their use is related to several side effects. Baclofen is a stereoselective gamma-aminobutyric acid (GABAB) receptor agonist. Recent studies show that baclofen is able to suppress alcohol withdrawal symptoms. At present there are no data on the effects of baclofen administration in AWS complicated by DT. Here, we report a case of DT successfully treated with baclofen. This result indicates that the efficacy of baclofen in the treatment of DT should be examined in future clinical trials.     

Immunotherapy with recombinant SFV-replicons expressing the P815A tumor antigen or IL-12 induces tumor regression

Replicons based on alphaviruses are emerging as candidate vectors for vaccination and gene therapy purposes. We have reported previously that mice vaccinated with a recombinant Semliki Forest virus (a member of the alphavirus genus) carrying the gene encoding the P815A tumor antigen (rSFV/E-P1A) were protected against a lethal challenge with the P815 tumor. In this study we investigated the anti-tumor therapeutic efficacy of rSFV/E-P1A or rSFV expressing the cytokine interleukin 12 (rSFV/IL12) on Day 5-established tumors. The results show that both antigen-specific and cytokine-mediated rSFV treatments exhibited a significant effect on P815 tumor growth, by delaying tumor progression and even inducing complete tumor regressions in several mice. The therapeutic potency of these vectors was dependent on the size of the treated tumor, as treatment of mice bearing larger tumors showed lower efficacy. In addition, rSFV treatment resulted in long-term immunity as observed by the lack of tumor recurrence in the majority of tumor-regressing mice after rechallenge with the tumor. Furthermore, the anti-tumor therapeutic effect was only achieved by local intratumoral injection of rSFV, as treatment by injection in the contralateral site resulted in tumor progression comparable to control-untreated mice. Accordingly, expression of a rSFV-RNA was localized to the tumor and draining lymph node. These results further demonstrate the potential of rSFV replicons as tumor therapeutic agents.     

Environmental prevention in atopic eczema dermatitis syndrome (AEDS) and asthma: avoidance of indoor allergens

 Indoor allergens represent an important precipitating factor for both asthma and atopic eczema dermatitis syndromes (AEDS). There is also accumulating evidence that sensitization to those allergens is associated with the onset of atopic disorders. Patients with AEDS present aeroallergen-specific T-cell responses associated with worsening of symptoms when exposed to specific aeroallergens. Furthermore, application of indoor allergens to the skin of patient with AEDS induces a local eczematous response in one-third of these patients. Exposure to high concentrations of mite allergens in early infancy have been demonstrated to be a risk factor for developing atopic dermatitis during the first 3 years of life. Moreover, a clear dose–response relationship has been documented between mite exposure and disease activity. Primary prevention of AEDS by avoiding indoor allergen exposure has been proved to be effective only when allergenic foods have also been avoided. Mite allergen avoidance in infants with AEDS and food allergy may however, prevent mite sensitization and the onset of asthma. Indoor allergen avoidance has been demonstrated to be effective in the majority of studies performed in patients with established AEDS. Negative results may be explained either by individual susceptibility variation, by long duration of disease with the consequent irreversible pathological changes in the target tissue or by exposure to allergens outside the house. Education of the patients and public consciousness of the problems are crucial for the efficacy of indoor allergen avoidance in allergic diseases.     

Endothelin‐1 effects on spontaneous oscillations in choroidal arterioles

Acta Ophthalmol. 2010: 88: 742–747

Abstract.

Purpose: This study characterizes the effects of endothelin‐1 (ET‐1) on the perfusion pressure of the choroidal vasculature using in situ perfused isolated rabbit eyes. Methods: Rabbit external ophthalmic arteries (n = 12) in a head‐mounted preparation were cannulated and perfused with warmed tyrode. The three‐way polypropylene catheter was further connected to a pressure transducer and the effect of intraluminal pressure as a measure of total vascular resistance was assessed. Response curves to intra‐arterial injections of ET‐1 (group A; n = 6) and to an intravitreal injection followed by an intra‐arterial injection of ET‐1 (group B; n = 6) were obtained. Data were studied using paired t‐test and fast Fourier transform. Results: Before any drugs were administered, spontaneous oscillations were observed in the 12 rabbit models. In group A, ET‐1 induced a short and weak vasodilating effect followed by a strong and long‐lasting vasoconstrictor tone. Vasomotion became more evident, showing a higher frequency and shorter amplitude of oscillations. In group, B the intravitreal injection produced no significant changes in registered pressure or vasomotion characteristics. The intra‐arterial injection produced effects similar to those observed in group A. Conclusion: Our study has three main findings: (i) the choroidal vasculature demonstrated spontaneous oscillations in perfusion pressure in basal conditions in all rabbit eye models; (ii) ET‐1 applied intra‐arterially induced a short drop in perfusion pressure followed by a long withstanding contraction; and (iii) intra‐arterial ET‐1 modulated the frequency and amplitude of the spontaneous oscillations, causing a faster rate of pulsatility.     

Nutritional Status and Body Fluid Distribution in Chronic Alcoholics Compared With Controls

BACKGROUND: At present few data are available on the total body water (TBW) content and in particular on the distribution of water in the intra- and extracellular compartments (ICW and ECW) of alcoholics. The aim of this study was to evaluate TBW, ICW, and ECW in chronic alcoholic patients. METHODS: Thirty-six alcoholics meeting DSM-III-R criteria for diagnosis (20 men, 16 women; body mass index [BMI] 22.3+/-2.57 kg/m2) were enrolled. Fifty-four healthy social drinkers (31 men, 23 women; BMI 23.7+/-1.68 kg/m2) matched for age and height were used as controls. Systolic and diastolic blood pressure was measured for all cases. All patients were assessed using specific anthropometric measurements. The waist-to-hip ratio (WHR) was used as an indicator of body fat distribution. TBW was measured by isotopic dilution by giving 100 microCi of tritiated water. ICW and ECW were assessed by multifrequence bioelectric impedance analysis (BIA). Basal metabolic rate (BMR) was measured by indirect calorimetry. RESULTS: Body weight was lower in the alcoholics than in the controls (61.9+/-5.5 kg vs. 65.8+/-5.2 kg;p < 0.01), essentially due to a reduction in fat mass. Significantly higher WHR values were found in both male (p < 0.001) and female (p < 0.001) alcoholics than in healthy subjects. A higher ECW/TBW ratio was found in the alcoholics compared with the controls, both as a whole (0.53+/-0.04 vs. 0.41+/-0.03; p < 0.0001) and separated by gender (p < 0.001). CONCLUSIONS: The increased ECW could derive from an increase in cellular permeability related to endothelial damage linked to the vasoconstriction present in the alcoholics and/or to a direct toxic effect of ethanol on cellular membranes. In addition, because the high ECW volumes correlated positively with WHR in the alcoholics, a potential association of these two factors in determining an increased risk of liver disease, hypertension, and cardiovascular disease may exist. Finally, the lower TBW characteristic of women may be one of the reasons for the observed greater rate of toxic effects of ethanol that occur in women.     

Epidemiology and outcomes of peritonitis in children on peritoneal dialysis in Australasia

Peritonitis is a common complication and major cause of morbidity in children on peritoneal dialysis. In this retrospective longitudinal study, we analysed data retrieved from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) on 167 patients aged less than 18 years of age who were treated with peritoneal dialysis during the period from October 2003 to December 2007. During this period there were 100 episodes of peritonitis in 57 patients (0.71 episodes/patient-year), with Gram-positive organisms most commonly isolated (44%). Peritonitis occurred frequently in the first 6 months after starting dialysis, with survival analysis showing peritonitis-free survival rates of 72%, 56% and 36% at 6 months, 1 year and 2 years respectively. Age was a weak predictor of peritonitis on univariate analysis, but previous peritonitis was the only significant predictor in a multivariate Cox proportional hazards model (adjusted hazard ratio 2.02; 95% CI: 1.20 to 3.40, p = 0.008). Peritonitis episodes infrequently resulted in relapse (5%), recurrence (7%) or the need for either temporary or permanent haemodialysis (5% and 7% respectively) and there were no patient deaths directly attributable to peritonitis. Compared with single organism peritonitis, polymicrobial peritonitis was not associated with any statistically significant differences in outcome. Further prospective studies are required to determine the most appropriate prophylactic measures and antibiotic regimens for use in pediatric patients.     

Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical characterization, and medical conditions

The objective of this study was to estimate the prevalence of autistic spectrum disorder (ASD) and identify its clinical characterization, and medical conditions in a paediatric population in Portugal. A school survey was conducted in elementary schools, targeting 332 808 school-aged children in the mainland and 10 910 in the Azores islands. Referred children were directly assessed using the Diagnostic and Statistical Manual of Mental Disorders (4th edn), the Autism Diagnostic Interview–Revised, and the Childhood Autism Rating Scale. Clinical history and a laboratory investigation was performed. In parallel, a systematic multi-source search of children known to have autism was carried out in a restricted region. The global prevalence of ASD per 10 000 was 9.2 in mainland, and 15.6 in the Azores, with intriguing regional differences. A diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders.     

Genome-wide expression patterns of invasion front, inner tumor mass and surrounding normal epithelium of colorectal tumors

Background

The normal human prostate glandular epithelium has the unique function of accumulating high levels of zinc. In prostate cancer this capability is lost as an early event in the development of the malignant cells. The mechanism and factors responsible for the ability of the normal epithelial cells to accumulate zinc and the loss of this capability in the malignant cells need to be identified. We previously reported that Zip1 is an important zinc uptake transporter in prostate cells and is down regulated in the malignant cells in situ along with the depletion of zinc levels. In this report we investigated the expression of two other Zip family zinc transporters, Zip2 and Zip3 in malignant versus nonmalignant (normal and BPH) glands. Zip2 and Zip3 relative protein levels were determined by immunohistochemistry analysis of human prostate tissue sections.

Results

Normal and BPH glandular epithelium consistently exhibited the strong presence of both Zip 2 and Zip3; whereas both transporters consistently were essentially non-detectable in the malignant glands. This represents the first report of the expression of Zip3 in human prostate tissue; and more importantly, reveals that ZiP2 and Zip3 are down regulated in malignant cells in situ as we also had demonstrated for Zip1. Zip2 and Zip3 transporter proteins were localized predominantly at the apical cell membrane, which is in contrast to the Zip1 localization at the basolateral membrane. Zip2 and Zip3 seemingly are associated with the re-uptake of zinc from prostatic fluid.

Conclusion

These results coupled with previous reports implicate Zip2 and Zip3 along with Zip1 as important zinc uptake transporters involved in the unique ability of prostate cells to accumulate high cellular zinc levels. Zip1 is important for the extraction of zinc from circulation as the primary source of cellular zinc. Zip 2 and Zip3 appear to be important for retention of the zinc in the cellular compartment. The down regulation of all three transporters in the malignant cells is consistent with the loss of zinc accumulation in these cells. Since zinc imposes tumor suppressor effects, the silencing of the gene expression for these transporters is a required event for the manifestation of the malignant activities of the neoplastic cells. This now provides new insights into the genetic/molecular events associated with the development of prostate cancer; and supports our concept of Zip1, and now Zip2 and Zip3, as tumor suppressor genes and zinc as a tumor suppressor agent.