Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease. / Análisis de la relación entre polimorfismos en regiones diana de micro-ARN y la enfermedad hepática alcohólica.

INTRODUCTION: Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. PATIENTS AND METHODS: The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. RESULTS: Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. CONCLUSIONS: Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development.

Inter-relationship between serum potassium and plasma catecholamines and 3':5' cyclic monophosphate in alcohol withdrawal.

Serial analyses of serum potassium and plasma epinephrine, norepinephrine and adenosine 3':5'-cyclic monophosphate (cyclic AMP) concentrations were measured in 13 patients with alcohol withdrawal, six of whom presented delirium tremens. Patients with delirium showed at admission levels of potassium (3.45 +/- 0.45 mmol/l) lower (P less than 0.02) than patients without delirium (3.81 +/- 0.14 mmol/l). Three patients were hypokalemic, all of them with delirium. Serum potassium increased significantly in all the patients during evolution. A close negative correlation (r = -0.751) between the intensity of withdrawal and serum potassium was observed. Plasma epinephrine concentrations were increased at admission (623 +/- 192 pmol/l), patients with delirium showing greater values (705 +/- 137 pmol/l). As the alcohol withdrawal improved, plasma epinephrine concentration decreased. Plasma norepinephrine concentrations were also increased at admission (3422 +/- 1451 pmol/l), but did not change significantly during evolution, being similar in patients with and without delirium. Plasma cyclic AMP levels were high at admission (40.4 +/- 24.3 nmol/l) and increased significantly (P less than 0.05) during evolution. The data obtained suggest that in patients with alcohol withdrawal, as symptomatology improves, plasma epinephrine decreases, while plasma norepinephrine remains increased. The combined actions of the two facts--less beta-stimulus, maintaining of alpha-stimulus--would comprise a significant increase of kalemia, that in cases of initial hypokalemia would lead to normal values of serum potassium.

[Olivo-pontocerebellar atrophy. Report of a case (author's transl)]. / Atrofia olivo-pontocerebelosa: a propósito de un caso.

A case of hereditary olivo-pontocerebellar atrophy is reported. The patient presented with intentional tremor and slurred speech, and physical examination disclosed a bi-hemispherical cerebellar syndrome, involvement of the IX and X cranial nerves, and retinitis pigmentosa. Computerized axial tomography demonstrated a supra and infratentorial atrophy, predominating in the brain stem and cerebellum. The literature on olivo-pontocerebellar atrophy is reviewed, verifying the ample clinical spectrum of this disorder amongst the spinocerebellar degeneration syndromes, and emphasizing the diagnostic value of computerized axial tomography.

[Amplitude of the distribution of erythrocyte size in the differential diagnosis of microcytic anemia]. / Amplitud de distribución del tamaño eritrocitario en el diagnóstico diferencial de una anemia microcítica.

A prospective study was carried out in 83 patients with microcytic anemia. 43 had iron deficiency anemia, 28 had heterozygous beta thalassemia not associated with iron deficiency (beta-THNID) and 12 had both conditions. The behavior of red blood cell volume distribution width (RDW) was evaluated in all patients. RDW was higher in patients with iron deficiency (20.62 +/- 4.64) and beta-THNID (15.76 +/- 1.41) than in controls (13.29 +/- 0.92) (p less than 0.0001 for both comparisons). There also were statistically significant differences (p less than 0.0001) between both patient groups. In patients with both heterozygous beta thalassemia and iron deficiency (beta-THID), RDW reached similar values to those from patients with only iron deficiency anemia. A significant negative correlation was also found between the transferrin saturation index and RDW (r = -0.614, p less than 0.02). In 34 patients controlled during iron replacement therapy a significant increase of RDW was found after one month of treatment, while hemoglobin concentration and mean corpuscular volume became normal. When 18 was taken as cutoff value for RDW, its positive predictive value was very high in iron deficiency (95%), while it was only 59% in beta-THNID. England's index may help to differentiate between isolated iron deficiency anemia and beta-THID: in patients with RDW higher than 18, the positive predictive value of England's index was 89% for iron deficiency and 57% for beta-THID.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gallbladder torsion: report of a case]. / Torsión de la vesícula biliar: a propósito de un caso.

A case of an 81 year old woman who had fever, abdominal pain and a palpable mass in epigastrium and right hypochondriac region is presented. She was diagnosed as having acute cholecystitis and hydrops of the gallbladder. The surgical operation was performed and the findings were: dilated gallbladder with necrotic aspect, free floating with torsion of the cystic duct (greater than 180 degrees) wrapped in the mentum. There was no hepatic bed of the gallbladder. After correcting the torsion, the gallbladder was extirpated, with good clinical evolution. The etiopathogenia is discussed and the literature is reviewed. Despite the rareness of the gallbladder's torsion and the disease being relatively unknown, it has to be considered in the differential diagnosis of acute abdomen in the elderly.

A genetic variant in the microRNA-146a gene is associated with susceptibility to alcohol use disorders.

BACKGROUND: Polymorphisms in the microRNA (miRNA) regulatory pathways are novel functional genetic variants whose association with alcoholism susceptibility has not been previously studied. Given the potential relationship between certain miRNAs and alcohol use disorders (AUDs), this study was designed to explore the association between two polymorphisms within hsa-miR-146a and hsa-miR-196a2 genes and susceptibility to these diseases. METHODS: Three hundred and one male patients with AUDs and 156 sex-matched healthy volunteers were enrolled. Polymorphisms were genotyped using TaqMan(®) PCR assays. Allele and genotype frequencies were compared between groups and logistic regression analysis was also performed to analyze the model of inheritance. RESULTS: There was a significantly higher prevalence of allele C carriers (47.8%) of the miR-146a G>C polymorphism (rs2910164) among patients with AUDs when compared with controls (35.9%), and multivariable logistic regression analysis showed that the C allele was associated with these AUDs (OR=1.615, 95% CI 1.067-2.442; P=0.023). Neither the genotype nor the allele distribution of miR-196a2 polymorphism (rs11614913) was significantly different between groups. CONCLUSIONS: This is the first genetic association study to explore the relationship of miRNA polymorphisms with AUDs and to show an association of the miR-146a C>G rs2910164 allelic variant with this disease.

Systematic review with meta-analysis: the I148M variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis.

BACKGROUND: Several studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409 (C>G) in adiponutrin/patatin-like phospholipase domain-containing 3 gene (PNPLA3). AIM: To evaluate the influence of this variant on ALC and other forms of ALD. METHODS: We performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta-analysis was conducted in a random-effects model. Calculations of the odds ratios (ORs) and their confidence intervals (CIs), tests for heterogeneity and sensitivity analyses were performed. RESULTS: Database search identified 11 previous studies available for inclusion with a total of 3495 patients with ALD (2087 with ALC) and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD). Patients with ALC compared to controls had a significantly higher prevalence of the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25-5.69; P < 0.00001) or GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67-2.17) or under a recessive or dominant model. Similar results were found when comparing separately patients with ALC vs. alcoholics without ALD or healthy subjects. An association of the G allele with ALD emerged when comparing ALD patients vs. alcoholics without ALD and/or healthy subjects although moderate to large heterogeneity was observed. Our data suggested an additive genetic model for this variant in ALD. CONCLUSION: Our meta-analysis shows that the rs738409 variant of PNPLA3 is clearly associated with alcoholic liver cirrhosis.

[Impact of short-stay units on the quality of medical care in Spain]. / Influencia de las unidades de corta estancia en la calidad de la atención hospitalaria en España. Revisión sistemática.

OBJECTIVE: Short-stay units (SSUs) have been developed as an alternative to conventional hospitalisation. The aim of this study is to analyse the impact of short-stay units on the quality of medical care in Spain. MATERIAL AND METHODS: A systematic review was performed by retrieving studies that analysed the results of SSUs in Spain, in terms of clinical effectiveness, efficiency and satisfaction among patients, using an electronic database search (Pubmed/Medline and Spanish Medical Index) and a review of selected references. The data collected included, mortality, length of stay and re-admission rates, as well as other variables. RESULTS: Twenty-seven articles were found, with a great heterogeneity in both study design and type of SSU analysed. After analysing results, it was observed that SSUs in Spain provided effective clinical care. Low-quality evidence was also found supporting the hypothesis that SSUs are able to reduce overall length of stay in the whole hospital or department where they were created. There are not enough data to support any other advantages or benefits of SSUs, when compared with other hospitalisation units. CONCLUSIONS: SSUs may be able to effectively improve clinical care in selected patients, and may help to shorten overall length of stay. Further research is needed in order to define their exact role and to establish their optimal model.

Meta-analysis: glutathione-S-transferase allelic variants are associated with alcoholic liver disease.

BACKGROUND: Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione-S-transferases (GST) have been associated with ALD vulnerability with controversial results. AIM: To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta-analysis. METHODS: We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta-analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed. Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta-analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR=1.43; 95% CI: 1.14, 1.78; P=0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR=2.04; 95% CI: 1.09, 3.80; P=0.03). CONCLUSIONS: Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione-S-transferase as a potential therapeutic target in alcoholic liver disease is reinforced.