Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients.

INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Heart disease in eosinophilic granulomatosis with polyangiitis (EGPA) patients: a screening approach proposal.

OBJECTIVE: To define the pattern of cardiac involvement in eosinophilic granulomatosis and polyangiitis (EGPA) and propose an algorithm for heart disease screening. METHODS: This was a retrospective study of EGPA patients attending a specialized vasculitis clinic (1989-2016). Clinical characteristics and cardiovascular evaluation (CE) results (serum troponin, ECG, echocardiography and cardiac magnetic resonance) were collected and compared according to symptoms and inflammatory cardiac disease (ICD). RESULTS: A total of 131 EGPA patients were included, of whom 96 (73%) had undergone CE. The median (interquartile range) age was 50 (38-58) years and 36% showed ANCA+. Asthma preceded diagnosis by a median of 97 (36-240) months. Among the 96 patients who underwent CE, 43% were symptomatic, with dyspnea (47%) and chest pain (29%) being the predominant symptoms. In asymptomatic patients, CE reported abnormalities in 45% of cases, with a subsequent earlier diagnosis (4 vs 11 months). Overall, 27 patients had EGPA-related ICD (EGPA-rICD) that was already present at diagnosis in 20 cases, preceded it in 2 cases and developed later in 5 cases. EGPA-rICD patients were younger (46 vs 50 years; P = 0.04), had more frequently abnormal ECG (30.8 vs 2.1%; P < 0.001), negative ANCA (85 vs 69%; NS), higher BVAS score (3 vs 1; P = 0.005), higher eosinophil count (5.60 vs 1.60 × 109/l; P = 0.029) and higher CRP (52 vs 15 mg/l; P = 0.017). Overall, 11% of cases with EGPA-rICD were asymptomatic. CONCLUSION: In our study, 45% of asymptomatic patients had an abnormal baseline cardiac evaluation, which allowed an earlier diagnosis of cardiac disease. We recommend prompt cardiac screening in all EGPA patients, instead of a symptoms-guided algorithm.

Effectiveness and Safety of Entecavir or Tenofovir in a Spanish Cohort of Chronic Hepatitis B Patients: Validation of the Page-B Score to Predict Hepatocellular Carcinoma.

BACKGROUND: Long-term antiviral therapy has resulted in viral suppression and biochemical response in chronic hepatitis B, although the risk of hepatocellular carcinoma has not been abolished. The Page-B score could be useful to estimate the probability of HCC. AIMS: To analyze the effectiveness and safety of entecavir or tenofovir for more than 4 years and the usefulness of Page-B score in the real-world setting. METHODS: Analysis of Caucasian chronic hepatitis B subjects treated with entecavir or tenofovir from the prospective, multicenter database CIBERHEP. RESULTS: A total of 611 patients were enrolled: 187 received entecavir and 424 tenofovir. Most were men, mean age 50 years, 32% cirrhotic and 16.5% HBeAg-positive. Mean follow-up was 55 (entecavir) and 49 (tenofovir) months. >90% achieved HBV DNA <69 IU/mL and biochemical normalization by months 12 and 36, respectively. Cumulative HBeAg loss and anti-HBe seroconversion were achieved by 33.7 and 23.8%. Four patients lost HBsAg; three HBeAg-positive. Renal function remained stable on long-term follow-up. Fourteen (2.29%) developed HCC during follow-up all of them with baseline Page-B ≥10. Nine were diagnosed within the first 5 years of therapy. This contrasts with the 27 estimated by Page-B, a difference that highlights the importance of regular HCC surveillance even in patients with virological suppression. CONCLUSIONS: Entecavir and tenofovir achieved high biochemical and virological response. Renal function remained stable with both drugs. A Page-B cut-off ≥10 selected all patients at risk of HCC development.

Core amino acid variation at position 110 is associated with sustained virological response in Caucasian patients with chronic hepatitis C virus 1b infection.

The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.

The nephrologist's role in metformin-induced lactic acidosis.

Metformin is an antihyperglycemic agent commonly used in diabetic patients. It is very effective and is able to reduce the plasma glucose and HbA1C. However, in some patients, specially those with comorbidities, metformin can provoke severe lactic acidosis with high morbimortality. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures; in severe cases, procedures of extrarrenal purification like hemodialysis or continuous hemodiafiltration have been successfully used.

[Treatment of uraemic anorexia with megestrol acetate]. / Tratamiento de la anorexia urémica con acetato de megestrol.

BACKGROUND: Anorexia is a common disorder in patients treated with regular haemodialysis and is a contributing factor to malnutrition. The aim of this study was to evaluate the effectiveness of megestrol acetate, an appetite stimulant used in cancer patients, as a treatment for anorexia in dialysis patients. MATERIAL AND METHOD: In 2009, 16 patients in our haemodialysis unit, three with diabetes mellitus, were treated with megestrol (160 mg/day single dose) for anorexia defined according to a Likert scale of appetite. The schedule and dialysis dose were not changed during the study. RESULTS: In the third month of treatment there was, in the overall group, an increase in dry weight (60.8 vs 58.9 kg, P<.01), in albumin concentration (4.02 vs 3.8 g/dl, P<.05), in creatinine concentration (9.73 vs 8.26 mg/dl, P<.01), and protein catabolic rate (1.24 vs. 0.97 g/kg/day, P<.0001). Non-significant variations in the concentration of haemoglobin, erythropoietin dose, and lipid concentrations were found. One patient with diabetes mellitus had to increase the dose of insulin and two other patients suffered mild hyperglycaemia. Megestrol acetate did not suppress the secretion of pituitary sex hormones, but in 3 of 10 patients studied was found inhibition of ACTH secretion. The response was not homogeneous: one patient did not respond and reduced his dry weight, in 5 the weight gain was minimal (less than 1 kg) and in the remaining ten the response was good, with an increase in dry weight ranging between 1.5 and 5.5 kg. CONCLUSIONS: Megestrol acetate can improve appetite and nutritional parameters in patients treated with periodic haemodialysis who report anorexia. Megestrol acetate may induce hyperglycaemia and inhibit the secretion of ACTH in some patients. These side effects should be assessed when administering this treatment.

[Approach to quality objectives in incidents of patients in peritoneal dialysis]. / Cumplimiento de objetivos de calidad y evolución de los pacientes incidentes en diálisis peritoneal.

INTRODUCTION: In 2007 the Scientific Quality-technical and Improvement of Quality in Peritoneal Dialysis was edited. It includes several quality indicators. As far as we know, only some groups of work had evaluated these indicators, with inconclusive results. AIM: To study the evolution and impact of guidelines in Peritoneal Dialysis. METHODS: Prospective cohort study of each incident of patients in Peritoneal Dialysis, in a regional public health care system (2003-2006). We prospectively collected baseline clinical and analytical data, technical efficacy, cardiovascular risk, events and deaths, hospital admissions and also prescription data was collected every 6 months. RESULTS: Over a period of 3 years, 490 patients (53.58 years of age; 61.6% males.) Causes of ERC: glomerular 25.5%, diabetes 16%, vascular 12.4%, and interstitial 13.3%. 26.48% were on the list for transplant. Dialysis efficacy: Of the first available results, the residual renal function was 6.37 ml/min, achieving 67.6% of all the objectives K/DOQI. 38.6% remained within the range during the entire first year. Anaemia: 79.3% received erythropoietic stimulating agents and maintained an average Hb of 12.1 g/dl. The percentage of patients in the range (Hb: 11-13 g/dl) improved after a year (58.4% vs 56.3% keeping in the range during this time of 25.6%). Evolution: it has been estimated that per patient-year the risk of: 1) mortality is 0.06 IC 95% [0.04-0.08]; 2) admissions 0.65 [0.58-0.72]; 3) peritoneal infections 0.5 [0.44-0.56]. CONCLUSION: Diabetes Mellitus patients had a higher cardiovascular risk and prevalence of events. The degrees of control during the follow-up in many topics of peritoneal dialysis improve each year; however they are far from the recommended guidelines, especially if they are evaluated throughout the whole study.

Treatment with N-acetylcysteine in stable renal transplantation.

The primary cause of morbidity and mortality in renal transplantation is cardiovascular disease. Increased oxidative stress implies a greater degree of atherogenesis in these patients. N-acetylcysteine (NAC) which has a thiol group that is the source of l-cysteine and reduced glutathione, acts against atherosclerosis via a decrease in apoptosis, vasoconstriction, and endothelial dysfunction. Experimental models have examined the antioxidant effects of NAC during and after ischemia-reperfusion, but few studies have shown an effect in renal transplantation in human beings. In 8 months, we studied the effect of NAC treatment on oxidative stress, lipids, and renal function in 25 patients with stable renal function and no diabetes after transplantation. Data were collected on oxidative parameters: malondialdehyde, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, lipid profile, and renal function (creatinine concentration, Cockroft-Gault formula, and Modified Diet in Renal Disease study). There were no significant differences in oxidative profile before and after treatment with NAC. The mean serum high-density lipoprotein cholesterol fraction increased after treatment and showed a significant positive correlation with glutathione peroxidase (r = 0.495). Serum creatinine concentration decreased, and Cockroft-Gault and Modified Diet in Renal Disease study estimates of renal function increased in the treatment period. In conclusion, NAC treatment in patients with stable renal function after transplantation increased high-density lipoprotein cholesterol and antioxidant molecules in relation to glutathione peroxidase, with a positive influence on renal function.

Timing ovulation for intrauterine insemination with a GnRH antagonist.

BACKGROUND: We aimed to assess the efficacy of a GnRH antagonist in intrauterine insemination (IUI) cycles to increase number of mature ovulatory follicles and pregnancy rates. METHODS: Prospective randomized study. Women (18-38 years old) with primary/secondary infertility were included. Eighty-two patients were randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH + GnRH antagonist or rFSH alone. RESULTS: A non-significant increase in the total amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm) was significantly higher in the GnRH antagonist group than in the control group (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly increased in the group of patients receiving the GnRH antagonist (38%) compared to the control group (14%). The only non-single pregnancy (triplets) occurred in the antagonist group. CONCLUSIONS: In this preliminary study, adding the GnRH antagonist to the COS protocol for IUI cycles significantly increased pregnancy rates. Nevertheless, these results may not be associated directly with the antagonist itself but with the fact that more mature ovulatory follicles are present by the day of the hCG. Finally, the risk for multiple gestations needs to be carefully evaluated.

Atypical thyroiditis in Huelva, Spain.

OBJECTIVE: To report an epidemic of atypical thyroiditis that occurred in southwestern Europe during 1995. METHODS: We present the clinical, laboratory, morphologic, and histologic features of 672 cases of thyroiditis and describe the results of treatment. RESULTS: During 1995, atypical thyroiditis was diagnosed in 672 of 725 patients with thyroid disorders encountered at our medical center in Huelva, Spain. Of these patients, 98% were women with normal ovarian function. The clinical findings were acute or subacute manifestation of diffuse nodular enlargement of the thyroid and spontaneous, severe pain on deglutition and palpation of the gland. Initial hematology and serum biochemistry studies, free triiodothyronine, free thyroxine, thyrotropin, and thyroid-stimulating immunoglobulins were in the normal range, but after the second week, the thyrotropin level began to increase. Thyroid antibodies (thyroglobulin and thyroid peroxidase) increased up to 300 times the high-normal level. Ultrasonography exhibited diffuse nodular enlargement of the thyroid gland, with irregular hypoechoic, normal, and hyperechoic zones. Fine-needle aspiration biopsy showed abundant lymphocytic infiltration. The best treatment results were obtained with the combination of levothyroxine and deflazacort. Because the epidemic appeared after a severe drought of 5-year duration (1991 to 1995) and affected women with normal ovarian function, our etiopathogenetic hypothesis was that an estrogen-like chemical substance polluted the area swamps. The high concentration of the pollutant was attributable to diminished water levels (8% of their capacity at the end of the drought period), and this situation may have affected the population through tap water used for human consumption. CONCLUSION: We describe an atypical autoimmune thyroiditis that affected primarily women of reproductive age, after a severe drought. The main features were a very painful, diffuse nodular enlargement of the thyroid gland, substantially increased thyroid antibodies, good response to levothyroxine and deflazacort combination treatment, and a benign evolution to chronic thyroiditis. Pollutants from various sources should be considered when atypical thyroiditis occurs in any community.

Dual genitotropic human papillomavirus infections in genital warts.

BACKGROUND AND METHODS: We have carried out a prospective study of dual genitotropic human papillomavirus (HPV) infections by means of two different DNA detection methods in biopsy specimens obtained from patients who were examined for genital warts at the STD clinic of the School of Medicine in Seville, between January 1990 and December 1991. RESULTS: 100 patients with a clinical diagnosis of condilomata acuminata were seen during the study period. DNA of the genitotropic HPV 6/11, 16/18 and 31/33/35 was detected by an in situ hybridisation method in 75 (77%) of the 98 evaluable samples; one of the genotypes tested in 59 (61%) samples, and two or more genotypes tested in the remaining 16 (15%) samples. In 21 (98%) of the 23 negative samples by in situ hybridisation, we were able to detect DNA of genital HPV using a polymerase chain reaction amplification method (PCR). Among the 34 samples where PCR was applied we confirmed the presence of two different HPV genotypes in eight samples. CONCLUSIONS: The frequency of dual infections with human genitotropic papillomavirus in genital warts was 8%, although we believe that this rate should be higher as we have not used the PCR method in all of the samples.

[Chlamydia trachomatis detection by DNA-RNA hybridization]. / Detección de Chlamydia trachomatis mediante hibridación de ADN-ARN.

BACKGROUND: A one-chain DNA probe, that complements ribosomal RNA of Chlamydia trachomatis was used as a detection method for this microorganism on clinical samples. We compare the method with the cell culture one. METHODS: A total of 175 samples (cervix swabs) from women seen at the STD center of the Facultad de Medicina de Sevilla were examined by both diagnostic techniques. When the results were different, a third method (ELISA) was also used. RESULTS: Using serial dilutions of a C. trachomatis cell culture as reference pattern, we determine the minimum number of inclusion forming units needed in order to be detected by the probe was 1000. Of all 175 samples, in 24 (14%) cell culture was positive for C. trachomatis, and 26 were positive using the DNA probe test. Sensitivity and specificity for this test were 93% and 95%, respectively. CONCLUSIONS: We believe that the DNA probe test was similar to the cell culture test as screening test in Chlamydia trachomatis infections diagnosis, specially among high risk populations.