Leukopenia in Kidney Transplant Patients with the Association of Valganciclovir and Mycophenolate Mofetil

Cytomegalovirus (CMV) is the most common viral infection after transplantation. Valganciclovir (VGC) is established for prophylaxis and treatment of CMV infections, but leukopenia which appears in 10% to 13% (severe in 4.9%) is the principal side effect. We have recently noted an increased incidence of leukopenia and severe neutropenia among our renal transplant patients and thought to identify the associated factors. We conducted a retrospective analysis of all kidney transplantations performed between January 2005 and December 2006. All patients received mycophenolate mofetil (MMF), tacrolimus, and steroids. VGC was used for targeted prophylaxis and preemptive therapy of CMV infection, with doses adjusted to renal function. Of the 64 patients undergoing renal transplantation 13 (20.3%) developed leukopenia within 3 +/- 2 months after transplantation with severe neutropenia in 5 (7.8%). All patients were on MMF and VGC (VGC 605 +/- 296 mg/d). Leukopenia was significantly associated with simultaneous liver-kidney transplantation and with second kidney transplantations (P < .01). The incidence of leukopenia was higher among patients under VGC since day 1 of transplantation (P = .008) with maximal incidence observed among patients prescribed 900 mg/d as opposed to those on lower doses (P < .01). There was no increase in CMV infection among patients with a low dose of VGC. No patient developed clinical CMV disease. In conclusion, VGC prophylaxis was associated with an increased frequency of leukopenia on MMF-tacrolimus treated patients or regimens. Low-dose VGC for CMV prophylaxis appeared to be as effective as high-dose treatment, and associated less frequently with leukopenia and neutropenia.

High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil

In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29%, HIV-1 B in 22.6% and, the recently identified CRF31_BC, in 23.4% of 128 volunteers. Other variants were HIV-1 F in 10% and other mosaics in 5.5%. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

Association of Intestinal Malrotation and Bochdalek Hernia in an Adult: a Case Report

Background Late presentations of congenital diaphragmatic hernia are rare and differ from the classic neonatal presentation. The association with other congenital malformations in children, mainly intestinal malrotation, is well documented. The diagnosis of this association in adults is very rare, and depends on a high degree of suspicion. Case presentation We report a case of a 50-year-old female Caucasian patient with a previous history of intestinal malrotation diagnosed in adolescence and treated conservatively. She was referred to the hospital with signs and symptoms of intestinal obstruction. The patient undertook computed tomography that confirmed small bowel obstruction with no obvious cause, and a right subphrenic abscess with right empyema was also present. An exploratory laparotomy was performed that revealed an intestinal malrotation associated with a right gangrenous and perforated Bochdalek hernia. Resection of the affected small bowel, closure of the Bochdalek foramen and the Ladd procedure were carried out. Conclusion This case shows a rare association of two rare conditions in adults, and highlights the challenge in reaching the diagnosis and management options.

PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS

Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation.

The association of Schistosoma mansoni infection with hepatocellular carcinoma

The association of Schistosoma mansoni infection with hepatocellular carcinoma (HCC) was studied in Espirito Santo State, Brazil. Schistosoma infection was diagnosed by stool examinations or by histological finding at autopsy. HCC was diagnosed by biopsy, laparoscopy and biopsy or at autopsy. Among 45 cases of HCC six had Schistosoma mansoni infection (13.04%). The occurrence of Schistosoma infection among HCC HBs Ag positive or negative was similar (13.3 3% and 13.63% respectively). The chi squared comparison showed no significant differences between the frequency of schistosomiasis in patients with HCC and the frequency of Schistosoma infection among people living in the Espirito Santo State (5.9% among children of elementary school from all the counties of the State and 6.7% in people that attended medical care in Vitoria, the capital of the State). Therefore, the authors believe that the association of schistosomiasis mansoni with HCC may be casual, specially in areas where the Schistosoma mansoni infection is frequent.

Association of chagasic megacolon and cancer of the colon: case report and review of the literature

There are few descriptions of association between chagasic megacolon and colon cancer. We report a case of obstructive abdomen caused by adenocarcinoma of the left colon in chagasic megacolon. A review of the literature revealed 8 cases of this association and, analyzing together the series of findings of cancer in chagasic organomegalies, we found a frequency of 4.8% in megaesophagus and 0.1% in megacolon.

Association of ants (Hymenoptera: Formicidae) with bacteria in hospitals in the State of Santa Catarina

The objective of this study was to identify ant occurrence in hospital environments in the State of Santa Catarina, along with associated bacteria. Ants were collected monthly from five inpatient clinics in two hospitals in the municipality of Chapecó, from August 2003 to June 2004. They were collected under aseptic conditions using swabs moistened with sterile distilled water and put into test tubes containing BHI for microbiological analysis. After 24 hours, cultures were made in both 5% sheep blood and MacConkey agar, which were incubated for 24 hours at 35/37°C. The Gram characterization, culture identification and biochemical characterization followed standardized rules for clinical microbiology. Seven species of ants were identified, of which the most frequent were Monomorium pharaonis (71.5%) and Solenopsis saevissima (57%), and nineteen species of bacteria was isolated from hospital "A".

Association of pulmonary atresia with intact ventricular septum and aortic valve stenosis. Prenatal diagnosis

A rare association of pulmonary atresia with an intact septum was diagnosed through echocardiography in a fetus 32 weeks of gestational age. The diagnosis was later confirmed by echocardiography of the newborn infant and further on autopsy. The aortic valve was bicuspid with a pressure gradient of 81mmHg, and the right ventricle was hypoplastic, as were the pulmonary trunk and arteries, and the blood flow was totally dependent on the ductus arteriosus.

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

Association of Aortic Valve Sclerosis with Previous Coronary Artery Disease and Risk Factors

Background: Aortic valve sclerosis (AVS) is characterized by increased thickness, calcification and stiffness of the aortic leaflets without fusion of the commissures. Several studies show an association between AVS and presence of coronary artery disease. Objective: The aim of this study is to investigate the association between presence of AVS with occurrence of previous coronary artery disease and classical risk factors. Methods: The sample was composed of 2,493 individuals who underwent transthoracic echocardiography between August 2011 and December 2012. The mean age of the cohort was 67.5 ± 15.9 years, and 50.7% were female. Results: The most frequent clinical indication for Doppler echocardiography was the presence of stroke (28.8%), and the most common risk factor was hypertension (60.8%). The most prevalent pathological findings on Doppler echocardiography were mitral valve sclerosis (37.1%) and AVS (36.7%). There was a statistically significant association between AVS with hypertension (p < 0.001), myocardial infarction (p = 0.007), diabetes (p = 0.006) and compromised left ventricular systolic function (p < 0.001). Conclusion: Patients with AVS have higher prevalences of hypertension, stroke, hypercholesterolemia, myocardial infarction, diabetes and compromised left ventricular systolic function when compared with patients without AVS. We conclude that there is an association between presence of AVS with previous coronary artery disease and classical risk factors.

Association of N-acetylaspartate and cerebrospinal fluid Aβ42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (Aβ42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aβ42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.

Association of serum homocysteine with major depressive disorder: results from a large population-based study.

BACKGROUND: Studies on the association between homocysteine levels and depression have shown conflicting results. To examine the association between serum total homocysteine (tHcy) levels and major depressive disorder (MDD) in a large community sample with an extended age range. METHODS: A total of 3392 men and women aged 35-66 years participating in the CoLaus study and its psychiatric arm (PsyCoLaus) were included in the analyses. High tHcy measured from fasting blood samples was defined as a concentration ≥15μmol/L. MDD was assessed using the semi-structured Diagnostic Interview for Genetics Studies. RESULTS: In multivariate analyses, elevated tHcy levels were associated with greater odds of meeting the diagnostic criteria for lifetime MDD among men (OR=1.71; 95% CI, 1.18-2.50). This was particularly the case for remitted MDD. Among women, there was no significant association between tHcy levels and MDD and the association tended to be in the opposite direction (OR=0.61; 95% CI, 0.34-1.08). CONCLUSIONS: In this large population-based study, elevated tHcy concentrations are associated with lifetime MDD and particularly with remitted MDD among men.

Association of the Epstein-Barr virus latent membrane protein 1 with lipid rafts is mediated through its N-terminal region.

The latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus acts like a constitutively activated receptor of the tumor necrosis factor receptor (TNFR) family and is enriched in lipid rafts. We showed that LMP1 is targeted to lipid rafts in transfected HEK 293 cells, and that the endogenous TNFR-associated factor 3 binds LMP1 and is recruited to lipid rafts upon LMP1 expression. An LMP1 mutant lacking the C-terminal 55 amino acids (Cdelta55) behaves like the wild-type (WT) LMP1 with respect to membrane localization. In contrast, a mutant with a deletion of the 25 N-terminal residues (Ndelta25) does not concentrate in lipid rafts but still binds TRAF3, demonstrating that cell localization of LMP1 was not crucial for TRAF3 localization. Moreover, Ndelta25 inhibited WT LMP1-mediated induction of the transcription factors NF-kappaB and AP-1. Morphological data indicate that Ndelta25 hampers WT LMP1 plasma membrane localization, thus blocking LMP1 function.