Occult hepatitis C virus infection among hemodialysis patients

Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.     

Identification of Marteilia refringens infecting the razor clam Solen marginatus by PCR and in situ hybridization

Marteilia refringens is a protozoan parasite recognized as a significant pathogen of the European flat oyster Ostrea edulis. It is believed to have a complex life-cycle involving several hosts. In this study, we applied molecular approaches to identify this parasite in samples of the razor clam Solen marginatus from the south west coast of Spain. We used a PCR assay to amplify a fragment of the IGS rDNA region. PCR products were sequenced and the phylogenetic affinity of the sequences was determined. In situ hybridization analysis showed tissue distribution and presence of different developmental stages of the parasite in the digestive diverticula epithelium, which suggested a true parasitism in these individuals. This is the first report of the occurrence of M. refringens in the razor clam S. marginatus in the south Atlantic. The methodology described herein may be useful for accurate identification of the parasite strain in different hosts and thus provide valuable information for marteiliosis control programmes.     

Segmental heterogeneity in Bcl-2, Bcl-xL and Bax expression in rat tubular epithelium after ischemia-reperfusion

Summary: Aims: Studies in rats with bilateral clamping of renal arteries showed transient Bcl‐2, Bcl‐xL and Bax expression in renal tubular epithelium following ischemia‐reperfusion. However, current data on the preferential localization of specific mRNAs or proteins are limited because gene expression was not analysed at segmental level. This study analyses the mRNA expression of Bcl‐2, Bcl‐xL and Bax in four segments of proximal and distal tubules localized in the renal cortex and outer medulla in rat kidneys with bilateral renal clamping for 30 min and seven reperfusion times versus control animals without clamp. Methods: Proximal convoluted tubule (PCT), distal convoluted tubule (DCT), proximal straight tubule (PST) and medullary thick ascending limb (MTAL) were obtained by manual microdissection. RT‐PCR was used to analyse mRNA expression at segmental level. Results: Proximal convoluted tubule and MTAL showed early, persistent and balanced up‐regulation of Bcl‐2, Bcl‐xL and Bax, while PST and DCT revealed only Bcl‐2 and Bcl‐xL, when only Bax was detected in PST. DCT expressed Bcl‐xL initially, and persistent Bcl‐2 later. Conclusion: These patterns suggest a heterogeneous apoptosis regulatory response in rat renal tubules after ischemia‐reperfusion, independently of cortical or medullary location. This heterogeneity of the expression patterns of Bcl‐2 genes could explain the different susceptibility to undergo apoptosis, the different threshold to ischemic damage and the different adaptive capacity to injury among these tubular segments.     

Seminal vesicle cyst with renal agenesis associated with vascular anomalies. Case report

OBJECTIVE: We report a case of seminal vesicle cyst with ipsilateral renal agenesis associated wit abnormalities of the abdominal great vessels, not described previously in the bibliography. METHODS: 33 year-old-male with history of abdominal pain and fever. This case was evaluated by ultrasound, IV urography, CT scan and MRI. RESULTS/CONCLUSIONS. Congenital cystic disease of the seminal vesicle is an uncommon disorder. It is associated with genitourinary anomalies, often renal agenesis, and even anomalies of the lower spine. However, anomalies of the abdominal great vessels have not been described previously. CT scan provided excellent demonstration of associated anomalies.     

Clostridium myonecrosis: a complication of inguinal hernia repair

Clostridial myonecrosis is a necrotizing soft tissue infection characterized by muscular necrosis and, by extension, that of the surrounding tissue. If this infection develops quickly, it can cause septic shock and death if treatment is delayed. This infection does not occur frequently in civil medicine but nor is it exceptional after traumatic injuries or as a septic infection resulting from certain surgical interventions. Spontaneous development of clostridial myonecrosis is not uncommon (most commonly produced by the Clostridium septicum genus), propagated mainly from the colon in patients with neoplasia and in poor health. Consequently, in patients of bacteremia caused by C. septicum, colonic tumor must be ruled out. We present a new case of C. septicum myonecrosis of the abdominal after elective inguinal hernia repair.     

Abatacept improves health‐related quality of life,pain, sleep quality,and daily participation in subjects with juvenile idiopathic arthritis

Objective

To assess health‐related quality of life (HRQOL) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis (JIA).

Methods

In this phase III, double‐blind, placebo‐controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to ≥1 disease‐modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4‐month open‐label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined “responders”) were randomized to abatacept or placebo (plus MTX) in the 6‐month double‐blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100‐mm visual analog scale), the Children's Sleep Habits Questionnaire, and a daily activity participation questionnaire.

Results

A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept‐treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents' usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus ?1.3 [P = 0.109] school days/month and parents' usual activity days/month, respectively, in abatacept‐ versus placebo‐treated subjects).

Conclusion

Improvements in HRQOL were observed with abatacept, providing real‐life tangible benefits to children with JIA and their parents/caregivers.

     

The platelet of the patients with ischemic cardiopathy and cardiac valve disease showed a reduction of 8OH-DPAT binding sites

Depression is prospectively associated with increased risk of coronary artery disease in individuals initially free of clinical cardiovascular disease probably by an increased platelet activity. The serotonergic receptors mainly implied in depression are 5-HT1A and 5-HT2 receptors. Activation of 5HT2 receptor induces platelet aggregation. Drugs with 5-HT1A receptor agonist and 5-HT2A receptor antagonist effects reduced the receptor-mediated platelet aggregation. There are only indirect data about 5-HT1A receptors presence in platelet membranes, thus our aims were to study the characteristics of the platelet membranes 5-HT1A binding sites of both healthy volunteers and patients with cardiac valve disease and ischemic cardiopathy. The bound of the 5-HT1A selective agonist 3H-8OH-DPAT to the platelet membranes 5-HT1A binding sites of patients with cardiac valve disease and ischemic cardiopathy were compared with a control group of healthy voluntaries using radioligand binding methods. The patients with cardiovascular disease showed a reduction (-50.40%) (p<0.01) of the 3H-8OH-DPAT bound to the platelet membranes 5-HT1A receptors (1.652+/-0.79 fmol/mg protein) with respect to the control group (3.331+/-0.16 fmol/mg protein). 3H-8OH-DPAT binding to human platelet membranes is saturable, of high affinity, and seems selective for 5-HT1A receptors, and similar to that described in animal brain and in other human cells. Patients with ischemic cardiopathy and cardiac valve disease showed a reduction of the 8OH-DPAT bound to the platelet membranes. Taken together, these findings suggest that the 8OH-DPAT bound to the human platelet membranes is modulated by modifications produced by cardiovascular disease conditions.     

Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.