Clonidine transdermal system for treatment of spasticity in spinal cord injury.

Clonidine tablets have been used in the past for treatment of spasticity with some success. The use of clonidine, however, has been limited by adverse effects, mainly hypotension. Over a two-year period, 17 patients were started on clonidine transdermal delivery system. They were followed for up to 18 months. Twelve of the 17 patients had a beneficial response and have continued on the patch. In ten of these 12 patients, other antispasticity drugs were either reduced or discontinued. In another three of the 17 patients, the response was good, but the patch was discontinued. No patient demonstrated persistent problematic hypotension. Clonidine Transdermal Patch appears to be an effective treatment for spasticity after a spinal cord injury. Adverse effects appear to be minimized using this mode of delivery.     

International proficiency study of a consensus L1 PCR assay for the detection and typing of human papillomavirus DNA: evaluation of accuracy and intralaboratory and interlaboratory agreement

The PGMY L1 consensus primer pair combined with the line blot assay allows the detection of 27 genital human papillomavirus (HPV) genotypes. We conducted an intralaboratory and interlaboratory agreement study to assess the accuracy and reproducibility of PCR for HPV DNA detection and typing using the PGMY primers and typing amplicons with the line blot (PGMY-LB) assay. A test panel of 109 samples consisting of 29 HPV-negative (10 buffer controls and 19 genital samples) and 80 HPV-positive samples (60 genital samples and 20 controls with small or large amounts of HPV DNA plasmids) were tested blindly in triplicate by three laboratories. Intralaboratory agreement ranged from 86 to 98% for HPV DNA detection. PGMY-LB assay results for samples with a low copy number of HPV DNA were less reproducible. The rate of intralaboratory agreement excluding negative results for HPV typing ranged from 78 to 96%. Interlaboratory reliability for HPV DNA positivity and HPV typing was very good, with levels of agreement of >95% and kappa values of >0.87. Again, low-copy-number samples were more prone to generating discrepant results. The accuracy varied from 91 to 100% for HPV DNA positivity and from 90 to 100% for HPV typing. HPV testing can thus be accomplished reliably with PCR by using a standardized written protocol and quality-controlled reagents. The use of validated HPV DNA detection and typing assays demonstrating excellent interlaboratory agreement will allow investigators to better compare results between epidemiological studies.     

Heterologous expression of Trypanosoma cruzi trans-sialidase in Leishmania major enhances virulence

Earlier studies showed that mice primed for a few hours with the trans-sialidase (TS) of Trypanosoma cruzi, the agent of Chagas' disease, become highly susceptible to trypanosomal infection. These studies suggest that TS affects parasite virulence independent of antigenic stimulation. Potentially, TS could enhance or reduce the virulence of heterologous microbes depending on the mechanism of TS action and on the type of immune response elicited by the particular parasite. We tested this hypothesis by expressing heterologous TS in Leishmania major, a protozoan parasite that causes cutaneous leishmaniasis and lacks TS and the TS product alpha2-3-linked sialic acid. Leishmania cells transfected with a T. cruzi TS expression construct made high levels of active enzyme, which was present in the promastigotes and shed into the extracellular milieu. TS expression did not affect L. major binding to and entry into cultured macrophages or its tropism for macrophage infection in vivo. However, TS-expressing L. major exhibited elevated virulence in BALB/c mice, as determined by lesion progression, parasite numbers, and macro- and microscopic examination of cutaneous lesions. Several genetic tests proved that the enhanced virulence was directly attributable to TS expression. The results are consistent with TS functioning to sabotage the mouse immune system to confer a growth advantage on T. cruzi and transgenic L. major. These data suggest that heterologous expression of T. cruzi virulence factors in Leishmania may provide a new approach for dissecting their function in vivo.     

Apoptosis in brain biopsies of subacute sclerosing panencephalitis patients

Subacute sclerosing panencephalitis (SSPE) is associated with inflammatory infiltration, neuronal loss, and demyelination. The pathogenesis of these changes is unclear. We examined DNA fragmentation and Bcl-2 expression in brain biopsies of nineteen SSPE patients to investigate the role of apoptosis in tissue damage. DNA fragmentation was present in oligodendroglia, and, in tissues with neuronal loss, in neurons. Reactive astrocytes had no DNA fragmentation, but strong Bcl-2 expression. These results suggest apoptosis as one of the mechanisms for oligodendroglial and neuronal death in SSPE.     

Estratificación basal de riesgo en pacientes mayores de 75 años con infarto y shock cardiogénico referidos para angioplastia primaria

Background and objectivesPatients older than 75 years with ST-segment elevation myocardial infarction undergoing primary angioplasty in cardiogenic shock have high mortality. Identification of preprocedural predictors of short- and long-term mortality could be useful to guide decision-making and further interventions.MethodsWe analyzed a nationwide registry of primary angioplasty in the elderly (ESTROFA MI + 75) comprising 3576 patients. The characteristics and outcomes of the subgroup of patients in cardiogenic shock were analyzed to identify associated factors and prognostic predictors in order to derive a baseline risk prediction score for 1-year mortality. The score was validated in an independent cohort.ResultsA total of 332 patients were included. Baseline independent predictors of mortality were anterior myocardial infarction (HR 2.8, 95%CI, 1.4-6.0; P = .005), ejection fraction < 40% (HR 2.3, 95%CI, 1.14-4.50; P = .018), and time from symptom onset to angioplasty > 6 hours (HR 3.2, 95%CI, 1.6-7.5; P = .001). A score was designed that included these predictive factors (score “6-ANT-40”). Survival at 1 year was 54.5% for patients with score 0, 32.3% for score 1, 27.4% for score 2 and 17% for score 3 (P = .004, c-statistic 0.70). The score was validated in an independent cohort of 124 patients, showing 1-year survival rates of 64.5%, 40.0%, 28.9%, and 22.2%, respectively (P = .008, c-statistic 0.68).ConclusionsA preprocedural score based on 3 simple clinical variables (anterior location, ejection fraction < 40%, and delay time > 6 hours) may be used to estimate survival after primary angioplasty in elderly patients with cardiogenic shock and to guide preinterventional decision-making.     

Shared Sanitation versus Individual Household Latrines in Urban Slums: A Cross-Sectional Study in Orissa,India

A large and growing proportion of the global population rely on shared sanitation facilities despite evidence of a potential increased risk of adverse health outcomes compared with individual household latrines (IHLs). We sought to explore differences between households relying on shared sanitation versus IHLs in terms of demographics, sanitation facilities, and fecal exposure. We surveyed 570 households from 30 slums in Orissa, India, to obtain data on demographics, water, sanitation, and hygiene. Latrine spot-checks were conducted to collect data on indicators of use, privacy, and cleanliness. We collected samples of drinking water and hand rinses to assess fecal contamination. Households relying on shared sanitation were poorer and less educated than those accessing IHLs. Individuals in sharing households were more likely to practice open defecation. Shared facilities were less likely to be functional, less clean, and more likely to have feces and flies. No differences in fecal contamination of drinking water or hand-rinse samples were found. Important differences exist among households accessing shared facilities versus IHLs that may partly explain the apparent adverse health outcomes associated with shared sanitation. As these factors may capture differences in risk and promote sanitary improvements, they should be considered in future policy.     

Clinical outcomes of dexamethasone-eluting stent implantation in ST-elevation acute myocardial infarction.

OBJECTIVES: The aim of our study was to evaluate the safety and midterm clinical results of dexamethasone-eluting stent (DexES) implantation in ST-segment elevation acute myocardial infarction (STEMI). BACKGROUND: Inflammation plays a pivotal role in both inestabilization of coronary atherosclerotic plaques and development of restenosis after stent placement. Antiinflammatory agents may attenuate those mechanisms and improve clinical outcomes. There is little information about clinical results of DexES and no data are available about their utilization during percutaneous coronary intervention (PCI) in STEMI. METHODS: Consecutive patients with STEMI that underwent primary or rescue PCI in our institution were treated with DexES. Clinical follow-up with routine realization of noninvasive test for detection of myocardial ischemia and coronariography if necessary, were performed. The objective of the study was to evaluate the rate of MACE (death, reinfarction, or target lesion revascularization) during midterm follow-up. RESULTS: The procedure was successful in 96.7% of cases. There were no in-hospital deaths or reinfarctions. One acute stent thrombosis occurred and no subacute thrombosis were observed. During a mean follow-up period of 384 days, cardiac-related death was 1.1%, there were no reinfarctions or late stent thrombosis and target lesion revascularization rate was 4.2%. CONCLUSION: We conclude that utilization of DexES for PCI in STEMI is safe and provides good midterm clinical outcomes.     

TWEAK transactivation of the epidermal growth factor receptor mediates renal inflammation

TWEAK, a member of the TNF superfamily, binds to the Fn14 receptor, eliciting biological responses. EGFR signalling is involved in experimental renal injury. Our aim was to investigate the relationship between TWEAK and EGFR in the kidney. Systemic TWEAK administration into C57BL/6 mice increased renal EGFR phosphorylation, mainly in tubular epithelial cells. In vitro, in these cells TWEAK phosphorylated EGFR via Fn14 binding, ADAM17 activation and subsequent release of the EGFR ligands HB‐EGF and TGFα. In vivo the EGFR kinase inhibitor Erlotinib inhibited TWEAK‐induced renal EGFR activation and downstream signalling, including ERK activation, up‐regulation of proinflammatory factors and inflammatory cell infiltration. Moreover, the ADAM17 inhibitor WTACE‐2 also prevented those TWEAK‐induced renal effects. In vitro TWEAK induction of proinflammatory factors was prevented by EGFR, ERK or ADAM17 inhibition. In contrast, EGFR transactivation did not modify TWEAK‐mediated NF‐κB activation. Our data suggest that TWEAK transactivates EGFR in the kidney, leading to modulation of downstream effects, including ERK activation and inflammation, and suggest that inhibition of EGFR signalling could be a novel therapeutic tool for renal inflammation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.