Vesical sequelae of transverse myelitis. Long-term urodynamics observations in adult patients

Transverse myelitis is a rare autoimmune inflammatory disease often secondary to viral infection of the spinal cord; it frequently has vesico-sphynteric complications. Between January 2000 and December 2005 we performed urodynamic examination on 13 consecutive patients (7 females and 6 males) with previous diagnosis of transverse myelitis. Mean age was 54.5 years; transverse myelitis had been diagnosed a mean of 6.3 years earlier; etiology of myelitis was viral infection in 5 cases, autoimmune in 3 cases, insect bite in 1 case, unknown in 4 cases. The neurological sequelae included paraparesis in 3 cases and tetraparesis in 2 cases. Symptoms: dysuria 46%, slow stream 15%, pollakiuria 23%, urgency 30%; urge incontinence 38%, stress incontinence 15%. 3 patients performed 4 clean intermittent catheterisms (CIC), 2 patients 2 CICs. Eight patients had maximum cystometric capacity above 350 mL, the others had a mean capacity of 223 mL. Four patients showed no bladder sensitivity. Voluntary micturitional reflex was observed in 4 patients. Detrusor overactivity was diagnosed in 9 patients, 10 patients had mean residual post-micturition (RPM) of 218 mL, 2 patients showed detrusor-sphincter dyssynergia, 2 patients were found to be obstructed at pressure-flow study. Urodynamic follow-up is indicated in these patients with or without neurological complications (possibility of detrusor overactivity, urinary retention, detrusor-sphincter dyssynergia); the follow-up personalizes the diagnosis and therapy, and prevents complications.     

Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes

BackgroundContemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of patients with acute coronary syndrome (ACS) remains unclear.ObjectivesThe aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.MethodsPatients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.ResultsAmong 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio [HR]: 2.37; 95% confidence interval [CI]: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 [95% CI: 1.06 to 11.79]; major: HR: 13.32 [95% CI: 3.01 to 58.98]).ConclusionsAmong patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627)     

Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene (CASQ2). We engineered and characterized a homozygous CASQ2(R33Q/R33Q) mouse model that closely mimics the clinical phenotype of CPVT patients. CASQ2(R33Q/R33Q) mice develop bidirectional VT on exposure to environmental stress whereas CASQ2(R33Q/R33Q) myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology, CASQ2(R33Q/R33Q) hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the CASQ2(R33Q/R33Q) CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.     

Influenza vaccination in patients with end-stage renal disease

Introduction: Patients with end-stage renal disease (ESRD) are considered at higher risk of influenza-related complications and are listed worldwide among the subjects for whom yearly influenza vaccination is strongly recommended. However, influenza vaccination coverage of patients with ESRD is significantly lower than desired.

Areas covered: This paper explores why compliance with official recommendations for influenza vaccination is poor in patients with ESRD and analyzes the true risk of infection as well as the immunogenicity, the effectiveness and the safety of influenza vaccination in these patients.

Expert opinion: Epidemiological and clinical data support the importance of influenza in conditioning clinical deterioration of patients with ESRD, particularly in relation to their level of immunosuppression. However, the variable levels of immunodeficiency detected in patients with ESRD may reduce the immune response to influenza vaccination, which appears to be lower than that usually found in healthy subjects. However, few studies are available, and they are difficult to compare for several reasons. Additionally, limited data have been collected on influenza vaccine effectiveness, although the available studies support positive results of vaccination on outcomes of severe disease. Despite such limitations, it is important to highlight that all the available studies have confirmed the good safety and tolerability of inactivated influenza vaccines. These findings, together with the risks associated with influenza in these patients, support annual influenza vaccination in patients with ESRD as well as vaccination of their close contacts and should be presented in educational programs organized for nephrologists and patient associations.     

A protein phosphatase related to the vaccinia virus VH1 is encoded in the genomes of several orthopoxviruses and a baculovirus.

The vaccinia virus VH1 gene product is a dual specificity protein phosphatase with activity against both phosphoserine- and phosphotyrosine-containing substrates. We investigated the potential presence of VH1 analogs in other viruses. Hybridization and sequence data indicated that a phosphatase related to the VH1 phosphatase is highly conserved in the genomes of smallpox variola virus and other orthopoxviruses. The open reading frames from the raccoonpox virus and the smallpox variola virus Bangladesh major strain genomes encoding the VH1 analogs were sequenced and found to be highly conserved with the vaccinia virus VH1. An open reading frame from the baculovirus Autographa californica has sequence similarity to the VH1 phosphatase. The viral proteins appear to be structurally related to the cell cycle control protein p80cdc25. A recombinant phosphatase expressed from the baculovirus gene was found to share with the VH1 phosphatase the ability to hydrolyze substrates that contained both phosphoserine and phosphotyrosine.     

Meiosis in haploid yeast

Haploid yeast cells normally contain either the MATa or MATα mating-type allele and cannot undergo meiosis and spore formation. If both mating-type alleles are present as a consequence of chromosome III disomy (MATa/MATα), haploids initiate meiosis but do not successfully form spores, probably because the haploid chromosome complement is irregularly partitioned during meiotic nuclear division. We have demonstrated that the ochre-suppressible mutation spo13-1 enables haploid yeast cells disomic for chromosome III and heterozygous at the mating-type locus to complete meiosis and spore formation, yielding two haploid spores. Previous studies have shown that the absence of the wild-type SPO13 gene function permits diploid cells to bypass homologous chromosome segregation at meiosis I and proceed directly to meiosis II. During spo13-1 haploid meiosis, cells enter prophase of meiosis I. Genetic recombination, monitored on the chromosome III disome, occurs at levels similar to those seen in diploids, indicating that the level of exchange between homologs is an autonomous property of individual chromosomes and not dependent on exchange elsewhere in the genome. Exchange is then followed by a single meiosis II equational chromosome division. Recombination in spo13-1 haploids is blocked by the spo11-1 mutation, which also eliminates recombination between homologous chromosomes during conventional diploid meiosis. We conclude that Spo⁺ haploids expressing both a and α mating-type information attempt a SPO13-dependent meiosis I division, and that this division, in the absence of paired homologous chromosomes, is responsible for the failure of such haploids to complete normal gametogenesis. Our observations support the conclusion that initiation and completion of meiosis II and spore formation are not dependent on either completion of meiosis I or the presence of a diploid chromosome complement.