Surveillance and modification of immunosuppression minimizes BK virus nephropathy.

BACKGROUND/AIMS: Infection of a transplanted kidney with the polyomavirus, BK, is associated with poor allograft survival. METHODS: In an attempt to prevent this transplant complication, we studied 144 consecutive transplant recipients for the presence of BK infection with plasma and urine PCR testing at 1, 2, 3, 6 and 12 months. Viruria alone was followed by serial studies. If plasma PCR became positive at >2.6 log copies, mycophenolate was reduced until there was no detectable plasma viral load. RESULTS: Urine PCR was positive in 34 (24%), while plasma PCR turned positive in 22 cases (15%). No patients developed viremia with <6.8 log copies in the urine. Viremia resolved within 3 months or less in 20 of 22 patients after reduction of immunosuppression. Surveillance biopsies at 2 and 6 months revealed no BK nephropathy. Eight patients had acute rejection during reduced immunosuppression; however, all of these reversed with pulse steroids. Patient and graft survival at 1 year was 99 and 98%, respectively. Use of the cell-mediated immunity assay (ImmuKnow, Columbia, Md., USA) was not useful in identifying infected patients. CONCLUSION: Active surveillance for BK virus by urine/plasma PCR with prompt reduction in immunosuppression can prevent BK nephropathy.

Research in patients with heart failure: challenges in recruitment.

BACKGROUND: Published studies of patients with heart failure may not include details about the challenges in the recruitment process. OBJECTIVES: To describe the recruitment process during the first 18 months of a study being conducted to evaluate cognitive deficits in patients with chronic heart failure. METHODS: Details of the recruitment process are described for 2 clinic sites. RESULTS: A total of 4,027 echocardiograms were screened at site 1 to evaluate eligibility. Of the 161 patients eligible, 61 (38%) were invited to participate, and 29 of the 61 (48%) completed the study. At site 2, four hundred thirty-seven medical records of patients were screened, resulting in 163 eligible patients (37%). The staff invited 70 of the 163 patients (43%) to participate, and 52 of the 70 (74%) completed the study. The refusal rate was 23% at site 1 and 21% at site 2. CONCLUSIONS: Successful recruitment in studies involving patients with heart failure often requires screening of a large group of patients.

Prosthetic management of children with unilateral congenital below-elbow deficiency.

BACKGROUND: There is substantial controversy concerning the prosthetic management of children with unilateral congenital below-elbow deficiency. The optimal age at the time of the initial fitting, the value of intensive prosthetic training, and the preferred prosthetic design for these children have not been established. METHODS: The outcomes of prosthetic management for 260 children with unilateral congenital below-elbow deficiency, treated between 1954 and 2004, were analyzed with respect to ongoing clinic attendance and self-reported prosthetic use. A successful prosthetic outcome was defined as a child and parents who continued to attend the limb-deficiency clinic and claimed at the time of the most recent follow-up that the prosthesis had been worn for any period of time. An unsuccessful prosthetic outcome was defined as a child and parents who were lost to follow-up or who claimed at the time of the most recent follow-up that the child never wore the prosthesis. Survival analysis was performed. RESULTS: An unsuccessful prosthetic outcome was noted for 127 children (49%). Initial fitting prior to the age of three years was associated with improved prosthetic outcome (p < 0.001). With the numbers studied, there was no additional benefit noted for fitting before one year of age (p = 0.60). Improved prosthetic outcomes were noted in children who had received intensive training at the time of fitting with an active terminal device (p = 0.005). Provision of a variety of prosthetic designs over the growing years was also associated with improved prosthetic outcome (p < 0.001). CONCLUSIONS: This study supports the initial prosthetic fitting for a child with unilateral congenital below-elbow deficiency prior to the age of three years, the provision of intensive training under the direction of an occupational therapist when an active terminal device is applied, and utilization of a variety of prosthetic designs over the child's years of growth. Further analysis of outcomes for the prosthetic management of these children will require more precise definitions of outcome in multiple domains and the development and validation of specific outcome instruments.

Barriers to Disaster Preparedness among Medical Special Needs Populations.

A medical special needs (MSN) assessment was conducted among 3088 respondents in a hurricane prone area. The sample was female (51.7%), Hispanic (92.9%), aged >45 years (51%), not insured for health (59.2%), and with an MSN (33.2%). Barriers to preparedness were characterized for all households, including those with inhabitants reporting MSN ranging from level 0 (mild) to level 4 (most severe). Multivariable logistic regression tested associations between hurricane preparedness and barriers to evacuation by level of MSN. A significant interaction effect between number of evacuation barriers and MSN was found. Among households that reported individuals with level 0 MSN, the odds of being unprepared increased 18% for each additional evacuation barrier [OR = 1.18, 95% CI (1.08, 1.30)]. Among households that reported individuals with level 1 MSN, the odds of being unprepared increased 29% for each additional evacuation barrier [OR = 1.29, 95% CI (1.11, 1.51)]. Among households that reported individuals with level 3 MSN, the odds of being unprepared increased 68% for each additional evacuation barrier [OR = 1.68, 95% CI (1.21, 1.32)]. MSN alone did not explain the probability of unpreparedness, but rather MSN in the presence of barriers helped explain unpreparedness.

Therapeutic Molecular Phenotype of ß-Blocker-Associated Reverse-Remodeling in Nonischemic Dilated Cardiomyopathy.

BACKGROUND: When ß-blockers produce reverse-remodeling in idiopathic dilated cardiomyopathy, they partially reverse changes in fetal-adult/contractile protein, natriuretic peptide, SR-Ca(2+)-ATPase gene program constituents. The objective of the current study was to further test the hypothesis that reverse-remodeling is associated with favorable changes in myocardial gene expression by measuring additional contractile, signaling, and metabolic genes that exhibit a fetal/adult expression predominance, are thyroid hormone-responsive, and are regulated by ß1-adrenergic receptor signaling. A secondary objective was to identify which of these putative regulatory networks is most closely associated with observed changes. METHODS AND RESULTS: Forty-seven patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction, 0.24±0.09) were randomized to the adrenergic-receptor blockers metoprolol (ß1-selective), metoprolol+doxazosin (ß1/α1), or carvedilol (ß1/ß2/α1). Serial radionuclide ventriculography and endomyocardial biopsies were performed at baseline, 3, and 12 months. Expression of 50 mRNA gene products was measured by quantitative polymerase chain reaction. Thirty-one patients achieved left ventricular ejection fraction reverse-remodeling response defined as improvement by ≥0.08 at 12 months or by ≥0.05 at 3 months (Δ left ventricular ejection fraction, 0.21±0.10). Changes in gene expression in responders versus nonresponders were decreases in NPPA and NPPB and increases in MYH6, ATP2A2, PLN, RYR2, ADRA1A, ADRB1, MYL3, PDFKM, PDHX, and CPT1B. All except PDHX involved increase in adult or decrease in fetal cardiac genes, but 100% were concordant with changes predicted by inhibition of ß1-adrenergic signaling. CONCLUSIONS: In addition to known gene expression changes, additional calcium-handling, sarcomeric, adrenergic signaling, and metabolic genes were associated with reverse-remodeling. The pattern suggests a fetal-adult paradigm but may be because of reversal of gene expression controlled by a ß1-adrenergic receptor gene network. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique Identifier: NCT01798992.

Whole-Genome Sequencing to Identify Mutants and Polymorphisms in Chlamydomonas reinhardtii.

Whole-genome sequencing (WGS) provides a new platform for the identification of mutations that produce a mutant phenotype. We used Illumina sequencing to identify the mutational profile of three Chlamydomonas reinhardtii mutant strains. The three strains have more than 38,000 changes from the reference genome. NG6 is aflagellate and maps to 269 kb with only one nonsynonymous change; the V(12)E mutation falls in the FLA8 gene. Evidence that NG6 is a fla8 allele comes from swimming revertants that are either true or pseudorevertants. NG30 is aflagellate and maps to 458 kb that has six nonsynonomous changes. Evidence that NG30 has a causative nonsense allele in IFT80 comes from rescue of the nonswimming phenotype with a fragment bearing only this gene. This gene has been implicated in Jeune asphyxiating thoracic dystrophy. Electron microscopy of ift80-1 (NG30) shows a novel basal body phenotype. A bar or cap is observed over the distal end of the transition zone, which may be an intermediate in preparing the basal body for flagellar assembly. In the acetate-requiring mutant ac17, we failed to find a nonsynonymous change in the 676 kb mapped region, which is incompletely assembled. In these strains, 43% of the changes occur on two of the 17 chromosomes. The excess on chromosome 6 surrounds the mating-type locus, which has numerous rearrangements and suppressed recombination, and the changes extend beyond the mating-type locus. Unexpectedly, chromosome 16 shows an unexplained excess of single nucleotide polymorphisms and indels. Overall, WGS in combination with limited mapping allows fast and accurate identification of point mutations in Chlamydomonas.