Cystic fibrosis in a black child with hemoglobin S-D disease

A 9-year-old black patient with the simultaneous occurrence of cystic fibrosis and hemoglobin S-D disease is reported. She was placed on chronic transfusion therapy from 1 year of age because of her rapidly worsening pulmonary condition. Her pulmonary function is now stable. The role of this therapy in the overall management of this unusual syndrome is discussed.     

Effect of reading additional safety information on planned use of over-the-counter analgesics

OBJECTIVES: This study was used to test the effect on planned safe use of over-the-counter (OTC) analgesics of adding information about the potential for nonsteroidal anti-inflammatory drug (NSAID) interaction with antihypertensive medications, the potential for interaction of alcohol and acetaminophen, and NSAID ceiling effects to the Federal Drug Administration's (FDA's) OTC analgesics pamphlet. DESIGN: A randomized posttest-only double-blind experimental design was used to test an intervention with a comparison group reading the FDA pamphlet, and treatment group reading the pamphlet with added information. SAMPLE: Participants included 137 adults. INTERVENTION: Participants read the treatment or the comparison pamphlet. RESULTS: Both groups responded with similar planned use of OTC analgesics. The majority were likely to read the label before taking an OTC analgesic, but were unlikely to give acetaminophen to a family member using antihypertensive medication. CONCLUSIONS: Reading additional information about OTC analgesics resulted in no greater intention to safely use analgesics. Responses indicated reluctance to use OTC analgesics, and the potential need for increased health teaching regarding use of OTC analgesics with antihypertensive medication. Public health teaching should include the importance of treating pain and selecting the safest OTC analgesics for the clinical situation.     

Human immunodeficiency virus 1 envelope glycoprotein complex-induced apoptosis involves mammalian target of rapamycin/FKBP12-rapamycin-associated protein-mediated p53 phosphorylation

Syncytia arising from the fusion of cells expressing a lymphotropic human immunodeficiency virus (HIV)-1-encoded envelope glycoprotein complex (Env) gene with cells expressing the CD4/CXCR4 complex undergo apoptosis through a mitochondrion-controlled pathway initiated by the upregulation of Bax. In syncytial apoptosis, phosphorylation of p53 on serine 15 (p53S15) precedes Bax upregulation, the apoptosis-linked conformational change of Bax, the insertion of Bax in mitochondrial membranes, subsequent release of cytochrome c, caspase activation, and apoptosis. p53S15 phosphorylation also occurs in vivo, in HIV-1(+) donors, where it can be detected in preapoptotic and apoptotic syncytia in lymph nodes, as well as in peripheral blood mononuclear cells, correlating with viral load. Syncytium-induced p53S15 phosphorylation is mediated by the upregulation/activation of mammalian target of rapamycin (mTOR), also called FKBP12-rapamycin-associated protein (FRAP), which coimmunoprecipitates with p53. Inhibition of mTOR/FRAP by rapamycin reduces apoptosis in several paradigms of syncytium-dependent death, including in primary CD4(+) lymphoblasts infected by HIV-1. Concomitantly, rapamycin inhibits p53S15 phosphorylation, mitochondrial translocation of Bax, loss of the mitochondrial transmembrane potential, mitochondrial release of cytochrome c, and nuclear chromatin condensation. Transfection with dominant negative p53 has a similar antiapoptotic action as rapamycin, upstream of the Bax upregulation/translocation. In summary, we demonstrate that phosphorylation of p53S15 by mTOR/FRAP plays a critical role in syncytial apoptosis driven by HIV-1 Env.     

Co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy

The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0-12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV-RNA and hBoV-DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified.     

Risk of tearing the intact anterior cruciate ligament in the contralateral knee and rupturing the anterior cruciate ligament graft during the first 2 years after anterior cruciate ligament reconstruction: a prospective MOON cohort study

BACKGROUND: The risk of tear of the intact anterior cruciate ligament in the contralateral knee after anterior cruciate ligament reconstruction of the opposite knee and the incidence of rupturing the anterior cruciate ligament graft during the first 2 years after surgery have not been extensively studied in a prospective manner. Clinicians have hypothesized that the opposite normal knee is at equal or increased risk compared with the risk of anterior cruciate ligament graft rupture in the operated knee. HYPOTHESIS: The risk of anterior cruciate ligament graft rupture and contralateral normal knee anterior cruciate ligament rupture at 2-year follow-up is equal. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The Multicenter Orthopaedic Outcome Network (MOON) database of a prospective longitudinal cohort of anterior cruciate ligament reconstructions was used to determine the number of anterior cruciate ligament graft ruptures and tears of the intact anterior cruciate ligament in the contralateral knee at 2-year follow-up. Two-year follow-up consisted of a phone interview and review of operative reports. RESULTS: Two-year data were obtained for 235 of 273 patients (86%). There were 14 ligament disruptions. Of these, 7 were tears of the intact anterior cruciate ligament in the contralateral knee (3.0%) and 7 were anterior cruciate ligament graft failures (3.0%). CONCLUSION: The contralateral normal knee anterior cruciate ligament is at a similar risk of anterior cruciate ligament tear (3.0%) as the anterior cruciate ligament graft after primary anterior cruciate ligament reconstruction (3.0%).     

Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy

A cross-sectional study was carried out to improve the state of evidence regarding the spectrum of HPV types and HPV-16 LCR variants circulating among men and women infected with HIV-1 in Italy. This study, conducted in 518 HIV-positive subjects (346 males and 172 females), showed a high prevalence of HPV anal infections (88.7%) in men and of cervical infections (65.1%) in women.A wide spectrum of HPV genotypes has been observed, as both single and multiple infections. Low-risk HPV types 6, 11 and 61 were frequently detected. HPV-16 was the prevalent high-risk type. Fourteen different HPV-16 LCR variants were found. Ten belonged to the European lineage (78.7% were detected in Italian subjects and 21.3% in foreign-born, all homo/bisexual men), two to the Asiatic lineage and two to the African-2 lineage. This study underlines the great genotypic heterogeneity characterizing anal and cervical HPV infections and the marked polymorphism of the predominant HPV-16 in this high-risk population in Italy.     

Technique and early experience with posterior arthroscopic subtalar arthrodesis

BACKGROUND: Subtalar arthrodesis is a reliable procedure for pain relief and improved function in patients with isolated subtalar arthritis. Arthroscopic subtalar arthrodesis (ASTA) was designed to improve upon traditional methods by using a minimally invasive technique. However, posterior arthroscopic subtalar arthrodesis (PASTA) has not been described. The purpose of the present study was to investigate the early results of PASTA. METHODS: A retrospective review of 11 feet in 10 patients (one bilateral) that had PASTA was conducted. Inclusion criteria were isolated subtalar arthritis with no or minimal deformity and no significant bone loss. Exclusion criteria included patients requiring adjunctive open procedures or who had significant deformity. The technique involved prone positioning, two posterolateral portals and one posteromedial portal, posterior talocalcaneal facet debridement, percutaneous cancellous allografting and internal screw fixation. Outcome measures included patient satisfaction, the modified American Orthopaedic Foot and Ankle Society (AOFAS) score, union rate, time to union, and postoperative complications. RESULTS: All patients were discharged the day of surgery or stayed one night in the hospital. Eight patients were very satisfied, one satisfied, and one patient not satisfied with the results of their surgery. The average modified AOFAS score (maximum 94 points) improved from 36 points preoperatively to 86 points postoperatively. Ten joints fused by 10 weeks postoperatively, and one patient developed a nonunion. No other postoperative complications occurred. CONCLUSIONS: For surgeons familiar with posterior ankle or subtalar arthroscopy, PASTA offers superior exposure of the posterior talocalcaneal facet, high patient satisfaction, an excellent fusion rate, and less postoperative morbidity for patients with subtalar arthritis.