Walter Dehority

Bone and hormonal changes induced by skeletal unloading in the mature male rat

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

Zygomycetes infections in pediatric hematology oncology patients: a case series and review of the literature.

Fungi from the Zygomycetes class are increasingly recognized causes of infection in immunosuppressed children, but no comprehensive literature review and few case series have been published on the topic. A case series of 6 pediatric oncology patients with Zygomycetes infections cared for at our institution was constructed, and a concurrent search of the English language literature for Zygomycetes infections in children with oncologic disorders was undertaken. Our case series described 6 patients (5 male) between the ages of 2.5 and 19.5 years. One patient was diagnosed with rhinocerebral disease, 2 with rhinosinusitis, 2 with pulmonary involvement, and 1 with a gastrointestinal presentation. Five patients survived. Our literature review identified 82 cases from 61 studies. The mean subject age was 10.8 years (1.4 to 21.0 y). About 92.7% of all patients suffered from some form of leukemia, with 70.7% suffering from acute lymphoblastic leukemia. Overall, 58.5% of reported patients survived, with individuals with disseminated disease showing the worst prognosis (68.2% mortality) and those with cutaneous disease the best (14.3% mortality). Survival is increasingly reported in the literature, perhaps as a result of improved diagnostic capabilities, increased physician awareness and increased reliance on adjunctive surgical therapy.

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

Addition of ionic and nonionic water-soluble polymers to pulmonary surfactants in the presence of inactivating substances prevents surfactant inactivation in vitro and improves lung function in several models of lung injury. However, a recent report found opposite effects when surfactant plus polyethylene glycol (PEG) was used to treat lung injury caused by saline lung lavage. Therefore, we examined the reasons why the polymer effect is less evident in the saline lung lavage lung injury model. We treated rats with lavage lung injury with a commercial lung surfactant extract derived from bovine lung (Survanta) with or without addition of PEG. Groups treated with Survanta + PEG had significantly higher static post mortem lung volumes than groups treated with Survanta. However, groups treated with Survanta + PEG had more tracheal fluid and no significant benefit in arterial oxygenation compared with the group treated with Survanta, despite our use of measures to reduce pulmonary edema. Measurements after intravascular injections of 125I-labeled albumin confirmed that addition of PEG increased extravascular lung water and that this effect is mitigated by furosemide. We conclude that surfactant + PEG mixtures are less effective in lavage injury than in other forms of lung injury because of increased extravascular lung water.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States – A Case-Series

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.

Complete genome sequence of a KI polyomavirus isolated from an otherwise healthy child with severe lower respiratory tract infection.

Unbiased, deep sequencing of a nasal specimen from an otherwise healthy 13‐month‐old boy hospitalized in intensive care revealed high gene expression and the complete genome of a novel isolate of KI polyomavirus (KIPyV). Further investigation detected minimal gene expression of additional viruses, suggesting that KIPyV was potentially the causal agent. Analysis of the complete genome of isolate NMKI001 revealed it is different from all previously reported genomes and contains two amino acid differences as compared to the closest virus isolate, Stockholm 380 (EF127908). J. Med. Virol. 89:926–930, 2017.

Effect of HIV genotypic drug resistance testing on the management and clinical course of HIV-infected children and adolescents

Summary The clinical utility of genotypic drug resistance testing (DRT) in HIV-infected children on antiretroviral therapy (ART) is not well understood. HIV-infected patients aged <19 years undergoing DRT for virological failure were retrospectively enrolled. Indications for DRT and changes in HIV RNA load were recorded. Between January 2000 and December 2006, 57 patients had DRT. The most common indication for DRT was poor ART adherence (57.7% of patients). ART was changed in 50.9% of patients after DRT. Poor adherence was cited by clinicians for not changing ART significantly more often than any other reason (47.3%, P < 0.001). After DRT, significant improvement in HIV RNA load occurred independent of ART changes, though patients whose ART was modified were more likely to become undetectable (31.5% versus 7.0%, P < 0.001). Poor adherence was a significant factor for ordering DRT and for not changing ART in HIV-infected children.

Complete Genome Sequence of a Novel Human WU Polyomavirus Isolate Associated with Acute Respiratory Infection

ABSTRACT We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, NM040708, collected from a patient with an acute respiratory infection in New Mexico. The double-stranded DNA (dsDNA) genome of NM040708 is 5,229 bp in length and differs from the WUPyV reference with accession no. NC_009539 by 6 nucleotides and 2 amino acids.

Non–Type b Haemophilus influenzae Septic Arthritis in Children

Invasive disease caused by non-type b Haemophilus influenzae serotypes has been increasingly reported. Although to date it has been a rarely described cause of septic arthritis, we present 10 cases of non-type b H influenzae septic arthritis in children seen in a tertiary care center that serves a large Native American population.

Suppurative complications of acute hematogenous osteomyelitis in children

We carried out a case–control study in children with acute hematogenous osteomyelitis (AHO) with and without suppurative complications discharged from our institution over an 11-year period to test the hypothesis that abscess formation was associated with a delayed presentation to care. Of 102 children with AHO, 54 abscesses were documented in 46 patients (25 bone, 29 muscle). A delay in presentation was not associated with abscess formation (6.5 vs. 5.0 days, P=0.26). Overall, 78% of all bone abscesses were visible on initial MRI. Consistent use of MRI at presentation may identify children with suppurative complications of AHO.

Profile of etravirine in the treatment of HIV in pediatrics

Correspondence: Rolando M Viani University of California, San Diego School of Medicine, 9500 Gilman Drive, MC 0672, La Jolla, CA 92093-0672, USA Tel +1 619 471 9177 Fax +1 858 534 7411 Email rviani@ucsd.edu Abstract: Etravirine is a non-nucleoside reverse transcriptase inhibitor now licensed for treatment of human immunodeficiency virus (HIV)-1 infection in both children over 6 years of age and adults. Etravirine demonstrates a high genetic barrier to the development of resistance, as multiple mutations are typically required prior to the onset of reduced susceptibility to the drug. It retains in vitro and clinical activity against many HIV-1 isolates, demonstrating resistance to other non-nucleoside reverse transcriptase inhibitors, such as efavirenz and nevirapine. Given the ability of HIV to develop resistance rapidly across the non-nucleoside reverse transcriptase inhibitor class of antiretrovirals, etravirine has a welcome place in the management of HIVinfected patients, particularly treatment-experienced individuals harboring non-nucleoside reverse transcriptase inhibitor mutations. Etravirine has been shown to improve CD4 counts and viral load significantly in HIV-infected adults on combination antiretroviral therapy when compared with placebo in a large, randomized controlled trial. Data on the utility of etravirine in children are still somewhat limited, although a recent pediatric trial has demonstrated adequate pharmacokinetics, safety, and efficacy of etravirine in a small number of HIV-infected children and adolescents. In both children and adults, rash appears to be the most common adverse effect described. Despite its high genetic barrier to resistance, evidence of mutations conferring etravirine resistance has been documented in both adult and pediatric patients. Such mutations have been best described in treatment-experienced populations, including those who have never been exposed to the drug. This review describes the existing literature on the use of etravirine in the pediatric population, and highlights future and ongoing directions of investigation.