Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.     

Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

Genome Expression Profiling-Based Identification and Administration Efficacy of Host-Directed Antimicrobial Drugs against Respiratory Infection by Nontypeable Haemophilus influenzae

Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection.     

The fit of gold-alloy full-crown castings made with ceramic casting ring liners.

Measurements were made of the fit of gold-alloy full-crown castings produced with dry ceramic ring liners. When used with vacuum investing, these liners absorb relatively large amounts of water from the investment mix (thereby reducing its original W/P ratio) and then function as wet liners, thus increasing the investment's potential expansion and giving castings which are consistently larger than when air investing is used. With four of the five liners tested, investing in air produced many castings which were unacceptably undersized (inaccuracy worse than -0.2%). The fifth liner, an industrial material 2 mm thick, gave only one casting out of 12 which was outside this limit, although all castings were undersized to a lesser extent. Vacuum investing gave improved casting accuracy; with four of the five liners, the improvement was highly significant (p < 0.001), and with the fifth, probably significant (p < 0.05). Even with vacuum investing, however, with only two of the liners did all castings show inaccuracies within +/- 0.2%. With the other three liners, some castings (ranging from 2/10 to 7/9) had inaccuracies worse than -0.2%. With both air and vacuum investing, changing from one liner to another caused changes in relative casting accuracy which were often significant (p < 0.01) or highly significant (p < 0.001). In casting techniques where a ceramic ring liner is used, the choice of specific lining material and the choice between investing in air or under vacuum are important factors which can have a major effect on the fit of castings.     

Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan

As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron‐rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age‐related changes of susceptibility were in good agreement with the findings from R2^* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. Hum Brain Mapp 35:2698–2713, 2014. © 2013 Wiley Periodicals, Inc .     

Multifocal metachronous giant cell tumour in bilateral upper limb: a rare case presentation

Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour and accounts for 20 % of all benign bone tumours and 5 % of all bone tumours. Multicentric GCT of bone is a rare entity and has increased prevalence of involvement of the small bones of hands and feet in multicentric GCT. The clinical behaviour in multicentric GCTs tends to be aggressive as in recurrent GCTs. En-bloc resection remains the most successful surgical technique for treating both multicentric and solitary lesions. We report a 14-year-old female patient presenting with metachronous benign GCT located at the right proximal humerus and subsequent lesions in left hand and left proximal humerus. The case was treated with multimodality therapy including en-bloc resection along with bisphosphonate therapy over a period of 5 years.     

Bladder neck contracture

Bladder neck contracture (BNC) is a well-described complication of the surgical treatment of benign and malignant prostate conditions. Nevertheless, etiologies of BNC development are highly dependent on the primary treatment modality undertaken with BNC also occurring after pelvic radiation. The treatment options for BNC can range from simple, office-based dilation procedures to more invasive, complex abdomino-perineal reconstructive surgery. Although numerous strategies have been described, a patient-specific approach is usually necessary in the management of these complex patients. In this review, we highlight various therapeutic maneuvers described for the management of BNC and further delineate a tailored approach utilized at our institution in these complicated patients.