A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r² = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.     

Providence School Asthma Partnership: School-based Asthma Program for Inner-City Families

Over 3 years, 972 families participated in an after-school asthma program at their child's school. Parents and children attended concurrent 2¹/₂ -hour workshops. Parents were 74% Latino; 45% non-English speaking, with 77% of children on Medicaid. Asthma symptoms were significantly reduced, from multiple times per week to less than once per week on average. Oral steroid use decreased to one third of baseline use. Hospital days decreased from 11% to 2%; emergency visits decreased 35% to 4%; and school days missed decreased 48% to 20%. This program has now become sustainable with both private and Medicaid insurance coverage.     

Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism (eg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m²) women with PCOS (ie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apprarent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor.     

Kinetics of bactericidal and sporicidal effects of a disinfectant against bacteria isolated from hospital units]

The bactericidal and sporicidal activities of a peracetic acid disinfectant commonly used in hospitals (Acetoper 200) was studied using three bacterial species recovered in water from hemodialysis machines and humidifiers, i.e., Pseudomonas aeruginosa, Serratia liquefaciens, and Bacillus subtilis (spores). The method used was derived from AFNOR norms NF T 72-151 and NF T 72-231. For each strain, three concentrations of disinfectant were tested. Counts were performed every five minutes for one hour to evaluate killing kinetics. For both Gram-negative organisms, survival curves were biphasic, whereas B. subtilis counts decreased logarithmically. Both concentration and time influenced the 5 log10 decrease in counts. With S. liquefaciens and B. subtilis (spores), the 5 log10 decrease was not reached with low levels of disinfectant. In every case, the D value decreased substantially with increasing levels of disinfectant.     

Prostaglandin E2 level in tissue surrounding aseptic failed total hips

Summary Production of inflammatory mediators (IM) by cells and specifically macrophages around loosened implants may be responsible for their loosening. Our hypothesis was that different materials give rise to different amounts of these IM. It is thought that alumina/alumina for total hip replacement (THR), which has been used for 15 years in our orthopedic department, may produce less IM than other systems. We initiated a clinical prospective study to measure the level of prostaglandin E₂ (PGE₂) in tissue surrounding loosened prostheses to quantify PGE₂ production regarding the types of material involved in the friction couple, i.e., alumina/alumina versus metal/polyethylene, and the type of fixation, i.e., cemented versus cementless. A total of 29 THR revisions were performed in 28 patients. Four implant groups were identified: alumina/alumina cemented, alumina/alumina cementless, metal/polyethylene cemented, and metal/polyethylene cementless. For each revision, tissues surrounding the failed implants were harvested and processed, and the PGE₂ was measured in a blind manner using an immunoassay technique. As the measuring technique was difficult, at least three determinations for each sample were necessary. Some samples were excluded from the analysis for various reasons, for example, second or further revisions involving many different materials in the past, conjunction of metallic and alumina debris and samples taken from nonloosened components. Finally, 15 samples were considered adequate for inclusion in this study. Two groups were analyzed and compared: the alumina/alumina couple and the metal/polyethylene couple. Tissue surrounding the first group demonstrated a PGE₂ level of 69 ± 56 fmol/mg wet weight compared to 202 ± 156 fmol/mg for the second. The Wilcoxon test was applied, and there was a statistical difference (P < 0.05). When the alumina/alumina cemented group was compared to the alumina/alumina cementless group, there was a tendency to less PGE₂ with the cemented, but the difference was not statistically significant. Results thus demonstrate that alumina/alumina produces less IM than metal/polyethylene. However, these results do not indicate whether this is related to the type of debris, the amount, or both. This remains a preliminary study. Further studies with more samples, other mediators and growth factors, and a precise comparison to histological findings are still necessary.     

Self-mutilation in personality disorders: psychological and biological correlates.

OBJECTIVE: The goal of this study was to determine whether self-mutilators with personality disorders differ from nonmutilators with personality disorders in impulsivity, aggression, and other psychopathology and whether serotonergic dysfunction contributes to self-mutilation. METHOD: Twenty-six self-mutilators with personality disorders were matched to 26 control subjects with personality disorders for gender, age, education, axis I diagnosis of affective disorder, and axis II diagnosis of personality disorder. Numerous indexes of psychopathology as well as CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and platelet imipramine binding sites (Bmax) and affinity (Kd) were determined. RESULTS: Self-mutilators had significantly more severe character pathology, had greater lifetime aggression, and were more antisocial than the control subjects. The self-mutilators scored higher on the Hamilton Rating Scale for Depression but not on the Beck Depression Inventory or the Beck Hopelessness Scale. The two groups did not differ on the Buss-Durkee Hostility and Guilt Inventory or on the Sensation Seeking Scale. The degree of self-mutilation was significantly correlated with impulsivity, chronic anger, and somatic anxiety. Both self-mutilation and impulsivity showed significant negative correlations with Bmax, although the two groups did not differ in CSF 5-HIAA levels or in platelet imipramine binding. CONCLUSIONS: The results demonstrate the contribution of severe character pathology, aggression, impulsivity, anxiety, and anger to self-mutilation and provide preliminary support for the hypothesis of underlying serotonergic dysfunction facilitating self-mutilation.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.