Factors influencing the acceptance of changes in antiretroviral therapy among HIV-1-infected patients

Physicians routinely consider modifying antiretroviral therapy (ART) regimen for their patients with HIV. Little is known about the factors associated with patients' willingness to accept providers' recommended ART changes. This multicenter prospective observational study examined factors associated with willingness to accept ART changes recommended by their providers among HIV-infected adults from six urban outpatient HIV clinics. Patients were surveyed using the Patient Attitudes about Altering Antiretroviral Therapy Survey questionnaire (PAAARTS). Factors associated with willingness to accept ART changes were assessed using a multivariate generalized estimating equation (GEE) model to account for correlated responses. The Classification and Regression Trees (CART) analysis was also performed to determine subgroups of patients with higher acceptance of change. 216 of 289 patients (75%) definitely accepted recommended changes. Odds for acceptance were 3.2, 2.3, and 2.8 times higher for patients with higher attitudes and beliefs about ART (p < 0.01; 95% confidence interval [CI] = 1.59, 6.52), patients who rated their provider's care as excellent (p < 0.05; 95% CI = 1.07, 4.78), and non-Hispanic patients (p < 0.05; 95% CI 1.03, 7.57), respectively. CART analysis showed similar results and identified that when patients had less positive attitude about ART, acceptance rates were higher for non-Hispanic patients with higher assessments of their patient-provider communication. While most patients accepted providers' recommendation for ART changes, this willingness was influenced by both patients' attitudes and beliefs about ART and their assessment of either the effectiveness of patient-provider communication or their rating of providers' care. ART acceptance rates among Hispanic patients were lower.     

The influence of aging on pharyngeal collapsibility during sleep

BACKGROUND: Aging increases vulnerability to obstructive sleep apnea (OSA), but the underlying mechanisms remain unclear. Recent data in awake healthy volunteers show a decrease in the genioglossus negative pressure reflex and anatomic compromise with increasing age, suggesting an age-related predisposition to pharyngeal collapse. However, aging effects on pharyngeal collapsibility have not been studied extensively during sleep. We tested the hypotheses that upper airway closing pressure (PCLOSE) and the increase in pharyngeal resistance during sleep (primary outcomes) as well as measures of arousal threshold (secondary outcomes) increase with age. METHODS: We studied 21 healthy individuals (8 women [mean (+/- SD) age, 36 +/- 18 years] and 13 men [mean age, 41 +/- 23 years]) who were between 18 and 75 years of age. During overnight polysomnography, we measured nasal pressure (PMASK) and epiglottic pressure (Pepi) during stage 2 sleep before and after airway occlusion (external valve) until arousal. PCLOSE was defined as the pressure at which PMASK plateaued despite further decreases in PEPI. RESULTS: Increasing age was correlated with both pharyngeal collapsibility ([PCLOSE] r = 0.69; p < 0.01) and an increase in pharyngeal resistance during sleep (r = 0.56; p < 0.01) independent of body mass index (BMI) and gender. There was no evidence for an effect of age on arousal threshold after airway occlusion during stage 2 sleep. CONCLUSIONS: Older age is associated with increased pharyngeal airway collapsibility during sleep independent of gender and BMI. These data may at least partially explain the mechanisms underlying the predisposition for pharyngeal collapse in the elderly.     

Alteration of peripheral blood T-reg cells and cytokines production in angiography personnel exposed to scattered X-rays

Angiocardiography is an X-ray examination of the blood vessels or chambers of the heart. Cardiologists and staff members applying this procedure are exposed to high levels of scattered radiation. In our previous study the incidence of unstable chromosomal aberrations and cytokinesis-blocked micronuclei were found to be significantly higher in exposed individuals than the age and sex matched controls. In the present study we assessed cytokine production by peripheral blood mononuclear cells of the above cases and the percentage of Treg cells. According to film dosimeter analysis, personnels received 0.25-15 mSv during the previous year (average of 3 mSv/y). Isolated PBMCs from the test and control groups were stimulated with Phorbol Myristate Acetate/ Ionomycin (PMA/I). Cytokine production was measured in the supernatants of cultured lymphocytes. The percentage of Treg cells was studied by flow cytometry. The production of IL-10 and IL-5 was significantly down-regulated in the test group compared to the control group. In contrast, IL-12 was up-regulated. Yet, no statistically significant difference was found for IFN- gamma between two groups. In addition, we found higher percentage of CD4+CD25+(bright) Treg cells in the study group compared to the controls. Taken together, it was shown that low doses of scattered X-rays could skew cytokine profile of peripheral blood mononuclear cells in favour of inflammatory response causing the increase of Treg cells.     

HLA Class II (DRB,DQA1 and DQB1) Allele and Haplotype Frequencies in the Patients with Pemphigus Vulgaris

Introduction  Pemphigus vulgaris (PV), an autoimmune disease affecting the skin and mucous membranes, is associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. Materials and Methods  In order to evaluate the association of HLA-DR and DQ alleles and haplotypes in Iranian non-Jewish patients with PV, 52 patients with PV and 180 normal subjects as control group were investigated in this study. Results and Discussion  HLA-DRB1*04, -DRB1*1401, -DRB4, -DQA1*0104, -DQA1*03011, -DQB1*0302, and -DQB1*0502 alleles have been significantly increased in our patients group. Moreover, the haplotypes HLA-DRB1*04/-DQA1*03011/-DQB1*0302 and HLA-DRB1*1401/-DQA1*0104/-DQB1*0502 increased significantly in our patients. In contrast, the following alleles decreased significantly in our patients: HLA-DRB1*15, -DRB1*0301, -DRB1*07, -DRB1*11, -DRB5, -DQA1*0101, -DQA1*0103, -DQA1*201, -DQA1*05, -DQB1*0201, -DQB1*0301, -DQB1*06011, and -DQB1*0602. In addition, HLA-DRB1*15/-DQA1*0103/-DQB1*06011, HLA-DRB1*0301/-DQA1*05011/-DQB1*0201, HLA-DRB1*07/-DQA1*0201/-DQB1*0201, and HLA-DRB1*11/-DQA1*05/-DQB1*03011 decreased significantly in our patients. Genetic factors are involved in the occurrence of PV; HLA-DRB1*04 and -DRB1*1401 alleles and the related haplotypes are suggestive to be two major PV susceptibility factors in our population study.     

Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men

We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings.     

Mirror movement associated with neural tube defects

Objective

Association of mirror movements with special kinds of neural tube defects, particularly cranial dermal sinus and cervical myelomeningocele, is extremely rare. We have tried to explain the probable pathophysiology underlying this rare condition.

Clinical presentation

Two cases are presented. Case 1: A right-handed 3-year-old boy brought to the outpatient clinic for evaluation of mirror movement had been operated on at 10 days of age to repair a cervical myelomeningocele. At examination, mirror movements were observed on both sides. Case 2: A right-handed 7-year-old boy referred for vertigo and occasional vomiting since 3 months of age. The mirror movements were present in the upper extremities, and reportedly had existed since early childhood. Brain magnetic resonance imaging disclosed the dermal sinus, tract, and midline dermoid tumor.

Conclusion

To describe a meaningful association between mirror movements and congenital abnormalities in 2 cases reported here, we propose development of an abnormality in the cervical spinal cord (case 1) and cervicomedullary junction (case 2) associated with gross anomalies in the affected areas.     

Initial management of childhood brain tumors: neurosurgical considerations

Intracranial tumors are the most common solid tumors in children. The infratentorial compartment will be the primary site for 60% to 70% of these tumors, including astrocytomas, medulloblastomas, and ependymomas. Several technological advancements have increased our knowledge of the cell biology of pediatric brain tumors, facilitated earlier diagnosis, and improved neurosurgical resections while minimizing neurological deficits. These in turn have not only improved the survival of children with brain tumors but also their quality of life. Current management strategies in most cases rely on surgery coupled with adjuvant therapies, including radiation therapy and chemotherapy. The vulnerability of the immature brain to adjuvant therapies creates many challenges for the treating physician. We review current diagnostic and therapeutic approaches and outcome for children harboring the most common pediatric brain tumors: astrocytomas (low-grade and high-grade glioma), ependymoma, medulloblastoma, and craniopharyngioma. The emphasis will be on the neurosurgical management of children with these tumors.     

Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration

Previous studies have revealed a novel interaction between deoxyhemoglobin and nitrite to generate nitric oxide (NO) in blood. It has been proposed that nitrite acts as an endocrine reservoir of NO and contributes to hypoxic vasodilation and signaling. Here, we characterize the nitrite reductase activity of deoxymyoglobin, which reduces nitrite approximately 36 times faster than deoxyhemoglobin because of its lower heme redox potential. We hypothesize that physiologically this reaction releases NO in proximity to mitochondria and regulates respiration through cytochrome c oxidase. Spectrophotometric and chemiluminescent measurements show that the deoxymyoglobin-nitrite reaction produces NO in a second order reaction that is dependent on deoxymyoglobin, nitrite and proton concentration, with a bimolecular rate constant of 12.4 mol/L(-1)s(-1) (pH 7.4, 37 degrees C). Because the IC(50) for NO-dependent inhibition of mitochondrial respiration is approximately 100 nmol/L at physiological oxygen tensions (5 to 10 mumol/L); we tested whether the myoglobin-dependent reduction of nitrite could inhibit respiration. Indeed, the addition of deoxymyoglobin and nitrite to isolated rat heart and liver mitochondria resulted in the inhibition of respiration, while myoglobin or nitrite alone had no effect. The addition of nitrite to rat heart homogenate containing both myoglobin and mitochondria resulted in NO generation and inhibition of respiration; these effects were blocked by myoglobin oxidation with ferricyanide but not by the xanthine oxidoreductase inhibitor allopurinol. These data expand on the paradigm that heme-globins conserve and generate NO via nitrite reduction along physiological oxygen gradients, and further demonstrate that NO generation from nitrite reduction can escape heme autocapture to regulate NO-dependent signaling.