Alternative impression technique for a speech-aid prosthesis.

OBJECTIVE: Prosthetic treatment for speech disorders attributable to surgically acquired soft palate defects are introduced. CASE: A patient who underwent soft palate resection for cancer is presented. The resected portion of the soft palate was confined to the posterior segments. A prosthesis with a speech bulb was adapted to the patient. CONCLUSION: Excellent restoration of speech and improvement of velopharyngeal function was achieved following placement of the special prosthesis.     

Evaluation of neointimal hyperplasia on tranilast-coated synthetic vascular grafts: an experimental study.

Tranilast is an antiallergic drug that interferes with proliferation and migration of vascular smooth muscle cell induced by platelet-derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1). We investigated the local effect of tranilast on neointimal hyperplasia using tranilast-coated prosthetic grafts. The inner sides of the thin-walled polytetrafluoroethylene (PTFE) grafts were coated with chitosan and tranilast containing chitosan solution. Wistar albino rats (32) were used in the study. Patches (1 x 2 mm) for vascular grafts were prepared. Three groups were tested: group 1 (n = 12; tranilast coated), group 2 (n = 10; adhesive-only film-layer-coated), and group 3 (n = 10; normal ePTFE patch grafts sutured to the carotid arteries of the rats). Recipient sites of the carotid arteries were excised 4 weeks after surgery. All sections were examined histologically for graft patency, thrombus formation, and neointimal thickness. Expression of PDGF, fibroblast growth factor, and TGF-beta1 on cross-sections of the neointima were evaluated by immunohistochemistry. No significant differences were found regarding mean neointimal thicknesses. PDGF and TGF-beta-1 expressions were significantly lower in group 1. Although a decrease in local effect of tranilast was observed for growth factor expressions at a drug concentration of 0.05 mg/cm(2), a significant reduction in neointimal hyperplasia was not achieved. The coating concentration of 0.05 mg/cm(2) may have been too low to produce an antiproliferative effect. Given our promising results, further studies are recommended and planned using different drug concentrations and time intervals.     

Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model

We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated ¹²V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of ¹²V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.     

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.     

The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8 levels in stable COPD patients

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800 microg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6 months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/-2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of borderline (P=0.058) significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL.     

Effectiveness of anemia and chronic kidney disease as predictors for presence and severity of coronary artery disease in patients undergoing stress myocardial perfusion study

Chronic kidney disease (CKD) and anemia portend a higher risk of cardiac events and mortality. We sought to ascertain whether coronary artery disease (CAD) by myocardial perfusion single-photon emission computed tomography is more common in patients with CKD (glomerular filtration rate < or =60 ml/min/1.73 kg/m(2)) and/or anemia (hemoglobin level < or =13 g/L) and the impact of different degrees of CKD. One thousand five hundred eighty patients (mean age 65 +/- 10 years) underwent gated myocardial perfusion single-photon emission computed tomography and clinical evaluation. Patients were divided into 4 groups (group 1, no anemia/no CKD, n = 800; group 2, anemia/no CKD, n = 195; group 3, CKD/no anemia, n = 332; group 4, anemia/CKD, n = 253). Multivariate logistic regression analysis was undertaken to examine the association of these diagnoses with abnormal myocardial perfusion single-photon emission computed tomogram. Compared with patients with neither diagnosis, an abnormal scan was more common in those with anemia or CKD. Patients with anemia and CKD exhibited more severe CAD (mean summed stress score 6.8 vs 4.7, p <0.01). Established high-risk findings were more prevalent in patients with anemia and/or CKD, including a summed stress score > or =8, transient ischemic dilation, or a left ventricular ejection fraction < or =40% (group 1 28%, group 2 38%, group 3 38%, group 4 48%, all p values <0.01). Patients with moderate CKD demonstrated an increased risk of an abnormal scan (odds ratio 2.66, p <0.0001). After adjustment in multivariate analysis, anemia and CKD each remained predictors for an abnormal scan. The association was stronger in those with the 2 conditions (odds ratio for high-risk scan 1.89, p = 0.0002). In conclusion, in patients with suspected CAD, anemia and CKD are predictors of myocardial perfusion single-photon emission computed tomographic markers for worsened outcomes. The relation was independent of other risk factors, supporting the inclusion of anemia and CKD in global risk assessment for patients with suspected CAD.