Pseudomonas aeruginosa elastase stimulates ERK signaling pathway and enhances IL- 8 production by alveolar epithelial cells in culture

OBJECTIVE AND DESIGN: Bacterial products as well as the host airway inflammatory responses contribute to the pathogenesis of Pseudomonas infections. We sought to determine if Pseudomonas elastase (PE) induces mitogen-activated protein (MAP) kinase activity in association with interleukin-8 (IL-8) production by alveolar epithelial cells. METHODS: We utilized Western blot analysis to detect phosphorylation of signaling intermediates and ELISA was used to measure IL-8 production. RESULTS: We found that PE induces phosphorylation of the extracellular signal-regulated (ERK1/2) proteins of the MAPK pathway in A549 epithelial cells. Similar results were obtained using primary cultures of rabbit alveolar type II epithelial cells. PE also enhanced IL-8 production, which was abolished in the presence of the ERK activation inhibitor U0126. CONCLUSIONS: We conclude that PE activates the ERK1/2 arm of the MAPK pathway and that activation of this pathway results in enhanced IL-8 production. The results demonstrate that PE may augment pulmonary inflammation via cellular signaling that regulates expression of IL-8.     

The incidence of Hill-Sachs lesions in initial anterior shoulder dislocations

We undertook a prospective study using arthroscopy to determine the intraarticular derangement caused by initial anterior shoulder dislocations. Of our 32 patients, 15 (47%) had a grade I, grade II, or grade III Hill-Sachs lesion. The patients were 29 men and 3 women whose ages ranged from 15 to 28 years (mean 22 years). All of the patients studied were United States military personnel or members of their families. None of the patients had had prior injuries of the affected shoulder, and all underwent arthroscopy within 72 h of injury. Few reports describe a Hill-Sachs lesion in a patient following a single anterior dislocation. Early reports of this lesion were based on indirect (radiographic) evidence. Our arthroscopic findings indicate that the incidence of this lesion after one anterior dislocation is higher than previously thought.     

The reliability of three methods for evaluating dental sealants

Three evaluation instruments (global, check-list, and criterion referenced) were used by experienced and inexperienced examiners to evaluate dental sealant end products on 40 extracted teeth. Intra- and interexaminer reliabilities were measured. Experienced examiners achieved higher intrarater reliabilities with all three evaluation instruments than did inexperienced examiners. The highest intraexaminer agreement for all examiners occurred with use of the global evaluation. The highest interexaminer reliability was achieved with the second use of the criterion-referenced evaluation by the experienced examiner. Interexaminer reliability was improved for both types of examiners with the criterion-referenced evaluation.     

在"医学教育国际标准研讨会"上的致辞

<西太平洋地区本科医学教育指导原则>为医学院校提供了基准和质量改进的努力方向,并将有助于实现可持续的课程改革.本次会议将是中国在改善本科医学教育质量上迈出的重要一步.世界卫生组织愿与中国政府合作并提供支持.     

Nails in systemic disease

Nail plate and nail unit abnormalities may be helpful as diagnostic tools or as a part of the puzzle for confirmation of systemic disease. There are specific and nonspecific nail signs, which can be seen involving one or more nails, that occur simultaneously or secondary to systemic disease. Occasionally these clues can be diagnostic, while most are nonspecific reaction patterns. Nail changes occur in the nail plate as a result of nail matrix abnormalities caused by systemic disease and other systemic insults such as reactions to medications. In this article we review some of the more common nail signs that can be used to help diagnose systemic disease.     

Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.     

Integrating PET and CT information to improve diagnostic accuracy for lung nodules: A semiautomatic computer-aided method.

Our objective was to develop and evaluate 3 semiautomatic computer-aided diagnostic (CAD) schemes for distinguishing between benign and malignant pulmonary nodules by use of features extracted from CT, 18F-FDG PET, and both CT and 18F-FDG PET. METHODS: We retrospectively collected 92 consecutive cases of pulmonary nodules (<3 cm) in patients who underwent both thoracic CT and whole-body PET/CT. Forty-two of the nodules were malignant and 50 benign, as confirmed by pathologic examination and clinical follow-up. The interval between CT and PET was less than 1 mo. Four clinical parameters, including patient age, sex, smoking status, and history of previous malignancy, were used for the CAD schemes. Sixteen CT features based on size, shape, margin, and internal structure of nodules were independently rated subjectively by 2 chest radiologists. Four PET features were viewed on a PET/CT workstation. CAD schemes based on clinical parameters together with CT features, PET features, and both CT and PET features were then used to differentiate benign from malignant nodules. Finally, the output from the CAD schemes was evaluated by use of receiver-operating-characteristic analysis. RESULTS: When we used clinical parameters and CT features as input units (CAD scheme 1), the area under the receiver-operating-characteristic curve (A(z) value) of the CAD scheme was 0.83. When we used clinical parameters and PET features as input units (CAD scheme 2), the A(z) value for the computer output was 0.91. However, when we used all data as input units (CAD scheme 3), the A(z) value for the computer output was 0.95. The performance of CAD scheme 3 was better than that of CAD scheme 1 or 2. A statistically significant difference existed between the A(z) values of CAD schemes 3 and 2 (P = 0.037) and between those of CAD schemes 3 and 1 (P = 0.015). CONCLUSION: Our CAD scheme based on both PET and CT was better able to differentiate benign from malignant pulmonary nodules than were the CAD schemes based on PET alone and CT alone.