Closed versus open mitral commissurotomy in pure noncalcific mitral stenosis: hemodynamic studies before and after operation

Controversy persists regarding whether the efficacy of closed instrumental mitral commissurotomy compares well enough with that of open commissurotomy to warrant its continued use. The purpose of this study was to compare the results of operation as determined by catheterization studies in 63 patients with pure, severe, and noncalcified mitral stenosis. The patients were randomly assigned to one of two groups: thirty-two patients were operated on by the closed technique (group I) and 31 by the open technique (group II). All patients underwent left-sided and right-sided catheterization before and 4 months after operation. Preoperatively the two groups were statistically similar with regard to major clinical data and hemodynamic findings. There were no deaths at operation or systemic embolism in the two groups. The prevalence of surgically induced mitral regurgitation was similar in the two groups (12.4% versus 12.9%). Pulmonary arterial pressure and arteriolar and total pulmonary vascular resistance decreased significantly in the two groups. Pulmonary capillary wedge pressure decreased from 23.3 +/- 8.5 to 15.8 +/- 7 mm Hg in group I (p less than 0.001) and from 23.7 +/- 6 to 14 +/- 5.8 mm Hg in group II (p less than 0.001). Cardiac index increased from 2.86 +/- 0.84 to 3.14 +/- 0.78 L/min/m2 in group I, but this increase did not reach statistical significance. In group II cardiac index increased from 2.89 +/- 0.6 to 3.6 +/- 0.6 L/min/m2 (p less than 0.005). The mean and end-diastolic transmitral pressure gradients decreased significantly in the two groups, but the decrease was statistically greater in the open mitral commissurotomy group (p less than 0.001). Mitral valve area increased from 0.82 +/- 0.18 to 1.4 +/- 0.40 cm2 in group I (p less than 0.01) and from 0.84 +/- 0.15 to 2.14 +/- 0.53 cm2 in group II (p less than 0.001). The mean increase in mitral valve area was 0.61 cm2 in group I and 1.34 cm2 in group II (p less than 0.001). At exercise, in patients with resting pulmonary capillary wedge pressures of 18 mm Hg or less, cardiac index increased by 36% in group I (23 patients) and 48% in group II (24 patients), because of a smaller mitral valve area in group I (1.61 +/- 0.39 cm2) than in group II (2.45 +/- 0.65 cm2). Thus open commissurotomy improved hemodynamic values to a greater extent than closed commissurotomy at both rest and exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Health-seeking behavior and the meaning of medications in Balochistan, Pakistan

A wide variety of health care options--home-based, indigenous, and cosmopolitan--exists in northern Balochistan, Pakistan. This paper examines health-seeking behavior in the area of mother and child health for villagers in this pluralistic medical setting. The analysis of a specific series of illness episodes shows that the majority of cases obtain treatment from different medical systems for a single episode. Interest in medications takes precedence over practitioners, and the meaning the villagers attach to such substances is explored. Long-established patterns of behavior relating to indigenous medicine continue to occur when cosmopolitan medicine is utilized. Information presented here helps to explain problems in utilization of cosmopolitan pharmaceuticals and delineates areas for future health programme activity.     

IGF-I signalling in bone growth: inhibitory actions of dexamethasone and IL-1beta.

OBJECTIVE: To determine if glucocorticoids and proinflammatory cytokines inhibit bone growth through a common mechanism involving impaired IGF-I signalling. DESIGN: IGF-I (100 ng/ml), dexamethasone (dex) (10(-6)M) and IL-1beta (10 ng/ml) with inhibitors of the PI3K (LY294002) and Erk 1/2 (PD98059 and UO126) IGF-I pathways (all 10 microM) were studied using the ATDC5 chondrocyte cell line and murine fetal metatarsal cultures. RESULTS: IGF-I stimulated ATDC5 chondrocyte proliferation (322%; P < 0.001 versus control). Addition of PD or LY individually to IGF-I supplemented ATDC5 cultures partially reduced proliferation by 32% (P < 0.001), and 66% (P < 0.001), respectively. PD and LY in combination blocked all IGF-I stimulated ATDC5 proliferation. LY significantly reversed IGF-I stimulatory effects on metatarsal growth (P < 0.001), whereas PD and UO treatment had no effect. IGF-I induced ATDC5 proliferation was further decreased when Dex (24%; P < 0.01) or IL-1beta (33%; P < 0.001) were added to PD but not LY cultures. Metatarsal growth inhibition by LY was unaltered by Dex or IL-1beta addition. CONCLUSIONS: Both the PI3K and Erk 1/2 pathways contributed independently to IGF-I mediated ATDC5 proliferation. However in metatarsal cultures, the Erk 1/2 pathway was not required for IGF-I stimulated growth. Dex and IL-1beta may primarily inhibit IGF-I induced bone growth through the PI3K pathway.     

C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria

The immunogenicity of recombinant protein or anti-viral DNA vaccines can be significantly improved by the addition of tandem copies of the complement fragment C3d. We sought to determine if the efficacy of a circumsporozoite protein (CSP)-based DNA vaccine delivered to mouse skin by gene gun was improved by using this strategy. Instead, we found that C3d suppressed the protective immunity against Plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the induction of antibodies specific for the CSP C-terminal flanking sequence and by suppressing the induction of CSP-specific IL-4-producing spleen cells. We further showed that C3d bound to the C-terminal flanking sequence of the CSP, which may explain the immune deviation observed in CS/C3d chimeric antigen. We have thus identified C3d-mediated epitope masking and shifting of both the humoral and cellular immune responses as a potential novel escape mechanism, which plasmodia may use to divert the induction of protective immunity.     

Architectural remodelling in lungs of rabbits induced by type V collagen immunization: a preliminary morphologic model to study diffuse connective tissue diseases

The pathogenesis of diffuse connective tissue diseases (DCTD) is still unknown and has been extensively studied regarding its autoimmunity aspects related to extracellular matrix (ECM) remodelling, with an emphasis on the collagens at the inflammatory site. The present paper describes the pulmonary architectural and repair/remodelling responses to injury after immunization of rabbits with human type V collagen. The animal model consisted of rabbits immunized with collagen mixed with Freund's adjuvant and sacrificed 7, 15, 30, 75, and 120 days after the first of four doses of antigen. Pulmonary architecture remodelling response was evaluated by histology, morphometry, and the immunofluorescence method, according to compartments of reference (parenchyma and interstitium) and injury: 1 inflammation (polymorphonuclear and mononuclear cells); 2-repair (fibrosis) and 3-ECM remodelling (collagen system). The results showed an intense inflammatory involvement of the pulmonary vascular and bronchiolar parenchyma, characterized by increased wall thickness in small arteries, infiltrations by pseudoeosinophils, and mononuclear cells. Progressive remodelling of the pulmonary ECM was characterized by collagen deposition in the septal and bronchovascular interstitium, especially in rabbits sacrifices at 75 and 120 days. The ECM remodelling process was not reproduced when rabbits were inoculated with collagen types I and III. We conclude that the model reproduces morphologic changes similar to those observed in many DCTD, encouraging realization of other experiments to gain a better understanding of the pathogenesis of these diseases.     

循证病例报告 原发性脑出血患者是否应该进行抗血小板或抗凝治疗？

原发性脑出血伴有血栓危险因素的患者治疗比较棘手，如以下病例：老年男性，55岁，因右侧肢体无力入院。既往患有难治陛高血压、Ⅱ型糖尿病、心绞痛及高脂血症。约10年前右侧肢体曾有一次轻微卒中。入院时所服药物为：阿司匹林75mg，1次／日；阿托伐他汀10mg，1次／日；苄氟噻嗪2．5mg，1次／日；雷米普利2．5mg，1次／日；氨氯地平5mg，1次／日；