Heat shock protein 47 (HSP47) antisense oligonucleotides reduce cardiac remodeling and improve cardiac function in a rat model of myocardial infarction.

BACKGROUND: Cardiac remodeling after acute myocardial infarction is regulated by components of the extracellular matrix. The 47 kD heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that plays a major role during procollagen processing and/or secretion. OBJECTIVE: The purpose of the study was to determine whether HSP47 inhibition can mitigate ligated left anterior descending (LAD) coronary artery-induced myocardial infarction in rats. METHODS: Rats were randomly divided into four experimental groups and subjected to the following treatments: 1) intravenous (IV) administration of saline; 2) ligation of the LAD coronary artery; 3) ligation of the LAD coronary artery + IV administration of HSP47 antisense oligonucleotides; or 4) IV administration of HSP47 antisense oligonucleotides. We investigated cardiac histopathology, performed immunoblot and immunohistochemical analyses, and examined cardiac function. RESULTS: Rats with ligated LAD coronary artery experienced upregulation of HSP47 expression, remodeling of the left ventricle, and cardiac dysfunction. In contrast, rats with ligated LAD coronary artery treated with HSP47 antisense oligonucleotides had significantly reduced HSP47 expression, cardiac remodeling, and improved cardiac function. Intravenous (IV) administration of HSP47 antisense oligonucleotides alone had no effect on cardiac morphology. CONCLUSION: The data strongly support the idea that changes in the extracellular matrix and its components are important determinants of cardiac remodeling after myocardial infarction.

Translation, Adaptation and Validation of Rapid Geriatric Assessment to the Brazilian context.

OBJECTIVES: Translate, cross-culturally adapt and validate the Rapid Geriatric Assessment (RGA) for Brazilian community-dwelling adults. DESIGN: Cross-sectional study, using a quantitative approach. SETTING: Urban population from the city of São Carlos, located in the interior of São Paulo State, Brazil. PARTICIPANTS: 148 individuals aged 60 or over. MEASUREMENTS: Participants were assessed using the RGA, Fried Frailty Phenotype, International Physical Activity Questionnaire - long version, Addenbrooke´s Cognitive Exam - Revised Version, Mini Nutritional Assessment, short Form - 36, EuroQol 5-Dimension, Geriatric Depression Scale - short version, in addition to performing Dual Energy X-ray Absorptiometry to diagnose sarcopenia, according to the criteria established by the European Working Group on Sarcopenia in Older People. RESULTS: In the translation and adaption process of the RGA, steps recommended by the literature were followed: initial translation, synthesis of translations, backward translation, evaluation from the panel of judges, and pre-test. When evaluating the psychometric properties of the scale, satisfactory reliability (internal consistency and stability) and validity (content, concurrent criterion and convergent, divergent and discriminant construct) were verified. CONCLUSION: The Brazilian version of the RGA is reliable and valid, and can be used in the Brazilian context to evaluate the elderly population.

New method of evaluating the surgical margin and safety margin for musculoskeletal sarcoma, analysed on the basis of 457 surgical cases.

The evaluation of surgical margin is useful in determining the curative success of surgical treatment of musculoskeletal sarcoma and the degree to which later surgery will be reduced by the preoperative therapy. However, until recently no reliable evaluation method has been developed for these purposes. In this paper we propose a new method for evaluating the surgical margin as drafted in 1989 by the Bone and Soft Tissue Tumor Committee of the Japanese Orthopaedic Association (JOA). In this method, surgical margin was classified into four types based on the distance between the surgical margin and the reactive zone of the tumour. These classifications of surgical margin (in order to surgical extent) are curative wide margin (curative margin), wide margin, marginal margin, and intralesional margin. The surgical margin is said to be curative if the margin is more than 5 cm outside the reactive zone. It is referred to as wide if the margin is less than 5 cm. Similarly, a margin that is in the reactive zone is considered as marginal, and a margin passing through a tumour as intralesional. Moreover, wide margin is classified as adequate (at least 2 cm outside the reactive zone) or inadequate (1 cm). In our evaluation, a "thin" barrier is considered to be a 2-cm thickness of normal tissue, a "thick" barrier as a 3-cm thickness, and joint cartilage is said to be equivalent to a 5-cm thickness. In addition, a surgical margin that is outside a barrier, with normal tissue between the barrier and the reactive zone of the tumour, is considered to be curative. This method was applied in 457 cases (involving 499 surgeries) at the Cancer Institute Hospital to determine clinical significance in the treatment of musculoskeletal sarcoma (1979-1994). From the results of this study we were able to conclude that this evaluation method can be highly useful in clinical practice for establishing optimum surgery. Moreover, we found that the safety margin for high-grade musculoskeletal sarcoma is a curative margin providing an adequate wide margin of 3 cm or more when preoperative therapy is not performed or is not effective, while the safety margin for high-grade sarcoma that responds to preoperative chemo- or radiotherapy seems to be an adequate wide margin of 2 cm. Here, radiotherapy is more effective compared to chemotherapy for reducing surgical margin. An inadequate wide margin, however, combined with radiotherapy, is not enough to ensure local curative success following surgery for musculoskeletal sarcoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Determination of creatine kinase isozymes in sera and tissues of patients with various lung carcinomas.

Three creatine kinase isozymes (CK-BB, CK-MB and CK-MM) were estimated by immunoassay in tumor tissues and in sera of patients with various lung carcinomas. CK-BB was increased in small cell carcinoma, but not in other lung carcinomas. CK-MM and CK-MB were not increased in any types of carcinoma. Serum CK-BB was increased in all types of lung carcinoma examined, while serum CK-MM and CK-MB were within normal limits in all patients. Serum CK-BB of healthy adults was estimated as 0.32 +/- 0.14 (mean +/- SD) ng/ml, ranging from 0.11-0.68 ng/ml. If CK-BB values above 1.0 ng/ml were considered abnormal, elevation occurred in 28/40 (70%) of patients with small cell carcinoma, 25/67 (37%) with adenocarcinoma, 21/51 (41%) with squamous cell carcinoma, 4/11 (36%) with other carcinoma of the lung and 10/42 (24%) with lung tuberculosis. Since serum CK-BB with lung cancer changed in parallel with the clinical course, this isozyme may be a marker for monitoring the clinical course, especially in small cell carcinoma of the lung.

[Collective health: a challenge for nursing]. / Saúde Coletiva: um desafio para a enfermagem.

This study takes public health as the point of departure to discuss both the concept of collective health and its object and field of action, emphasizing the concepts of man, collective and individual spheres, and health-disease, through a discussion of the interdisciplinary construction of the collective health field. The authors then place nursing within this field, emphasizing what appears to be the greatest challenge, i.e., to approach nursing as a practice of relationships.

[Activation of complement and serial changes of anaphylatoxin (C3a, C5a) in patients for open-heart surgery using a membrane oxygenator].

Activation of complement and serum changes in anaphylatoxin (C3a and C5a) were studied in 8 patients who underwent open-heart surgery using a membrane oxygenator. C1 esterase inhibitor (C1-EI), C3, C5, CH50, C3a and C5a were measured serially at 7 points. C1-EI, C3, and C5 were measured by single radial immunodiffusion, CH50 by Mayer's method, and C3a and C5a by radioimmunoassay. Levels of C1-EI, C3 and C5 decreased significantly from 10 min after initiation to 120 min after the end of CPB compared with base line values. Degree of activation of complement increased in proportion to duration of CPB. Significant decreases of C3 and C5 continued until first postoperative day. Level of C3a increased significantly 10 min after initiation of CPB, and gradually increased till immediately after the end of CPB, when the level was maximum (4625 +/- 560 ng.ml-1) among 7 points. Level of C3a decreased gradually till 120 min after end of CPB. C5a was not detected during whole course. No patient showed respiratory distress of pulmonary edema. In conclusion, membrane oxygenator activated classical pathway of complement at 10 min after initiation of CPB. C3a increased significantly from 10 min after initiation of CPB to 120 min after end of CPB, but C5a was not detected at all during the whole course. The significant activation of complement continued till first postoperative day.

[Changes in cellular immunity and their effect on pulmonary infections and prognosis after surgery of esophageal cancer patients].

In esophageal cancer patients, pneumonia in an early (20%) and a late (3.5%) period, pythorax except for leakage (8%) and pulmonary tuberculosis (1.4%) were observed characteristically through the post operative course. Changes in cellular immunity through the course were indicated with remarkable depression of PHA stimulation index (s.i.) and T cell number. The lowest values during 5-year survey were observed 2 weeks after surgery. Especially, cases with post operative pulmonary infections had low PHA s.i. and low T cell number for long time, different from cases without them. As regards T cell subsets, both helper T and suppressor T decreased dramatically early after surgery and helper T kept in low value for long time, in contrast to suppressor T returned to normal range gradually, and then H/S ratio also depressively changed. Therefore, suppressive immunity after surgery must result in pulmonary infections and cause critical conditions. Cases with well reacted lymphocytes indicated high 5 year survival rate (40%).

Eosinophil cationic protein in peripheral blood of pediatric patients with allergic diseases.

We have studied the levels of eosinophil cationic protein (ECP) and tumour necrosis factor (TNF) in peripheral blood obtained from 68 children with bronchial asthma and 11 children with atopic dermatitis. The ECP mean concentrations of the patients were 23.7 +/- 21.4 micrograms/l and 21.2 +/- 18.7 micrograms/l for bronchial asthma and atopic dermatitis respectively, which were significantly higher than the control value, 5.8 +/- 2.3 micrograms/l (P less than 0.005). TNF was unmeasurable in almost all the samples and no significant difference was observed between normal controls and asthmatic children. A significant correlation was observed between serum levels of ECP and blood eosinophil counts in both diseases (r = 0.873; P less than 0.01 and r = 0.740; P less than 0.01, respectively). However, no obvious correlation was observed between serum levels of ECP and IgE levels. ECP levels were significantly reduced by treatment and normalized in parallel with blood eosinophil counts in the patients with total IgE levels less than 800 U/ml. Irrespective of the total IgE levels, the reduction of serum ECP levels was correlated with a decrease in the number of asthmatic attacks and/or improvement of pulmonary function. These results suggest that the ECP levels in peripheral blood indicate an increased activity of eosinophil and would be a more useful marker than eosinophil counts for making clinical analyses and estimating treatment efficacy in paediatric patients with allergic diseases.