Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder

The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhesive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients undergoing surgery for another pathology who had a normal capsule and synovium. Immunohistochemical localization with monoclonal antibodies to transforming growth factor-β and its receptor, platelet-derived growth factor and its receptor, basic fibroblast growth factor, interleukin-1β, tumor necrosis factor-α, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency of cytokine staining was correlated with the clinical diagnosis Synovial cells, fibroblasts, T-cells, and B-cells were identified with specific antibodies, and newly synthesized matrix was examined for type-I and type-III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for type-III collagen in adhesive capsulitis tissues indicated new deposition of collagen in the capsule. There was staining for transforming growth factor-β and its receptor, platelet-derived growth factor and its receptor, interleukin-1β, and tumor necrosis factor-α in adhesive capsulitis and nonspecific synovitis tissues, compared with minimal staining in normal capsule. Staining was more frequent in snovial cells than in capsular cells. The frequency of cell and matrix staining for transforming growth factor-β, platelet-derived growth factor, and hepatocyte growth factor was greater in adhesive capsulitis tissues than in those from patients with nonspecific synovitis. No difference in the frequency of staining between primary (idiopathic) and secondary adhesive capsulitis was found. The results of this study indicate that adhesive/capsulitis involves both synovial hyperplasia and capsular fibrosis. Cytokines such as transforming growth factor-β and platelet-derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix-bound transforming growth factor-β may act as a persistent stimulus, resulting in capsular fibrosis. Understanding the basic pathophysiology of adhesive capsulitis is an important step in the development of clinically useful antifibrotic agents that may serve as novel treatments for patients with this condition.     

The efficacy of propafenone in preventing recurrent auricular fibrillation and flutter]

In order to investigate the efficacy of propafenone in the prevention of paroxysmal flutter or fibrillation, we treated 21 patients without left ventricular disfunction. Age was 60 +/- 14 (mean +/- sd) years, left atrial diameter by echocardiography 37 +/- 7 mm, cardiothoracic index 0.48 +/- 0.05 (0.41-0.57) and P wave duration 100 +/- 17 ms. The frequency of recurrences before treatment was: daily in five (23%), weekly or more in eight (38%), monthly-weekly in seven (33%) and quarterly-monthly in one (5%). Propafenone (671 +/- 187 mg/24 h) was given after recurrences were demonstrated under treatment with 1-3 antiarrhythmic drugs per patient. During 8.9 +/- 3.5 months of follow-up (range 6-19) 5 patients (23%) were completely free of recurrences; in seven (33%) the incidence decreased by greater than 50% with a marked decrease in duration. Side effects appeared in 12 cases (57%), leading to its discontinuation in four (19%). Arrhythmogenic effects were observed in 2 cases (9%). Propafenone is effective in greater than 50% of patients with paroxysmal atrial flutter or fibrillation, resistant to other antiarrhythmic agents. The incidence of side effects is high, but they are usually not severe and reversible.     

Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

AIMS: To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO-1985 and 1999 and ADA-1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes. METHODS: A cross-sectional population study with two-step sampling. One thousand and 34 people were selected randomly. A 75-g oral glucose tolerance test (OGTT) was performed and venous blood samples were obtained fasting and at 2 h. RESULTS: The prevalence of known Type 2 diabetes mellitus (DM-2) is 4%[95% confidence interval (CI) 2.8, 5.1]. By WHO-1985 criteria the prevalence of unknown DM-2 is 5.9% (4.5, 7.4); by ADA-1997 criteria 3.5% (2.5, 4.6) and by WHO-1999 criteria 7.3% (5.8, 8.8). Diagnostic overlap and statistical concordance (coefficient K) are WHO-1985/ADA-1997 29.3%, K=0.42; WHO-1985/WHO-1999 80%, K=0.88; ADA-1997/WHO-1999 48%, K=0.63. If only fasting glucose was used (following ADA-1997), 36.3% of those with diabetes (2-h glucose > or =11.1 mmol/l) would be diagnosed. If OGTT was performed (i) in those with a fasting glucose between 6.1 mmol/l and 6.9 mmol/l (9.8% of the population) we would diagnose 66.6%, and (ii) in all those between 5.7 mmol/l and 6.9 mmol/l (18.9% of the population) 81.8% would be diagnosed. CONCLUSIONS: The ADA criteria decrease the prevalence of DM in the adult population of Asturias by 2.4% and concordance with the classical criteria (WHO-1985) was only 29.3%. Using fasting glucose only (ADA-1997) diagnoses 36.3% of those with diabetes. The recent recommendations of the WHO-1999 increases this to 66.6%. To improve the diagnostic strategy for diabetes and detect up to 81.8% of patients, we propose the use of OGTT for all those with a fasting glucose between 5.7 mmol/l and 6.9 mmol/l.     

Area 3a in the cat. I. A reevaluation of its location and architecture on the basis of Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining.

Current knowledge on the anatomy of area 3a of the cat mainly derives from the cyto- and myeloarchitectonic study of Hassler and Muhs-Clement (J Hirnforsch 6:377, 1964). Previous investigations in the cat had failed to identify a cortical region comparable to monkey's area 3a. In the present study, Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining techniques were applied to coronal and sagittal serial sections of the cat brain. Area 3a appears as a slender band of cortex between areas 4 and 3b, and in Nissl-stained sections it is mainly characterized by an attenuated granular layer IV, overlying a thin layer V with pyramidal cells of various sizes, including a few large ones. These cytoarchitectonic features are sufficient to differentiate area 3a from neighboring areas, although the borders between them are not sharp in many cases. After the Nissl staining, the acetylcholinesterase staining proved to be the most helpful in defining the structure and borders of area 3a. Acetylcholinesterase staining was dense in layer I (in contrast with a lighter staining of outer layer I in area 4), and light in layers II and IIIa, changing to moderate in IIIc and IV (a pattern which is accentuated in area 3b). Myelin and cytochrome oxidase techniques also yielded differential staining patterns of area 3a and neighboring areas 4 and 3b, although the borders were not easily drawn with these techniques. Whereas our cyto- and myeloarchitectonic findings were comparable to those of Hassler and Muhs-Clement ('64) and applied well to area 3a in the convexity of the hemisphere, we found that most of the area 3a described by these authors in the medial face of the hemisphere had a number of distinguishing architectonic (as well as connectional and physiological) features which enabled us to define it as a separate area (7m). The techniques we used to delineate area 3a are compatible with most current procedures of histo- and immunohistochemical staining of the brain, and may also provide valuable supporting data for electrophysiological studies.