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 Role of Instructional Set on Alcoholic Performance

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.     

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.     

Predictive testing for Huntington's disease: I. Predictors of uptake in South Wales

In Wales, predictive testing for Huntington's disease (HD) has not been offered proactively to families and uptake of testing is low in comparison to other centres. Little is known of those not requesting testing, particularly those not in direct contact with the genetics service. This study examined differences between a cohort of 22 test applicants and a random group of 32 'non-requesters', drawn from the South Wales HD register. Respondents were interviewed by means of a semi-structured schedule in their own homes. The study groups differed significantly on a number of variables including: knowledge of the availability of testing; perceived attitudes of family members and significant others to testing; length of knowledge and perceived stressfulness of being at risk; and perceived ability to cope with an unfavourable result. Overall, knowledge of testing procedures was poor and at-risk individuals' understanding of genetic terminology was at odds with scientific distinctions. Discussion focuses on the organisational and psychological factors associated with lack of knowledge of the availability of testing and the interpretation of reported coping capacities.     

Select types of supporting cell in the inner ear express aquaporin-4 water channel protein

Aquaporins (AQPs) confer a high water permeability on cell membranes and play important parts in secretory and absorptive epithelia in kidney and other organs. Here we investigate whether AQPs are expressed in the sensory epithelia of the inner ear, where a precise volume regulation is crucial. By use of specific antibodies it was found that the inner ear contains AQP1 and 4 while being devoid of detectable levels of AQP2, 3 or 5. Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. In contrast, AQP4 protein and mRNA (visualized by in situ hybridization) were concentrated in select types of supporting cell, including Hensen's cells and inner sulcus cells. Immunogold particles signalling AQP4 were confined to the basolateral plasma membrane of Hensen's cells and to the basal plasma membrane of Claudius cells and inner sulcus cells. AQP4 was also found in supporting cells of the vestibular end organs, but was absent from transitional epithelial cells and dark cells. Strong labelling for AQP4 and AQP4-mRNA was associated with the central part of the cochlear and vestibular nerves. Hair cells were consistently unlabelled. Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites.     

Successful management of laryngotracheosophageal cleft through an anterior approach

Laryngotracheoesophageal cleft is an uncommon disease that is difficult to diagnose and treat. Repair of the cleft depends on length and localization of the defect as well as the associated anomalies. A successful repair of a type II cleft is reported in this paper. An anterior split of the larynx and trachea was used and provided excellent exposure and safe repair without injury to the neurovascular structures. This is the best approach and should be used to correct all type II defects.     

The hepatic immune system

The liver regulates T-cell homeostasis, induces T-cell tolerance, and supports intrahepatic T-cell responses against hepatotropic pathogens. Many data from clinical and preclinical systems provide supportive evidence for these diverse roles of the liver in modulating peripheral (systemic, mucosal, and intrahepatic) T-cell immunity. Little information is available on the cellular and molecular mechanisms that mediate the dual role of the liver in tolerizing T-cell responses and in supporting intrahepatic priming of T-cell responses. Understanding these immunoregulatory effects in the liver may offer insight into clinically relevant immunopathologies of this organ.     

Policies of academic medical centers for disclosing financial conflicts of interest to potential research participants.

PURPOSE: To document the current state of institutional review board (IRB) and conflict of interest committee policies regarding disclosures of financial conflicts of interest to potential research participants, and to use this information to identify and share models for effectively achieving disclosure. METHOD: The authors identified the 123 U.S. academic medical centers that have IRBs and sought their IRB and institutional policies regarding financial conflicts of interest. In February and March 2004, using manual and key word searches, each institution's Web site was searched to identify documents containing information regarding the disclosure of financial conflicts of interest. Letters were sent to 24 institutions that had either no information or incomplete information posted on their Web sites. To assess institutions' guidelines for disclosure, the authors extracted and content coded each institution's information on disclosure. RESULTS: Relevant information was obtained from 120 (98%) academic medical centers (AMCs), of which 57 (48%) mentioned disclosing financial conflicts to potential research participants. Of these 57, 33 (58%) included verbatim language that could be used in informed consent documents. AMCs' recommendations and requirements for disclosure included details of the financial arrangement, administrative management of conflicts of interest, and encouragement of dialogue between the investigator and the potential research participant. CONCLUSIONS: Considerable variability exists concerning the specific information that should be disclosed. Most of the AMCs' policies were consistent with the goal of protection from legal liability. Significant questions remain, however, concerning the goals of disclosure and the most effective methods for achieving those goals.     

Electrophysiological and pharmacological evidence in favor of amino acid neurotransmission in fimbria-fornix fibers innervating the lateral septal complex of rats

Summary Electrical stimulation of fimbria-fornix (fifx) fibers monosynaptically activated many of the neurons tested in the lateral septal complex (LSC) of the rat. The orthodromically activated LSC neurons were classified as strongly orthodromically activated (SOA) or weakly orthodromically activated (WOA) cells according to their threshold for eliciting a response, stability of the response latency, frequency following and the stimulus-response ratio.Microiontophoretically applied glutamate (GLU) could excite both SOA and WOA neurons. However, the expelling currents needed to activate the SOA cells were often considerably lower than those necessary to excite the WOA cells suggesting higher sensitivity to GLU of those cells which receive a strong fi-fx innervation. Iontophoretically administered glutamic acid diethylester (GDEE) in general reversibly attenuated excitatory responses of LSC cells to GLU but not to acetylcholine. GDEE was also effective in blocking the synaptic responses of SOA septal cells to fi-fx stimuli. In addition, GDEE administered topically reversibly suppressed the field potential induced in the LSC by fi-fx stimulation.These electrophysiological and pharmacological results support recent biochemical observations suggesting that the excitatory innervation of LSC neurons by fi-fx fibers is mediated by GLU or a closely related excitatory amino acid.The investigations were supported by the Foundation for Medical Research FUNGO which is subsidized by the Netherlands Organization for Advancement of Pure Research (Z.W.O.), grant 13-31-045 awarded to I.J. A. Urban