Serum p55 and p75 tumour necrosis factor receptors as markers of disease activity in juvenile chronic arthritis.

OBJECTIVE: To determine the expression of tumour necrosis factor alpha (TNF alpha) and its soluble receptors (p55 and p75) in the sera and synovial fluid of patients with juvenile chronic arthritis (JCA), and their correlation with disease activity parameters. METHODS: Ninety eight sera from 45 patients with JCA (14 systemic, 12 polyarticular, 19 pauciarticular), 20 sera from age matched healthy controls, and five synovial fluids from five antinuclear antibody (ANA) positive pauciarticular JCA patients were tested for the presence of TNF alpha, soluble TNF receptors p55 and p75 (sTNFRp55, sTNFRp75), and interleukin-6 (IL-6) by an enzyme amplified sensitivity immunoassay. Physician global estimate of disease activity, weekly fever score and joint score, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and haemoglobin concentration were evaluated as parameters of disease activity. The expression of p55 and p75 on peripheral mononuclear cells (MNCs) from five patients with systemic JCA and synovial MNCs from five ANA positive patients with pauciarticular JCA was evaluated by flow cytometry. RESULTS: TNF alpha serum concentrations did not differ significantly between the patients with active JCA and the control group. No correlation was found between TNF alpha and parameters of disease activity, but both p55 and p75 showed a significant positive correlation with the physician global estimate of disease activity (p < 0.001), ESR (p < 0.001), CRP (p < 0.001), and serum concentrations of IL-6 (p < 0.001). Serum concentrations of haemoglobin correlated inversely with the concentrations of p55 and p75 (p < 0.001). Synovial lymphocytes selectively expressed the p75 surface receptor. CONCLUSIONS: sTNFRp55 and sTNFRp75 each represent a sensitive marker of disease activity in JCA. Their increased expression in biological fluids may support the hypothesis that TNF alpha has a role in the pathogenesis of JCA.     

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

Angiodysplasia as the cause of massive lower gastrointestinal hemorrhage in a young adult

PURPOSE: This study was undertaken to clarify the importance of bleeding vascular ectasia of the colon as the etiology of massive lower gastrointestinal hemorrhage in patients 40 years of age or younger. METHODS: An otherwise healthy 21-year-old male was admitted to a tertiary medical center with massive lower gastrointestinal hemorrhage. Technetium-labeled red blood cell scan, selective visceral angiography, and colonoscopy identified the source of bleeding as vascular abnormality of the descending colon. Segmental colonic resection was performed. RESULTS: Histologic review of the specimen demonstrated a vascular ectasia. The patient recovered uneventfully and has had no further stigmata of hemorrhage. A review of the literature was undertaken to make clear the significance of vascular ectasia as the source for massive colonic hemorrhage in the young adult. CONCLUSION: This is the first report that documents histologically a vascular ectasia as the source of massive lower gastrointestinal hemorrhage in an otherwise healthy patient less than 40 years of age. Vascular ectasia is an uncommon cause of lower gastrointestinal hemorrhage in the young adult.The Chief, Bureau of Medicine and Surgery, Navy Department, Washington, DC, Clinical Investigation Program sponsored this report #84-16-1968-532, as required by HSETCINST 6000.41A. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.     

The Presence of Insulin-degrading Enzyme in Human Ileal and Colonic Mucosal Cells

The aim of this research is to characterize the presence of insulin-degrading enzyme in human colon and ileal mucosal cells. Biochemical studies, including the activity-pH profiles, the effects of enzyme inhibitors, immunoprecipitation and western blots, were conducted. The majority of insulin-degrading activity in colon mucosal cells was localized in the cytosol. In both colon and ileum, cytosolic insulin-degrading activities had a pH optimum at pH 7.5, and were extensively inhibited by each of N-ethylmaleimide, p-chloromercuribenzoate, and 1,10-phenanthroline, but were very weakly affected by each of leupeptin, chymostatin, diisopropyl phosphofluoridate and soybean trypsin inhibitor. In the colon and ileum, more than 93% and 96%, respectively, of cytosolic insulin-degrading activities were removed by the mouse monoclonal antibody to human RBC insulin-degrading enzyme, as compared with less than 20% by the normal mouse IgG for both tissues. Further, a western blot analysis revealed that a cytosolic protein of 110 kD, in both human colon and ileum, reacted with the monoclonal antibody to insulin-degrading enzyme. It is concluded that insulin-degrading enzyme is present in the cytosol of human colon and ileal mucosal cells.     

Rational diagnosis and treatment in unclassified arthritis: how clinical data may guide requests for Lyme serology and antibiotic treatment.

To improve the appropriateness and efficiency of diagnostic serological tests and subsequent antibiotic treatment, clinical data from 102 patients with unclassified arthritis were analysed to investigate whether the presence of positive IgG antibodies to Borrelia burgdorferi could be predicted. The clinical data were blindly ranked from 1 to 4 (1, Lyme arthritis unlikely; 4, Lyme arthritis very likely). Antibodies to B burgdorferi were positive in nine of 102 patients (9%). Six of 15 (40%) patients with rank numbers 3 and 4 were positive for antibodies to B burgdorferi, in contrast with only three of 87 (3%) patients with rank numbers 1 and 2. The likelihood ratio of positive Lyme serology for patients ranked 3 and 4 was 12.0, for patients ranked 2 to 4, 4.5, and for patients with arthritis of the knee, 3.0. These likelihood ratios were associated with a post-test probability of 55, 30, and 20% respectively. The clinical history in patients with unclassified arthritis can largely predict the presence of antibodies to B burgdorferi. The absolute value of a likelihood ratio can be a contributing factor in deciding to request tests for antibodies to B burgdorferi in patients with unclassified arthritis.     

Bicycle helmet use by adults: the impact of companionship.

Most of the nearly 1,000 fatal bicycle-related injuries annually could be prevented if riders used safety helmets. Helmet use by adult bicyclists has received relatively little attention because educational campaigns to promote helmet use generally focus on children. Helmet use by adult and child bicyclists at 120 suburban and rural sites in three Maryland counties was observed on two Saturdays in 1990-91 during an evaluation of the impact of a mandatory helmet law. Concordance or discordance of helmet use within various groups of bicyclists--adults only, adults with children, and children only--was recorded. Helmet use among 2,068 adult bicyclists was 49 percent, 51 percent, and 74 percent in the three counties. In two counties combined, 52 percent (365 of 706) of solo adult bicyclists wore helmets compared with only 5 percent (5 of 94) of solo child bicyclists (P < .001). Helmet use or nonuse was concordant among 87 percent of 277 adult-adult pairs, 94 percent of 50 child-child pairs, and 91 percent of 32 adult-child pairs of bicyclists observed. Concordance rates of helmet use or nonuse were similarly high among pairs of adult bicyclists of the same or mixed sexes. These data are consistent with the concept that both adults and children tend to adopt the helmet-wearing behaviors of their companions. Public health efforts focused on adults should encourage helmet use by adult bicyclists both to prevent head injuries and to provide a role model for children.