Therapeutic impasse in osteoarthritis.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
J H Herman
Publications and source records attributed to J H Herman.
Refractory thrombocytopenia in a 27-year-old female following allogeneic bone marrow transplantation.
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Adult↗
Nonsteroidal antiinflammatory drug modulation of prosthesis pseudomembrane induced bone resorption.
OBJECTIVE: To study the in vitro effect of therapeutic levels of select nonsteroidal antiinflammatory drugs (NSAID) on prosthesis associated pseudomembrane induced bone resorption and cytokine and prostanoid synthesis using tissue obtained from osteoarthritic patients undergoing revision of cemented implants. METHODS: Pseudomembranes were cultured in the presence and absence of therapeutic levels of select NSAID: Processed conditioned media were evaluated for bone resorbing capacity by assessing murine neonatal limb rudiment release of 45Ca. Interleukin 1 (IL-1) and tumor necrosis factor (TNF) were analyzed by bioassay and prostaglandin E2 (PGE2) by radioimmunoassay. RESULTS: Piroxicam, in contrast to indomethacin and sodium salicylate, significantly decreased membrane associated bone resorption. The NSAID effect correlated more consistently with piroxicam downregulation of TNF synthesis than that of IL-1. Consistent drug associated suppression of PGE2 synthesis did not enable differentiation of NSAID effectiveness in suppressing pseudomembrane induced bone resorption. CONCLUSION: Results provide a rational basis for design of animal models and/or further human studies to test the hypothesis that the prophylactic administration of an NSAID can potentially retard the pseudomembrane effected bone resorptive process associated with aseptic cemented prosthesis failure.
Adult↗
Autoimmune neutropenia after bone marrow transplantation.
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Autoantibodies↗
Comparison of two preservation solutions for erythrocyte transfusions in newborn infants.
To determine whether one of the newer preservation solutions for packed red blood cells (PRBC) is safe and effective in the transfusion of the very low birth weight infant, we conducted a randomized trial comparing PRBC preserved with the anticoagulant solution mannitol-adenine-dextrose (AS-1) and PRBC preserved with citrate-phosphate-dextrose-adenine (CPDA-1). Sixteen infants (birth weight 863 +/- 218 gm) with a gestational age of 26 +/- 3 weeks received one to three small-volume replacement transfusions with PRBC, 17 ml/kg, preserved with either AS-1 or CPDA-1 in a double crossover design. Transfusion with AS-1-preserved PRBC resulted in an equivalent increase in hemoglobin concentration when adjustment was made for the difference in the hemoglobin concentration of the transfused PRBC. During the transfusion, the percentage decrease in serum glucose values was greater with the CPDA-1 preservative than with the AS-1 preservative (54% +/- 13% vs 42% +/- 11% at 1 hour; p < 0.001). No other significant difference in blood chemistry values was found. Urine output was unaffected by AS-1 in the posttransfusion period. We conclude that (1) small-volume PRBC transfusions with AS-1 can be used in the very low birth weight infant without apparent detriment, (2) AS-1-preserved cells are as effective as cells preserved with CPDA-1 for increasing hemoglobin concentration, and (3) the higher dextrose content of the AS-1-preserved blood allows for improved glucose homeostasis during transfusion.
Adenine↗
Graft failure following neutrophil-specific alloantigen mismatched allogeneic BMT.
We report a case of unexplained graft failure in a 33-year-old man who received an allogeneic bone marrow graft that contained a donor-recipient mismatch involving the highly immunogenic NA1 neutrophil-specific alloantigen system. Laboratory and clinical data suggest that an alloimmune process related to the neutrophil alloantigen mismatch played a role in the development of the graft failure.
Adult↗
Autoimmune neutropenia following peripheral blood stem cell transplantation.
The differential diagnosis of unexpected neutropenia following bone marrow transplantation includes several potentially life-threatening complications including graft rejection, overwhelming infection, relapse of the underlying neoplasm, and intrinsic graft failure. However, a number of recent reports document that the differential diagnosis also includes autoimmune neutropenia, which, although potentially life-threatening, often responds well to corticosteroids or splenectomy. Autoimmune neutropenia has been reported following both autologous and allogeneic bone marrow transplantation. Herein we report a 31-year-old woman who developed a rapidly falling neutrophil count 11 days following peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. A laboratory evaluation supported a diagnosis of autoimmune neutropenia, and the neutropenia resolved following treatment with steroids and granulocyte-colony stimulating factor.
Adult↗
NSAID induction of interleukin 1/catabolin inhibitor production by osteoarthritic synovial tissue.
Select classes of nonsteroidal antiinflammatory drugs (NSAID), independent of their cyclooxygenase suppressing property, may potentially regulate pathophysiologic mechanisms operative in accelerated cartilage catabolism occurring in osteoarthritis (OA). Piroxicam has been shown to downregulate the expression of interleukin 1 (IL-1) associated chondrocyte enzyme inducing activity (catabolin) produced by OA synovium. In situ membrane synthesis of catabolin/IL-1 inhibitors functioning at various levels in thymocyte and catabolin bioassay systems is currently shown. The piroxicam effect appears due to a selective increase in production of a naturally occurring inhibitor(s) and/or induction of new inhibitor formation acting on chondrocytes at a post-IL-1 receptor level.
Anti-Inflammatory Agents, Non-Steroidal↗
Polychondritis.
Few advances in our understanding of the polychondritic disease process have been made within the past year. Clinical studies have emphasized pulmonary manifestations and newer means of evaluation of functional and anatomic upper and lower airway disease. Esophageal dysfunction has been described. Further associations have been established with Sjögren's syndrome and with malignancy. Active disease during pregnancy was not associated with neonatal transmission. Although lacking diagnostic specificity, preliminary studies suggest that serum quantitation of a noncollagenous cartilage matrix protein may correlate with disease activity. Differential diagnosis must now include a recently described form of hereditary chondropathy. Segmental tracheal resection and splinting techniques including use of stents have been advocated for therapeutic management of severe tracheobronchial disease.
Anti-Inflammatory Agents, Non-Steroidal↗
Hypofrontality and cognitive impairment in schizophrenia: dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function.
Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.
Adult↗
A randomized, placebo-controlled trial of intravenous gammaglobulin in alloimmunized thrombocytopenic patients.
In a placebo-controlled, randomized blinded study, we evaluated the efficacy of intravenous gammaglobulin (IV-IgG) in alloimmunized thrombocytopenic patients. IV-IgG was administered at a dose of 400 mg/kg for 5 days. An incompatible platelet transfusion from the same donor was used before and after treatment. Seven patients received IV-IgG and five patients received placebo. Although platelet recovery in 1 to 6 hours was satisfactory in five patients after IV-IgG treatment, 24-hour survival was not improved in most patients. None of the patients receiving the placebo achieved satisfactory 1-hour platelet-corrected count increments (CCIs). By t test, the posttreatment mean values 1 hour after transfusion CCIs in the IV-IgG group were significantly greater than in the control group (8,413 v 1,050, P less than .007). Using a regression model to adjust for any distributional assumptions of the study population, the parameter estimate for IV-IgG treatment was positive, indicating that IV-IgG treatment is associated with higher CCIs. Although IV-IgG may improve 1-hour platelet recovery, clinical benefit was not demonstrated since 24-hour survival was not improved. IV-IgG treatment before unmatched platelet transfusions should not be considered as a replacement for HLA-compatible platelets in alloimmunized patients.
HLA Antigens↗
Prosthesis-associated pseudomembrane-induced bone resorption.
A pseudomembranous structure invariably develops at the cement-bone interface of implanted prostheses in association with aseptic loosening. The tissue has histological characteristics of a foreign body reaction presumably initiated by repetitive microtrauma-associated release of methacrylate cement and polyethylene wear debris. Explant cultures of pseudomembrane and synovial tissue derived from osteoarthritic patients undergoing revision for cemented hip implant failure have been shown to produce interleukin-1, tumour necrosis factor and prostaglandin E2, recognized mediators of bone resorption. Further, the conditioned media obtained from pseudomembrane cultures could directly effect bone resorption by inducing 45Ca release from prelabelled limb bone rudiments. Results implicate the prosthesis-associated pseudomembrane in the pathogenesis of the bone resorptive process responsible for prosthesis failure.
Adult↗
Th activation of maternal and cord blood.
Th activation of red cells is characterized by agglutination with the peanut lectin from Arachis hypogaea and is diminished by treatment with proteolytic enzymes. The first cases of Th activation were associated with bacterial infections. More recently, a high incidence of Th activation in congenital hypoplastic anemia has been reported, along with the finding that 13.5 percent of cord bloods are Th activated. The incidence of Th reactivity in newborn infants was confirmed by studying 200 paired samples of maternal and cord blood. Twenty-two (11%) of the cord samples and 13 (6.5%) of the maternal samples were Th activated. In 6 paired samples (6/22), both the mother and child had Th activation, a finding that demonstrates a high degree of concordance. Additionally, 3 (6%) of 50 pregnant women were Th positive. These findings indicate that Th activation is another of the red cell antigen alterations related to pregnancy.
Arachis↗
Polymethylmethacrylate-induced release of bone-resorbing factors.
A pseudomembranous structure that has the histological characteristics of a foreign-body-like reaction invariably develops at the bone-cement interface in the proximity of resorption of bone around aseptically loosened cemented prostheses. This study was an attempt to implicate polymethylmethacrylate in this resorptive process. Unfractionated peripheral-blood mononuclear cells (consisting of lymphocytes and monocytes) and surface-adherent cells (monocyte-enriched) were prepared from control subjects who did and did not have clinical evidence of osteoarthrosis and from patients who had osteoarthrosis and were having a revision for failure of a cemented hip or knee implant. Cells were cultured for varying periods in the presence and absence of nonpolymerized methacrylate (one to two-micrometer spherules), pulverized polymerized material, or culture chambers that were pre-coated with polymerized cement. Conditioned media that were derived from both methacrylate-stimulated cell populations were shown to contain specific bone-resorbing mediators (interleukin-1, tumor necrosis factor, or prostaglandin E2) and to directly affect bone resorption in 45Ca-labeled murine limb-bone assays.
Animals↗
In vitro effect of select nonsteroidal antiinflammatory drugs on the synthesis and activity of anabolic regulatory factors produced by osteoarthritic and rheumatoid synovial tissue.
Nutriment replenished conditioned media derived from cultures of osteoarthritic and rheumatoid synovial tissue contain factors of variable molecular weight, independent of prostaglandin activity, which are capable of reversibly down-regulating cartilage matrix proteoglycan synthesis. Piroxicam significantly reduced anabolic suppressant factor production on an apparent selective basis. It could be shown to partially modify the chromatographic profile of newly synthesized osteoarthritic synovial tissue protein fractions containing suppressant activity. Dependent on experimental design, piroxicam also partially blocked inhibitory activity at a chondrocyte level. Indomethacin and sodium salicylate were essentially without effect.
Animals↗
Transfusion therapy in pediatric oncology.
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Anemia↗
Modulation of cartilage proteoglycan synthesis by osteoarthritic synovium.
Conditioned media derived from explant cultures of human osteoarthritic synovial tissue have been shown to contain preformed and newly synthesized factors of variable molecular weight which are capable on a concentration dependent basis of modulating cartilage proteoglycan metabolism. Anabolic inhibitory and stimulatory activity often appeared to coexist, a reversible down-regulation usually dominating in unfractionated preparations. The size of newly synthesized proteoglycan aggregates and monomers and the length of glycosaminoglycan chains produced in the presence of conditioned media were normal. The pattern of anabolic response did not necessarily correlate with the presence of catabolic inducing activity.
Cartilage, Articular↗
In vitro effects of Nd:YAG laser radiation on cartilage metabolism.
Laser therapy is being increasingly applied in the treatment of diverse forms of arthritis without a firm scientific basis for its safety or efficacy. Our study in part addresses this issue by assessing the in vitro effect of Nd:YAG laser radiation on mature normal bovine articular cartilage metabolism. Normal pulsed mode delivery of defined energy levels could be shown to consistently upregulate cartilage proteoglycan, collagen, noncollagen protein and DNA synthesis in the absence of histologic or biochemical evidence of enhanced matrix catabolism. Laser induced repair could be shown biochemically in in vitro model systems of enzymatically mediated cartilage matrix depletion. Results suggest that Nd:YAG radiation applied directly at surgery or via arthroscopy may provide a potential means of effecting cartilage healing. Further studies are necessary to substantiate such usage.
Animals↗