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Biomedical subjects

J H Herman

Publications and source records attributed to J H Herman.

At least 19 recordsLinked to original sources

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

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

Identification of Bakb, a new platelet-specific antigen associated with posttransfusion purpura.

Baka is a platelet alloantigen whose putative allele, Bakb, has not been identified previously. By using a serum, "Har," obtained from a patient with posttransfusion purpura, we describe the platelet alloantigen Bakb. The Har serum reacted with an NP-40-extractable platelet membrane protein of 142 kd with mobility similar to platelet glycoprotein IIb alpha. We found that the antigen recognized by the Har serum is inherited in an autosomal dominant mode with an apparent gene frequency of .39. Chi-square analysis of observed and expected phenotype frequencies indicated that serum Har recognizes Bakb, the anticipated allele of Baka. Our findings provide new evidence for polymorphism of glycoprotein IIb and for the association of posttransfusion purpura with alloimmunization to determinants on this glycoprotein.

Antigens, Human Platelet

Modulation of cartilage destruction by select nonsteroidal antiinflammatory drugs. In vitro effect on the synthesis and activity of catabolism-inducing cytokines produced by osteoarthritic and rheumatoid synovial tissue.

Non-enzymatic factors produced by synovial tissue can potentially mediate cartilage destruction by inducing the synthesis and release of matrix-degrading proteinases from chondrocytes. Pharmacologic control of this process is of potential clinical relevance. The in vitro effect of therapeutic concentrations of select nonsteroidal antiinflammatory drugs on the synthesis and activity of catabolism-inducing cytokines produced by 6-day explant cultures of osteoarthritic and rheumatoid synovial tissue was studied. Piroxicam regularly suppressed such factor synthesis by both types of tissue without significantly affecting total protein synthesis. This did not occur using sodium salicylate or indomethacin in osteoarthritis tissue cultures and was observed only occasionally in rheumatoid arthritis cultures. None of the nonsteroidal antiinflammatory drugs studied consistently blocked catabolism-inducing activity in osteoarthritis tissue, whereas piroxicam more consistently inhibited activity produced by rheumatoid arthritis tissue. Results suggest that the catabolism-inducing factors produced by the 2 tissue sources may differ.

Anti-Inflammatory Agents, Non-Steroidal

Red cell Th activation: biochemical studies.

The peanut agglutinin from Arachis hypogea is a lectin that reacts with red blood cells expressing the Th antigen. The Th antigen has been said to be qualitatively similar to the T antigen, a well-defined antigen due to desialylation of glycophorin A and B that also reacts with the peanut agglutinin. We examined Th activated red blood cells from two patients with Fanconi's anaemia using 125I radiolabelled peanut agglutinin as a probe in Western blotting of red blood cell membrane proteins. We also probed the surface of intact Th activated red blood cells for structures related to the T antigen using [3H]sialic acid and a purified sialyltransferase. Neither of these techniques found antigens on the Th activated red blood cells that were similar to the antigen found on T activated red blood cells. These results show that the Th antigen in Fanconi's anaemia is qualitatively different to the antigen found in T activation.

Anemia, Aplastic

Immunologic modulation of cartilage metabolism.

Preservation of the structural integrity of cartilage requires that metabolic homeostasis be maintained between chondrocyte anabolic and catabolic functions. This critical balance is perturbed in osteoarthritis (OA) in which synovial tissue and subchondral intratrabecular marrow often contain a focal and at times more diffuse mononuclear cell infiltration. Cytokines derived from T lymphocytes and monocytes have a capacity to: a) cause qualitative changes in and reversibly suppress chondrocyte proteoglycan, collagen, and non-collagen protein synthesis, and b) induce the synthesis and release of chondrocyte proteinases. Factors having comparable metabolic regulatory activity are produced by synovial tissue derived from idiopathic and secondary forms of OA.

Biological Products

Platelet transfusion. Current techniques, remaining problems, and future prospects.

The use of platelet transfusions to stop or to prevent bleeding in patients with thrombocytopenia or platelet dysfunction has accelerated in the past decade. Platelet counts and bleeding times, performed in conjunction with careful clinical evaluation of the patient, are appropriate guides in assessing the need for platelet transfusion. Complications of platelet transfusions are similar to those of red cell transfusions, with some additional concerns. Pooled random donor or single-donor apheresis concentrates, either randomly or selectively matched, are the major platelet products available. In most cases, transfusion requirements can be satisfied by use of random donor units. Proper evaluation of the effectiveness of transfused platelets is essential in determining the dose and frequency of future platelet transfusions. Refractoriness to random donor platelets eventually occurs in many recipients. This is most commonly associated with alloimmunization to histocompatibility antigens, but other platelet alloantigens may play a role. Many in vitro tests for platelet antibodies have been developed, and the clinical utility of these assays in selecting compatible platelets is now under evaluation. Strategies and different approaches to the management of thrombocytopenic patients with hypoplastic bone marrow states are also reviewed.

Bleeding Time

Hereditary complement (C6) deficiency associated with systemic lupus erythematosus, Sjögren's syndrome and hyperthyroidism.

Results of clinical, serologic and histologic studies documenting an association between hereditary C6 deficiency and a connective tissue disease are provided. The propositus had systemic lupus erythematosus with prominent discoid features, Sjögren's syndrome and hyperthyroidism. Serum C6 was undetectable by radial immunodiffusion and hemolytic assays. Serologic and typing studies performed on 9 family members suggested an autosomal codominant transmission. No correlation with a specific HLA phenotype was established.

Complement C6