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ID PMID Title PublicationDate abstract
8803821 Quality of life in multiple sclerosis: the disability and impact profile (DIP). 1996 Jun Seventy-three Dutch and Flemish patients with definite multiple sclerosis (MS) were assessed by means of the Disability and Impact Profile (DIP), which is a 2 x 39 item, self-administered questionnaire with parallel questions about disabilities and their importance for or impact on the patient, resulting in a profile of weighted scores. It was designed as a tool for clinical assessment of quality of life (QoL) domains in MS patients. Group data showed more than 50% loss on weighted scores for "walk", "clean home", "work" and "worry about deterioration". In individual patients a median of 7 (range 0-23) major disruptions of quality of life (MD-QoL: loss on weighted score more than 50%) was found. Prevalence of MD-QoL in more than 10% of the patients was found for as many as 31 disabilities and > 50% for 3 ("clean home", "work" and "worry about deterioration"). Results in the MS group were compared with available data from 25 patients with rheumatoid arthritis (RA) and 25 patients with a spinal cord lesion (SCl). Weighted scores of "read", "memory" and "concentration" were significantly lower in the MS group than in the RA and SCl groups. Significantly lower weighted scores in both the MS and RA groups were found for "worry about deterioration", "physical endurance", "clean home", "work", "see" and "write". In conclusion, major disruptions in many domains of QoL were found in MS patients. Weighted score profiles for MS were in accordance with clinical manifestations. Unlike Kurtzke's Extended Disability Status Scale, DIP assesses a wide range of potentially MS-affected human activities, and also takes into account the subjective perception of disabilities.
8735810 Correlation of GP53 and P-selectin expression in myeloproliferative disorders and normal c 1996 Mar Platelet degranulation occurs when platelets are activated. Alpha degranulation releases P-selectin whereas lysosomal degranulation releases GP53. A correlation between these two markers might therefore be expected. We studied the correlation between P-selectin and GP53 in 50 patients with myeloproliferative disorders (MPD), 35 normal controls and 105 disease controls (patients with inflammatory bowel disease [IBD, n = 52], rheumatoid arthritis [RA, n = 26] and coronary artery disease [CAD, n = 27]) by flow cytometry before and after stimulation with thrombin ex vivo. There was no significant correlation between percentage expression of P-selectin and GP53 in unstimulated samples in normal individuals; r = 0.13, P = 0.3, n = 34. Mild thrombin stimulation (10 mU/ml) led to both alpha and lysosomal degranulation with a strong correlation (r = 0.62, P < 0.001, n = 35). Disease controls (IBD, RA and CAD) showed similar trends. In patients with MPD, in contrast, a strong correlation between the expression of these platelet activation markers was demonstrable in unstimulated samples (r = 0.37, P = 0.007, n = 50). P-selection and GP53 expression in stimulated samples also correlated well. The data support the existence of different control pathways for the steady state expression of P-selection and GP53. Heterogeneous steady state responses of P-selectin and GP53 may be physiological and loss of this heterogeneity may be a hitherto unreported and pathologically important feature of MPD. This lack of correlation appears to be specific to MPD and is not simply a function of increased in vivo platelet activation.
8894134 Mechanisms of loss of lean body mass in patients on chronic dialysis. 1996 Patients on chronic dialysis treatment often have reduced lean body mass. Certain aspects of bio-incompatibility in dialysis can be viewed as leading to a chronic inflammatory state. In most chronic inflammatory diseases, loss of mean body mass is independent of reduced caloric intake. However, reduced caloric intake accounts for most of the weight loss in these patients and also dialysis patients. Refeeding is associated with increased fat deposition more than restoration of muscle mass. In addition to reduced caloric intake, patients with rheumatoid arthritis, a classic example of a chronic inflammatory disease, have an elevated resting energy expenditure associated with decreased lean body mass. Elevated cellular tumor necrosis factor (TNF) and IL-1 beta production can be demonstrated in these patients. However, in many dialysis patients, increased cytokine production can be 'normal' or reduced. This takes place as the level of malnutrition increases. Thus, cytokines such as IL-1 and TNF play a decreasing role in the pathogenesis of loss of body mass as malnutrition increases and curtails the synthesis of cytokines. Similar to patients with AIDS, progressive disease in patients on chronic dialysis may exhibit subclinical malnutrition which leads to decreased cytokine production. Reduction in cytokine production can be viewed as a protective mechanism.
7654061 Reduced expression of peptide-loaded HLA class I molecules on multiple sclerosis lymphocyt 1995 Aug Lymphocytes from patients with HLA class II-linked autoimmune diseases such as type I diabetes, systemic lupus erythematosus, rheumatoid arthritis, and Graves' have recently been shown to have a decrease in the expression of self-peptide-filled HLA class I antigens on the surface of peripheral lymphocytes. The human demyelinating diseases of multiple sclerosis in some cases are also associated with the presence of certain HLA class II genes, which may in turn be linked to genes in the class II region that control class I expression. Hence, we studied fresh peripheral blood mononuclear cells (PBMCs) and newly produced Epstein-Barr virus (EBV)-transformed cell lines from multiple sclerosis patients for the class I defect. Unseparated PBMCs, as well as T cells, B cells, and macrophages from multiple sclerosis patients had a decrease in the amount of conformationally correct peptide-filled HLA class I molecules on the cell surface compared with matched controls detectable by flow cytometry. To demonstrate the independence of this defect from exogenous serum factors, newly produced EBV-transformed cell lines from B cells of patients with multiple sclerosis maintained the defect. In addition, DR2 +/+, +/-, and -/- EBV-transformed B cells from these patients similarly demonstrated the self-antigen presentation defect. Analysis of a set of discordant multiple sclerosis twins revealed the class I defect was exclusively found on the affected twin lymphocytes, suggesting a role of this class I complex in disease expression. These data indicate that multiple sclerosis patients have abnormal presentation of self-antigens.(ABSTRACT TRUNCATED AT 250 WORDS)
7570209 [Detection of anti small nuclear ribonucleoprotein antibody in patients with collagen dise 1995 Jun OBJECTIVE: To compare the sensitivity of four techniques that can detect the presence of anti small nuclear ribonucleoprotein (snRNP) antibodies. MATERIAL AND METHOD: Sera from eighty three patients with connective tissue disease were positive for antinuclear antibody by indirect immunofluorescence test. Patients consisted of 30 cases of systemic lupus erythematosus, 19 of rheumatoid arthritis, 9 of mixed connective tissue disease, 8 of systemic sclerosis, 3 of polymyositis, 13 of Sjögren syndrome, 1 of unclassified connective tissue disease. Four methods including double immunodiffusion (DID), enzyme linked immunosorbent assay (EIA), immunoprecipitation (IP) and immunoblotting (IB) were compared concerning their sensitivities of detecting anti-Sm and anti-RNP antibodies in these sera. RESULTS: Overall sensitivities for detecting the presence of each antibody were similar among four methods (DID: 32/83, EIA: 43/83, IP: 44/83, IB: 35/83). Concordance ratio of positive patterns between DID and EIA was 63/83 (81.9%). However, both EIA and IP could detect anti-U1 RNP antibody with higher sensitivity than DID. Although EIA seemed to detect anti-Sm antibody most sensitively in all methods, a coincidental decrease of specificity might be considered. IB could not classify anti-snRNP antibodies into anti-Sm and/or anti-RNP antibody because these antibodies might share some antigenic peptides of snRNP. Analysis of RNA in immunoprecipitate could not discriminate anti-RNP antibodies from anti-Sm antibodies because of shared RNA epitopes (e.g., U1-RNA, U1U2-RNA). CONCLUSION: These results suggested that EIA might be the most suitable method for detecting anti-RNP antibody and that several methods should be combined for detecting anti-Sm antibody.
7724185 Scleritis associated with systemic vasculitic diseases. 1995 Apr PURPOSE: Scleritis may occur associated with systemic vasculitic diseases. The detection of systemic vasculitic diseases in patients with scleritis is a sign of poor general prognosis because it indicates potentially lethal systemic complications. This study was undertaken to analyze the ocular prognosis of patients with scleritis and the different systemic vasculitic diseases. METHODS: Patient characteristics, scleritis type, and ocular complications were evaluated in 82 patients with scleritis with systemic vasculitic diseases; comparisons were made between patients with scleritis with a specific systemic vasculitic diseases and patients with scleritis with the other systemic vasculitic diseases. RESULTS: Patients with scleritis with Wegener granulomatosis had more necrotizing scleritis (79%, P = 0.0001), decrease in vision (79%, P = 0.014), and peripheral ulcerative keratitis (50%, P = 0.0139) than patients with scleritis with the other systemic vasculitic diseases. Patients with scleritis with spondyloarthropathies had less decrease in vision (8%, P = 0.001) and peripheral ulcerative keratitis (0%, P = 0.0256) than patients with scleritis with the other systemic vasculitic diseases. Patients with scleritis and systemic lupus erythematosus had less necrotizing scleritis (0%, P = 0.0412) than patients with scleritis with the other systemic vasculitic diseases. CONCLUSIONS: Ocular prognosis of scleritis with systemic vasculitic diseases varies depending on the specific systemic vasculitic diseases: scleritis in spondyloarthropathies or in systemic lupus erythematosus is usually a benign and self-limiting condition, whereas scleritis in Wegener granulomatosis is a severe disease that can lead to permanent blindness; scleritis in rheumatoid arthritis or relapsing polychondritis is a disease of intermediate severity, which should be monitored closely for the development of ocular complications.
7734123 Direct electron transfer bioelectronic interfaces: application to clinical analysis. 1995 Bioelectronic interfaces based on direct electron transfer to proteins and enzymes immobilised at functional electrode surfaces are currently under development and the potential of two such systems for application to clinical measurement will be outlined. The first is the detection of free radical production via direct electrochemistry of cytochrome c immobilised covalently at modified gold electrodes. The redox protein cytochrome c has been immobilised covalently to gold electrodes surface-modified with N-acetyl cysteine via carbodiimide condensation. The electrodes thus produced were used to measure directly the enzymatic and cellular production of the superoxide anion radical (O2(-). The superoxide radical reduced the immobilised cytochrome c which was immediately re-oxidised by the surface-modified gold electrode poised at a potential of +25 mV (vs Ag/AgCl). The electron transfer rate constant (ket) of this process was 3.4 +/- 1.2 s(-1). The rate of current generation was directly proportional to the rate of O2(-) production. The essentially reagentless system produced was designed to be applied ultimately to continuous monitoring of free radical activity in vivo since there is evidence that oxygen-derived free radical species act as mediators which cause and perpetuate inflammation in disease states, including rheumatoid arthritis and neurodegenerative disorders. The second systems are pseudo-homogeneous immunoassays based on direct electron transfer to horseradish peroxidase. Horseradish peroxidase enzyme electrodes based on activated carbon (HRP-ACE) have been constructed by simple passive adsorption.(ABSTRACT TRUNCATED AT 250 WORDS)
7699633 Phenotype and functional profile of T cells expressing gamma delta receptor from patients 1994 Dec OBJECTIVE: Our aim was to investigate the TCR gamma delta+ subset in Behçet's disease (BD) inflammatory sites, which better reflects changes associated with the pathologic process than peripheral blood. METHODS: Forty-five patients with active BD, 10 patients with recurrent aphthous ulcers, 12 patients with rheumatoid arthritis, 5 patients with noninflammatory neurologic diseases and 15 healthy individuals were studied. Three monoclonal antibodies TCR delta 1, BB3, and A13 were used to assess the percentage of TCR gamma delta+ in peripheral blood mononuclear cells (PBMC), in bronchoalveolar lavage and cerebrospinal fluid (CSF). CD11a/CD18 was used to study adhesion molecules. TCR gamma delta+ cells isolated by immunomagnetic separation were tested for cytolytic activity against K562 target cells after interleukin 2 stimulation. RESULTS: The PBMC TCR gamma delta BB3+ subset was significantly increased in BD. In BD inflammatory sites, TCR gamma delta+ cells were also present, composed mainly of A13+ cells from these sites also expressed CD11a marker. TCR gamma delta+ cells from inflammatory sites displayed a higher cytotoxic activity than controls, mediated by the A13+ subset. CONCLUSION: The accumulation of cytotoxic TCR gamma delta+ cells at the sites of inflammation suggests their involvement in the local injury process.
8043758 [High-resolution computed tomography (HRCT) of the lung in collagenoses: a prospective stu 1994 Jul To determine pulmonary features of collagenous vascular diseases as assessed by high resolution computed tomography (HRCT) we performed a prospective study of 73 consecutive patients, 44 with rheumatoid arthritis (ra), 11 with progressive systemic sclerosis (pss), 8 with systemic lupus erythematosus (sle), 5 with sjögren's syndrome, 3 with dermato-/polymyositis and 2 with mixed connective-tissue disease. Pathological lung changes were demonstrated in 70% of patients with ra, 91% with pss, 63% with sle and 60% with the rest. HRCT features included: intralobular thickening (48%) with a predominance in posterior lower and middle lung areas, pleural thickening (48%) with a predominance in upper lung areas, prominent interlobular septa (37%), subpleural lines (33%), parenchymal bands (33%) with a predominance in lower and anterior lung areas, honeycombing (33%), ground glass pattern (29%) with a predominance in upper and middle, micronodules (18%) with a predominance in upper lung areas and bronchiectasis (14%). HRCT is an important means for the assessment of lung changes associated with collagenous vascular diseases and a definite diagnosis is possible in most cases.
7516571 Amino acids in the peptide-binding groove influence an antibody-defined, disease-associate 1994 Jun A shared amino-acid sequence on the alpha helix of certain DR beta 1 chains is predicted to generate a 'shared epitope' that is implicated in susceptibility to the development of rheumatoid arthritis (RA). Different relative risks (RR) for disease susceptibility and severity conferred by these DR beta 1 chains suggest that their 'shared epitopes' are not equivalent. A set of monoclonal antibodies (MoAb) that map to the critical region, and for which optimal binding depends on DR context and cell lineage, was used to test this idea. Mapping experiments using mutated DR beta 1* molecules showed that the antibody-binding epitopes are overlapping; residue 70Q is pivotal for each, but neighbouring residues on the alpha helix and on the floor of the groove are also involved. Importantly, these epitopes are profoundly modified by peptide loading of DR beta 1*0401 molecules. These data suggest that 'shared epitopes' on DR molecules that are associated with RA are influenced by their context; such structural modifications may be the basis for the varying susceptibilities conferred by these DR molecules for the development of RA.
7508441 The 56K autoantigen is identical to human annexin XI. 1994 Feb 11 Anti-56K autoantibodies are present in sera from patients with various autoimmune diseases, predominantly in sera from patients with rheumatoid arthritis, systemic lupus erythematosus, or Sjögren's syndrome. To clarify the molecular structure of this autoantigen, we isolated a 2.0-kilobase pair cDNA clone considered to encode the full-length 56K autoantigen. The longest open reading frame encodes a 505-amino acid polypeptide, with a predicted molecular mass of 54.4 kDa. The in vitro translated protein is recognized by all anti-56K positive patient sera tested. Antibodies affinity-purified using the bacterially expressed recombinant protein recognized the 56K autoantigen in a HeLa cell extract. cDNA sequencing revealed that the 56K cDNA shares a high degree of homology in both nucleotide (87%) and amino acid sequence (92.5%) with bovine annexin XI, indicating that the 56K cDNA encodes the human homologue of annexin XI, a member of the Ca(2+)-dependent phospholipid binding protein family. Anti-56K autoantibody exhibits both a cytoplasmic and a nuclear staining in immunofluorescence experiments. Patients' sera recognize preferentially the N-terminal region of the protein, which is specific for 56K/annexin XI and not shared by other annexins, indicating that the autoimmune response to 56K/annexin XI in these patients is specific for this annexin family member.
8309812 Psychopharmacology of disorders in children. 1993 Dec Several features of pediatric pharmacology applied to psychiatry were mentioned throughout this review. The use of medications in young children requires attention to nuances of informed consent because of limited data and many potentially beneficial, possibly safer medications that are not approved for children. Children more rapidly metabolize and eliminate medications. They differ in sensitivity to main effects and side effects of a variety of medications. Therefore, it is important to start low and aim for the lowest effective dose. Ultimate doses may be higher, split and frequent doses may be necessary, and both clinical and laboratory follow-up may need to be more frequent. Finally, childhood onset of psychiatric disorders, similar to pediatric experience with diabetes or rheumatoid arthritis, frequently confers devastating stress and chronicity. The child's physician shares the frustration of poor treatment response or responses that cannot be sustained in a developing, dependent organism with a more aggressive variant of a disorder and an inevitably longer course. Despite a heartening increase in pediatric psychopharmacology interest and knowledge, much remains to be learned.
8415397 Liposome-mediated delivery of gallium to macrophage-like cells in vitro: demonstration of 1993 Aug Gallium (Ga) prevents the activation of macrophages and might be useful as an immunosuppressive agent. It is taken up by the malignant cells through the transferrin (Tf) receptor pathway, but this pathway may be insufficient in the case of non-malignant cells. We studied the Tf-independent, liposome-mediated delivery of Ga to macrophage-like cells in vitro by a growth inhibition assay. The growth inhibitory properties of Ga for other types of cells was also evaluated. Ga complexed with nitrilotriacetate (GaNTA) and encapsulated in DSPG-liposomes was 16 and 48 times more potent for RAW 264 cells than free GaNTA and Ga-nitrate, respectively. CV1-P cells were also somewhat sensitive to liposomal Ga, but other cell lines with lower endocytotic capacity were insensitive. The inhibition of RAW 264 cell growth induced by liposomal or free GaNTA was partially reversed with iron-loading of the cells, indicating that this form of Ga causes an intracellular iron deficiency similar to that produced by Tf-bound Ga. Our results indicate that encapsulation of Ga in negatively charged liposomes provides a transferrin independent route for intracellular delivery of the compound to macrophages, which is of special interest in the treatment of autoimmune diseases, such as rheumatoid arthritis.
8472311 Therapeutic applications of anti-CD4 antibodies. 1993 The CD4 molecule represents a major functional T-cell surface molecule, defining an important T-cell subset, which also is expressed on monocyte, dendritic, and Langerhans cells. Various in vivo studies have demonstrated its implication in various steps of physiological T-cell activation: 1. CD4 interacts with its physiological ligand, the class II molecules, thus increasing the affinity of the conjugation between CD4+CD(3+)-TCR+ and class II+ antigen-presenting cells. 2. Through CD4, the signal transduction machinery is stimulated via its association with p56lck. In addition, CD4 has proved to be the receptor for gp120, the surface glycoprotein of HIV, that allows the virus to penetrate the CD4+ T cells and monocytes. Based on in vitro studies in various animal models, CD4 mAbs have proved to be efficient in the prevention and/or therapy of a variety of immunologically based diseases: 1. When injected early in the prodromic phase of autoimmune diseases (AID) such as diabetes, either delay or prevention is achieved with or without maintenance after therapy. 2. These mAbs have proved to be self-tolerogenic, thus allowing prolonged in vivo therapy and suppression of immunogenicity of mAb of a distinct specificity. In humans, CD4 mAbs are, or could be, used and evaluated in AID (lupus, diabetes, rheumatoid arthritis, etc.), transplantation, leukemias and lymphomas expressing CD4, and, finally, in AIDS patients, in whom CD4 mAbs can block HIV-CD4 binding and deliver a negative signal to T cell, thus blocking T-cell activation and HIV transcription. CD4 mAbs at least provide evidence that the CD4 molecules are suitable for immunomodulation and could be the target for a new pharmacological antagonist.
8342343 [Eight years experience with the "Erlangen Model" titanium prosthesis--results of cementle 1993 Between March 13, 1984 and March 28, 1988, 233 patients (age range from 21 to 73 years) with osteoarthritis of one or both hips were treated with the uncemented hip replacement "Erlanger Modell" (Prof. H. Beck/P. Brehm Chirurgie-Mechanik GmbH). The cause of the osteoarthritis was variable. Hip replacement was carried out for the following conditions: rheumatoid arthritis including ankylosing spondylits (n = 29), aseptic necrosis of the femoral head including posttraumatic and idiopathic forms (n = 17), osteoarthritis of unknown origin (n = 111), osteoarthritis following dysplasia or subluxation of the hips (n = 56) and loosened cemented hip prostheses (n = 37). Full weight bearing was not permitted for 50 days postoperatively, but mobilization and isometric exercises began 2 days after operation and isotonic exercises are introduced later. Complications included fracture of the femoral shaft during operation (3.3%), fracture of the femoral shaft postoperative (1.6%), dislocation (0.8) and infection early after operation (0.4%) and aseptic loosening (3.7%). Our results of 233 patients (250 joints), ranging from 4 to 8 postoperative years giving an average of 5.3 years, are encouraging. Good results based on patients satisfaction were obtained in 95.2% (83.8% after revision) and poor results in 1.0% (2.7% after revision). 3.8% (13.5 after revision) judged their situation as unchanged. 93.3% of the patients can walk without hooked stick (53.3% after revision), 90.2% of the patients can walk more than 1000m (69.4% after revision).
1464951 [Characteristics of medical institutions visited by 30 intractable disease patients receiv 1992 Oct In order to determine the characteristics of medical institutions which patients with 30 intractable diseases visited, we analyzed data of a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee in 1989. Each of 47 prefectural governments in Japan reported information of all patients with 30 intractable diseases who received financial aid for the diseases between April 1988 and March 1989. Information collected about each patient consisted of identification numbers, which included the disease code, sex, age, the code of the municipality where the patient lived, the medical institution which treated the patient, etc. Out of 173,637 patients whose information was reported by prefectural governments, we used data of 159,910 patients whose medical institutions were reported completely. The results can be summarized as follow: 1) Of the 159,910 patients, 8.6 percent visited medical institutions outside of the prefectures where the patients lived. Many patients living in prefectures located close to large cities, such as Tokyo, visited medical institutions in large cities. 2) The proportion of patients who visited hospitals of medical schools was 27.9 percent. 3) Patients who were affected by diseases causing physical disabilities such as SMON and malignant rheumatoid arthritis tended to visit medical institutions located in their neighborhoods and were treated in small hospitals or clinics. Old patients had the same tendency as patients with such diseases. 4) Although the number of patients receiving aid in 1988, whose data we analyzed in the current study, was larger than that in 1984, the proportion of patients visiting medical institutions outside of the prefecture where the patients lived, and the proportion of patients visiting hospitals of medical schools were nearly equal to those in 1984.
8961238 The role of tumor necrosis factor-alpha in the pathogenesis of anorexia and bulimia nervos 1996 Dec In this paper a new immunological model of anorexia and bulimia nervosa will be presented in which the inflammatory cytokines are conceived as the fundamental regulators of body metabolism. This conception differs from the conventional view in which the inflammatory cytokines are perceived primarily as peptide molecules utilized by the immune system to control infection, inflammation and tissue or neuronal damage. Given that the inflammatory cytokines are also fundamental regulators of body metabolism, when they become dysregulated they create physiological chaos which results in the development of a number of autoimmune, metabolic and psychiatric disorders. In this proposed immunological model of anorexia and bulimia nervosa, elevated tumor necrosis factor-alpha features as the primary cause of these conditions. Pathophysiological parallels are drawn between anorexia nervosa and cancer cachexia in terms of the causal role the cytokines, neuropeptides and neurotransmitters play in the manifestation of shared symptoms. These shared symptoms include elevated tumour necrosis factor-alpha, down-regulated interleukin-2 and interleukin-4 and depletion of lean body mass. Furthermore, the following neuropeptides are dysregulated in both anorexia nervosa and cancer cachexia: vasoactive intestinal peptide, cholecystokinin, corticotropin-releasing factor, neuropeptide Y, peptide YY and beta-endorphin. In addition, in anorexia and bulimia nervosa, secretion of the neurotransmitter serotonin is inhibited while norepinephrine is enhanced. It will be argued that the causal interplay between the cytokines, neuropeptides and neurotransmitters initiates a cascade of biochemical events which may result in either anorexia or bulimia nervosa, or cancer cachexia. The extent to which these inflammatory cytokines, neuropeptides and neurotransmitters are causally efficacious in the pathogenesis of other autoimmune disorders, such as diabetes mellitus and rheumatoid arthritis, will also be addressed.
9021694 Clinical and prognostic implications of bone lesions in childhood leukemia at diagnosis. 1996 Sep We studied 168 children with acute lymphoblastic leukemia (ALL) and 57 with acute nonlymphoblastic leukemia (ANLL) by retrospectively analyzing clinical symptoms, bone or joint involvement, and hematological findings to verify the clinical features and prognosis of children with acute leukemia who showed radiographic bone changes at the time of diagnosis. Of these, 36 with ALL (21.4%) and 6 with ANLL (10.5%) had symptoms referable to the bones or joints. Thirteen patients (7.7%) with ALL showed bone lesions radiographically. Phenotypically, 12 of the 13 had common ALL, 8 were incorrectly diagnosed and had received treatment for osteomyelitis or juvenile rheumatoid arthritis for 1 to 7 months prior to diagnosis of ALL. Leukocyte count was nearly normal with few or no blasts, and anemia and thrombocytopenia were mild or absent in all patients. Twelve of them remained in a complete remission for 26 to 148 months. Our data suggest that children with bone lesions related to acute leukemia exhibit clinical features that mimic infectious or collagen disease at diagnosis, and may belong to a subgroup of ALL with a better prognosis.
8818309 Percutaneous absorption of ketoprofen. I. In vitro release and percutaneous absorption of 1996 Aug Ketoprofen (KP) is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of KP can cause gastric irritation and renal adverse effects. Topical application of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug levels at the site of action. Since the efficacy of an ointment depends on the type of ointment base and the concentration of the drug, four different bases (white petrolatum, cold cream, hydrophilic ointment and Carbopol 940 gel) were used at 1, 3, 5, 7 and 10% concentrations of KP to evaluate the effect of ointment base and concentration. The general rank order of the drug release was found to be: Carbopol gel > hydrophilic ointment > cold cream > white petrolatum. There was a positive correlation between the concentration of KP and release rate for all bases except Carbopol gel. The in vivo percutaneous absorption of KP from different ointment bases at 3% concentration was studied by carrageenan-induced paw edema in mice. The rank order of the percent edema inhibition was as follows: Carbopol gel > or = hydrophilic ointment > cold cream > white petrolatum. There was a good correlation between the in vitro and in vivo results.
8679688 Reversible inhibition by protamine of human synovial and rabbit platelet secretory phospho 1996 May 20 We investigated the effects of protamine on the release and the activity of 14 kDa type II phospholipase A2 (sPLA2). Protamine blocks both release and activity of sPLA2 from thrombin-stimulated platelets in a concentration-dependent manner. Heparin, an anionic sulfate polysaccharide which has a high affinity for this enzyme, has no inhibitory effect on sPLA2 by itself but it is able to reverse the inhibitory effect of protamine. The liberation by thrombin of platelet factor 4, an alpha-granule constituent, unlike to that of ATP stored in dense bodies, was suppressed by protamine. Platelet aggregation, determined in parallel, was not affected by protamine. Also, protamine did not inhibit platelet arachidonic acid liberation, which is mainly produced by cytosolic PLA2. The non-proteinaceous polycationic hexadimethrine and acidic protein casein failed to inhibit platelet sPLA2 activity. By contrast, the basic polypeptides poly(L-arginine) and poly(L-lysine) potently inhibited sPLA2 activity, indicating the important role of basic amino acids in the inhibitory effect evoked by protamine. Activities of the human recombinant sPLA2 and the unpurified synovial enzyme of patients with rheumatoid arthritis were also inhibited by the same range of protamine, poly(L-arginine) and poly(L-lysine) concentrations. Our results demonstrate that protamine, unlike heparin, blocks platelet sPLA2 release and exerts a reversible inhibitory effect on its activity, probably through the interaction of basic amino acids with the enzyme.