Circulating L-selectin is elevated in patients with Plasmodium falciparum malaria.
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Animals↗
Biomedical subjects
W Graninger
Publications and source records attributed to W Graninger.
Sulfadoxine/pyrimethamine or chloroquine/clindamycin treatment of Gabonese school children infected with chloroquine resistant malaria.
In a randomized trial, a high dosage chloroquine monotherapy (45 mg/kg over 3 days) was compared with combination regimens of sulfadoxine/pyrimethamine and chloroquine/clindamycin for treating Gabonese school children with Plasmodium falciparum malaria. In chloroquine treated patients only 32% were ultimately cured. In contrast, more than 90% of patients were cured after treatment with either combination regimen.
Adolescent↗
Destructive lymphadenopathy and T-lymphocyte activation in adult-onset Still's disease.
Recurrent arthritis, fever and lymphadenopathy are symptoms of adult onset of Still's disease (AOSD). Differential diagnosis requires the exclusion of infections or malignant lymphomas. We report on a case of AOSD showing destructive lymphadenopathy, immunophenotyping of peripheral blood leucocytes revealed strong activation of T-lymphocytes. Bone marrow biopsy also showed an increase of lymphopoietic cells to 23%. Analysis of peripheral blood lymphocytes (PBL) after remission showed no remaining signs of activation. Analysis of lymphocyte activation by flow cytometry correlated with disease activity.
Adult↗
Reactive arthritis: urogenital swab culture is the only useful diagnostic method for the detection of the arthritogenic infection in extra-articularly asymptomatic patients with undifferentiated oligoarthritis.
Reactive arthritis (ReA) is a seronegative oligoarthritis triggered by a preceding extra-articular infection. While evidence of a microbial infection is mandatory for establishing the diagnosis of ReA, the sensitivity of bacteriological and serological tests has not been determined in patients without symptoms of infection. In a retrospective study, we evaluated the usefulness of urogenital swab cultures, serology and stool culture to identify infections in 234 patients with undifferentiated oligoarthritis. One hundred and forty-four patients complaining about joint pain who had no sign or history of inflammatory arthritis served as controls. Urogenital swab cultures showed a microbial infection in 44% of the patients with oligoarthritis (15% Chlamydia, 14% Mycoplasma, 28% Ureaplasma), whereas in the control group only 26% had a positive result (4% Chlamydia, 7% Mycoplasma, 21% Ureaplasma) (P < 0.001). A Chlamydia IgG-antibody titre > or = 1:256 was found in 22% of the patients in the oligoarthritis group and in 9% of the controls (P < 0.01). However, for only half of Chlamydia IgG-positive patients could a Chlamydia infection be confirmed by urogenital swab culture. Twenty-one per cent of patients with oligoarthritis vs 23% of the controls had positive antibody titres for Salmonella (not significant), 15% vs 5% for Yersinia (P < 0.05) and 17% vs 3% for Borrelia IgG (P < 0.01). In two patients, stool cultures were positive for Campylobacter. Urogenital swab culture is a sensitive diagnostic method to identify the triggering infection in ReA. A single determination of antibodies against Chlamydia trachomatis is of limited value because of the high prevalence of positive results in the control group.
Adult↗
Pentoxifylline in severe inflammatory response syndrome.
It is increasingly evident that sepsis triggers a complex host reaction that is responsible for a variety of pathophysiologic changes during the inflammatory process. Pentoxifylline (PTX) is a methylxanthine with selective anti-inflammatory activity. Because of the current concept of an exaggerated immune response during severe inflammatory response syndrome (SIRS), this drug has received interest as a potential beneficial modulator of SIRS. Animal studies suggest that randomized clinical trials should be carefully planned with regard to dose-response relationship, disease severity, etiologic pathogens, and mechanisms that result in SIRS. The efficacy of PTX has been promising in human malaria. It is probably also effective in other hyper-tumor necrosis factor (TNF) states. The effective dosage is unclear to date, and its use is restricted by intolerance. Potential adverse effects may be related to the selective depression of TNF expression and to the depression of granulocyte phagocytic activity and the neutrophil/endothelium interaction. However, it is unlikely that any single agent will prove to be the magic bullet in the therapy of sepsis and SIRS. Multiple agents, perhaps tailored to individual circumstances, will most probably be needed, raising dramatic economic and ethical challenges.
Animals↗
Polymorphonuclear leucocyte dysregulation in patients with gram-negative septicaemia assessed by flow cytometry.
Flow cytometry was used to study phagocytic function and release of reactive oxygen intermediates (ROI) following phagocytosis by granulocytes in 14 patients (six female, eight male) with gram-negative septicaemia prior to, during, and after therapy compared with a group of healthy controls. Phagocytic capacity was assessed by measuring uptake of fluorescein isothiocyanate (FITC)-labelled bacteria. Reactive oxygen generation after phagocytosis was measured by the quantification of dihydrorhodamine 123 converted to rhodamine 123 intracellulary. Compared with results in healthy controls granulocytes of septicaemic patients exhibited a decreased capacity to phagocytize Escherichia coli and to generate reactive oxygen products. Both phagocytosis and ROI production increased after initiation of therapy and normalized within 7 days of treatment. The results suggest that granulocytes do not only participate in, but are also a target of, the septic host inflammatory response.
Adolescent↗
Serum laminin in Graves' disease.
We determined serum levels of laminin in 23 patients with Graves' disease (GD) and in 24 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin were observed in patients with GD prior to treatment (median concentration 1376 ng mL-1 [range 712-2402]), compared to patients with TNG (median 442 ng mL-1 [284-891]), and normal controls (median 492 ng mL-1 [range 235-675], n = 26), respectively. In GD patients serum laminin levels decreased during thiamazole treatment and normalized within 8 weeks of therapy. There was no correlation between serum laminin levels and serum levels of thyroid hormones and/or auto-antibodies, respectively. Whether serum laminin is a marker for alterations of extracellular matrix during GD and release of basement membrane components in the circulation and/or reflects an impaired clearance remains to be elucidated.
Adolescent↗
High efficacy of short-term quinine-antibiotic combinations for treating adult malaria patients in an area in which malaria is hyperendemic.
In a randomized trial, a three-dose quinine monotherapy was compared with short-term combination regimens of quinine-clindamycin and quinine-doxycycline for treating adult Gabonese patients with Plasmodium falciparum malaria. In quinine-treated patients, only 38% were ultimately cured. In contrast, more than 90% of patients were cured after treatment with either combination regimen.
Adolescent↗
Effect of various pentoxiphylline concentrations on macrophage inflammatory protein 1 alpha production.
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Chemokine CCL3↗
Effect of cefodizime and ceftriaxone on phagocytic function in patients with severe infections.
Thirty patients with severe bacterial infections were treated with 50 mg of cefodizime per kg of body weight once daily or 50 mg of ceftriaxone per kg once daily for 10 +/- 3 days. The effect of cefodizime and ceftriaxone on the phagocytic capacity and generation of reactive oxygen intermediates after phagocytosis by granulocytes was assessed prior to, during, and after therapy. Flow cytometry was used to study phagocytic capacity by measuring the uptake of fluorescein-labeled bacteria. The generation of reactive oxygen intermediates after phagocytosis was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Prior to therapy, patients in both groups exhibited a decreased capacity to phagocytize Escherichia coli and subsequently to generate reactive oxygen intermediates. Granulocyte function increased after the initiation of therapy and normalized within 7 days for the ceftriaxone-treated patients and within 3 days for the cefodizime group (P < 0.05). In the cefodizime group, an enhancement of phagocytic capacity was observed 14 days after the initiation of therapy (P < 0.05). Prior to therapy, phagocytic capacity was significantly correlated with the generation of reactive oxygen products (r = 0.674 and P < 0.005).
Adolescent↗
Are soluble factors relevant for polymorphonuclear leukocyte dysregulation in septicemia?
Polymorphonuclear leukocytes (PMNs) of twelve patients with gram-negative septicemia exhibited a decreased capacity to phagocytize Escherichia coli and generate reactive oxygen products which normalized within 7 days of treatment. Ex vivo exchange of plasma from age-, sex-, and blood-group-identical normal controls resulted in an increase of both phagocytic capacity and reactive oxygen intermediate generation in PMNs of septicemic patients and transiently reduced phagocytosis and reactive oxygen intermediate production in PMNs of normal controls. These results suggest that extrinsic factors are crucial for PMN function.
Adolescent↗
Discrete lung involvement in systemic lupus erythematosus: CT assessment.
PURPOSE: To study the computed tomographic (CT) appearance of early lung involvement in systemic lupus erythematosus (SLE). MATERIALS AND METHODS: In a prospective study, 48 patients with serologically confirmed SLE but no prior clinical evidence of lung involvement underwent chest radiography, CT, and lung function tests. Radiographs and CT scans were compared, and CT scans were evaluated for signs suggestive of parenchymal and pleural disease. Extent and distribution of disease were determined. CT findings were correlated with clinical and functional data. RESULTS: Of 45 patients with normal chest radiographs, 17 (38%) had abnormal CT findings. Extent of disease was statistically significantly correlated with duration of clinical history (r = .93) and decreased single-breath diffusing capacity for carbon monoxide (r = .8) and ratio of forced expiratory volume in 1 second to forced vital capacity (r = .77). CONCLUSION: CT is superior to chest radiography for detection of functionally relevant pulmonary disease and is an important adjunct in early assessment of SLE.
Adult↗
Upregulation of ICAM-1, IL-1 and reactive oxygen intermediates (ROI) by exogenous antigens from Plasmodium falciparum parasites in vitro, and of sICAM-1 in the acute phase of malaria.
After 4 hours of stimulation of human mononuclear leukocytes in the presence of 300 ng/ml exogenous Plasmodium falciparum antigens, the ICAM-1 expression increased variably from 15% to 375%. Simultaneously, an increase of IL-1 mRNA production could be observed in Northern blot hybridizations with a specific cDNA gene probe for human IL-1 alpha labelled with digoxigenin. Furthermore, the reactive oxygen intermediates (ROI) production was also found to be enhanced in similar conditions. Additionally, when the levels of soluble ICAM-1 (sICAM-1) in plasma of 122 patients with P. falciparum or Plasmodium vivax malaria were analyzed in an enzyme immunoassay (EIA), significant sICAM-1 increases were found, more pronounced in patients with P. falciparum malaria, in comparison with healthy controls and with the same patients 4 weeks after chemotherapy. The presented results indicate that the expression of ICAM-1 may also be upregulated by exogenous Plasmodium antigens besides cytokines like IL-1 during the acute phase of malaria, with subsequently elevated sICAM-1 concentrations in blood.
Acute Disease↗
Circulating selectins, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in hyperthyroidism.
Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble P-selectin, and soluble L-selectin (sL-selectin), tumor necrosis factor-alpha, and interleukin-6 were measured in patients with Graves' disease (GD) (n = 33), in patients with toxic nodular goiter (n = 34), and in a group of healthy controls (n = 36). The serum levels of sICAM-1, sVCAM-1, sE-selectin, and sL-selectin were markedly elevated in patients with GD and in patients with toxic nodular goiter before treatment with methimazole (P < 0.05 for all). After 8 weeks of therapy, serum concentrations of sVCAM-1 and sE-selectin normalized, whereas serum levels of sL-selectin and sICAM-1 remained elevated. Hormone concentrations normalized after 2 weeks, clearly preceding falling levels of circulating adhesion molecules. Serum concentrations of soluble P-selectin, TNF-alpha, and interleukin-6 did not differ among patients with GD and toxic nodular goiter and healthy subjects. Serum levels of sVCAM-1 and sICAM-1 correlated with the serum concentrations of TSH receptor antibodies (n = 33; r = 0.921 and r = 0.792, respectively) and thyroid peroxidase antibodies (n = 33; r = 0.682 and r = 0.761, respectively) but not thyroglobulin antibodies. However, no correlation between serum levels of sE-selectin, sL-selectin, and soluble P-selectin or cytokines and serum levels of thyroid peroxidase antibodies, TSH receptor antibodies, or thyroglobulin antibodies, respectively, was found. In addition, no correlation between serum levels of adhesion molecules or cytokines and thyroid hormones was seen. We conclude that both the action of thyroid hormones and the autoimmune process in GD may contribute to elevated levels of soluble adhesion molecules.
Adult↗
Effect of ciprofloxacin and other quinolones on granulocyte function assessed by flow cytometry.
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Adult↗
Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production.
Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy; adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria. High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy. In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence. A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria. In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients. These findings illustrate the dual role of TNF in the protection and pathology of malaria.
Adolescent↗
Differential expression of the protooncogene bcl-2 in normal and osteoarthritic human articular cartilage.
OBJECTIVE: To investigate the expression of bcl-2 in healthy and osteoarthritic articular cartilage at the transcriptional level and at the protein level. METHODS: bcl-2 mRNA was detected by reverse transcriptase/polymerase chain reaction. The expression of bcl-2 protein was studied using flow cytometry analysis with a monoclonal antibody against intracellular bcl-2 and by immunohistochemistry. RESULTS: mRNA for bcl-2 was detectable in chondrocytes of both healthy and osteoarthritic cartilage. bcl-2 protein was present in the chondrocytes of the middle layer of cartilage by immunohistochemical staining. In osteoarthritis (OA), chondrocytes adjacent to cartilage defects expressed a particularly high signal intensity. Flow cytometry analysis demonstrated the presence of bcl-2 protein in virtually all chondrocytes. CONCLUSION: Our results show that bcl-2 is expressed in healthy adult and osteoarthritic human cartilage. The increased staining of chondrocytes adjacent to osteoarthritic defects indicates a differential regulation of programmed cell death during the degenerative process in OA.
Adult↗
Autoimmune-thrombocytopenia and SLE in a patient with 5q-anomaly and deletion of the c-fms oncogene.
Autoimmune-thrombocytopenia was the striking feature in a patient with typical clinical symptoms of systemic lupus erythematosus (SLE), complement C4 deficiency, and positive lupus serology. However, myelodysplasia was found in the bone marrow and chromosome analysis revealed a deletion of the long arm of chromosome 5 (5q-anomaly), which was confirmed by a hemizygosity for the c-fms oncogene (CSF-1-receptor) on Southern blot. Autoimmune phenomena reported in conjunction with myelodysplastic syndromes (MDS), e.g., an elevation of antinuclear antibodies, are usually regarded as nonspecific. This case report suggests that SLE can occur in patients with MDS and that a concomitant autoimmune-thrombocytopenia may mask the typical signs of the 5q- syndrome.
Adult↗