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Biomedical subjects

W Graninger

Publications and source records attributed to W Graninger.

At least 163 records · Page 9Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Soluble intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and tumor necrosis factor receptor (55 kDa TNF-R) in patients with acute Plasmodium falciparum malaria.

Adhesion of Plasmodium falciparum-infected erythrocytes to vascular endothelium is in part mediated by ICAM-1 and ELAM-1 (E-selectin), which can be induced via the 55-kDa TNF-receptor (TNF-R55kDa). We have studied serum levels of soluble ICAM-1 (sICAM-1), ELAM-1 (sELAM-1), and soluble TNF-R55kDa (sTNF-R55kDa) in 37 patients with uncomplicated P. falciparum infection and in 17 control subjects in Bangkok, Thailand. The serum levels of sICAM-1 were markedly elevated in patients prior to treatment (601 +/- 239 ng/ml versus 160 +/- 47 ng/ml in healthy controls). In addition, elevated levels of sELAM-1 (53.6 +/- 23.1 ng/ml versus 21.5 +/- 10.1 ng/ml) and sTNF-R55kDa (4.7 +/- 3.2 ng/ml versus 1.0 +/- 0.4 ng/ml) were observed (P < 0.05 for all). Soluble ELAM-1 reached normal levels on Day 3, and sTNF-R55kDa on Day 14, while sICAM-1 was still significantly elevated 28 days after treatment was started (P < 0.05 for all). A correlation between sTNF-R55kDa (P < 0.05) and sELAM-1 (P < 0.05), respectively, with parasitemia prior to antimalarial treatment was found. These results suggest that a TNF-mediated expression of adhesion molecules induced by the asexual stage of malaria parasites serves as an immune-evasion mechanism.

Acute Disease↗
PubMed1994

Intravenous teicoplanin does not prevent Clostridium difficile associated diarrhea.

A 59-year-old man with the diagnosis of endocarditis of the mitral valve due to Streptococcus mitis was treated with penicillin G, gentamicin, and later with clindamycin as inpatient for 3 weeks. Thereafter outpatient therapy with parenteral teicoplanin 3 x per week was initiated. After 17 days of teicoplanin treatment he developed severe diarrhea, and stool samples were positive for Clostridium difficile toxin. In addition to the ongoing parenteral therapy with teicoplanin, oral teicoplanin was administered. On the third day of this regimen the diarrhea and other disabling symptoms subsided, and test results for C. difficile toxin became negative. Oral teicoplanin was continued for 10 days and cleared C. difficile effectively after treatment as assessed by consecutive stool cultures (until 60 days thereafter). The parenteral administration of teicoplanin could not prevent the onset of C. difficile associated diarrhea in this patient, who previously had been treated with clindamycin. Thus, the administration of parenteral teicoplanin does not seem to be a treatment option for C. difficile associated diarrhea in patients in which oral therapy is not possible.

Clostridioides difficile↗
PubMed1994

Tolerance of high doses of amphotericin B by infusion of a liposomal formulation in children with cancer.

Conventional amphotericin B (Amph-B) is the drug of choice for treating systemic fungal infections. Recently, a new formulation has become available, encapsulated in liposomes (Amph-lip). This new form of administration was developed in order to lower the acute side effects and to offer the possibility of administering high doses of amphotericin B. Experience with Amph-lip is limited, especially in children. We treated four children with documented systemic fungal infections with Amph-lip and administered it empirically to 12 children. Fifteen of these 16 children were severely granulocytopenic oncologic patients. One 3-month-old baby suffered from systemic candidiasis. Amph-lip was preferred to conventional Amph-B in children with organ dysfunction developing as a consequence of conventional chemotherapy or bone marrow transplantation, after failure of conventional Amph-B to improve a fungal infection, and after adverse drug reactions had occurred. The daily doses of Amph-lip ranged from 1 to 6 mg/kg (median 3 mg/kg), the cumulative doses from 13 to 311 mg/kg (median 75 mg/kg). Acute adverse reactions or organ function abnormalities attributable to Amph-lip did not occur in 402 administrations. Amph-lip has proven to be well tolerated by children in terms of acute toxicity and in the long term. Although large cumulative doses were given, organ function abnormalities attributable to Amph-lip doses were not detected in any of ten long-term survivors over a median observation time of 36 months (range 30-44 months). Amph-lip appears to be a promising alternative antifungal treatment, especially for patients with impaired organ function, when high doses of amphotericin B are necessary.

Adolescent↗
PubMed1994

Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients. Multicentre Study Group.

In a non-comparative multicentre trial 51 patients aged 24 days to 17 years received treatment with intravenous or oral fluconazole for suspected systemic fungal infections. Twenty-seven patients had confirmed infections, 26 being confirmed mycologically and 1 histologically. All isolates were Candida species. Of the 43 clinically assessed patients, 30 were considered cured, 7 improved and 6 experienced failure of therapy. Of 27 patients with confirmed fungal infections, 25 were assessed mycologically and all but one were considered cured. Of the six patients experiencing clinical failure, two had a confirmed infection and only one of these experienced mycological failure. This patient had a primary diagnosis of candidemia with persistence of Candida albicans and Candida parapsilosis. All 51 patients were evaluable for safety. No treatment-related adverse events required termination of treatment. Treatment-related side effects (diarrhea, vomiting, deafness) were reported by three of 51 patients, three patients had laboratory test abnormalities possibly related to fluconazole treatment, including elevation of liver enzyme levels and of the eosinophil count. Results of this study confirm the efficacy and safety of fluconazole in the treatment of pediatric patients with severe fungal infection.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Color-coded duplex sonography of the parotid gland in Sjögren's syndrome].

27 patients with confirmed Sjögren's syndrome were examined prospectively by means of colour coded duplex sonography and pulsed Doppler sonography in order to determine blood flow in the parotid gland in this condition. Organ perfusion was divided semi-quantitatively into 4 groups: grade 0 (no intraglandular perfusion recognised) to grade 3 (numerous intra-glandular flow signals). Low perfusion values (grade 0 or grade 1) were found in normals and this was also observed in 13 patients (48%). 6 patients (22%) showed moderate increase (grade 2), and 8 patients (30%) showed gross increase (grade 3) in glandular perfusion. The increase in perfusion correlated with the severity of the sono-morphological glandular changes, such as reduced echogenicity, increased size and heterogeneous structure. Increased perfusion was associated with intra-glandular flow velocity as measured by Doppler sonography; maximal systolic flow velocity was significantly higher in patients with markedly increased perfusion than in normals.

Adult↗
PubMed1994

Clindamycin in combination with chloroquine or quinine is an effective therapy for uncomplicated Plasmodium falciparum malaria in children from Gabon.

Multidrug resistance of Plasmodium falciparum is becoming common in Africa. In a randomized trial, four short-term regimens were compared for treating uncomplicated P. falciparum malaria in children 4-15 years old in Gabon. One hundred thirty patients received chloroquine (25 mg/kg over 48 h; group C), chloroquine (as above) plus clindamycin (5 mg/kg every 12 h for 6 doses; group CCl), quinine (12 mg/kg every 12 h for 6 doses; group Q), or quinine (as above) plus clindamycin (as above; group QCl). In group C, only 9% of patients were cured by day 28, 44% showed recrudescent malaria (RI), and 47% showed intermediate or high-grade resistance (RII/RIII). In group CCl, 70% of patients were cured and 30% showed recrudescences. In group Q, 32% were cured and 68% showed recrudescences. In group QCl, 88% were cured and 12% showed recrudescences after day 14. All treatment regimens were well tolerated. Thus, the combination of clindamycin with chloroquine or quinine enhances parasite clearance and improves response to therapy.

Adolescent↗
PubMed1994

Soluble endothelium-associated adhesion molecules in patients with Graves' disease.

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.

Autoantibodies↗
PubMed1994

Upregulation of ICAM-I by Plasmodium falciparum: in vitro and in vivo studies.

AIMS: To monitor the expression of intercellular adhesion molecule I (ICAM-I) in vitro after stimulation of human macrophages with Plasmodium falciparum antigens, as well as the plasma concentrations of soluble ICAM-I (SICAM-I) in vivo in malarial patients. METHODS: Human mononuclear leucocytes were cultured and stimulated for four hours with 300 ng/ml exogenous P falciparum antigens. CD14 and CD54 (ICAM-I) expression was monitored using flow cytometry. Soluble ICAM-I (s ICAM-I) was also measured in the blood of 122 outpatients with malaria before and after treatment (Rio Branco, Acre, Brazil). RESULTS: ICAM-I expression increased from 15% to 375% after four hours of stimulation. When sICAM-I was analysed in the plasma of 122 patients with P falciparum or Plasmodium vivax malaria by enzyme immunoassay, significant increases were found. These were more pronounced in patients with P falciparum malaria, compared with healthy controls, and with the same patients four weeks after treatment. CONCLUSION: ICAM-I expression may also be upregulated in human macrophages by exogenous Plasmodium antigens as well as by cytokines during the acute phase of malaria. sICAM-I concentrations are downregulated after treatment, probably caused by the absence of circulating Plasmodium antigens.

Adolescent↗
PubMed1994

Serum laminin in malaria.

AIM: To determine serum laminin concentrations in patients with uncomplicated Plasmodium falciparum malaria. METHODS: An enzyme linked immunosorbent assay (ELISA) was used to determine serum laminin concentrations in 54 patients with acute uncomplicated P falciparum malaria during and after treatment, and in 17 control subjects in Bangkok, Thailand. RESULTS: Raised concentrations of soluble laminin were observed in patients (mean (SD) concentration 628 (225) ng/ml), compared with normal controls (490 (116) ng/ml), during the acute phase of the disease. During treatment, serum laminin concentrations decreased and returned to normal within three days. Serum laminin concentrations were correlated with parasite counts before treatment, and with the serum concentration of soluble intercellular adhesion molecule-1 (ICAM-1), soluble E-selectin, and soluble tumour necrosis factor receptor at 55 kilodaltons. CONCLUSIONS: These findings are compatible with an increased production or release of laminin in P falciparum malaria, which could indicate a role for the subendothelial basement membrane in the pathogenesis of the disease.

Acute Disease↗
PubMed1994

Effects of 17 beta-estradiol on circulating adhesion molecules.

The effects of 17 beta-estradiol (E2) on the serum levels of the circulating endothelial-leukocyte, intercellular, and vascular adhesion molecules [ELAM-1, ICAM-1 (CD54), and VCAM-1] were evaluated in healthy male volunteers after single im injection of 10 mg E2 valerate. In addition, a time course of the effects of E2 on circulating adhesion molecules (AMs), cortisol serum levels, differential blood counts, and surface expression of the lymphocyte function-associated antigen-1 (CD11a/CD18), CD3, CD4, CD19, and CD25 on leukocytes was studied in another group of volunteers. A 5% decrease in circulating ICAM-1 (P = 0.045 vs. placebo) was found when a single time point (96 h after E2 injection) was studied. However, this decrease was smaller than the intrasubject (day to day) variability observed, and there was no consistent and time-dependent effect of E2 on circulating AMs. Circulating neutrophils increased 2.3-fold over baseline after E2 treatment (P = 0.0008 vs. placebo). The mean coefficients of variation for the intrasubject (day to day) and intersubject variability of circulating AMs were between 5.4-7.5% and 20-29%, respectively. Our findings indicate that the effect of E2 on circulating AMs is not distinguishable from the intrasubject variability observed after placebo treatment. Thus, an effect of E2 on adhesion molecules is unlikely to contribute to the antiatherogenic-cardioprotective effect of E2. The pronounced E2-mediated increase in neutrophils deserves further studies to elucidate its (patho-)physiological implications.

Adult↗
PubMed1994

Comparison of micronized halofantrine with chloroquine-antibiotic combinations for treating Plasmodium falciparum malaria in adults from Gabon.

Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. In Lambarene, Gabon where chloroquine-resistant malaria is prevalent, a randomized comparative trial with three regimens for treating P. falciparum malaria in adults was performed. One hundred two patients evaluated received either a new micronized formulation of halofantrine (8 mg/kg every 6 hr in three doses) (group H) or chloroquine (25 mg/kg for a 48-hr period) plus clindamycin (5 mg/kg every 12 hr in six doses) (group CC1), or chloroquine (as above) plus doxycycline (2 mg/kg every 12 hr in six doses) (group CD). All treatment regimens were well-tolerated. In group H, 100% of the patients were cured, and in group CC1, 97% of the patients were cured by day 28 of follow-up. In group CD, a significantly lower cure rate of 75% (P < 0.01) and a slower parasite clearance was observed, but only low grade (RI) resistance occurred.

Administration, Oral↗