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Biomedical subjects

W J Stevens

Publications and source records attributed to W J Stevens.

At least 19 recordsLinked to original sources
PubMed2000

High bone mass and hypocalcaemic myopathy in a patient with idiopathic hypoparathyroidism.

The clinical manifestations of hypoparathyroidism are mainly characterised by increased neuromuscular irritability as a consequence of hypocalcaemia. Occasionally, elevation of the muscle enzymes may mimic polymyositis. Reduced parathyroid hormone production, but also vitamin D treatment and calcium supplementation, may contribute to the increased bone mass found in patients with postsurgical hypoparathyroidism. We report the case of a 36-year-old woman with untreated idiopathic hypoparathyroidism and a high bone mass despite severe muscle impairment due to hypocalcaemic myopathy.

Absorptiometry, Photon↗
PubMed2000

Long-term effects of specific immunotherapy, administered during childhood, in asthmatic patients allergic to either house-dust mite or to both house-dust mite and grass pollen.

In a retrospective study, asthmatic patients allergic to either house-dust mite (HDM) (Dermatophagoides pteronyssinus) (n = 34) or to both HDM and grass pollen (GP) (n = 14), and who were treated with specific immunotherapy (SIT) during childhood (mean duration of SIT: 61 +/- 9.70 months), were re-evaluated in early adulthood after mean cessation of SIT for 9.3 +/- 2.76 years. The results were compared to those of a control group of asthmatic patients (n = 42) with comparable asthma features, who were treated with appropriate antiasthmatic drugs during childhood, but who never received SIT. Re-evaluation was carried out with a standardized questionnaire, skin prick tests (SPT), and lung-function assessments. At the time of re-evaluation, the mean age in the SIT-treated group was 23.1 +/- 3.50 years; in the control group, it was 22.7 +/- 3.40 years. At re-evaluation, the risk of frequent asthmatic symptoms was three times higher in the control group than in the SIT-treated group (prevalence ratio: 3.43; P = 0.0006). The frequent use of antiasthmatic medication was also more pronounced in the control group, although the difference was not statistically significant (P=0.38). Lung-function parameters and results of SPT with HDM were comparable in both groups. It is concluded that SIT has long-term effects on asthmatic symptoms in young adults.

Adult↗
PubMed2000

Determination of T-cell subpopulations and intracellular cytokine production (interleukin-2, interleukin-4, and interferon-gamma) by cord blood T-lymphocytes of neonates from atopic and non-atopic parents.

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T-cell subsets and percentage of cytokine-producing cord blood T-helper (Th) and T-suppressor/cytotoxic lymphocytes of neonates from atopic and non-atopic parents were compared. A group of 33 healthy, full-term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T-cell subsets and to determine the percentage of interleukin (IL)-2-, IL-4-, and interferon-gamma (IFN-gamma)-producing cord blood Th and T-suppressor/cytotoxic lymphocytes following stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3+ CD4+ (Th lymphocytes), CD3+ CD8+ (T-suppressor/cytotoxic lymphocytes), CD19+ (B lymphocytes), CD3+ CD4+ CD45RO+ (memory Th lymphocytes), and CD3+ CD4+ CD45RA+ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL-2- and IFN-gamma-producing Th and T-suppressor/cytotoxic lymphocytes, whereas the number of IL-4-producing T lymphocytes remained very low or undetectable. No differences in the percentage of TL-2-, IL-4- and IFN-gamma-producing Th and T-suppressor/cytotoxic lymphocytes were found between neonates from atopic and non-atopic parents. These results will be re-evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.

Animals↗
PubMed2000

Influence of blood and synovial fluid immune complexes of patients with rheumatoid arthritis on production of nitric oxide and growth and viability of chondrocytes.

OBJECTIVE: To determine whether blood and synovial fluid (SF) immune complexes (IC) of patients with rheumatoid arthritis (RA) influence the production of nitric oxide (NO) and growth and viability of chondrocytes. METHODS: IC were precipitated and IgM and IgG were determined in the precipitates by ELISA and nephelometry, respectively. Primary cultures of bovine articular chondrocytes were incubated with the IC precipitates. After 48 h NO was determined as nitrite. After 7 days, growth was determined by incorporation of tritiated thymidine and viability was detected by neutral red uptake. RESULTS: Patient sera were positive in 8/12 for IgM IC and 9/12 for IgG IC, and 1/8 control sera was slightly positive for IgM IC. Seven of 12 SF samples were IgM IC and 10/12 IgG IC positive. With and without additional interleukin 1alpha (IL-1alpha) stimulation, NO production by chondrocytes was significantly higher with SF IC precipitates than with control serum precipitates (p = 0.03, p = 0.04, respectively). NO production by chondrocytes that were not stimulated with IL-1alpha was significantly increased with SF IC precipitates compared to RA serum IC precipitates (p = 0.03). SF IC significantly inhibited growth compared to control serum precipitates (p = 0.04) and RA serum IC (p = 0.012). Neutral red uptake by chondrocytes was significantly decreased when incubated with RA serum IC in comparison with control serum IC (p = 0.012) and SF IC (p = 0.006). With and without additional IL-1alpha stimulation, NO production by chondrocytes after incubation with SF derived IC was positively correlated to the Ritchie score (r = 0.8, r = 0.7, respectively) and the number of swollen joints (r = 0.8, r = 0.6, respectively). CONCLUSION: These results support the hypothesis that, especially in active RA, SF derived IC stimulate NO production and inhibit chondrocyte growth.

Antigen-Antibody Complex↗
PubMed1999

Flow cytometric detection of type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5) cytokines in T-helper and T-suppressor/cytotoxic cells in rheumatoid arthritis, allergic asthma and atopic dermatitis.

Type 1 cytokines (a.o. IL-2 and IFN-gamma) play an important role in the pathogenesis of rheumatoid arthritis. On the other hand, IgE-mediated diseases such as allergic asthma and atopic dermatitis show a type 2 cytokine (amongst others IL-4 and IL-5) profile. This study examined simultaneously the intracellular production of IL-2, IFN-gamma, IL-4 and IL-5 in T-lymphocytes of patients with rheumatoid arthritis during treatment with methotrexate or salazopyrin, patients with allergic asthma or atopic dermatitis under stable treatment, compared to healthy controls.A three-colour flow cytometric analysis was used for cytokine detection in T-helper cells and T-suppressor/cytotoxic cells. Compared to controls, patients with symptomatic atopic dermatitis showed an increased number of IL-4-producing T-helper lymphocytes in basal circumstances (P=0.001), in contrast to asymptomatic allergic asthma patients. Compared to controls, rheumatoid arthritis patients, treated with salazopyrin, showed an increased number of IL-2-producing T-helper and T-suppressor/cytotoxic lymphocytes after in vitro stimulation with PMA and ionomycin (P=0.01). In contrast, rheumatoid arthritis patients, treated with methotrexate, a more potent disease modifying drug, did not show this type 1 cytokine profile. A positive correlation was found between the number of IFN-gamma producing T-helper cells and disease activity (Ritchie Index and number of swollen joints) in both rheumatoid arthritis patient groups. Active atopic dermatitis patients showed a type 2 cytokine profile, whereas stable asthma patients with lower disease activity did not show a predominance of type 2 cytokines. Rheumatoid arthritis patients under treatment with salazopyrin had a type 1 cytokine profile, which could not be demonstrated in patients treated with methotrexate. This imbalance between type 1 and type 2 cytokines in different immune mediated disorders can be related with treatment and the grade of disease activity. These results stress the need for further investigation of the influence of therapy on cytokine profiles.

Adolescent↗
PubMed1999

Flow cytometrical determination of interleukin 1beta, interleukin 6 and tumour necrosis factor alpha in monocytes of rheumatoid arthritis patients; relation with parameters of osteoporosis.

Experimental data suggest that pro-inflammatory cytokines such as interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) are important in the pathogenesis of osteoporosis in rheumatoid arthritis. Therefore we compared the production of these cytokines by monocytes in 10 rheumatoid arthritis patients and 10 controls. Cytokine levels in rheumatoid arthritis patients were related to disease activity parameters, bone mineral density (BMD) corrected for age and sex (Z scores) and osteocalcin as a laboratory parameter of bone remodelling. Cytokines were determined by a flow cytometrical technique. There was a tendency for higher IL-1beta levels in patients compared with controls. A positive correlation between erythrocyte sedimentation rate and spontaneous production of monocytic cytokines was found. Z scores of the lumbar spine showed a negative correlation with spontaneous production of IL-1beta and IL-6. Plasma osteocalcin levels were positively correlated with spontaneous production of IL-1beta, IL-6 and TNF-alpha. In conclusion, the correlation of the levels of these cytokines with parameters of bone metabolism and osteoporosis suggest that especially IL-1beta and IL-6 are associated with more pronounced osteoporosis in active rheumatoid arthritis.

Absorptiometry, Photon↗
PubMed1999

Effects of suramin on anastomotic colon tumors in a rat model.

BACKGROUND: The development of antiangiogenic drugs offers new promise in the treatment of malignancy. Suramin has been reported to inhibit tumor growth by blocking angiogenesis and has been used in clinical trials. The aim of the present study was to examine the effects of suramin on colonic anastomotic tumors in the rat. METHODS: (a) Colonic anastomotic tumor was induced in 120 WAG/RIJ rats. Half of the animals were given 100 mg/kg of suramin intraperitoneally at the time of tumor induction. Rats were sacrificed after 2, 4 and 8 weeks; tumor take and tumor weight were evaluated. (b) The number of red blood cell clusters per x 400 field was counted in each tumor. (c) A lymphocyte transformation test was performed in four groups of animals, 2 weeks before and 2 weeks after tumor implantation and/or suramin administration. RESULTS: (a) A significant enhancement of tumor growth was observed in the suramin-treated animals. (b) This was accompanied by a significant increase in functional blood vessels. (c) Suramin-treated rats had markedly decreased lymphocyte stimulation, pointing to a possible immunosuppressive effect. CONCLUSIONS: The growth of an anastomotic colon tumor is rather enhanced by a single intraperitoneal administration of 100 mg/kg suramin in the rat, possibly by an unexpected immunosuppressive effect.

Adenocarcinoma↗
PubMed1998

Evolution of lymphocyte transformation to wasp venom antigen during immunotherapy for wasp venom anaphylaxis.

BACKGROUND: Venom immunotherapy (VIT) has proven to be safe and effective in wasp venom anaphylaxis. However, there are no good parameters to indicate when to stop venom immunotherapy. OBJECTIVE: To evaluate the relationship of the lymphocyte transformation test (LTT) to history and specific IgE determination, and to address the time course of lymphocyte transformation responses to wasp (Vespula) venom during VIT and the possible utility of LTT to determine the duration of therapy. METHODS: Peripheral blood mononuclear cells (PBMCs) of 18 individuals with a history of wasp sting anaphylaxis and a positive serum-venom-specific IgE, were stimulated with wasp venom before immunotherapy, at the end of a 5-day semi-rush immunotherapy and at 24 months during venom immunotherapy. Results, expressed as stimulation index (SI), were compared with the SI in seven asymptomatic stung controls. RESULTS: In controls the median (minimum-maximum) of the SI were 2.39 (0.52-3.39) before therapy and 2.39 (1.12-6.02) when repeated after 24 months. For patients the median (minimum-maximum) of the SI were 10.13 (1.19-44.88) before immunotherapy (d0), 2.73 (0.67-12.03) at the end of the build-up immunotherapy (d5) and 4.21 (0.88-14.66) at the end of 24 months of maintenance therapy (m24). The proliferation responses in vespid-allergic patients were significantly higher than in stung controls (P = 0.006) but only 13/18 patients showed a positive LTT result before the start of immunotherapy (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build-up hyposensitization course the SI significantly dropped as compared to the pre-treatment levels (P = 0.002). The SI of the LTT was negative in eight out of 18 patients at 24 months and the median values were significantly lower than before therapy (P = 0.03). CONCLUSIONS: Although, in the absence of sting challenge data it is not possible to draw conclusions about the predictive value of the LTT, our data may suggest that abolition of the LTT during VIT might indicate clinical insensitivity. Further studies, comparing the results of sting challenges, with the results of lymphocyte transformation will be necessary in order to evaluate the role of LTT in stopping immunotherapy.

Adolescent↗
PubMed1998

Comparison between the in vitro cytokine production of mononuclear cells of young asthmatics with and without immunotherapy (IT)

BACKGROUND: The underlying mechanisms of immunotherapy (IT) are still unknown but may be related to modifications of cytokine production of T lymphocytes. OBJECTIVE: In this study we determined the in vitro allergen-induced production of IL-2, IL-4, IL-5, IL-12 and IFNgamma of peripheral blood mononuclear cells (PBMC) of eight young asthmatics, aged 15+/-2 years, receiving IT (IT group) and of eight comparable asthmatics, aged 13+/-3.5 years, who never received IT (non-IT group). METHODS: All patients suffered from perennial asthma and were allergic to house dust mite (HDM). They were selected if they showed a positive stimulation index (SI) of PBMC after in vitro incubation with HDM (i.e. SI > 2). Cells were incubated with and without HDM (10 microg/mL) during 24 h, 48 h and 7 days. Cytokines were determined in the supernatant at the three time points and are expressed as median values in pg/mL. RESULTS: In the IT group the secretion of IL-2 was lower compared with the non-IT group after 7 days incubation of PBMC with HDM (0 vs 33.2, P = 0.008). In both groups maximal secretion of IL-2 was observed after 48 h. In the non-IT group a high value of IL-2 persisted after 7 days, whereas in the IT group a significant decline of IL-2 occurred after 7 days. Although IL-4 secretion was low in all subjects, more patients of the non-IT group showed detectable IL-4 in the HDM cultures after 24 h and 48 h, although the difference was not statistically significant (P = 0.08 and P = 0.28, respectively). Furthermore, IL-4 secretion was lower in the HDM cultures after 24 h in the IT group (1.75 vs 4.1, P = 0.011) and 48 h (2.2 vs 4.1, P=0.035). IL-5 secretion was lower in the HDM cultures after 24h (12.4 vs 47.6, P = 0.035) and 48 h (26.8 vs 135, P = 0.046) in the IT group than in the non-IT group. After 7 days of incubation with HDM there was no difference between the groups. There was no difference between both groups in secretion of IFNgamma and IL-12. CONCLUSIONS: These results show a difference in vitro cytokine secretion of PBMC of asthmatics receiving IT compared with asthmatics who never received IT. PBMC of patients receiving IT secrete less IL-2 and IL-5 after in vitro incubation with HDM and show a tendency to secrete less IL-4. The efficacy of IT may be attributed to a modified cytokine secretion of PBMC.

Allergens↗
PubMed1998

Immunotherapy for allergic reactions.

In this review, hyposensitization or immunotherapy will be discussed. The earliest immunotherapy was applicated in allergic respiratory diseases such as asthma and rhinitis. The most important indication has become the treatment of hymenoptera allergy. Some less frequently indications are associated with drug allergy. Immunotherapy is most frequently indicated in IgE mediated diseases, but new applications for cell mediated reactions will be described. With the introduction of molecular biology in allergology new theoretical possibilities emerged: use of peptide antigens, recombinant allergens, anticytokines.... Unfortunately, these newer approaches did not (yet) cause a breakthrough. The cost of these products will be a major draw back, even when ethical problems for using them on a larger scale will have been solved.

Desensitization, Immunologic↗
PubMed1998

Influence of antirheumatic drugs on nitric oxide and interleukin 8 production in human articular chondrocytes.

OBJECTIVE: To determine whether antirheumatic drugs can inhibit chondrocyte nitric oxide and interleukin 8 (IL-8) production. METHODS: IL-1beta stimulated human chondrocytes were incubated with indomethacin, methotrexate, sulfasalazine, dexamethasone, and methylprednisolone. Nitric oxide was detected as nitrite; IL-8 was detected by a radioimmunoassay method. RESULTS: Nitric oxide production was partly (< or = 50%) inhibited and IL-8 almost completely suppressed (> 80%) by dexamethasone and methylprednisolone. Sulfasalazine in pharmacological concentration and indomethacin slightly increased IL-8. No effect of methotrexate on nitric oxide or IL-8 production was found. CONCLUSION: Dexamethasone and methylprednisolone are inhibitors of human chondrocyte nitric oxide production, although to a lesser extent than for IL-8 production. Indomethacin, sulfasalazine, and methotrexate had no major influence on these mediators.

Antirheumatic Agents↗
PubMed1997

Actin polymerisation in neutrophils of rheumatoid arthritis patients in relation to treatment with non-steroidal anti-inflammatory drugs.

There is evidence that neutrophil functions such as chemotaxis and oxygen radical formation are disturbed in rheumatoid arthritis (RA). Medication might also influence these functions. Cyclic formation and depolymerisation of actin microfilaments is crucial in cell motility, but this phenomenon has not been studied in RA. The aim of this study was to investigate basal and dynamic (formyl-methionyl-leucyl-phenylalanine (fMLP)-induced) neutrophil actin polymerisation in ten RA patients (a) during therapy with non-steroidal anti-inflammatory drugs (NSAIDS) and (b) after stopping NSAIDS> The results were compared with those of ten age-matched controls. Basal F-actin content in RA patients with NSAIDS was significantly lower than in RA patients without NSAIDS and controls: 35.5 (25.0-49.0), 50.5 (27.0-75.0) and 52.5 (32.0-85.0), respectively. Conversely, upon stimulation with fMLP, the actin polymerisation curve of RA patients with NSAIDS was higher than for RA patients without NSAIDS and controls. These results suggest that, in RA, the effects orf NSAIDS on neutrophil functions might be related to changes in the actin polymerisation-depolymerisation cycle.

Actins↗
PubMed1997

Latex-specific IgE, skin testing, and lymphocyte transformation to latex in latex allergy.

BACKGROUND: This study was designed to determine the discriminative value of latex-specific IgE tests, latex skin tests, and lymphocyte transformation tests (LTTs) to latex in 38 patients with latex allergy (12 nonatopic and 26 atopic) and 44 control subjects (24 nonatopic and 20 atopic). We also evaluated the recommended positive cutoff (i.e., 0.35 kU/L) of both in vitro latex-IgE tests. METHODS: Latex-specific IgE levels were determined by the Immuno-CAP (Upjohn-Pharmacia) and the ALaSTAT-RIA (Diagnostic Products Corp.) assays. Skin tests and LTFs were performed with a nonammoniated latex extract (DPC). Sensitivities and specificities were defined according to the 95th percentile value of nonatopic control subjects. For the in vitro IgE tests, sensitivity and specificity were also calculated by using the proposed positive threshold of 0.35 kU/L. Sensitivities and specificities of both cutoffs were compared. RESULTS: Compared with a clinical history of latex allergy and according to the 95th percentile value of nonatopic control subjects (0.44 kU/L), latex-specific IgE determined by the Immuno-CAP assay achieved a sensitivity of 97% and a specificity of 86%. For the ALaSTAT-RIA assay, with 0.54 kU/L as the 95th percentile threshold value in nonatopic control subjects, sensitivity was 100%, and specificity was 83%. According to the threshold value of 0.35 kU/L, a sensitivity of 97% and a specificity of 83% for the Immuno-CAP assay and a sensitivity of 100% and a specificity of 33% for the ALaSTAT-RIA assay were observed. The latex skin test reached a sensitivity of 97% and a specificity of 100%. The LTF to latex showed a sensitivity of 39% and a specificity of 95%. No relation between symptoms and latex-specific IgE tests, latex skin tests, or LTTs was found. CONCLUSIONS: Our results confirm that latex skin tests and latex-specific IgE assessments are sensitive and specific methods for establishing the diagnosis of latex allergy, although the specificity of the ALaSTAT-RIA assay was very low when interpreted according to the threshold of 0.35 kU/L. The LTT to nonammoniated latex is too insensitive for diagnosis of allergy to latex. This reemphasizes that in order to evaluate the sensitivity and specificity of diagnostic procedures, one should always include an appropriate control group.

Adolescent↗
PubMed1997

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies.

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.

Adult↗