Presence of rheumatoid factor and antibodies to citrullinated peptides in systemic lupus erythematosus.
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Adult↗
Biomedical subjects
F Hulstaert
Publications and source records attributed to F Hulstaert.
A prospective multicenter study of the efficacy and tolerability of cryopreserved allogenic human keratinocytes to treat venous leg ulcers.
Allogeneic human keratinocyte cultures have been used to treat burn wounds, donor sites, and chronic skin ulcers with some success. Cryopreservation of these cultures allows for the production of large standardized batches that are readily available for use. The aim of the study presented in this report was to study effects of cryopreserved cultured allogenic human keratinocytes (CryoCeal) on chronic lower extremity wounds. Parameters were measured to study efficacy, tolerability, pain associated with chronic wounds, and quality of life of patients. Twenty-seven patients with hard-to-heal venous leg ulcers received a maximum of 9 applications of CryoCeal in a prospective, uncontrolled multicenter study lasting 48 weeks. Eleven out of 27 patients (41%; 95% CI: 22%-61%) had complete wound closure within 24 weeks (1 week). The time required for complete wound closure in these 11 patients ranged from 4.1 to 24.9 weeks. Only 1 patient had recurrence of the ulcer at 48 weeks. Local (wound) pain scores decreased from a mean of 2.5 at baseline to 0.9 at week 24. Fifty percent of the patients attained a pain score of 0 after 12 weeks and remained stable at this score until the end of the study. Overall, the patient quality of life was better at week 24, compared to baseline values. The treatment was well tolerated, and wound infection was the most frequently occurring adverse event.
Adult↗
Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus.
OBJECTIVES: To study associations between antinuclear antibodies (ANA) and signs/symptoms in patients with systemic lupus erythematosus (SLE). METHODS: A consecutive cohort of 289 patients with SLE was included; 235 fulfilled ACR criteria for SLE and were further analysed. ANA profiles were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae. An extensive list of signs/symptoms was evaluated. RESULTS: Five clusters of antibodies were defined by cluster analysis: 1-antibodies to SmB, SmD, RNP-A, RNP-C, and RNP-70k; 2-antibodies to Ro52, Ro60, and SSB; 3, 4, and 5-antibodies to ribosomal P, histones and dsDNA, respectively. Significant associations (p< or =0.01) were found between anti-RNP-70k, anti-RNP-A, anti-RNP-C and Raynaud's phenomenon, between anti-RNP-A, anti-RNP-70k and leucopenia, and between anti-RNP-A, anti-RNP-C and a lower prevalence of urine cellular casts. Anti-SSA, anti-SSB were associated with xerostomia, and anti-SSB with pericarditis. Antibodies to ribosomal P were associated with haemolytic anaemia, leucopenia, and alopecia. Patients with anti-dsDNA antibodies had a higher risk for cellular casts and a lower risk for photosensitivity. Antihistone antibodies were associated with arthritis. CONCLUSIONS: In a large and consecutive cohort of patients with SLE, clusters of antibodies were identified. Previously reported associations of antibodies with symptoms were confirmed and new associations found.
Adolescent↗
CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Phospho-Tau International Study Group.
Tau and beta-amyloid (1-42) (Abeta42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Abeta42 and phospho-tau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Abeta42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782 +/- 0.048 (mean +/- SE) for tau and to 0.839 +/- 0.042 for phospho-tau (p = 0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB.
Alzheimer Disease↗
Cerebrospinal fluid tau and beta-amyloid(1-42) in dementia disorders.
The reliability of cerebrospinal fluid (CSF)-tau and CSF-beta-amyloid assays for diagnosis of Alzheimer's disease and other dementing disorders such as frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD) is reviewed. CSF assessment of the two proteins is useful in early diagnosis of AD and to differentiate it from FTD and DLB. Extremely high CSF-tau levels can discriminate CJD from AD.
Amyloid beta-Peptides↗
Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies.
Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children. A sandwich-type ELISA (INNOTEST hTAU-Ag) was used for measuring CSF-tau. Sixteen out of 50 patients with hematological malignancies, including the patients with proven leukemic CNS invasion, already showed high CSF-tau levels at baseline (>300 pg/ml). The pre-induction treatment for non-B-ALL, consisting of only corticosteroids and methotrexate (MTX), resulted in a significant increase of tau at day 8 (on average to 535 pg/ml). Larger increases as compared to baseline levels of CSF-tau were observed in patients treated for B-NHL with systemic vincristine, corticosteroids and cyclophosphamide, and intrathecal MTX (mean 776 pg/ml at day 8). In two AML patients with CNS invasion, CSF-tau increased during chemotherapy up to 1,500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2,000 pg/ml. Almost one-third of the patients with hematological malignancies had elevated CSF-tau levels at diagnosis. Transient high levels of CSF-tau, reaching levels observed in other neurodegenerative disorders, were observed during induction chemotherapy for non-B-ALL, B-NHL and CNS+ AML. The clinical implications of both observations will be the subject of further study.
Antineoplastic Agents↗
Validation of the INNO-LIA syphilis kit as a confirmatory assay for Treponema pallidum antibodies.
The commercially available diagnostic tests for syphilis are mostly based on the use of extracted antigens of Treponema pallidum. Pronounced cross-reactivities with other spirochete antigens are often reported. The aim of this study was to validate a novel multiparametric assay (the assay performed with the kit) INNO-LIA Syphilis for the confirmation of syphilis antibodies in a set of 840 documented human serum samples. All serum samples were previously tested at the French World Health Organization reference center for venereal diseases (Institute Alfred Fournier, Paris, France), with a consensus result provided for each sample. The study was conducted in two phases, with each phase involving a validation set (500 well-documented serum samples) and an exploratory set (340 serum samples) of serum samples, respectively. By measuring the sensitivity and specificity, we compared the result of the new assay with the consensus result on the basis of the results of a variable number of classical serological methods and clinical information when available. A sensitivity of 99.6% (95% confidence internal [CI], 98.5 to 99.9%) and a specificity of 99.5% (95% CI, 98.1 to 99.9%) were found for the new line immunoassay. Six of seven samples with indeterminate results by classical serology tested positive with the INNO-LIA Syphilis kit. This single multiparametric assay provides reliable confirmatory diagnostic information that must currently be obtained by the performance and interpretation of results of a combination of serological assays.
Antibodies, Bacterial↗
Serological confirmation of Chagas' disease by a recombinant and peptide antigen line immunoassay: INNO-LIA chagas.
Although screening for Trypanosoma cruzi antibodies is mandatory in most South American countries, current tests are insensitive and have poor specificity. A recently optimized line immunoassay (the INNO-LIA Chagas assay) for the serological confirmation of Chagas' disease was evaluated at a large blood bank in São Paulo, Brazil. Sera from blood donors who reacted in at least one of three serological screening assays (n = 1,604) and who returned for a follow-up were retested, and the donors were interviewed to assess their epidemiological risk. The results obtained by the confirmatory assay evaluated in this study were compared to those obtained by the three different screening assays. Upon consideration of the consensus results obtained by the three different screening assays as a "gold standard," the INNO-LIA Chagas assay showed a sensitivity of 99.4% (95% confidence interval [CI], 98.3 to 99.9) and a specificity of 98.1% (95% CI, 96.6 to 99.0) for positive (n = 503) and negative (n = 577) sera. The INNO-LIA Chagas assay confirmed the results for significantly larger numbers of positive samples of at-risk individuals independent of the number of positive screening tests (P = 0.017, Mantel-Haenszel test). In conclusion, the INNO-LIA Chagas assay reliably confirmed the presence of antibodies to T. cruzi and can be implemented as a confirmatory assay for Chagas' disease serology.
Animals↗
Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF.
OBJECTIVE: To evaluate CSF levels of beta-amyloid(1-42) (Abeta42) alone and in combination with CSF tau for distinguishing AD from other conditions. METHODS: At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Abeta42 and tau. RESULTS: Median levels of Abeta42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Abeta42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95% CI: 81% to 91%) compared with 55% (95% CI: 47% to 62%) for Abeta42 alone and 65% (95% CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95% CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Abeta42 levels not only in AD but also in NAD. CONCLUSIONS: The combined measure of CSF Abeta42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.
Adult↗
A recombinant peptide antigen line immunoassay optimized for the confirmation of Chagas' disease.
BACKGROUND: The transfusion of contaminated blood has become the major route of transmission for Chagas' disease in Brazil. Current screening tests are insensitive and yield conflicting results, while confirmatory assays do not exist. A line immunoassay (INNO-LIA Chagas Ab [INNO-LIA]) combining relevant, immunodominant recombinant and synthetic antigens on a single nylon membrane strip was evaluated for the serologic confirmation of Chagas' disease. STUDY DESIGN AND METHODS: Sera from 1062 patients and healthy residents of four Brazilian regions endemic for Chagas' disease were used for test optimization. The established confirmation algorithm was evaluated with an independent set of positive (n = 75) and negative (n = 148) samples. RESULTS: In the optimization phase, without an established comparative gold standard, the results with the INNO-LIA were compared with those obtained in four other screening assays. In the validation phase, the INNO-LIA showed a sensitivity of 100 percent (95% CI, 95.21-100) and a specificity of 99.32 percent (95% CI, 96.29-99.98) for well-characterized sera. Moreover, its specificity reached 100 percent with a set of 40 sera obtained from patients with documented leishmaniasis. The interpretation criteria defined in this study indicated that the INNO-LIA accurately detected the presence of antibodies to various specific antigens of Trypanosoma cruzi. CONCLUSION: The INNO-LIA Chagas Ab assay may become the first commercial assay to reliably confirm the presence of antibodies to T. cruzi.
Animals↗
Tropisetron for treating established postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled study.
UNLABELLED: Tropisetron can prevent postoperative nausea and vomiting (PONV) at doses smaller than those used to control chemotherapy-induced nausea and vomiting. In this placebo-controlled study, the efficacy and tolerability of three different doses of tropisetron were compared for the treatment of established PONV after surgical procedures in general anesthesia. Of 1513 patients who satisfied inclusion criteria, 314 experiencing PONV during the first 2 h after recovery from anesthesia were treated with one of three different doses of tropisetron (0.5, 2, or 5 mg) or placebo, administered i.v. as a single dose. Patients were then observed during 24 h for efficacy and tolerability. All three doses of tropisetron were significantly better than placebo in controlling emetic episodes and in reducing the need for rescue treatment. There were no significant differences among the three doses. However, in the subgroup of patients who had previous PONV, and in those randomized for nausea alone, the 2-mg and 5-mg doses controlled emetic episodes better than the 0.5-mg dose. All studied doses of tropisetron were well tolerated and did not affect vital signs. We conclude that a single i.v. administration of tropiestron significantly reduces the recurrence of emetic episodes in patients with established PONV after elective surgery with general anesthesia. Its optimal dose seems to be 2 mg. IMPLICATIONS: Three hundred-fourteen patients suffering from postoperative nausea and vomiting received different i.v. doses of a new antiemetic drug, tropisetron, to determine the lowest effective dose. We found that a single i.v. administration of tropisetron significantly reduced postoperative nausea and vomiting after elective surgery with general anesthesia.
Abdomen↗
Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy.
Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).
Acute Disease↗
Single dose i.v. tropisetron in the prevention of postoperative nausea and vomiting after gynaecological surgery.
In a prospective, randomized, multicentre, double-blind, placebo-controlled study, we have compared the efficacy of a single i.v. dose of tropisetron 0.5 mg, 2 mg and 5 mg in the prevention of postoperative nausea and vomiting (PONV). We studied 385 ASA class I and II female patients undergoing abdominal or vaginal gynaecological surgery, including laparoscopy. Tropisetron or placebo were administered before a standardized general anaesthetic. The frequency of vomiting in the 24-h period after entry into the recovery room was reduced from 44% after placebo to 31%, 26% and 30% after tropisetron 0.5 mg, 2 mg and 5 mg, respectively (P = 0.06, P = 0.009 and P = 0.043; unadjusted). Compared with placebo, nausea was reduced from 55% to 46%, 34% and 46% (P = 0.25, P = 0.003, P = 0.22), and need for rescue treatment from 39% to 29%, 23% and 35% (P = 0.13, P = 0.017 and P = 0.59) for the same groups. Tropisetron 2 mg appeared to be the optimal dose for prophylaxis against PONV with a side-effect profile similar to that of placebo.
Adult↗
The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients.
It is widely believed that multiple sclerosis is a T-cell mediated autoimmune disease associated with abnormalities in immunoregulation. This large, prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS patients, divided clinically into a remitting/relapsing group (n = 176) and a progressive group (n = 70), and compared their results to those of 117 healthy controls. All patients were found to have significantly elevated percentage and absolute numbers of IL2R+CD3+ cells as well as depressed percentages of CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide (CY) versus no treatment or treatment with other agents was used to group patients, dramatic declines in both percentages and absolute numbers of CD45RA+CD4+ cells were discovered. These declines were associated specifically with CY and and could be explained by this factor independent of the clinical state of the patient. The effects were seen in patients undergoing current treatment or in those exposed to CY in the near or remote past. These findings highlight the confounding effect of specific treatments on the immune profile of MS patients groups and suggest that there may be important implications for cellular function and clinical outcome in these and other patient groups.
Adult↗
Tropisetron in the prevention of nausea and vomiting in 131 children receiving cytotoxic chemotherapy.
Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a selective antagonist of the serotonin receptor (5-HT3) dosed once-daily at 0.2 mg/kg (with a maximum of 5 mg daily), was evaluated in the prevention of chemotherapy-induced nausea and vomiting in 131 children with a median age of 5 years (age 10 weeks to 21 years). Acute lymphocytic leukemia was the most common malignancy (49%). Most children (82%) had received cytotoxic chemotherapy before enrollment. Patients received tropisetron during one or more courses of chemotherapy (455 courses in total). Tropisetron was administered slowly intravenously as a single dose before the start of chemotherapy on day 1 and intravenously or by mouth the subsequent days as a single daily dose (median treatment duration: 5 days). Response to tropisetron per 24 hour period on the first 5 days of each chemotherapy course was graded as complete (absence of both nausea and vomiting), partial (one to four vomits and/or less than 5 hours of nausea), or failure. Overall complete response on day 1 was observed in 305 out of 455 chemotherapy courses (67%). The patients receiving intravenous chemotherapy (N = 92) had a 70% complete response rate and a 26% partial response rate on day 1, both for course 1 and course 2. The percentage of complete responders increased the subsequent days of the course. Emesis after day 1 was observed primarily during courses with the most emetogenic chemotherapy. No side-effects of tropisetron other than a single case of diarrhoea were documented in this study.
Adolescent↗
Control of nausea and vomiting by Navoban (tropisetron) in 131 children receiving cytotoxic chemotherapy.
One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer chemotherapy. The most common malignancy (in 49% of patients) was acute lymphocytic leukaemia. Patients received Navoban during one or more courses of emetogenic chemotherapy for a total of 455 courses administered intravenously or intravenously and intrathecally (IV + IT). Most patients (89%) had already received cytotoxic chemotherapy before enrollment for the trial. On Day 1, Navoban was administered slowly and intravenously as a single dose before the start of chemotherapy, or by mouth as a single daily dose on subsequent days (median treatment duration = 5 days). On the first 5 days of each course of chemotherapy, response to Navoban per 24-hour period was graded as: complete (absence of both nausea and vomiting), partial (1-4 vomits and/or less than 5 hours of nausea), or failure (more than 4 vomits and/or at least 5 hours of nausea). Ninety-six per cent of the intravenous chemotherapy group and 97% of the IV + IT chemotherapy group had a complete (70% and 55% respectively) or partial (26% and 42% respectively) response during the first 24-hour period of the first course in which Navoban was used. The second and subsequent courses yielded similar percentages. Delayed emesis was observed mainly during those courses employing the most emetogenic chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Optimal combination therapy with Navoban (tropisetron) in patients with incomplete control of chemotherapy-induced nausea and vomiting. The Belgian Navoban Group.
Even with the availability of potent and selective serotonin antagonists, chemotherapy-induced nausea and vomiting remain a major problem for many patients. This study aims to evaluate the benefit of combination therapy based on Navoban (tropisetron) in patients who had incomplete control of nausea and/or vomiting induced by chemotherapy when using Navoban as a single antiemetic agent. In their first chemotherapy course, 1072 patients planned to receive at least two identical cycles of emetogenic chemotherapy were treated with 5 mg Navoban once daily. To evaluate three treatments additional to the recommended 5 mg once-daily Navoban regimen during Course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of Course 1, a 2 x 2 x 2 factorial design was employed. Of these patients, 445 were centrally randomised to receive an additional dose of open-label dexamethasone (Day 1, 0.2 mg/kg i.v.; Days 2-6, 8 mg p.o.) and/or open-label alizapride (Day 1, 100 mg i.v. and 4 x 50 mg p.o.; Days 2-6, 4 x 5 mg p.o.) and/or double-blind Navoban--that is, doubling the dose to 10 mg once daily or placebo. Complete response rates during Course 1 (CRR, no nausea and no vomiting) were, for Day 1, 72% and for Days 1-6, 48%. More complete responders were observed when dexamethasone was added during Course 2, both on Day 1 (76% vs. 66%, p = 0.020) and on Days 1-6 (50% vs. 34%, p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
An optimized method for routine HLA-B27 screening using flow cytometry.
Flow cytometry and monoclonal antibodies are promising tools for HLA-antigen detection. Previous approaches have been hampered by the lack of a carefully standardized system for calibration and sample analysis. A new system for HLA-B27 screening was developed using a FACScan flow cytometer, software for automated calibration and analysis, calibration beads, and the anti-HLA-B27-FITC/anti-Leu4-PE (CD3) monoclonal antibodies. The median fluorescence channel result for the HLA-B27-FITC signal of CD3+ T lymphocytes is compared to a decision marker. Values lower than this threshold are read as HLA-B27 negative and those above are recommended for retesting with the classic microcytotoxicity assay on the presumption of HLA-B27 positivity. The anti-HLA-B27 antibody reacts with all six HLA-B27 subtypes and shows a weaker binding to HLA-B7. The screening test results were compared with those from the microcytotoxicity assay for HLA-typing in studies involving several European centers. The observed sensitivity was 100% (95% Cl:98.6-100) and the specificity was 97.4% (95% Cl: 96.4-98.3). Other performance studies verified the reproducibility and reliability of results obtained with the screening system.
Anticoagulants↗