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At least 289 records · Page 16Linked to original sources
PubMed2002

[Multicentric reticulohistiocytosis with a 20-year follow-up ].

INTRODUCTION: Multicentric reticulo-histiocytosis also known as lipoid dermoarthritis is a rare systemic disease leading to a massive osteoarticular destruction and systemic complications. EXEGESIS: This case report is a 44 year old black woman who was first seen with a rheumatoid arthritis clinical presentation associated with the presence of rheumatoïd factor. Five years later the diagnosis has been reconsidered after skin nodules histological examination. After that the patient has been lost from the follow up clinic. After a twenty years evolution she presented a complex clinical picture including: a cutaneous syndrome with a non pruriginous and hyperchromic papulonodular rash on the arms and fore-arms; a very destructive polyarthritis with major handicap; and systemic manifestations like cardiomyopathy with heart failure. The heart failure treatment associated first corticosteroids and secondary chloroquine was successful. CONCLUSION: The rheumatoid factor presence should not avoid to consider the possibility of multicentric reticulohistiocytosis in case of polyarthritis associated with a papulonodular rash. Then skin biopsy must be performed. The severity of osteoarticular and systemic lesions require an early prescription of a treatment for which there is so far no compromise.

Adrenal Cortex Hormones↗
PubMed1989

Multicentric angiofollicular lymph node hyperplasia associated with a solitary osteolytic costal IgG lambda myeloma. POEMS syndrome in a South American (Paraguayan) patient.

We report the case of a 46-year-old woman presenting with a disorder characterized by the association of multicentric Castleman's disease, organomegaly, a solitary IgA lambda myeloma with lytic bone lesions but no serum monoclonal peak, peripheral neuropathy and skin changes. This unusual association resulted in an incomplete form of that peculiar multisystem syndrome described under a variety of names: Crow-Fukase syndrome, Shimpo's syndrome, Takatsuki's syndrome, PEP syndrome or POEMS syndrome. The possible relationship between localized and multicentric Castleman's disease with myeloma or extramedullary plasmacytoma on one hand and on the other hand with polyneuropathy and the other symptoms of the POEMS syndrome is discussed.

Bone Neoplasms↗
PubMed2005

Mortality and morbidity after surgery of mid and low rectal cancer. Results of a French prospective multicentric study.

BACKGROUND: The aim of the study was to assess both mortality and morbidity following resection of mid and low rectal cancers in a French prospective multicentric study. PATIENTS: From June to September 2002, consecutive patients undergoing resection for cancer of the mid- or lower rectum were prospectively included in a multicentric study. Both postoperative mortality and morbidity were recorded. Multivariate statistical analysis was performed in order to assess risk factors predictive of postoperative morbidity. RESULTS: 238 patients with a mean age of 66 +/- 13 years (range: 26-88) were included. Neoadjuvant radiotherapy was performed in 68% of the patients. Total mesorectal excision was performed in 218 patients (92%), of whom 151 (63%) had a sphincter saving procedure. Six patients died (2.5%). Overall postoperative morbidity rate was 43%, including anastomotic leakage (11%) and reoperation (5%). Mean hospital-in-stay was 20 +/- 16 days (range: 3191). Four independent risk factors of morbidity were found: perioperative fecal contamination (OR = 3.9 [1.1; 13.5]), mean operating time longer than 6 hours (OR = 4.5 [1.7; 12.1]), ASA score > 2 (OR = 3.2 [1.6; 7.9]), and smocking (OR = 3.3 [1.2; 8.9]). CONCLUSIONS: Resection of cancer involving the middle or lower rectum with sphincter saving procedures was possible in two-thirds of the patients and was associated with 2.5% mortality and 43% morbidity.

Aged↗
PubMed1997

The use of a systemic therapy checklist improves the quality of data acquisition and recording in multicentre trials. A study of the EORTC Soft Tissue and Bone Sarcoma Group.

The aim of this study was to verify whether the introduction of a systemic therapy checklist in the performance of multinational multicentre studies improves the quality of data acquisition and recording. We retrospectively analysed the results obtained through the use of this checklist in a study of the EORTC Soft Tissue and Bone Sarcoma Group. During the clinical trial, data were recorded in the hospital record with optional use of a predesigned EORTC Systemic Therapy Checklist. After completion of the study, 11 centres were monitored for the use of this checklist. Monitors were highly experienced medical oncologists. Items checked included all aspects of patient eligibility, drug administration, biochemical and haematological values, variables related to toxicities of treatment and response parameters. Data of 183 cycles given to 51 patients were checked. A total of 8983 items were checked. 91% of the data was reported correctly, 1% was missing and 6% was reported on the case record from (CRF) but could not be retrieved in the hospital record file. Compared with data obtained before the introduction of the checklist (68% correct, 4% incorrect, 0.1% missing and 28% on CRF but not in hospital files), these results show marked improvement generally. In centres where no Systemic Therapy Checklist was used, 85.9% of data were correct 2.8% incorrect, 0.7% missing and 10.6% only on CRF, which compares unfavourably with those where the Systemic Checklist was completely used (97.7% correct, 0.7% incorrect, 1% missing, 0.6% only on CRF). In addition the time required for data checking largely decreased by the use of the checklist-without this, a median of 3.5 cycles could be checked per hour, whilst if the checklist was used, this number increased to 6.5 cycles per hour. The use of a Systemic Therapy Checklist as an integral part of the hospital file for data recording in multicentre multinational trials is highly recommended and leads to a major improvement in data quality.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

One-hour paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicentre, phase II trial.

The aim of this phase II study was to determine the activity and toxicity of paclitaxel (administered by 1-h infusion) and carboplatin in advanced non-small cell lung cancer when used in a multicentre, community-based treatment setting. 100 chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer were treated between March 1995 and February 1996. All patients had Karnofsky performance status 70-100, measurable disease and adequate bone marrow, kidney and liver function. All patients received intravenous (i.v.) paclitaxel 225 mg/m2 by 1-h infusion followed immediately by carboplatin at a targeted area under the concentration time curve (AUC) of 6.0 using the Calvert formula. Courses were repeated every 21 days. Colony stimulating factors were not used routinely. 38 of 94 evaluable patients (40%) had objective responses to treatment (3 complete responses, 35 partial responses). An additional 32 patients had stable disease at initial re-evaluation. Weight gain during treatment was experienced by 47% of patients with objective response or stable disease. The median survival in this group of 100 patients was 8 months, with an actuarial 1-year survival of 42%. Leucopenia was common, but hospitalisation for treatment of neutropenia and fever occurred in only 3% of courses. Cumulative peripheral neuropathy was common, but usually appeared after the third or fourth course and was severe (grade 3) in only 15% of patients. Other grade 3 and 4 toxicity was uncommon. There was one treatment-related death due to sepsis. This large multicentre community-based phase II trial demonstrated the efficacy of paclitaxel and carboplatin combination chemotherapy in advanced non-small cell lung cancer. When paclitaxel is given by 1-h infusion, this regimen is easily administered in the outpatient setting.

Adult↗
PubMed2024

Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows.

BACKGROUND: Drug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis. METHODS: We conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing. FINDINGS: Between April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed. INTERPRETATION: This multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis. FUNDING: Unitaid.

Humans↗
PubMed2025

Rare variants and survival of patients with idiopathic pulmonary fibrosis: analysis of a multicentre, observational cohort study with independent validation.

BACKGROUND: Rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in idiopathic pulmonary fibrosis (IPF). We aimed to assess whether rare qualifying variants in monogenic adult-onset pulmonary fibrosis genes are associated with IPF survival. Using polygenic risk scores (PRS), we also evaluated the influence of common IPF risk variants in patients carrying the qualifying variants. METHODS: We identified qualifying variants in telomere and non-telomere genes using whole-genome sequences from individuals clinically diagnosed with IPF and enrolled in the Pulmonary Fibrosis Foundation Patient Registry (PFFPR), a large multicentre, observational cohort study (March 29, 2016 to June 15, 2018, n=888). We also derived a PRS for IPF (PRS-IPF) from known common sentinel IPF variants. The primary outcome was the association between qualifying variants and survival. The secondary outcome was the association between qualifying variants and PRS-IPF. We used logistic regression models adjusted for sex, age at diagnosis, and principal components of genetic heterogeneity to examine the mutual relationship of qualifying variants and PRS-IPF. The association between qualifying variants and PRS-IPF with survival was tested using Cox proportional hazard models adjusted for baseline confounders. Validation of the results was sought in data from an independent multicentre, prospective, observational cohort study of IPF in the UK (PROFILE, May 17, 2010 to Sept 5, 2017, n=472), and results were meta-analysed under a fixed-effects model. FINDINGS: We included 888 patients from PFFPR and 472 from PROFILE, totalling 1360 participants. In the PFFPR, carriers of qualifying variants in monogenic adult-onset pulmonary fibrosis genes were associated with lower PRS-IPF (odds ratio 1·79 [95% CI 1·15-2·81]; p=0·010) and shorter survival (hazard ratio 1·53 [1·12-2·10]; p=7·33 × 10-3). Individuals with the lowest PRS-IPF also had worse survival (1·61 [1·25-2·07]; p=1·87 × 10-4). These findings were validated in PROFILE and the meta-analysis of the results showed a consistent direction of effect across both cohorts. INTERPRETATION: We found non-additive effects between qualifying variants and common risk variants in IPF survival, suggesting distinct disease subtypes and raising the possibility of using PRS to guide sequencing prioritisation. Assessing the carrier status for qualifying variants and modelling PRS-IPF promises to further contribute to predicting disease progression among patients with IPF. FUNDING: Instituto de Salud Carlos III; Instituto Tecnológico y de Eenergías Renovables; Cabildo Insular de Tenerife; Fundación DISA; National Heart, Lung, and Blood Institute of the US National Institutes of Health; and UK Medical Research Council.

Humans↗
PubMed2003

Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility.

BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78-94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH. METHODS: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 micromol L(-1) in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min. RESULTS: After bolus administration of 4-chloro-m-cresol, 75 micromol L(-1), 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 micromol L(-1). Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH. CONCLUSIONS: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

Biopsy↗
PubMed2000

Fate of multicentric and ring chromosomes induced by a new gametocidal factor located on chromosome 4Mg of Aegilops geniculata.

A new gametocidal (Gc) factor was identified on chromosome 4Mg of Aegilops geniculata Roth. When transferred to Chinese Spring wheat, monosomic and disomic Triticum aestivum-Ae. geniculata chromosome 4Mg addition plants undergo regular first and second meiotic divisions. Male gametogenesis in disomic 4Mg addition plants also is normal. However, chromosome breakage and anaphase bridges were observed at ana/telophase of the first (29%) and second (11%) pollen mitosis in monosomic 4Mg addition plants. Gc-induced multicentric and ring chromosomes can be transmitted to the offspring and initiate breakage fusion bridge (BFB) cycles in dividing root tip meristem cells of the derived sporophytes. The fate of multicentric and ring chromosomes was analyzed in root meristems at different time intervals after seed germination. The majority of the BFB cycles ceased about 32 days after germination. Broken chromosome ends were healed either by the fusion of a centric and an acentric fragment forming terminal translocation chromosomes or as deficiencies or telocentric chromosomes. Lack of cytologically detectable telomeric repeats at the stabilized newly broken termini suggests that chromosome healing by addition of telomeric repeats may be a gradual process.

Centromere↗
PubMed2002

Efficacy of a prototype brush head for a powered toothbrush. A multicentre study.

PRIMARY OBJECTIVE: To evaluate a multicentre clinical trial design for testing powered toothbrushes. SECONDARY OBJECTIVE: To compare the efficacy of a prototype brush head (N2.3) for the Philips Jordan Sensiflex 2000 powered toothbrush (PTB) to that of Braun Oral-B D15 PTB in removing dental plaque MATERIAL AND METHODS: 137 volunteers (ages 18-25 years) were recruited to this 3-centre, 2-week, 2-group, 2-treatment, single-blind trial. Plaque was recorded at screening and again 14 days later at baseline. Stratification of subjects, for gender and screening PI, occurred at baseline. Subjects were then asked to abstain from all oral hygiene measures for 48 h followed by a supervised episode of brushing for 3 min with the allocated PTB. The allocated PTB was used at home for the next 12 days before a second abstinence from all oral hygiene measures for the 48 h prior to a second supervised brushing episode. Plaque levels were scored using a modification of the Quigley & Hein plaque index (PI) at full mouth (FM), interproximal (IP) and smooth surfaces (SS). To enable the means of the within subject differences (pre to postbrushing) to be compared between groups PIs were recorded before and after the supervised brushing episodes, differences between centres, groups and visits were examined. RESULTS: No significant differences in PI between groups at screening, baseline or prior to the supervised brushings were detected (P > 0.05 anova). The results of the analysis of variance showed there to be a highly significant difference (P < 0.001) between brushing groups, but, significant differences between centres (P < 0.001) and a significant interaction effect between centre and brushing group (P < 0.001) was also detected. Therefore the difference between groups was not present at all three centres. Further examination of the single centre data showed there to be greater levels of plaque removed by the N2.3 compared to the D15 (FM reduction in PI 1.95 vs. 1.13, respectively) at centre 3 in contrast to the other two centres where no difference was detected. The precise reason for these differences could not be established. CONCLUSIONS: A multicentre study design is applicable for evaluating PTBs but a minimum of 3 centres should be included so that differences between centres can be identified. The prototype brush head N2.3 for the Philips Jordan Sensiflex 2000 PTB has comparable plaque removal efficacy to the Braun Oral-B D15 PTB at FM, IP and SS sites.

Adolescent↗
PubMed2000

Multicentre study for the development of an in vivo model to evaluate the influence of topical formulations on irritation.

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short-time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2x a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5-day protocol. Furthermore, in spite of the expected inter-centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter-instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres.

Administration, Topical↗
PubMed2001

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.

Amino Acid Sequence↗
PubMed2006

Hydrogen multicentre bonds.

The concept of a chemical bond stands out as a major development in the process of understanding how atoms are held together in molecules and solids. Lewis' classical picture of chemical bonds as shared-electron pairs evolved to the quantum-mechanical valence-bond and molecular-orbital theories, and the classification of molecules and solids in terms of their bonding type: covalent, ionic, van der Waals and metallic. Along with the more complex hydrogen bonds and three-centre bonds, they form a paradigm within which the structure of almost all molecules and solids can be understood. Here, we present evidence for hydrogen multicentre bonds-a generalization of three-centre bonds-in which a hydrogen atom equally bonds to four or more other atoms. When substituting for oxygen in metal oxides, hydrogen bonds equally to all the surrounding metal atoms, becoming fourfold coordinated in ZnO, and sixfold coordinated in MgO. These multicentre bonds are remarkably strong despite their large hydrogen-metal distances. The calculated local vibration mode frequency in MgO agrees with infrared spectroscopy measurements. Multicoordinated hydrogen also explains the dependence of electrical conductivity on oxygen partial pressure, resolving a long-standing controversy on the role of point defects in unintentional n-type conductivity of ZnO (refs 8-10).

Journal Article↗
PubMed2002

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma.

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.

Aged↗
PubMed2006

Post-operative sequential high-dose chemotherapy with haematopoietic stem cell support as front-line treatment in advanced ovarian cancer: a phase II multicentre study.

In spite of multimodal management including aggressive surgery and chemotherapy, the prognosis of advanced ovarian cancer (AOC) remains poor. Multicycle high-dose chemotherapy (HDC) with haematopoietic stem cell (HSC) support has been shown to be a promising procedure in various cancers including AOC. We conducted a phase II multicentre study to evaluate feasibility, toxicity and efficacy of post-operative front-line sequential HDC with HSC support in AOC. Thirty four patients with stage IIIC/IV received a post-operative sequential combination of high-dose cyclophosphamide/epirubicin (D1, D21) with HSC harvesting, high-dose carboplatin (D42, D98) followed by HSC infusion, and dose-dense paclitaxel (D63, D77, D119, D133). Rh-G-CSF (filgrastim) was administered following all cycles. Primary endpoint was pathological complete response rate (pCR). Thirty patients received at least 7 of the scheduled 8 cycles. Haematological toxicity was significant but manageable. Grade 3/4 extra-haematopoietic toxicities were relatively uncommon and reversible. No toxicity-related death was observed. The observed pCR was 37% and did not reach the initial endpoint. Post-operative front-line sequential HDC in AOC is feasible and safe in a multicentre setting. The observed pCR does not support a clear advantage over conventional treatment. This approach remains an experimental strategy to further optimise and validate.

Adult↗
PubMed1999

A multicentre evaluation of the laser assisted ratio analyser (LARA): a novel device for measurement of 13CO2 in the 13C-urea breath test for the detection of Helicobacter pylori infection.

BACKGROUND: The laser assisted ratio analyser (LARA) was developed as a novel device to measure 13CO2 in the urea breath test for the detection of H. pylori infection. The analyser was tested in a prospective multicentre study in 444 patients in North America (Phase 1) followed by second study involving 160 patients (Phase 2). METHODS: Patients undergoing endoscopy for clinical indications had antral and gastric biopsies taken for histological examination, culture and CLO test. One hour after endoscopy, a baseline breath sample was obtained, 100 mg of 13C-urea were ingested and breath samples were obtained at 30 and 60 min post ingestion. Data obtained with the LARA were compared with the results of culture, rapid urease testing and central pathology in two different combinations {reference standards}. The study was conducted in two phases: in Phase 2, a modification was made to the LARA that improved the removal of water vapour from the breath sample. RESULTS: In Phase I, data from 331 patients were analysed using a cut off of (delta) 7.8 +/- 0.8, the sensitivity of the method was 91.7% and the specificity was 86.5%, using the reference standard of 2 of 3 tests (CLO, culture or histology) being positive. Positive and negative predictive values were, respectively, 85.2% and 92.5%. In Phase 2 of the study, 160 patients were enrolled and 141 patients were analysed using the same standards. We used the same reference standards but with a cut off of (delta) 6.1 +/- 0.6. The sensitivity and specificity increased to 96.8% and 98.6%, respectively. Positive and negative predictive values were, respectively, 98.4% and 97.3%. The detection rates for H. pylori were similar in patients with peptic ulcer or H. pylori associated gastritis. CONCLUSIONS: The LARA provides an accurate non-invasive means of detecting 13CO2 in the 13C-urea breath test for H. pylori in a multicentre clinical environment that compares well with invasive 'gold standard' methods.

Adolescent↗
PubMed2000

Triple therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer disease: results of a multicentre study in South-East Asia. South-East Asia Multicenter Study Group.

BACKGROUND: The efficacy of proton pump inhibitor based triple therapy in patients from South-East Asia, where metronidazole resistance is reportedly high, has not been formally assessed in randomized, multicentre trials. AIM: To compare the eradication rates of Helicobacter pylori, ulcer healing rates and side-effects of three regimens of omeprazole triple therapy in patients with duodenal ulcer from South-East Asia and to study the impact of metronidazole resistance. METHODS: A single blind, randomized parallel group, comparative multicentre study. A total of 246 patients from 15 centres in four South-East Asian countries were randomized to receive OAC (omeprazole 20 mg b.d., amoxycillin 1 g b. d., clarithromycin 500 mg b.d.), OAM (omeprazole 20 mg b.d., amoxycillin 1 g b.d., metronidazole 400 mg b.d.) or OMC (omeprazole 20 mg b.d., metronidazole 400 mg b.d., clarithromycin 500 mg b.d.) for 7 days. After triple therapy, the patients were further randomized to receive either omeprazole or placebo for 7 days. Upper gastrointestinal endoscopy was performed before treatment and 4 weeks after treatment. Biopsies for culture and for histopathological examination for H. pylori were taken from corpus and antrum before treatment and 4 weeks after treatment. RESULTS: The eradication rates were intention-to-treat/per protocol (95% CI): OAC 87% (79-94%)/94% (89-100%); OAM 80% (70-89%)/91% (83-98%); OMC 85% (77-93%)/94% (88-100%). The difference in eradication rates between the three groups was not statistically significant (P=0.419). Pre-treatment metronidazole resistance, was found in 34% of isolates and was a significant prognostic factor in patients receiving OAM (odds ratio 5.26) but not in patients receiving OAC or OMC. CONCLUSIONS: All three treatment regimens were safe, well tolerated and highly effective for eradication of H. pylori and ulcer healing. Pre-treatment metronidazole resistance reduced the efficacy of OAM but did not affect the efficacy of OMC.

Adolescent↗
PubMed2000

Multicentre study of thyroid nodules in patients with Graves' disease.

BACKGROUND: The association of Graves' disease with thyroid nodules and thyroid carcinoma is rarely reported. The incidence seems to be increasing according to recent literature. The aim of this multicentre study was to review patients who had surgery for Graves' disease associated with thyroid nodules, and to evaluate the risk of thyroid carcinoma. METHODS: A retrospective study was made of 557 consecutive patients who underwent operation for Graves' disease between 1991 and 1997 in five endocrine surgery departments. Each patient underwent clinical, biochemical, ultrasonographic and scintigraphic evaluation. None of the patients had had previous radioactive iodine therapy or external irradiation. Surgery consisted of either a subtotal or total thyroidectomy. RESULTS: Nodules were observed before operation in 140 patients (25.1 per cent). Thyroid carcinoma was diagnosed in 21 patients (15.0 per cent), always inside a nodule. The incidence of thyroid carcinoma associated with Graves' disease was 3.8 per cent (21 of 557 patients): 20 papillary and one follicular carcinoma. The carcinoma was multifocal in two patients. Tumour diameter ranged from 2 to 25 mm. A nodule was palpable in four patients. CONCLUSION: This multicentre study of patients having thyroidectomy for Graves' disease showed that 3.8 per cent had a carcinoma; the rate of carcinoma in cold nodules was 15.0 per cent. Surgery should be advised in any patient with Graves' disease and a thyroid nodule; the operation should be total thyroidectomy.

Adolescent↗