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Biomedical subjects

B Combe

Publications and source records attributed to B Combe.

At least 73 records · Page 4Linked to original sources
PubMed1994

Methotrexate concentrations in synovial membrane and trabecular and cortical bone in rheumatoid arthritis patients.

OBJECTIVE: To determine methotrexate (MTX) concentrations in the synovial membrane (SM) and cortical and trabecular bone of rheumatoid arthritis (RA) patients. METHODS: Ten RA patients (9 women, 1 man; mean +/- SD age 49.2 +/- 10.6, mean disease duration 13.2 +/- 9.9 years) undergoing surgical procedures for rheumatoid articular lesions participated in this study. Mean +/- SD MTX treatment duration was 26.4 +/- 21.3 months. The day preceding surgery, 10 mg of MTX was administered intramuscularly. During surgery, a mean +/- SD of 19.7 +/- 2.6 hours after MTX administration, SM, bone fragments, and blood were collected simultaneously. MTX was assayed by fluorescence polarization immunoassay in plasma and tissues. RESULTS: The mean +/- SD plasma concentration was 0.0252 +/- 0.01 nmoles/ml at the time of tissue sampling. The mean MTX concentration in SM was 0.285 +/- 0.159 nmoles/gm. The mean MTX concentrations in trabecular and cortical bone were 0.292 +/- 0.164 and 0.286 +/- 0.126 nmoles/gm, respectively. CONCLUSION: After intramuscular administration, high MTX concentrations are found in SM and cortical and trabecular bone of RA patients.

Adult↗
PubMed1994

[The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arthritis].

Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug.

Adult↗
PubMed1993

Increased percentage of CD3+, CD57+ lymphocytes in patients with rheumatoid arthritis. Correlation with duration of disease.

OBJECTIVE: To determine whether a small CD3+ lymphocyte population expressing 110-kd CD57 antigens (HNK1) is expanded in patients with rheumatoid arthritis (RA), as it is in patients who have undergone bone marrow transplantation and patients with the acquired immunodeficiency syndrome, and to investigate whether it is involved in the pathogenesis of RA. METHODS: The phenotype of CD3+, CD57+ lymphocytes was analyzed by flow cytometry, and correlations between the percentage of these cells in the blood and various clinical and biologic parameters were investigated. RESULTS: The percentage of CD3+, CD57+ lymphocytes was increased in RA patients compared with controls. These lymphocytes expressed T cell receptor alpha/beta. Eighty percent expressed the CD8 accessory molecule, and 20% expressed the CD4 accessory molecule. The leukocyte common antigen CD45RA isoform was expressed by these CD3+, CD57+ lymphocytes in blood. The HLA-DR antigen was expressed in synovial fluid but not in blood. Finally, the percentage of these lymphocytes in the blood correlated with the duration of RA. CONCLUSION: The expansion of the CD3+, CD57+ lymphocyte population and their activation in the synovial fluid of RA patients suggest that these cells are involved in the inflammatory process.

Adult↗
PubMed1993

Investigation of the HLA component involved in rheumatoid arthritis (RA) by using the marker association-segregation chi-square (MASC) method: rejection of the unifying-shared-epitope hypothesis.

In order to investigate the HLA component involved in rheumatoid arthritis (RA), we tested genetic models by the marker association-segregation chi 2 (MASC) method, using the HLA genotypic distribution observed in a sample of 97 RA patients. First we tested models assuming the involvement of a susceptibility gene linked to the DR locus. We showed that the present data are compatible with a simple model assuming the effect of a recessive allele of a biallelic locus linked to the DR locus and without any assumption of synergistic effect. Then we considered models assuming the direct involvement of the DR allele products, and we tested the unifying-shared-epitope hypothesis, which has been proposed. Under this hypothesis the DR alleles are assumed to be directly involved in the susceptibility to the disease because of the presence of similar or identical amino acid sequences in position 70-74 of the third hypervariable region of the DRBI molecules, shared by the RA-associated DR alleles DR4Dw4, DR4Dw14, and DR1. This hypothesis was strongly rejected with the present data. In the case of the direct involvement of the DR alleles, hypotheses more complex than the unifying-shared-epitope hypothesis would have to be considered.

Adult↗
PubMed1993

[A comparative controlled trial of 2 administration modalities of tiopronin in rheumatoid arthritis].

Thiopronin is a second line drug for rheumatoid arthritis with proven efficacy in controlled trials versus a placebo, D-penicillamine, or gold salts. This 4-month study was aimed mainly at comparing the efficacy and safety of two thiopronin regimens, i.e., 1 g/d for 2 weeks followed by 1.5 g/d (regimen A) versus 0.5 g/d for 1 month, 0.750 g/d during the second month, then 1 g/d (regimen B). Because earlier investigations have suggested a role for copper in the activity of D-penicillamine, a secondary goal of this study was to evaluate whether the clinical effects of thiopronin were related to changes in serum copper and ceruloplasmin levels. Among the 61 included patients, 32 received regimen A and 29 regimen B. The primary efficacy criterion was the physician's overall efficacy assessment. Efficacy was rated good or excellent in 65.5% of regimen A patients and 55.6% of regimen B patients. Eighteen of the 32 regimen A patients and 23 of the 29 regimen B patients experienced at least one adverse event (p = 0.055). Failure to tolerate the drug required withdrawal in 12 of the 32 regimen A patients (37.5%) versus 11 of the 29 regimen B patients (37.9%). Declines in serum copper and ceruloplasmin levels were not correlated with treatment efficacy or tolerance. These findings, together with previously reported data, suggest that treatment should be initiated in a dosage of 1 g/day and that thiopronin-related adverse events are not dose-dependent.

Adult↗
PubMed1993

Focal myositis: a localized form of polymyositis?

We describe an additional case of focal myositis presenting as a painful pseudotumor of the lower leg. Surgical biopsy showed typical features of myositis; the disease improved spontaneously, without clinical or biological abnormalities. Focal myositis can remain a localized process, but in some cases it can become an authentic polymyositis. These generalized forms are associated early with elevated erythrocyte sedimentation rate and/or muscular enzymes.

Adult↗
PubMed1993

[Cerebral thrombophlebitis disclosing Behçet disease. Value of high resolution MRI].

A 21-year-old male of Moroccan descent was admitted for inflammatory polyarthralgia and monoarthritis of the left knee. The patient reported a history of recurrent isolated aphthous ulcerations of the oral cavity. He was found to be positive for the HLA B5 antigen. The other investigations for Behçet's disease were negative. During hospitalization, headache responsible for insomnia developed. Neurologic evaluation was normal, as well as funduscopy and spinal tap findings. CT scan images were suggestive of cerebral thrombophlebitis. Magnetic resonance imaging (MRI) disclosed an old thrombosis of the right transverse sinus. Time-of-flight MRI (MRI with sequences adapted to the study of vessels) evidenced recent thrombophlebitis of the left transverse sinus. Cerebral angiography fully confirmed MRI findings. Treatment with a corticosteroid and an anticoagulant was successful. Final diagnosis was Behçet's disease. Subsequently, the patient developed additional features of the disease, including hypersensitivity to pinprick, retinal vasculitis, and erythema nodosum. This case is interesting for two reasons: cerebral thrombophlebitis in Behçet's disease can manifest as localized headache. It occurs in 6 to 13% of patients. Early diagnosis and treatment are essential; MRI features of cerebral thrombophlebitis were confirmed by the cerebral angiogram. MRI established that the thrombophlebitis was of recent onset. MRI may be appropriate as the initial investigation in patients with suspected cerebral thrombophlebitis.

Adult↗
PubMed1993

Accelerated nodulosis and systemic manifestations during methotrexate therapy for rheumatoid arthritis.

OBJECTIVES: Methotrexate is successfully used in the treatment of arthritis but little is known about its effects on extra-articular manifestations of rheumatoid arthritis. We focused this work on the incidence and clinical course of extra-articular manifestations during long-term treatment with methotrexate. METHODS: The effect of methotrexate on extra-articular manifestations was investigated in 176 patients with rheumatoid arthritis who had obtained, in a prospective study, a good clinical response to methotrexate (10 mg/week) taken for 33 months (range 4-68). RESULTS: Before taking methotrexate, 44 patients (25.1%) had extra-articular manifestations: nodules (n = 40) and vasculitis (n = 9). With methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and worsened in 10 (23%). Among the 132 patients without extra-articular manifestations before methotrexate therapy, 15 (11%) developed accelerated nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a pericarditis during methotrexate therapy. Extra-articular manifestations occurred between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was positive in 88% of the patients with extra-articular manifestations. No relationship was noted between extra-articular manifestations and HLA type or antinuclear antibodies. In 3 out of 4 patients who developed accelerated nodulosis while taking methotrexate, the addition of hydroxychloroquine (400 mg/day) resulted in a significant reduction in the number and size of the nodules within 3 to 10 months after starting combined therapy. CONCLUSION: These data suggest that methotrexate is not effective in the treatment of extra-articular manifestations in rheumatoid arthritis and that nodulosis may occur in about 11% of patients taking methotrexate therapy for rheumatoid arthritis. The combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis that needs to be evaluated.

Adolescent↗
PubMed1993

Influence of methotrexate on the frequency of postoperative infectious complications in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the influence of methotrexate (MTX) on the frequency of postoperative complications in patients with rheumatoid arthritis (RA). METHODS: We conducted a randomized unblinded prospective study in 64 patients with RA treated with MTX and who underwent orthopedic surgery. Two groups of patients were constituted: in Group A (32 patients), MTX was interrupted 7 days before the surgery; in Group B (32 patients), MTX was not discontinued. RESULTS: Fifty surgical procedures were performed in Group A and 39 procedures in Group B. No postoperative infection was observed in any group. A prolonged wound healing was noticed in 6 cases in Group A and in 4 cases in Group B (not significant). CONCLUSION: We suggest that the interruption of MTX is not required in patients with RA when an orthopedic surgical treatment is planned. However a large prospective study is needed to make a definitive conclusion.

Adult↗
PubMed1992

T cell receptor gamma variable gene locus polymorphism in patients with rheumatoid arthritis.

OBJECTIVE: We sought new susceptibility markers for rheumatoid arthritis (RA) among the T cell receptor gamma (TCR gamma) genes. METHODS: We analyzed restriction fragment length polymorphisms (RFLP) of the first variable subgroup of TCR gamma genes in a group of French control subjects and a group of French RA patients. RESULTS: No significant difference in Eco RI RFLP was found between the 2 study populations: Allele frequencies were virtually identical. There was no polymorphism using Hind III. CONCLUSION: These results exclude TCRV gamma I polymorphism as a disease susceptibility marker in RA.

Arthritis, Rheumatoid↗
PubMed1992

Evaluation of the efficacy and safety of oral tiludronate in Paget's disease of bone. A double-blind, multiple-dosage, placebo-controlled study.

OBJECTIVE: To assess the optimal dosage of oral tiludronate in Paget's disease of bone. METHODS: We studied 149 patients with Paget's disease, in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to 1 of 5 therapeutic groups: a daily dose of 100 mg, 200 mg, 400 mg, or 800 mg of oral tiludronate, or a placebo. Treatment was for 3 months, followed by 3 months of placebo-controlled followup. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured monthly, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale and a global pain index. RESULTS: Statistical analysis revealed that beginning at a dosage of 200 mg/day, there was a direct dose-dependent effect on the reduction of SAP and OH/Cr levels. Reduction of SAP levels was clinically significant at a dosage of 400 mg (44.9 +/- 4.2% reduction at 90 days and 49.2 +/- 4.5% at 180 days, mean +/- SEM) and at 800 mg (53.4 +/- 5% at 90 days and 59.3 +/- 4.6% at 180 days). There was a significant reduction in pain in all groups, including the group taking placebo. In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain (versus placebo). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance of all 5 regimens was good. Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800-mg daily dose investigated. CONCLUSION: Because of its significantly better antiresorptive effects and greater analgesic properties (compared with lower dosages), combined with the excellent clinical and biochemical tolerance, the 800-mg daily dose of tiludronate appears to be optimal for the treatment of Paget's disease of bone.

Administration, Oral↗
PubMed1992

IX 207-887 in rheumatoid arthritis. A double-blind placebo-controlled study.

OBJECTIVE: To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2-b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. METHODS: A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. RESULTS: Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between-group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo-treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008). CONCLUSION: The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow-acting drug for use in rheumatoid arthritis.

Adult↗
PubMed1992

Analysis of monoclonal rheumatoid factors obtained from the B-cell repertoire in rheumatoid arthritis.

We have sought to determine whether rheumatoid factors (RF) produced in rheumatoid arthritis (RA) were different from physiological RF produced in normal, healthy adults. RF-secreting clones were established following Epstein-Barr virus (EBV) stimulation of peripheral blood lymphocytes. Ten RF-secreting clones were established from seven RA patients and 16 from six healthy controls. All monoclonal RF (MRF), except two in each group, were monoreactive and ten of these were shown to have low to medium affinity for IgG,Fc, irrespective of their origin. A majority (74%) of the MRF bound to protein A, indicating that genes of the VHIII family were preferentially used for synthesizing these autoantibodies. The expression of cross-reactive idiotypes (CRI) by the MRF did not allow distinction between those derived from RA patients and controls. The VHI-associated CRI G8 and VHIII-associated CRID12 were expressed at low frequency in both panels of RF. These CRI have been shown to be expressed at high frequency in RF paraproteins. However, the idRQ idiotype was expressed within both panels of RF. A possible distinction between polyreactive and monoreactive MRF appeared to be light chain usage since all (four) polyreactive RF used lambda chains while the normal kappa/lambda ratio was observed for monoreactive RF. The frequency of EBV-activated cells secreting IgM bearing CRI or secreting RF was determined and showed that CRI expression occurred with a higher frequency than did RF, suggesting a dissociation between CRI expression and RF activity.

Animals↗
PubMed1992

Non-Hodgkin's lymphoma associated with primary Sjögren's syndrome.

OBJECTIVES: To evaluate the prevalence, the incidence and clinical presentation of non-Hodgkin's lymphoma associated with primary Sjögren's syndrome. METHODS: Sixty-two patients with primary Sjögren's syndrome were analyzed retrospectively in an open investigation. RESULTS: Of 62 patients with primary Sjögren's syndrome, 4 of them (6.4%) developed non-Hodgkin's lymphoma (6.9 cases per 1000 per year). All of them were women. Non-Hodgkin's lymphoma always developed after the onset of primary Sjögren's syndrome with a time interval ranging from 3 to 27 years. Pathological findings showed two diffused mixed small and large cell cleaved lymphomas and two diffused large cell cleaved lymphomas. Three cases had extra-nodular localizations. All of these 4 patients are still alive and in complete remission 2 to 8 years after the diagnosis of non-Hodgkin's lymphoma. CONCLUSION: This study confirms the association of non-Hodgkin's lymphoma in primary Sjögren's syndrome. These non-Hodgkin's lymphomas frequently had extra-nodal localizations. Good sensitivity to treatment, when necessary, provided good prognosis.

Adult↗
PubMed1992

[Rheumatoid aortic insufficiencies: severity of the prognosis].

Rheumatoid aortic incompetence is infrequent, with only 43 cases published in the literature. Seven additional patients (5 females and 2 males) with rheumatoid arthritis (RA) and aortic incompetence are reported herein. All seven patients had seropositive RA with severe joint disease and extraarticular manifestations (nodules, cutaneous vasculitis, multiple neuritis). Development of aortic incompetence was unrelated to age or duration of RA. The aortic disease was diagnosed upon the development of sudden heart failure (pulmonary edema) in three patients and during a routine evaluation in the other four. The course was extremely severe with a fatal outcome in five patients, of whom the youngest was only 24. Only one patient had valve replacement surgery; however, this patient died 8 days after the procedure. Mean survival in the seven patients was 20 months (range 7-56) from diagnosis and 11 months (range 1-28) from the first manifestation of heart failure. Histologic studies done in the only patient who had surgery demonstrated a rheumatoid granuloma in the pericardium and lymphocytic infiltrates in the pericardium and aortic valve.

Adolescent↗