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Biomedical subjects

V Breuil

Publications and source records attributed to V Breuil.

15 recordsLinked to original sources
PubMed2006

Pregnancy in rheumatology patients exposed to anti-tumour necrosis factor (TNF)-alpha therapy.

OBJECTIVES: Anti-tumour necrosis factor (TNF)-alpha therapies are considered category B drugs for pregnancy. Although sometimes prescribed to women of reproductive age, data in humans are limited with regard to safety for a developing fetus. The objectives of the present article are to report experience of anti-TNF-alpha use in pregnancy, and review the international literature. METHODS: Since 1999 the present authors have used anti-TNF-alpha (infliximab, etanercept, adalimumab) to treat patients with various chronic rheumatic conditions. All patients were prospectively followed during their treatment time and data were systematically collected. RESULTS: In a group of 442 patients treated with anti-TNF, three women with RA unexpectedly became pregnant One treated with etanercept chose a therapeutic termination at two and a half months, despite of any ultrasound anomaly, and satisfactory fetal growth. The other two patients (one with adalimumab exposure and one with etanercept exposure) delivered healthy infants. The following perinatal complications were observed: prematurity, neonatal jaundice, neonatal urinary Escherichia coli infection and adrenal congenital hyperplasia of probable hereditary origin. CONCLUSIONS: To date, there is no evidence that TNF-alpha antagonists are associated with embryo toxicity, teratogenicity or increased pregnancy loss. However, caution should be taken when anti-TNF agents are used during pregnancy, as human experience is still extremely limited, particularly in patients with rheumatic diseases among whom there are several alarming reports. The potential risk should be balanced against the known risks associated with DMARDs and steroid therapy. Large registries will be necessary before firm conclusions can be drawn.

Adalimumab↗
PubMed2006

Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies with concurrent B or C chronic hepatitis.

OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA) and concurrent chronic hepatitis B or C. METHODS: Records concerning 480 outpatients attending the Rheumatology Department of the University Hospital of Nice (France) for RA or SA were retrospectively reviewed for the duration of disease, treatment, serological status and biological data. RESULTS: Six relevant cases were identified: two of RA with chronic hepatitis B; one of SA with chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had received etanercept and one infliximab; two had been given adalimumab after an unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B were also given lamivudine. In none of the cases had changes in serum aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF-alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis B viral infection) appeared to be safe in that it had no effect on serum aminotransferases and/or viral load. However, repeated monitoring is necessary throughout the treatment period.

Adalimumab↗
PubMed2004

Pleural amyloidosis as the first sign of IgD multiple myeloma.

We describe a case of IgD myeloma with amyloid and plasmocytic pleural localisations. At the onset of the disease it mimicked rheumatoid arthritis, which can be the first presentation of both AL amyloidosis and multiple myeloma. Pleural effusion can happen first in IgD myeloma, but our observation is of interest in that it confirms the very rare possibility of pleural amyloid and plasmocytic localisations devoid of pleural effusion.

Amyloidosis↗
PubMed2002

[Etanercept--infliximab switch in rheumatoid arthritis 14 out of 131 patients treated with anti TNFalpha].

OBJECTIVE: Patients with severe rheumatoid arthritis and resistant to at least three DMARDS can benefit from anti-TNFalpha (tumor necrosis factor) therapy. In some patients, because of inefficacy or adverse events, treatment with one of the two available TNFalpha drugs (etanercept and infliximab) must be stopped. In this study, we explored the results in efficacy and tolerance of switching from one anti-TNFalpha to the other. PATIENTS: Between August 1999 and January 2002, we administered one of the two anti TNFalpha drugs to 131 patients: 67 patients received infiximab and 64 etanercept. RESULTS: Among the 67 patients treated with infliximab, 17 patients had to stop treatment. In 8 of them (4 allergies, 2 infections and 2 non responders) the switch from infliximab to etanercept was beneficial for 5 patients, 2 patients did not respond and 1 patient withdrew for personal reasons. Among the 64 patients treated with etanercept, 13 had to stop treatment. In 6 of them (2 adverse events, 4 failures) the switch from etanercept to infliximab was beneficial for 3 patients, 2 did not respond and 1 withdrew because of adverse events. CONCLUSION: In all, 14 patients with severe rheumatoid arthritis and treated by one of the two TNFalpha drugs (and in whom treatment was stopped because of adverse events or inefficacy) benefited from the switch to the other anti- TNFalpha, with excellent response in 8 out of 14 patients.

Aged↗
PubMed2001

Gonadal dysgenesis and bone metabolism.

Gonadal dysgenesis is defined as congenital hypogonadism related to abnormalities of the sex chromosomes. Because sex steroids play a central role in the acquisition and maintenance of bone mass, studies have been done to investigate bone status in patients with gonadal dysgenesis, particularly Turner's syndrome and Klinefelter's syndrome, which are the two most common types. The severe estrogen deficiency characteristic of Turner's syndrome (44, X0) is associated with a significant bone mass decrease ascribable to increased bone turnover, as shown by histological studies and assays of bone turnover markers. Estrogen therapy is followed by a significant bone mass gain and a return to normal of bone turnover markers, suggesting that it is the estrogen deficiency rather than the chromosomal abnormality that causes the bone mass deficiency, although abnormalities in the renal metabolism of vitamin D have been reported. Combined therapy with estrogens and growth hormone seems beneficial during the prepubertal period. In Klinefelter's syndrome (47XXY), serum testosterone levels are at the lower end of the normal range and dihydrotestosterone levels are low. Histological studies show depressed osteoblast function and a decrease in 5-alpha-reductase activity responsible for partial tissue resistance to androgens. Assays of bone turnover markers show evidence of increased bone turnover. The bone deficiency is most marked at the femoral neck and seems correlated with serum testosterone and estradiol levels. Androgen therapy has favorable effects on the bone only if it is started before puberty. Recent data suggest that estrogens may contribute to the development of demineralization in KS and that bisphosphonate therapy may be beneficial.

Androgens↗
PubMed1999

Occipitocervical fixation using hooks and screws for upper cervical instability.

OBJECTIVES: Occipitocervical fixation is used for the treatment of nontraumatic upper cervical instabilities. To date, plates have been fixed with screws or wires. However, these devices are not indicated in the treatment of patients with severe osteoporosis or in instances of significant thinning of the occipital bone. We performed a clinical trial of a new type of fixation that uses cervical interlaminar hooks and occipital claws with hooks or with screws (CCD type; Sofamor-Danek, Roissy, France) for the treatment of nontraumatic upper cervical instabilities. METHODS: Five women and one man ranging in age from 28 to 72 years (average age, 54 yr) were thus treated. The CCD type material had two rod plates and hooks allowing the proper placement of interlaminar and occipital claws. The occipital plate can also be directly screwed to the bone. Occipital hooks were used in four patients. The other two patients, who had occipitocervical congenital abnormalities that required an occipitocervical opening and an additional dural enlargement, underwent occipital screw fixation because of the previous opening of the foramen magnum. A cancellous iliac autograft allowed the usual fusion. RESULTS: No postoperative complications were observed, and all patients experienced significant improvement of their neck pain. Four patients had neurological symptoms. The condition of two patients improved, and the condition of the other two stabilized. CONCLUSION: This report confirms the interest of the CCD method to correct all types of upper cervical instabilities, even in cases of unusual thinning of the occipital bone or in osteoporotic states.

Adult↗
PubMed1999

Localization of rat cathepsin K in osteoclasts and resorption pits: inhibition of bone resorption and cathepsin K-activity by peptidyl vinyl sulfones.

We have localized cathepsin K in rat osteoclasts and within exposed resorption pits by immuno-fluorescence microscopy. Intracellular staining using an antibody raised against recombinant mouse cathepsin K was vesicular and uniformly distributed throughout the cell. Confocal microscopy analysis did not reveal an accumulation of cathepsin K containing vesicles opposing the ruffled border and the resorption lacuna. Exposed resorption pits exhibited a uniform distribution of cathepsin K, and no differences were observed between the edges and the centers of the pits. The immunostaining of resorption pits with anti-cathepsin K antibodies demonstrates that the protease is secreted into the sub-osteoclastic compartment. Cathepsin K-specific inhibition using peptidyl vinyl sulfones as selective cysteine protease inactivators reduced bone resorption by 80% in a dose-dependent manner at sub-micromolar concentrations. No reduction of bone resorption was observed at those low concentrations using a potent cathepsin L, S, B-specific inhibitor. That the inhibition of bone resorption can be attributed to cathepsin K-like protease inhibition was corroborated by the selective inhibition of the osteoclastic Z-Gly-Pro-Arg-MbetaNA hydrolyzing activity by the cathepsin K, L, S, B-inhibitor, but not by the cathepsin L, B, and S inhibitor. Z-Gly-Pro-Arg-MbetaNA is efficiently hydrolyzed by cathepsin K but only poorly by cathepsins L, S, and B. On the contrary, the intracellular hydrolysis of the cathepsin B-specific substrate, Z-Arg-Arg-MbetaNA, was prevented by both types of inhibitors. The identification of cathepsin K in resorption pits and the inhibition of bone resorption and intracellular cathepsin K activity by selective vinyl sulfone inhibitors indicate the critical role of the protease in osteoclastic bone resorption.

Animals↗
PubMed1998

Human osteoclast formation and activity in vitro: effects of alendronate.

Recent advances in technique have made it possible to study human osteoclast (OC) formation and activity in vitro. The object of the present study was to determine the effects of alendronate (ALN) on human OCs generated from precursors obtained from standard peripheral blood samples. Peripheral blood mononuclear cells from 14 postmenopausal women were cocultured with ST2 stromal cells on bone slices in the presence of 10(-7) M 1,25-dihydroxyvitamin D3, 10(-8) M dexamethasone, and 25 ng/ml human macrophage colony-stimulating factor. After 21 days, the cultures contained numerous OCs, which were characterized by multinuclearity, the presence of tartrate-resistant acid phosphatase, calcitonin and vitronectin receptors, and the ability to resorb substantial amounts of bone, which was inhibited by calcitonin. The percentage area of bone resorbed per slice was highly correlated (r = 0.89, p < 0.001) with the concentration of Type I collagen cross-linked C-telopeptides (CTx) released into the culture medium. When added to the medium, ALN inhibited bone resorption at concentrations < or =10(-7) M. At 10(-7) M, inhibition was achieved primarily by a reduction in OC activity without a marked effect on OC number. At the highest concentration studied (10(-5) M), both OC number and resorption were profoundly decreased. Overnight preincubation of bone slices in ALN, without further exposure to ALN, resulted in an inhibition of resorption that was similar to that seen when ALN was present in the medium throughout the entire culture period. We conclude that, except at very high concentrations, the predominant mechanism of action of ALN is to inhibit the activity of differentiated human OCs with little or no effect on recruitment. Interaction between the OC and ALN on the bone surface is an important component of the inhibitory mechanism. Measurement of CTx in tissue culture medium is a convenient method for assessment of bone resorption in human OC cultures and offers a number of advantages over morphometric analysis of the bone slice.

Aged↗
PubMed1996

Reactive arthritis induced by Strongyloides stercoralis.

Reactive arthritis induced by Strongyloides is exceedingly rare. A case in a 53-year-old man from the Guadeloupe (French Antilles) is reported. The outcome was rapidly favorable under thiabendazole therapy. The cycle of Strongyloides is reviewed, and the contribution of parasites to reactive arthritis in patients with genetic risk factors is discussed. Establishing the correct diagnosis is sometimes difficult but is essential in order to avoid inappropriate administration of corticosteroids that can lead to fatal, multivisceral dissemination of the parasite, particularly in patients with strongyloidiasis.

Animals↗
PubMed1992

[Prevention of pathological aging. The arterial hypertension example].

Studies conducted during the last decade have made it increasingly easier to distinguish between normal and pathological ageing. Previous studies on general populations had established a dogma: most of the major body functions, such as cardiac output, glomerular clearance, muscular strength, visual acuity and so forth, were supposed to decline with age. However, in recent studies on the effects of age on cardiac output all subjects with heart disease were excluded and as a result the negative correlation found between cardiac output and age disappeared, which shows that a phenomenon attributed to ageing was in fact caused by disease. This does not mean that there is no such thing as fundamental ageing, and indeed the mechanisms that maintain cardiac output are different in young and elderly subjects. These data are of more than theoretical interest, since it may be presumed that prevention, the instruments of which are already available in some fields, will modify the profile of ageing. The risk of arterial hypertension is not restricted to the classical cardiovascular diseases: it extends to other diseases, such as vascular dementia, which are potent factors of pathological ageing. Most of the controlled trials carried out in arterial hypertension have demonstrated that treating certain types of hypertension significantly reduces the morbidity and/or mortality of cardiovascular diseases. The specific properties of new antihypertensive drugs, such as angiotensin-converting enzyme inhibitors, open stimulating vistas on arterial ageing.

Adult↗