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Biomedical subjects

E Vignon

Publications and source records attributed to E Vignon.

At least 127 records · Page 7Linked to original sources

Screening of degradative enzymes from articular cartilage in experimental osteoarthritis.

Sixteen rabbits were killed 12 weeks after sectioning of the right knee anterior cruciate ligament. The left unoperated knee served as a control. The surface area of fibrillated cartilage from femoral condyles and tibial plateau was evaluated and expressed as a percentage of articular surfaces area. Cartilage from the femoro-patellar surfaces was homogenized for the quantification of several degradative activities, based on the release of digested products. Acid phosphatase, several glycosidases and neutral protease activity from the operated joint cartilage were significantly elevated, while collagenolytic activity was unmodified. The percentage of fibrillated cartilage correlated positively with arylsulfatase, glucosidase and neutral protease but negatively with mannosidase and fucosidase. The results may be consistent with the hypothesis of a sequential degradative process leading to cartilage destruction.

Animals↗

Histological cartilage changes in a rabbit model of osteoarthritis.

The anterior cruciate ligament was severed in the right knee of 36 rabbits which were then killed 12 weeks after surgery. Changes in water content and fixed charge density were correlated with the surface area of induced cartilage fibrillation. Histological changes including cartilage hypertrophy, reduced cell density, matrix alterations, cystic lesions, and enlarged perichondrocytic lacunae were found to precede cartilage fibrillation. The observed histological changes are in agreement with an enzymatic degradation of articular cartilage in osteoarthritis.

Animals↗

Kinetics of allopurinol and oxipurinol after chronic oral administration. Interaction with benzbromarone.

Previous studies have described a pharmacokinetic interaction between probenecid, a uricosuric drug, and oxipurinol, the major metabolite of allopurinol. In single dose studies, no interaction was found to occur between benzbromarone, another uricosuric agent, and oxipurinol. A cross over study was conducted in 12 volunteers to compare the kinetics of allopurinol and oxipurinol following treatment for 7 days with allopurinol alone or combined with benzbromarone 20 or 100 mg. The pharmacokinetic parameters of allopurinol were not modified by the uricosuric therapy, but those of oxipurinol were markedly altered by concurrent administration even of the lower dose of benzbromarone; the average plasma level fell by 30% and the renal elimination rate was increased by 50%. A parallel increase in the renal elimination rate of uric acid was observed (significant only with the higher dose of benzbromarone) and a positive linear correlation between the fractional excretion of uric acid and that of oxipurinol was established.

Adult↗

[Quantitative study of experimental osteoarthritic lesions in the rabbit. Value for the study of anti-osteoarthritis drugs].

Section of the anterior cruciate ligament of the right knee was performed in 20 rabbits which were sacrificed 3 months later. During that time, 10 animals were treated with a proteino-polysaccharide compound. The importance of cartilage destruction was evaluated by measuring the articular surfaces and the surface of the fissured areas using an automatic image analyzer; osteophytes were measured by a volumetric study. The percentage of the fissured areas appears to be without correlation with the osteophytosis, the increase of the water content or the decrease of glycosaminoglycans following the procedure. In animals which were treated, the extent of the fissure is significantly reduced but the biochemical and histometric modifications are not too different from those of the reference group.

Animals↗

[Hemodynamic effects of 2 different doses of midazolam in combination with fentanyl for induction of anesthesia in surgery of the abdominal aorta].

The haemodynamic effects of anaesthetic induction with midazolam, fentanyl and pancuronium bromide were studied in two groups of patients undergoing abdominal aortic surgery: group A (10 patients receiving 0.2 mg X kg-1 midazolam) and group B (9 patients receiving 0.3 mg X kg-1 midazolam). Haemodynamic parameters were measured before induction after fluid loading and 15 min after induction. Heart rate, mean right atrial pressure, systemic and pulmonary vascular resistances, mean pulmonary wedge pressure and right ventricular stroke work index remained steady. On the other hand, mean arterial and pulmonary arterial pressures, systolic, cardiac and left ventricular stroke work indices fell significantly in both groups. However there was no statistically significant difference between the two groups.

Anesthesia, General↗

Bacterial endocarditis presenting as acute vertebral osteomyelitis: 14 cases.

Association between bacterial endocarditis (BE) and vertebral osteomyelitis (VO) has infrequently been noted. In a retrospective analysis of BE (280 cases) and VO (150 cases) 14 cases were found to have this association. There were 12 males and 2 females, ages ranging from 39 to 72 years, mean age 56.6. Blood cultures were positive for Streptococcus viridans (6 cases). Str. faecalis (4 cases), staphylococcus (2 cases), Gram negative bacteria (1 case). Organism was not isolated in one case. Fever and severe back pain antedate the diagnosis of VO 3.5 and 2.5 months. X rays films of the spine and bone scans (4 cases) revealed lumbar (6 cases) or cervical (4 cases), or dorsal (3 cases) or combined cervical and dorsal (1 case) locations. History of murmur (4 cases) and development of mitral (8 cases) or aortic (4 cases) or combined mitral and aortic (2 cases) insufficiencies were consistent with concomitant BE. Echocardiogram revealed vegetations in 6 out of 9 cases. Patients received antibiotic therapy for 3.5 months. Ten patients were cured with antibiotics only, 4 required valve replacement. One died. Thus age, sex, history of heart disease, valvular involvement, duration of symptoms prior to admission and bacteriological pictures are the same in BE with VO as in BE without VO. Survival rates are also the same if early recognition of BE and VO with prompt and prolonged antibiotic therapy may prevent severe haemodynamic or vertebral problems.

Acute Disease↗

Cartilage destruction in experimentally induced osteoarthritis.

Section of the anterior cruciate ligament in the knee joint of mature dogs resulted in a progressive fibrillation of both tibial and femoral condylar cartilages. Reduced tissue microhardness and increased water content preceded fibrillation while fixed charge density remained unchanged. A different histological pattern of initial fibrillation was found, however, in femoral and tibial cartilages which exhibited tangential cleft and vertical splits, respectively. Tangential fibrillation alone was associated with necrosis of superficial cells. This suggests that the mechanism of early osteoarthritic cartilage destruction varies in different articular surfaces.

Animals↗

[Methods for evaluating non-steroidal anti-inflammatory agents in rheumatoid polyarthritis].

The study of the effectiveness of non-steroidal antiinflammatory drugs in rheumatoid arthritis requires only short term trials using simple, sensitive and reproducible tests based upon evaluation of pain. The estimation of spontaneous pain by the visual pain scale, number of nocturnal awakenings, Ritchie joint index, morning stiffness, grip strength and Lee functional index are the most informative parameters. The results of these quantitative tests of pain are usually in close agreement with patient judgement which remains the most important criterion.

Anti-Inflammatory Agents↗

Hypertrophic repair of articular cartilage in experimental osteoarthrosis.

Section of the anterior cruciate ligament has been performed in the knee of 11 mature dogs. The macroscopically normal cartilage from patella and femoral trochlea of animals killed from 2 to 32 weeks after operation was used for histological, histomorphometrical, and biochemical analysis. Previously undescribed degenerative lesions of the superficial matrix were observed, and there was evidence for secondary healing of these lesions. An early and progressive decrease in superficial cell density and a later progressive increase in cartilage thickness without any change in the cell density of the middle and deep cartilage layers was found. A slight increase in water content with no reduction in glycosaminoglycan content was observed. The results suggest that joint laxity results initially in superficial degenerative changes and later in hypertrophic regenerative changes due to cell proliferation and increased matrix synthesis. Hypertrophic remodeling of articular cartilage in response to abnormal mechanical stresses is postulated.

Animals↗

Treatment of Paget's disease of bone with ethane-1, hydroxy-1,1 diphosphonate (EHDP) at a low dosage (5 mg/kg/day).

Paget's disease of bone in 51 patients was treated with ethane-1, hydroxy-1,1 diphosphonate (EHDP) for six months at a dosage of 5 mg/kg/day. Clinically, the analgesic effect on bone pain is clear, with parallel reduction in radioisotope uptake observed by quantitative bone scintigraphy. There is also a reduction of about 70% of the excess level of serum alkaline phosphatase and total 24-hour urinary hydroxyproline. Histologically, there is a significant reduction in both the osteoclastic resorption surfaces and the number of osteoclasts. In contrast to that obtained by calcitonin, these clinical, biologic, and histologic changes continue for at least one year beyond the end of the treatment. That is the main characteristic of this treatment, of which the clinical and biologic tolerance is admittedly very satisfactory. Accumulation of osteoid tissue, which is indicative of a mineralization defect, does not appear at low dosages under the prescribed conditions. EHDP (5 mg/kg/day) can be regarded as effective treatment for some patients with Paget's disease of bone.

Adult↗

[Dichloromethylene diphosphonate (Cl2MDP) treatment of hypercalcaemia produced from bone metastases (author's transl)].

Cl2MDP, a potent inhibitor of osteoclast-mediated bone resorption, was tested in 8 patients with malignant hypercalcaemia. In a 2 months' double-blind, cross-over study the patients received Cl2MDP (3200 mg/day) during 4 weeks and a placebo during 4 weeks in a randomized sequence. The serum Ca level fell from a mean pre-trial value of 12.2 +/- 1.7 mg/dl to 10.3 +/- 1.4 mg/dl after 4 weeks of Cl2MDP (p = 0.01). Reduction was rapid, with a mean serum Ca value of 10.5 +/- 1.4 mg/dl as early as the 3rd day. At the end of the Cl2MDP treatment, 6 out of the 8 patients had normal serum Ca levels. Following active treatment, the serum Ca level significantly increased in 2 patients and remained low in one patient under placebo. Treatment with Cl2MDP resulted in a decrease in calciuria from 397 +/- 193 mg/g creatinine/24 hours to 241 +/- 211 mg/g creatinine/24 hours (p = 0.05), but there was no decrease in hydroxyproline. Serum phosphorus and PTH levels remained normal. It is concluded that Cl2MDP is an effective and convenient oral treatment of hypercalcaemia due to bone metastases.

Adult↗

Long-term effects of dichloromethylene diphosphonate (CI2MDP) on skeletal lesions in multiple myeloma.

We report the long-term effects of dichloromethylene diphosphonate (CI2MDP), an inhibitor of bone resorption, on the skeletal lesions in multiple myeloma. Thirteen patients received either CI2MDP 1600 mg/d (seven patients) or a placebo (six patients) in addition to other chemotherapy, and the effects of treatment were followed over a period of up to 18 months in a double-blind study. CI2MDP treatment resulted in a marked reduction in bone pain, with no progression of radiologic skeletal lesions during the first year. This contrasted with a clinical deterioration and the occurrence of new fractures in half of the patients receiving the placebo. Two patients with hypercalciuria and increased excretion of hydroxyproline before treatment had normalized values following CI2MDP. Finally, iliac crest bone biopsies showed a reduction in osteoclast number after CI2MDP administration. We conclude from these results that CI2MDP could be of use in preventing the bone loss that occurs in multiple myeloma.

Biopsy↗