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Biomedical subjects

P Lechat

Publications and source records attributed to P Lechat.

At least 127 records · Page 7Linked to original sources

Results of percutaneous catheter valvuloplasty for calcified aortic stenosis in the elderly.

Percutaneous catheter valvuloplasty was performed in 37 patients between 60-88 years of age (mean age 74.5 years): 16 of these patients were in functional class IV, with pulmonary oedema at the time of the procedure. A good haemodynamic result was obtained in 32 patients, but 3 of them had to be operated upon subsequently, because of persistence of their symptoms. Two successfully dilated patients died in the hospital, one of cardiac failure following myocardial dysfunction caused by multiple infarcts which had no relation to the aortic dilatation, the other of neurological complications after dilatation. Thus, the primary success rate was 27/37 (73%). The first 10 patients with good initial results have been followed up for more than 6 months. The functional result has been maintained in 8 cases with moderate myocardial dysfunction (left ventricular ejection fraction 0.41 to 0.7), one with restenosis at Doppler assessment. Two patients with severe myocardial dysfunction (left ventricular ejection fraction 0.22 and 0.25) had recurrent cardiac failure, with valvular restenosis in one case. One of them died at home. Percutaneous aortic valvuloplasty is therefore an effective means of treating calcified aortic stenosis in elderly patients. The benefits of this procedure have been maintained for as long as 6 months provided myocardial dysfunction was moderate. At its present stage of development, the technique allows only partial reduction of the aortic stenosis, which may explain the absence of long-term improvement in patients with severe myocardial disease.

Aged↗

1,25-Dihydroxycholecalciferol induces an increase in PGE1- and forskolin-stimulated cyclic-AMP production in T47D human breast cancer cell line.

The effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], the active form of vitamin D3, on cell growth, clonogenicity, and cyclic adenosine monophosphate (cAMP) production was examined in human breast cancer cell line T47D. 1,25(OH)2D3 markedly inhibited proliferation of T47D cells in a time- and concentration-dependent manner. 1,25(OH)2D3 5 X 10(-7) reduced to 70% [3H]thymidine incorporation into DNA. Specific high affinity nuclear receptors for 1,25(OH)2D3 were present in this cell line. The cAMP produced by T47D cells was measured during 10 min stimulation by effectors (prostaglandin E1 or forskolin). Without effector, T47D cells produced similar amounts of cAMP in control and 1,25(OH)2D3-treated cells. After 3 days in the presence of 1,25(OH)2D3, cAMP production was significantly increased compared to control cells when stimulated by 10(-4) M prostaglandin E1 or 5 X 10(-7) M forskolin (3.2- and 2.4-fold increase, respectively). This cAMP increase was concentration dependent within the same range that inhibited cell growth and clonogenicity. These results suggest that 1,25(OH)2D3 may indirectly affect cAMP production by modulating the target cell response to stimulatory agents of cAMP production.

Alprostadil↗

RO 13-6438 in congestive heart failure: dose-response relationship after 3 single doses.

The dose-response for the new cardiotonic agent RO13-6438 was studied in 6 patients with grade III or IV congestive heart failure. Oral doses of 10, 20, or 30 mg of RO 13-6438 were administered on 3 consecutive days in accordance with a double-blind, randomized cross-over pattern. Hemodynamic changes, which were dose-dependent, included an increase in cardiac index combined with decreases in pulmonary capillary wedge pressure and systemic and pulmonary arterial pressures. Heart rate remained unchanged. The area under the plasma RO 13-6438 concentration time curve and the peak plasma concentration were dose-related. At each measurement, the log concentration of RO 13-6438 correlated with the percent changes in both cardiac index and capillary wedge pressure recorded at that time.

Administration, Oral↗

Effects of long-term treatment with D-penicillamine on antigen-induced arthritis in rabbits: studies on in vivo articular chondrocyte damage and in vitro collagen biosynthesis by cultured chondrocytes.

The effects of a long-term (120 days) treatment with D-penicillamine (DP) (50 mg/kg/day; i.v.) on antigen-induced arthritis were studied in rabbit. They were investigated by the terminal histological examination of the joints of different groups of rabbits (unimmunized treated or untreated, immunized treated or untreated) and the study of collagen and non-collagen protein biosynthesis by cultured chondrocytes obtained from articular cartilage of the same groups of animals. Treatment with D-penicillamine diminished the intensity of the erosions of cartilage and subchondral bone, the severity of the inflammatory synovitis, and the loss of chondrocyte clusters found in cartilage sections. In cultures of chondrocytes obtained from immunized treated rabbits, a partial or complete inhibition of the decreased biosynthesis of collagen and non-collagen proteins seen in culture of chondrocytes obtained from immunized untreated animals was observed. These results show that DP could be effective in preventing damage of chondrocytes and inhibition of collagen biosynthesis in them, phenomena important in cartilage destruction induced by a chronic immunological inflammation.

Animals↗

[Results of percutaneous valvuloplasty in calcified aortic stenosis in the adult].

Aortic valvuloplasty by percutaneous valve dilatation was attempted in 52 patients aged from 60 to 88 years, 20 of whom were in functional stage IV with pulmonary oedema at the time of the procedure. Forty-seven stenoses could be dilated, with haemodynamic success (50 p. 100 increase of aortic valve area) in 44 patients. Among these 44 patients, 3 had to be operated upon because of persistent functional symptoms and 3 died during their stay in hospital (2 as a result of the procedure or the cardiopathy, 1 of heart failure unrelated to the aortic stenosis or the dilatation). The primary success rate therefore was 38/52 attempts, or 72.9 p. 100. The first 11 patients regarded as initial success could be followed up for at least 6 months: functional improvement with moderate myocardial alteration persisted in 9 of them, but Doppler examination in one showed restenosis. Two patients with severe myocardial dysfunction relapsed into cardiac failure; restenosis could be dilated in one of them. Percutaneous aortic valvuloplasty is an effective treatment of calcified aortic stenosis in elderly people who remain improved for at least 6 months when myocardial lesions are mild or moderate. The procedure incompletely reduces the aortic stenosis, which may account for the left of improvement in left ventricular function in patients with severe myocardial damage prior to dilatation. For this subgroup of patients, the choice lies between percutaneous valvuloplasty, which avoids surgery, and surgery which ensures a more complete haemodynamic result in the valve.

Aged↗

[Echocardiographic diagnosis of plurivalvular prolapse. Apropos of a case].

Sonocardiography, especially bi-dimensional, currently represents an examination of choice in the detection of valvular prolapses. The authors report one case of a triple aorto-mitral-tricuspid valvular prolapse, diagnosed with the ultrasound technique. In light of this report and the data from the literature, the frequency and the distribution of valvular affections are discussed. The technical difficulties of recording and interpreting sonographic images responsible for false positive or false negative diagnostic errors are also studied.

Adult↗

Calcium antagonists stimulate prostaglandin synthesis by cultured rat cardiac myocytes and prevent the effects of hypoxia.

The effect of three calcium antagonists on the synthesis of prostacyclin (PGI2, assayed as 6-Keto-PGF1 alpha) and PGE2 by cultured rat cardiac myocytes and fibroblasts was investigated. In myocytes only, bepridil, diltiazem and verapamil (10(-9) to 10(-7) M) stimulated PGs synthesis by two- to three-fold, dose-dependently. At a concentration of 10(-6) or 10(-5) M the intensity of the stimulation of PGI2 and PGE2 decreased. Cobalt chloride (2 X 10(-3) M) did not change PGs synthesis (pg/mg of protein/30 min; means +/- SE, N = 10; PGE2: 365 +/- 59 and 463 +/- 89 treated vs controls; PGI2: 824 +/- 214 and 799 +/- 143 treated vs controls). After 30 min exposure of myocytes to hypoxic conditions (glucose-free medium and low PO2), the glycogen content was half that of the controls (P less than 0.001), ATP content did not change and PGI2 and PGE2 synthesis increased (X1.5, P less than 0.05). When applied to myocytes 30 min before inducing hypoxia, the three calcium antagonists stimulated PGs synthesis by three- to seven-fold at maximal effect, and bepridil (10(-8) M) or diltiazem (10(-7) M) prevented the hypoxia-induced decrease in glycogen content. With 10(-5) M drug concentration, the effect on PGs was not significant, except for the effect of bepridil on PGI2 (P less than 0.05). It is concluded that therapeutic concentrations of calcium antagonists simultaneously prevent the decrease in myocyte glycogen induced by hypoxia and stimulate PGs synthesis by myocytes.

Animals↗

[Detection by contrast ultrasonography of patent foramen ovale before neurosurgery].

Air embolism may occur during neurosurgery if performed in the seated position. Paradoxical systemic air embolism represents a potentially severe complication in case of patent foramen ovale. Contrast echocardiography detected such a malformation in 10/100 patients, which contra-indicated the sitting position in these 10 patients. No episode of paradoxical air embolism was observed in the 90 remaining patients, although 16 cases of pulmonary air embolism were detected during surgery.

Adult↗

Verapamil depresses the synthesis of lipoxygenase products by hypoxic cardiac rat fibroblasts in culture.

Lipoxygenase metabolites of arachidonic acid are potent chemotactic and vasoconstrictive agents and their local production in the myocardium induces the migration of polymorphonuclear cells into ischemic myocardium. These cells have been shown to play a role in the development of ischemic myocardial lesions. In the present study, the synthesis of arachidonic acid lipoxygenase metabolites by rat cardiac cells in culture and the effect of verapamil were investigated under normal and hypoxic conditions. Myocytes and fibroblasts metabolized exogenous arachidonic acid into 12-HETE and an unidentified metabolite (X). Fibroblasts synthesized significantly greater amounts of 12-HETE than myocytes (P less than 0.01). Hypoxia (glucose-free medium and low PO2) and verapamil (10(-7) M) under normal conditions, did not change metabolite synthesis by either type of cells. Under hypoxia, verapamil decreased significantly 12-HETE and X production by fibroblasts (P less than 0.01 and P less than 0.05), whereas the synthesis in myocytes was not changed. It is concluded that the decrease in lipoxygenase product synthesis under hypoxia by verapamil may contribute to its therapeutic effects on the ischemic heart.

Anaerobiosis↗

[Angiographically tight coronary stenoses without transstenotic pressure gradient].

The availability of coronary angioplasty catheters has made it possible to measure transstenotic pressure gradients. This parameter provides direct information on coronary haemodynamics. In 2 patients with proximal concentric stenosis of the left anterior descending artery the gradient was zero in spite of a more than 50% reduction in vascular diameter. The reason for this emerged from a study of the characteristics of these stenoses: they were short, and the vascular area at their level clearly was superior to 1 mm2. None of the 2 patients suffered from angina. One had negative exercise ECG, the other had an inconclusive exercise test without pain but with ST segment depression on anterior leads. This patient had a history of posterior infarction with postero-inferior dyskinesia at angiography, and exercise scintigraphy with thallium showed no decreased uptake in the antero-septal territory. The presence of coronary transstenotic pressure gradient implies a fall in coronary blood pressure downstream of the stenosis, a pressure which constitutes the perfusion pressure in the territory fed by the narrowed artery. on the value of this perfusion pressure depends the possibility of coronary blood flow autoregulation in the territory threatened by ischaemia.

Blood Pressure↗

[Detection of cardiac graft rejection using proton nuclear magnetic resonance].

Rejection of cardiac transplants can be detected by NMR imaging if it is associated with a change in myocardial T1 and/or T2 proton relaxation time. T1 and T2 were studied in 14 Lewis rats that underwent heterotopic cardiac transplantation. T1 and T2 were measured in vitro immediately after sacrifice 3, 4, 7 or 11 days after the graft using a Minispec BRUKER PC20. The myocardial water content was measured by dehydration in a vacuum for 24 hours. Histological analysis of sections classified the rejection process in 4 stages according to the degree of lymphocyte infiltration and percentage of myolysis. There was a significant difference between the ortho and heterotopic hearts: (Formula: see text). In particular, there was highly significant relationship between T2 and the stage of rejection (r = 0.90, p less than 0.005), and between T2 and % myolysis (r = 0.84, p less than 0.005). In addition, there was a close relationship between the T2 of the ortho and heterotopic hearts and their water content (r = 0.95, p less than 0.001). If these results are confirmed in man, is should be possible to detect rejection by NMR imaging using sequences of activation concentrating on changes of T2.

Animals↗