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Biomedical subjects

J Robert

Publications and source records attributed to J Robert.

At least 397 records · Page 22Linked to original sources

Pharmacokinetics and metabolism of epirubicin during repetitive courses of administration in Hodgkin's patients.

We studied the pharmacokinetics and metabolism of epirubicin (4'-epidoxorubicin) in ten patients suffering from Hodgkin's disease and receiving three successive injections of epirubicin at 15-day intervals in a combined chemotherapy regimen. Doses were either constant (35 mg/m2) or escalated from 25 to 35 and 50 mg/m2. Epirubicin metabolism was characterized by the presence of high levels of epirubicin glucuronide in plasma and urine. The area under the time-concentration plasma curve of epirubicin glucuronide reached almost that of unchanged epirubicin (mean ratio = 0.7-0.85), whereas the cumulative urinary excretion of epirubicin glucuronide was one-half of that of epirubicin (mean ratio = 0.45-0.51). Repeating or escalating the doses did not change the levels of the glucuronide significantly. Only a trend towards higher relative levels of glucuronide could be noticed at the lowest dose. The pharmacokinetic parameters of epirubicin were characterized by a high total plasma clearance (mean value: 70-85 1/hr) and a mean elimination half-life of 25-35 hr. Repeating or escalating the doses was followed by a slight increase of the total plasma clearance in most patients, without changes of the elimination half-life. The cumulative urinary excretion was 11-12% of the dose administered and did not vary significantly as a function of time or dose.

Adult↗

Percutaneous transluminal coronary angioplasty for the treatment of variant angina.

Among 268 patients undergoing percutaneous transluminal coronary angioplasty between February 1980 and January 1983, a total of 21 patients had variant angina, documented before angioplasty in 14 and after angioplasty in 7. Before angioplasty, all 21 patients had rest angina and 17 also had effort angina; single vessel coronary artery disease with 60 to 95% stenosis was present in all patients and the left anterior descending coronary artery was involved in all but 3 patients. Coronary angioplasty was successful in 19 patients (90%). Eight of the 19 patients remained symptom-free without coronary restenosis after successful angioplasty; in the other 11 patients, angina reappeared within 4 months, usually in association with restenosis. Of the nine patients with coronary restenosis, six had repeat angioplasty (five successful procedures and one failure), two received medical therapy and one underwent coronary bypass surgery. Patients in whom calcium channel antagonists were discontinued immediately after angioplasty had an exceedingly high coronary restenosis rate (8 [80%] of 10 successful attempts), but when calcium antagonists were continued for an average of 6 +/- 4 months after angioplasty, the restenosis rate was low (3 [21%] of 14 successful attempts). After a mean (+/- SD) follow-up period of 33 +/- 13 months, 1 patient had died and the 20 others (95%) were symptom-free; among these 20, 15 patients (75%) had been taking no antianginal drugs for more than 1 year, 2 still received calcium channel antagonists and 3 had had coronary bypass surgery. Repeat coronary arteriography performed 14 +/- 7 months after angioplasty in the 17 patients without angioplasty-related infarction or surgery showed 50% or less coronary stenosis in 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Calcium, calcium-ATPase and cyclic AMP changes in Ehrlich ascites cells submitted to hyperthermia.

Increased radiocalcium influx, decreased Ca-ATPase activity and cAMP concentration were observed in Ehrlich carcinoma cells submitted to hyperthermia temperature (45 degrees C). The significant augmentation of mitochondrial calcium that is simultaneous to an inhibition of the calcium pump appears to indicate a heat-induced failure of the system of calcium-extrusion that may be responsible for cell inactivation and death through cell toxic death by calcium overloading. The decreased cAMP concentration appears to corroborate the influx of calcium.

Animals↗

Comparative pharmacokinetics and metabolism of doxorubicin and epirubicin in patients with metastatic breast cancer.

We have studied the metabolism and pharmacokinetics of epirubicin (4'-epidoxorubicin), as compared to those of doxorubicin, in a total of 16 patients with metastatic breast cancer. Epirubicin metabolism markedly differs from that of doxorubicin, in that large amounts of glucuronides of epirubicinol and epirubicin were observed in plasma as well as in urine samples. The total plasma clearance of epirubicin was significantly higher than that of doxorubicin; this was interpreted as due to an increase of the distribution volume of epirubicin, since the terminal plasma half-lives of both drugs were similar. No significant modifications were observed in patients with hepatic metastases. The differences in the pharmacokinetic and metabolic properties of the two drugs may be responsible for the differences in toxicity that have been noticed between them in previous phase I and II studies.

Antineoplastic Combined Chemotherapy Protocols↗

[Rapid ATB. A new system of antibiotic testing in 4 hours. Description and parameters of variation].

Rapid ATB is a new automated system which performs antibiotic sensitivity testing of Enterobacteriaceae in four hours. It is composed of strips containing dehydrated antibiotics and a medium which ensures rapid bacterial growth, and of the equipment required for standardization of the inoculum, reading of results and interpretation. Strains are classified as susceptible or resistant according to the value of the growth index (IC) which is the ratio of growth in the presence of the antibiotic to growth of a control inoculum. Use of this system requires standardization. The main factors to control are state of the culture used to prepare the inoculum, standardization of the inoculum, incubation temperature (35 to 37 degrees C), and duration of incubation (4 to 5 hours). Variations of these factors usually induce significantly delayed growth. Under well standardized conditions, results are highly reproducible, as proved by testing ten strains ten times each by three investigators.

Culture Media↗

[Radioisotopes for the study of right and left ventricular function in surgically treated Fallot's tetralogy].

Radio-nuclide angiography after surgical correction of tetralogy of Fallot (TOF) allows measurement of the ejection fraction, especially of the right ventricle, under basal conditions and on effort, parameters which are difficult to measure by other non-invasive methods. Twenty-two children with a mean age of 12.6 +/- 6.9 years who had undergone complete correction of TOF at a mean age of 6.7 +/- 3.8 years underwent Technetium 99m blood pool studies at equilibrium. The results were compared with those of a control group of children with a mean age of 10.2 +/- 3.3 years. No first passage studies were performed because the frequency of postoperative pulmonary regurgitation does not allow quantification of the shunt due to a possible residual ventricular septal defect. No significant difference was found between the patients and control subjects at rest: LV ejection fraction (66.7 +/- 11 p. 100 vs 63 +/- 7.7 p. 100), RV ejection fraction (50.3 +/- 7.2 p. 100 vs 54 +/- 14.8 p. 100). The response to effort of the right and left ventricles depends on the type of exercise. The LV ejection fraction increased normally whilst the RV ejection fraction showed a lot of individual variation. Equilibrium radionuclide angiography was also used to calculate the ratio of right to left end diastolic ventricular volumes. This ratio indicates the degree of RV diastolic overload when LV diastolic volumes are normal, which was the case in our series. The study group showed a significant increase in this ratio compared to control subjects (1.94 +/- 0.65 vs 1.2 +/- 0.23). Exercise radionuclide imagery should provide more accurate assessments of the surgical results and prognosis of these children providing standardised protocols are used. These investigations are best performed in patients over 15 years old, so as to avoid the technical difficulties related to small size. Resting studies are possible at all ages.

Adolescent↗

[Phase imaging of isotopic ventriculographies: contribution to the study of the Wolff-Parkinson-White syndrome].

This study compared the phase images of 12 normal subjects and 14 patients with right ventricular and 5 patients with left ventricular preexcitation. The phase images obtained from equilibrium radionuclide ventriculographies in the left anterior oblique portion with an ECG trigger: Fourier analysis was used to measure the phase and amplitude of the variations. In normal subjects the mean difference in phase was nearly zero: in 12 of the 14 patients with right ventricular preexcitation, right ventricular preceded left ventricular contraction (LV phase - RV phase = + 23 degrees); injection of Ajmaline normalised the ECG and suppressed the premature right ventricular contraction during right ventricular preexcitation (LV phase - RV phase = nearly zero), demonstrating a direct relationship between the abnormal depolarisation and abnormal contraction. In left sided Kent bundles, phase imaging did not seem to show significant premature ventricular contraction under basal conditions. Atrial pacing, which accentuated both left and right electrical preexcitation, increased the difference in ventricular phase. Finally, a satisfactory correlation was observed between the presumed locations of the accessory pathways and the zones of premature right and left ventricular contraction.

Adult↗

[Evaluation of a new rapid antibiogram method, the Rapid-ATB system. Comparison with the agar dilution reference method and the standard antibiogram].

Results given by Rapid-ATB, a new automated system for the four hour susceptibility testing of bacteria were compared in this study to results given by agar dilution test and disc agar diffusion test. For 100 Enterobacteriaceae strains tested against ten antibiotics, overall agreement between agar dilution test and Rapid-ATB was 99.4%. 6 major discordances concerning especially chloramphenicol were only detected in 1 000 realized susceptibility tests. Overall agreement between agar dilution test and disc agar diffusion test was 96.7%. Eighteen major discordances concerning alike chloramphenicol, but also doxycycline and nalidixic acid, and fifteen minor discordances were detected in this comparison. These results prove the high reliability of this new system which give results more precise than these of disc agar diffusion test.

Anti-Bacterial Agents↗

[Effect of a ticarcillin-clavulanic acid (timentin) combination on bacteria resistant to ticarcillin].

Sixty-nine ticarcillin-resistant strains (57 Gram negative bacilli and 12 S. aureus) were tested: MICs and MBCs were determined for clavulanic acid, ticarcillin, and both agents combined using a liquid micromethod. MICs were compared to results of disk antibiotic sensitivity tests. While clavulanic acid exhibits little antibacterial activity, its action is synergistic with that of ticarcillin making 100% of Staphylococci and 84.2% of Gram negative bacilli susceptible. Among the Gram negative bacilli tested, distribution is as follows: E. coli (9/9), Klebsiella (10/14), Enterobacter (1/3), Serratia (8/8), Proteus, Providencia (8/8), Salmonella (2/2), Acinetobacter (4/4), and Pseudomonas (6/9). Although strong bacteriostatic and bactericidal activities are already achieved with 4 mg, the best results are obtained with timentin 8 mg.

Acinetobacter↗

[Comparative bacteriologic activity of norfloxacin, ofloxacin and pefloxacin against 320 Gram-negative bacilli resistant and non-resistant to nalidixic acid and cephalosporins].

Bacteriostatic and bactericidal effects of three fluoroquinolones, norfloxacin, ofloxacin and pefloxacin, against 320 strains of Gram-negative bacilli were studied in vitro. For nalidixic acid-susceptible Enterobacteriaceae, susceptibility or resistance to second or third generation cephalosporins has no significant bearing on the MIC 90 of each of the three antibiotics. This is not so of nalidixic acid-resistant strains. All E. coli and K. pneumoniae strains are susceptible to the three quinolones (MIC 90 less than 3 mg/1); MICs 90 are higher for E. cloacae and S. marcescens; Serratia strains in particular have an MIC 90 greater than 6 mg/1. Nalidixic acid-susceptible Acinetobacter strains can be eliminated by ofloxacin or pefloxacin, whereas norfloxacin has the greatest activity against P. aeruginosa. We conclude that when multiresistant bacteria emerge, testing of susceptibility to the three quinolones studied may be useful.

Acinetobacter↗

[Internal jugular venous pulse. An interesting diagnostic tool].

Examination of the internal jugular veins is little if at all taught in French medical schools. However, it is useful for two reasons: estimation of the central venous pressure, the internal jugular veins acting as manometers, and the configuration of the jugular venous pulse which reliably reflects the pressure curve of the right atrium. Thus, by simple inspection, examination of the internal jugular veins can reveal important hemodynamic information from the right side of the heart.

Central Venous Pressure↗

Intracellular ionic changes during hyperthermia of tumor cells in the presence of lanthanum.

The experimental data suggest that permeability changes at the plasma membrane level are the most likely cause of the enhancement of tumor cell killing by hyperthermia in the presence of 1 mM La3+. The interaction of La3+ with the Na+, K+ ATPase and Ca2+-pump ATPase may be the probable cause of dramatic electrolyte changes which enhance the hyperthermia effects on tumor cells.

Animals↗

[Topographic aspects of threatened extension of transmural myocardial infarction. Electrocardiographic and coronarographic data].

The topographical and physiopathological aspects of the danger of extension of infarction of the myocardium are defined with the aid of data collected by electrocardiogram and coronarography in 50 patients. The danger of extension in situ, observed in 64% of the cases, is the most frequent and complicates particularly the progression of anterior infarcts. In fact, it is located in the same area as the initial infarct in 91% of the cases for anterior infarcts and in 40% of the cases for inferior infarcts. It is expressed by an elevation of the ST segment in 84% of the cases and corresponds to a monotruncular attack in 63% of the cases. The downstream bed of the vessel destined for the infarcted area and threatened secondarily remains permeable in the anterograde sense. Apart from infarcts, the danger of extension is less frequent, found in 36% of the cases, and complicates preferentially the progression of inferior infarcts. It finds expression in a depression of the ST segment in 77% of the cases and the coronary attack is always pluritruncular. The mortality in one month is 35% of 17 patients treated medically and 3% of 33 patients who have been equipped with a shunt or angioplasty. In situ the danger of extension denotes the presence of cellular islets, which are still healthy, in the region of an infarcted myocardial zone, the viability of which may be threatened secondarily by a phenomenon of coronary occlusion, which is intermittent and repeated. Except for an infarct, the danger of extension implies the diffusion of an atheromatous effect. The good results of surgical treatment or dilatation argues in favour of an early coronarographic exploration.

Coronary Angiography↗

Fluorescence polarization study of lipids and membranes prepared from brain hemispheres of a hibernating mammal.

The physical behavior of total lipids, microsomes and microsomal lipids prepared from brain hemispheres of European Hamsters (Cricetus cricetus) was approached by the measure of the fluorescence polarization of the probe 1,6-diphenyl 1,3,5-hexatriene. We compare in this study the results obtained for two critical periods for a hibernator: winter (torpid state) and summer (active state). An increase in fluidity was noticed in the winter lipid and membrane preparations. The difference was however of very low magnitude, suggesting that only the microenvironment of some proteins was involved, rather than the bulk membrane fluidity.

Animals↗

Mineral metabolism and in vivo uptake of [67 Ga]citrate.

The uptake of [67 Ga]citrate by normal rats of different ages has been compared with the mineral composition of the assayed tissues. Very young animals take up much more 67 Ga than the adults and there seems to be a correlation between the mineral composition (calcium, magnesium and iron) and the radioactivity uptake. The role of those elements and of cellular proliferation in this phenomenon is discussed.

Animals↗