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Biomedical subjects

J Robert

Publications and source records attributed to J Robert.

At least 433 records · Page 24Linked to original sources

Enhancement of hyperthermia lethality by Lanthanum.

The authors have studied the effects of La3+ during hyperthermia on tumor cells, Trypan blue exclusion and 86Rb release from previously labeled Ehrlich and DS carcinosarcoma ascites cells, indicate an increase of plasma membrane permeability by La3+ as a function of the hyperthermic level. The enhancement of hyperthermia lethality by concentration of Lanthanum over 0.5 mM after 2 hours at 44 degrees C has been demonstrated on HeLa S3 cells using a well known cloning technique. In vivo experiments have been performed on Rhabdomyosarcoma C3H bearing mice using an ultrasound heating technique at 44-46 degrees C. The preliminary in vivo results show a remarkable tumor growth inhibition and a significant increase of the survival time after only one hyperthermia treatment of 30 minutes combined with one intratumoral injection of 1 mM lanthanum. The control animal groups treated by hyperthermia alone or by lanthanum alone don't show any differences of the tumor volume evolution in comparison with untreated animal groups.

Animals↗

[Pharmacokinetic study of doxorubicin in the treatment of malignant non-Hodgkin's lymphomas].

We have studied the plasma kinetics of doxorubicin treatment in nine patients with non-Hodgkin's malignant lymphoma. Four patients were studied following the first two injections of this drug, the other five patients were studied only after the first injection. Our results corroborate the existence of three successive phases of doxorubicin plasma decay, with mean half-lives of 3.81 min, 1.19 h and 29 h. We observed an important variation of the pharmacokinetic parameters related to the distribution volumes. The total plasmatic clearance ranged between 32 and 67 l/h. The kinetics of doxurubicin are time-dependent, i.e. an important variation of the pharmacokinetic parameters related to the distribution volumes. The total plasmatic clearance ranged between 32 and 67 l/h. The kinetics of doxurubicin are time-dependent, i.e. an important variation of the pharmacokinetic parameters existed after the 2nd injection of the drug in three out of four patients. These 3 patients showed either an increase of the elimination half-life (1 case) or an increase of the distribution volume (1 case) or a decrease of the distribution volume (1 case) after the 2nd injection. We observed a significant correlation between the age of the patients and the early clearance of the drug, the youngest patients eliminating the drug more rapidly than the oldest ones. This observation may lead to the administration of different dosages of doxorubicin according to the age of the patient.

Adolescent↗

Age dependence of the early-phase pharmacokinetics of doxorubicin.

By gathering the results that we had obtained on the pharmacokinetics of doxorubicin in 37 patients, we observed a correlation between the early clearance of this drug and the age of the patients, the youngest patients having the highest clearances. The data presented by another group (Piazza et al., Cancer Treat. Rep., 64: 845-854, 1980) allow calculations leading to the same findings. In view of the clinical importance of the first phase of the kinetics of doxorubicin, which is in agreement with cellular pharmacology observations, we propose an age-dependent modulation of the dose of doxorubicin injected in patients.

Adolescent↗

Frequency dependence of water proton longitudinal nuclear magnetic relaxation times in mouse tissues at 20 degrees C.

We have measured the proton longitudinal relaxation times of tissue water of healthy and tumor-bearing mice as a function of the Larmor frequency in the range 6.7 to 90 MHz. These data can be rationalized according to T1-1 = A v -1/2 +B, where A and B are constants specific to the tissue species. We present an interpretation of this frequency dependence within the Fast Exchange Two States model. It is shown that involving a distribution of correlation times for water proton-proton interaction does not yield consistent results, whereas a physically meaningful translational diffusion model pertinent to the dipolar interaction between water protons and macromolecules protons leads to the required frequency dependence. Essentially tissues would differ by the 'bound' versus 'free' proportion, or by structural properties of cells, rather than by the time-scales governing water motion.

Animals↗

Metabolism of daunorubicin in sensitive and resistant Ehrlich ascites tumor cells. Determination by high pressure liquid chromatography.

The intracellular metabolism of daunorubicin (DNR) has been studied in sensitive and resistant Ehrlich ascites tumor (EAT) cells. The subcellular localization of metabolites has been followed by normal-phase and reverse-phase high-pressure liquid chromatography (HPLC). The metabolism of DNR by either sensitive or resistant EAT cells is not significant; unmetabolized DNR is always the main intracellular compound. Daunorubicinol (DOL) accounts for less than 5% after 24 h and an unidentified product is also observed. This highly apolar compound, having an intrinsic fluorescence one order of magnitude greater than that of DNR is formed in acellular conditions and could be a chemical artifact. DNR and DOL are mainly associated with DNA-containing fractions. No significant differences can be observed in the metabolism of DNR in sensitive and resistant EAT cells.

Animals↗

Pharmacokinetics of adriamycin in patients with breast cancer: correlation between pharmacokinetic parameters and clinical short-term response.

The pharmacokinetics of adriamycin was evaluated in the plasma of 12 patients with breast cancer after injection of an i.v. bolus. The patients were suffering from a locally advanced tumor, were free of metastases and had received no prior treatment. They received a chemotherapy consisting in adriamycin (50 mg/m2) on day 1, vincristine (1 mg/m2) on day 2 and methotrexate (6 mg/m2) on days 3, 4 and 5. The response to chemotherapy was assessed as the percentage of reduction of the palpable tumoral mass. Plasma samples were collected at various times after injection of the drug. Adriamycin and its metabolites were extracted using an original column purification technique and were evaluated by high-performance liquid chromatography with fluorometric detection. Pharmacokinetic parameters were calculated with a computer program based upon an algorithm of non-linear function minimization. The three successive half-lives presented little individual variations and were 4.75 min, 0.822 hr and 18.9 hr. On the other hand, the A, B and C parameters were highly scattered. The total plasma clearance of the parent drug ranged from 28.3 to 98.7 1/hr. A highly significant correlation was observed between parameter A and the short-term clinical response. Moreover, a mild correlation exists between the half-life of the 1st phase and the short-term clinical response. We can therefore assume that the efficacy of the drug may be dependent upon its distribution in the organism. Such a relationship may allow the development of new protocols of chemotherapy in order to obtain an optimal distribution of the drug in every patient.

Adult↗

Changes in lipid composition of the brain cellular membranes of an hibernating mammal during its circannual rhythm.

The lipid composition of whole brain hemispheres and subcellular fractions of European Hamsters (Cricetus cricetus) was investigated at four different periods of the year. 1. No difference was observed in winter between hibernating animals and active animals awake for 24 hr. 2. A slight increase of cholesterol/phospholipid molar ratio was observed in winter. 3. A slight increase of the ratio ethanolamine phosphoglycerides/choline phosphoglycerides was observed in summer and autumn. 4. Some changes in sugar moieties proportions of gangliosides were observed, with a tendency of increased polysialylation in winter. 5. An increase of docosahexaenoic acid was observed in summer, while a slight increase of linoleic acid and of the monounsaturated fatty acids was observed in winter. These changes were mainly exhibited in the synaptosomal fraction. All the changes observed were of very small magnitude and might not be sufficient for the maintenance of a fluid state of membranes during hibernation.

Animals↗

Cation transport in erythrocytes of patients with renal failure.

Na+, K+-ATPase activity in erythrocytes (RBC) has been assessed indirectly by the 86Rb uptake method in 10 patients with acute renal failure (ARF), 11 patients with chronic renal failure (CRF) on haemodialysis and 13 patients treated by kidney transplantation, and compared to age-matched healthy controls. In each patients, the sensitivity of 86Rb uptake to digoxin (IC50) has been measured. Na+, K+-ATPase activity was decreased in patients with ARF and in patients with CRF but not in transplanted patients. IC50 was lowered in transplanted patients. The implications of these findings are discussed in terms of possible mechanisms of the changes in Na+, K+-ATPase activity in RBC of patients with renal failure.

Acute Kidney Injury↗

[Detection and quantification of left-to-right intracardiac shunts by angiocardioscintigraphy].

The ratio of pulmonary/systemic output (QP/QS) was measured by angioscintigraphy in 70 patients from 1 to 22 years of age (average 10 years) admitted to the Department of pediatric cardiology for a left-to-right shunt. Fifty nine of these patients underwent cardiac cathetarisation and QP/QS determination by oxymetry. The correlation between the values of QP/QS calculated by the two techniques was R = 0,83 (p less than 0,001: n = 59); in 28 cases of atrial septal defect R = 0,85; in 20 cases of ventricular septal defect, R = 0,75; in 11 cases of other left-to-right shunts, R = 0,79. No significant shunt was detected in 16 patients by oxymetry and the QP/QS ratio on angioscintigraphy was less than or equal to 1,2 except in 3 cases. In 7 cases of isolated pulmonary stenosis and 4 cases of operated septal defects no shunt could be detected by isotopic investigation. We conclude that angioscintigraphy is a reliable non-invasive method of detection and assessment of left-to-right shunts. In some cases it may avoid the necessity of cardiac catheterisation. The advantages, limitations and applications of this method are discussed.

Adolescent↗

Ionic competition and 67Ga in vivo accumulation.

The effect of several citrates of trivalent cations on 67Ga citrate uptake by tumor-bearing animals has been studied. A relationship between the ionic size of the simultaneously injected cation and the 67Ga uptake inhibition indicates that the cation characteristics (ionic radius and electrical charge) seem to play the most important role in this radioactivity accumulation. The apparent agreement of this phenomenon with the isomorphous replacement hypothesis is discussed.

Animals↗