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Biomedical subjects

J Frühling

Publications and source records attributed to J Frühling.

At least 55 records · Page 3Linked to original sources

Iv administration of a water-insoluble antimitotic compound entrapped in liposomes. Preliminary report on infusion of large volumes of liposomes to man.

Five patients with advanced multiresistant neoplasms were infused with NSC-251635 (a water-insoluble antimitotic agent) entrapped in egg yolk lecithin, cholesterol, and stearylamine liposomes. The maximum volume injected was 400 ml containing 8 g of lipids, ie, a dose of 135 mg/kg of body weight. Overall tolerance of the treatment was excellent. This study indicates that liposomes may be used safely as carriers for the iv administration of water-insoluble drugs to humans.

Adenocarcinoma↗

Antitumor activity of a water-insoluble compound entrapped in liposomes on L1210 leukemia in mice.

The use of sonicated phospholipid vesicles (liposomes) as carriers of 2-[3'-(methoxycarbonylamino)-phenyl]-3-phenyl-6-methoxycarbonylamino-4-(3H)- quinazolone (NSC-251635), a water-insoluble antimitotic compound, was investigated in mice. NSC-251635 was incorporated in egg yolk lecithin, cholesterol, and stearylamine (4:3:1) liposomes. In vitro, NSC-251635 in suspension or entrapped in liposomes was not toxic for L1210 cells. In vivo, after ip or iv injections to CDF1 mice bearing intraperitoneal or intravenous L1210 leukemia, NSC-251635 was active only when it was incorporated in the liposomes and not when it was given as a suspension in Klucel or in saline. The NSC-251635 liposome preparation induced significantly prolonged survival of the treated animals.

Animals↗

Comparison and evaluation of different methods for alpha-MSH labelling.

We have studied the behaviour of 125I-labelled alpha-MSH under different experimental conditions. Until now, the chloramine T method had been used by most investigators with variable results. We have tested three other labelling techniques based on 125I mild oxidation: (1) an enzymatic method with lactoperoxidase, (2) a sparingly soluble chloramine method (T.D.G.U.) and (3) modified chloramine T procedure, 'the iodine volatilization method'. Labelled hormone obtained after each kind of iodination was assayed for immunoreactivity. In addition, time course degradation was measured by classical RIA incubation procedures. Charcoal-dextran was used to separate bound and free antigen. We have found chloramine T-iodinated alpha-MSH to be significantly more damaged than preparations obtained by other methods and to be less stable when stored at -18 degrees C. No differences were found between the differently labelled 125I-labelled alpha-MSH fresh preparations in binding to surface receptors of human melanoma cell lines in culture.

Animals↗

Radionuclide venography in the evaluation of superior vena cava syndrome.

Isotopic phlebography with Tc-99m-labeled microspheres was performed in 55 patients, 22 of whom presented with superior vena cava syndrome. The localization of the venous obstruction was visualized in each case, along with associated collateral views. Moreover, the transit times at different levels were markedly increased. In 11 patients, isotopic phlebography was repeated following treatment. Improvement, when it occurred, was largely due to diminished obstruction of the superior vena cava rather than to increased collateral supply. Therefore, isotopic phlebography of the upper extremities is a useful tool for the diagnosis of superior vena cava syndrome and for the evaluation of response to treatment.

Carcinoma, Papillary↗

Influence of 1% enflurane (Ethrane) anesthesia on regional cerebral blood flow repartition under normo-and hyperventilation.

This study is based on the same group of neurosurgical patients as our previous publication. All, except one, had suffered from head injury. We made a first measurement of rCBF under N2O anesthesia, a second under N2O + 1% enflurane anesthesia, both at a PaCO2 of 40 Torr. A third measurement was performed under N2O + 1% enflurane but at a PaCO2 of 30 Torr. The method we used consists of the intracarotid injection of 133Xe and recording of the radioactivity by a gammacamera. Mean arterial pressure was maintained constant by an intravenous phenylephrine drip. For each measurement of each patient, a map was drawn, representing the distribution of the regional cerebral blood flows (rCBF), compared to the mean value of the hemisphere. We have studied rCBF in one case of normal hemisphere, and in cases of traumtic lesions in acute and chronic states, taking into account that the normal brain exhibits areas with higher flow in the frontoparietal and insular regions. In the normal brain, introduction of 1% enflurane decreases uniformally mean CBF, rCBF repartition not being changed. Hyperventilation to 30 Torr shows that regions with previously higher flow react more to hypocapnia by a slightly more decreased flow. In severe brain trauma, mean CBF is generally low, and it is difficult to visualize the lesions under N2O and N2O + 1% enflurane anesthesia. Neither mean CBF, nor rCBF repartition are significantly modified. On the other hand, in the acute phase, hypocapnia causes a more decreased flow in the previously well irrigated areas, and shows a lack of vascular reactivity in the damaged region. Passing to the chronic state, the patient clinically recovering, the rCBF repartition is normalized and the contused area becomes agains vasoactive. Severe losses of neuronal tissue are characterized by definitive low flows without reactivity by hyperventilation.

Adolescent↗

Effect of 1% enflurane (Ethrane) anesthesia on cerebral blood flow and metabolism in neurosurgical patients during normo- and hyperventilation.

We have measured the CBF in ten neurosurgical patients. A first measurment was made during anesthesia with nitrous oxide 70% and a second with nitrous oxide 70% + 1% enflurane, both at a PaCO2 of 40 Torr. A third measurement was performed also with nitrous oxide + 1% enflurane, but at a PaCO2 of 30 Torr. We used the method of intracarotid 133Xe injection, with a gammacamera recording. In order to avoid any decrease of cerebral perfusion pressure, which might influence the CBF, an infusion of phenylephrine was used, if needed. At a constant PaCO2 of 40 Torr, there was no statistically significant difference in CBF with nitrous oxide + 1% enflurane compared to nitrous oxide alone. No change in cerebral vascular resistance was observed. When PaCO2 was lowered to 30 Torr, under 70% nitrous oxide + 1% enflurane, there was a 43% decrease in CBF (from a mean of 42 ml/100 G/min. to a mean of 24 ml/100 g/min.). Cerebral vascular resistance had an increase of 79%. In some instances, the decrease in CBF reached values around 20 ml/100 g/min. and in one case, even less. That level is generally considered to be the lowest acceptable limit in the conscious man, though not necessarily in the anesthetised one. Under hypocapnia, the cerebral arterio-venous oxygen difference increased, but the CMRO2 did not change. There were little differences in lactate and pyruvate cerebral metabolic rates, all values remaining within normal ranges. In conclusion, we believe that enflurane is a favorable anesthetic agent for neurosurgical operations at the concentration of 1%, CMRO2 is reduced, there is no significant effect on cerebral blood vessels, CBF and CVR do not change. However, a complementary use of hypocapnia may reduce CBF to dangerously low levels, if at the start, it shows already a pathological decrease and if hyperventilation is applied at a marked degree.

Adolescent↗

Correlation between liver scintigraphy and computed tomography in the detection of liver metastases.

Parallel scintigraphic and computed tomographic (CT-scan) examinations of the liver were carried out during the same observation period in 55 cancer patients in whom the liver status could be microscopically and macroscopically documented with regard to presence or absence of metastases. Scintigraphy was realized by means of 198Au or 99mTc-colloid using a rectilinear scanner or a gamma-camera; CT-scan images of the liver were obtained by a standard commercial instrument before and after injection of a contrast product. The liver was found to be normal in 38 out of the 55 observed patients and a metastatic involvement was seen in 17 cases. In 45 out of 55 cases, there was concordance between the results obtained by the two investigation methods and discordance in 10 cases. The sensitivity is 97% for the scintigraphy, 94% for the CT-scan and 100% for the common negative results. The specificity can be established as 64% for the scintigraphy, 65% for the CT-scan and 74% for common positive findings. It seems therefore that these two techniques present the same efficiency in the detection of liver metastases and that the results obtained are only partly complementary.

Female↗

Subcellular steroid distribution in the rat adrenal cortex.

The subcellular distribution of main steroids (pregnenolone, progesterone, corticosterone) and of cholesterol -- this last after correction according to exchanges occuring during differential centrifugation -- is presented in the rat adrenal cortex. The distribution patterns are not necessarily the same as established according to the localization of hydroxylating enzymes.

Adrenal Cortex↗

Cerebral blood flow under enflurane anesthesia.

Cerebral blood flow was measured, under controlled conditions of stable ventilation and PaCO2, in 11 patients suffering from cerebro-vascular lesions. Comparing the results under N2O-enflurane 1% anesthesia with those under N2O-fentanyl anesthesia shows an average 8.4% decrease of blood flow. In 5 cases, a third measurement was performed under N2O-enflurane 2% anesthesia. This caused an average 8.5% complementary decrease. Whereas most inhalational anesthetic agents produce an increase of cerebral blood flow, this is not observed with enflurane, the tendency rather being towards a decrease.

Adult↗