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Biomedical subjects

P Marion

Publications and source records attributed to P Marion.

At least 19 recordsLinked to original sources

Antiviral L-nucleosides specific for hepatitis B virus infection.

A unique series of simple "unnatural" nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3'-OH group of the beta-L-2'-deoxyribose of the beta-L-2'-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides beta-L-2'-deoxycytidine, beta-L-thymidine, and beta-L-2'-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (alpha, beta, and gamma) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 10(8) genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

Animals↗

Sodium transport by an ionizable and a neutral mobile carrier: effects of membrane structure on the apparent activation energy.

Temperature-jump relaxation experiments on Na+ transport by (221)C10-cryptand (ionizable mobile carrier) and nonactin (neutral mobile carrier) were carried out in order to study the effects of cholesterol and the degree of acyl chain unsaturation, and their temperature-dependence on ion transport through thin lipid membranes. The experiments were performed on large, negatively charged unilamellar vesicles (LUV) prepared from mixtures of phosphatidylcholine (egg phosphatidylcholine, dioleoylphosphatidylcholine and dilinoleolylphosphatidylcholine), phosphatidic acid and cholesterol (mole fractions 0-0.43), at various temperatures and carrier concentrations. The apparent rate constants of Na+ translocation by (221)C10 and nonactin increased with the carrier concentration, the degree of acyl chain unsaturation and the temperature. The incorporation of cholesterol into the membranes significantly reduced the carrier concentration-, acyl chain unsaturation- and temperature-dependence of this parameter. The apparent energy required to activate the transport decreased significantly with increasing (221)C10 concentrations and remained constant with increasing those of nonactin at any given cholesterol molar fraction and degree of acyl chain unsaturation. It increased significantly with increasing the cholesterol molar fraction at any given carrier concentration to an extent depending on the degree of acyl chain unsaturation. Our interpretation of the action of cholesterol on these transport systems is based on the assumption that the adsorption plane of Na(+)-(221)C10 and Na(+)-nonactin complexes is likely to be located towards the aqueous and the hydrocarbon side of the dipole layer, respectively. The results are discussed in terms of the structural, physico-chemical and electrical characteristics of carriers and complexes, and of the interactions occurring between an ionizable or a neutral mobile carrier and the membrane.

Anti-Bacterial Agents↗

Characterization of tissue amyloid by immunofluorescence microscopy.

Immunohistochemical classification of amyloid type was possible in 44 of 50 (88%) patients as judged by the concordance of immunofluorescence, clinical, serum, and urine immunoelectrophoresis, and bone marrow data. In frozen tissue sections incubated with a panel of antisera monospecific for immunoglobulin heavy chains, kappa and lambda light chains, and amyloid-A-related protein, the amyloid was classified as AL in 20 and AA in 24. In 6 patients the amyloid could not be classified because of the absence of reactivity in 2 and overlap staining in 4. The findings indicate that routine immunofluorescence examination of diagnostic biopsies is an important adjunct in the classification of amyloid.

Adult↗

Auditory field reduction in human following head trauma.

We measured the tonal auditory threshold for 500, 2000 and 4000 Hz, and made BAER recordings for both ears with unfiltered 125 dB SPL clicks, with 40 subjects between 18 and 23 years of age, 20 subjects having suffered minor cranial trauma during the preceding 48 hours and 20 being control subjects matched for age and sex. Compared to the control group, trauma patients showed a significantly higher auditory threshold: 19 dB SPL at 500 Hz, 9 dB SPL at 2000 and 4000 Hz. This threshold rise was bilateral. The head trauma patients showed, on average, one significantly earlier BAER wave I than did controls. This alteration was likewise bilateral. The latencies of waves II, III and V, the I-III, III-V, and I-V intervals, and the interaural wave latency and interval differences are comparable for trauma patients and control subjects. One to eight months after cranial trauma, 7 subjects manifested one sign of the subjective cranial trauma syndrome. Auditory threshold and BAER wave I earliness were not any greater for these subjects. Trauma patients seemed to show a reduction of the auditory field. They were hypersensitive to high stimulus intensities (shortening of BAER wave I) and less sensitive to low intensities (rise in tonal auditory threshold). This auditory alteration was bilateral. It can thus be thought that the trauma acts on the central nervous system to affect the operation of the cochlea via efferent pathways.

Adolescent↗

[Congenital esophagobronchial fistula in the adult].

The authors report the case of a 60-year-old man presenting with an esophagobronchial fistula. The congenital origin of the lesion was demonstrated by the history of the clinical symptomatology and by radiological, endoscopic and anatomical arguments. While it is a rare complaint in adults, it is worth considering in the diagnosis of a chronic cough, because it can be cured surgically without any problems.

Bronchial Fistula↗

[Cardiac prosthesis].

It has been demonstrated an intrathoracic artificial heart with membrane pump delivering a pulsed flow and connected with an extracorporeal source of energy can keep a cardiotomized animal alive for several months without biological organic disturbances. The next experimental step would be intrathoracic implantation in man of a similar heart with an energy converter connected to an extracorporeal source giving the patient a 6-8 hour period of autonomy. At rest or during the night the batteries attached to the patient's waist would easily be recharged. Current research concentrates on reduction of artificial heart volume and miniaturization of the energy converter and regulatory electronic circuits. Kinetic pumps, which are small and without valvular prosthesis facilitate miniaturization. They deliver a high-speed continuous flow and have not yet been shown in long-term experiments to be free from biological disturbances. The clinical phase of stage II artificial hearts, due to begin in 1990, will be preceded by attempts at implanting hearts animated by an extracorporeal source of energy, pending cardiac replacement.

Animals↗

[Budd-Chiari syndrome caused by obstruction of the hepatic veins].

A Budd-Chiari syndrome was observed in a 11 year-old girl who was admitted to hospital for abdominal pain and distension, soon followed by severe shock. X-ray investigations, surgery and autopsy showed partial stenosis of the common portion of the left hepatic veins associated with a complete obstruction of other hepatic veins but without alteration of the inferior vena cava.

Autopsy↗

[Thoraco-bisternotomy in cardiovascular surgery].

Median sternotomy associated with anterior lateral thoracotomy with section of the sternum opposite the gaping intercostal space is a classical, though rarely used, incisional approach. The authors are convinced that it is safe, easy to perform and well tolerated. Their experience in 14 cases without morbidity shows that its alleged problems are more theoretical than real. They recommend this approach for aneurysms of the thoracic aorta and in some cases for access to the atrial area and superior vena cava.

Aortic Dissection↗

[Value of cineradiography in the study of Budd-Chiari syndrome. Value of various angiographic technics. Apropos of 8 cases].

Eight cases of surgically proven Budd Chiari disease, have been explored pre- operatively by cine-angiography. This procedure is very safe and simple, and allows a dynamic study of the intra- and extra-hepatic pathways. The authors are reviewing the different modalities of radiologic evaluation of Budd-Chiari disease, including inferior vena cava phlebography, opacification of supra-hepatics veins, and coeliac arteriography. They propose a flow sheet in the radiological work-up of these patients.

Adult↗