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Biomedical subjects

A Rescigno

Publications and source records attributed to A Rescigno.

At least 55 records · Page 3Linked to original sources

Pharmacokinetic modeling of radiolabeled antibody distribution in man.

This paper describes a method for the interpretation of the pharmacokinetics in cancer patients of an anti-CEA monoclonal antibody labeled with 111In. To determine the fate of the radiolabeled antibody administered i.v. to ten colon patients, the radioactivity contained in liver, spleen, kidneys, bone marrow, and tumor was measured and serum samples were counted. In addition each serum and urine sample was also analyzed by HPLC. The labeled antibody and two other radioactive species were observed in serum: an immunocomplex and a catabolic product. The computer program SAAM was used to fit the data. Thus, the rate constants for a number of pharmacokinetic models were calculated using the time-dependent serum radioactivity curves for each of the three species and the time-dependent radioactivity contained in normal organs. We also computed the model parameters for different connections between different organs, and using noncompartmental methods, the transit time, permanence time, and yield of those organs. Our results suggest that the immunocomplexes are formed in the circulation between circulating antibody and antigen, and that the rate of uptake by the liver depends on the concentration of the antibody in blood and not of the immunocomplex. Following deposition in the liver, free antibody does not appear to reenter the circulation, but once there it is catabolized. All breakdown products are then cleared into urine via serum.

Antibodies, Monoclonal↗

Beagle puppy model of perinatal cerebral infarction. Acute changes in cerebral blood flow and metabolism during hemorrhagic hypotension.

Asphyxia, with its attendant hypotension, is by far the most common cause of neonatal cerebral infarction and frequently results in lesions of the parieto-occipital white matter. This study examines the effects of hypotension on regional cerebral blood flow (CBF), local cerebral glucose utilization (LCGU), and serum prostaglandin levels in newborn beagle pups. The animals (24 to 96 hours old) were anesthetized, tracheotomized, and paralyzed. Pups were randomly divided into two groups: one was subjected to hemorrhagic hypotension and the other received no insult. Hypotension was induced by slow venous hemorrhage to maintain a mean arterial blood pressure of 20 to 30 mm Hg. Autoradiographic determinations of LCGU using carbon-14 (14C)-2-deoxyglucose were performed 45 minutes after randomization to groups. Autoradiographic determinations of CBF were performed using 14C-iodoantipyrine on a second group of pups 15 minutes after randomization. Prostaglandins were measured immediately before and 15 minutes after insult or control manipulation. There were no significant differences in the values for thromboxane B2 or 6-keto-prostaglandin F1 alpha, the stable breakdown products of thromboxane A2, and prostacyclin. Prostaglandin E2 levels significantly increased in response to hemorrhagic hypotensive insult. In addition, although regional CBF was maintained in cortical and central gray matter structures during hypotension, CBF to the periventricular temporal and parietal white matter zones significantly decreased, and LCGU was increased in these same regions during hypotensive insult. The uncoupling of CBF and metabolism in these periventricular white matter regions may be responsible for the neuropathological sequelae of perinatal asphyxia.

Animals↗

The ramp injection of radiotracers for blood flow measurement by emission tomography.

A prototype instrument based on the coincidence detection of annihilation radiation was built to control the arterial concentration of a radionuclide as a uniformly increasing ramp function over a preset injection interval (ranging from 1.6 min to 13.6 h). The device was designed to accommodate radionuclides of different physical and biological half-life, and the physiological characteristics of the system being studied. A kinetic model based on the Kety-Schmidt integral was developed to permit the determination of cerebral blood flow (CBF). Both the kinetic model and the ramp injector were tested in cats studied with the PETT III positron emission tomograph and 4-(18F)-fluoroantipyrine as the CBF tracer. The ratio lambda/f of the brain-to-blood partition coefficient (lambda) and blood flow (f) were determined simultaneously by serial measurements with positron emission tomography.

Animals↗