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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

Determination of therapeutic doses of bisquaternary oximes in large animals.

This report presents a non-lethal method for estimating a range of therapeutic doses of bisquaternary oximes that serve as antidotes against organophosphorus poisoning. We have estimated therapeutic oxime doses that are equivalent in their relative toxicity rather than selecting arbitrary fractions of their LD(50). Thus, toxic signs of the oximes HI-6, HLö-7, Toxogonin, AB-8 and AB-13 were monitored quantitatively in baboon monkeys and beagle dogs. Using Toxogonin as a reference oxime, a calculated unit of equivalent dose (CED) was defined as the oxime dose equal to the ratio between its minimal toxic dose (MTD) and the therapeutic ratio (TR) of Toxogonin i.e. CED = MTD/TR. Assuming that the tails of dose-response curves of toxicity for bisquaternary oximes are shallow and similar to one another, one could substitute the ED(10) for the MTD. The ED(10) values for bisquaternary oximes were estimated using the log-log model following experimental observations and quantitative scoring of toxic signs in dogs and monkeys. The MTD values then were calculated using the ED(10) values and the experimental therapeutic dose of the reference oxime Toxogonin. The following CED values were obtained for AB-8, AB-13, Toxogonin, HI-6 and HLö-7 in dogs (d) and monkeys (m): 98.7, 74.2, 30.0, 14.5 and 12.1 (d) and 281.9, 232.1, 41.7, 192.9 and 92.9 (m) micromol kg(-1), respectively. The antidotal efficacy of these oximes against poisoning by the nerve agent tabun was determined in dogs and monkeys. These dose-dependent efficacy data were obtained at 0.3 x CED, 1 x CED and 3 x CED of oximes in combination with atropine. These data provide comparative therapeutic values using oxime doses based on their relative toxicity. The highest antidotal efficacy against tabun in dogs was obtained for toxogonin, whereas HLö-7 and AB-13 were most efficacious in monkeys.

Animals↗
PubMedDate not supplied

Utilization of prenatal cytogenetic diagnosis in women of advanced maternal age in Australia, 1979-1982.

This paper reports the results of a complete national survey to measure utilization rates of prenatal cytogenetic diagnosis (P.C.D.) in women of advanced maternal age in Australia. P.C.D. has been available throughout Australia for the last decade. Every laboratory in Australia providing a P.C.D. service for the years 1979-1982 took part in this study. Utilization rates (both National and State rates) by ages of mothers, are presented. Big interstate differences exist. The 1982 National P.C.D. utilization rate for pregnant women who were 40 years of age and over was 38.8 per cent, and this rate has shown an average annual increase of 9 per cent. In those four States which offered P.C.D. to pregnant women of 35 years or over the median utilization rate was 20 per cent. These Australian rates indicate an under-utilization of P.C.D. services with (in 1982) 50-80 per cent of 'at risk' women not being tested. Factors which influence this are discussed.

Adult↗
PubMedDate not supplied

Endothelin produces systemic vasodilation independent of the state of consciousness.

The effects of endothelin, ET-1, on pulmonary and systemic hemodynamics were studied in the open chest dog and changes in systemic arterial pressure in dogs under conscious and anesthetized states were compared. Rapid intravenous (IV) bolus injections of ET-1, 100-1,000 nanograms/kg, significantly decreased systemic arterial pressure, and significantly decreased systemic vascular resistance whereas left atrial pressure and pulmonary vascular resistance were not altered. Reductions in systemic arterial pressure in response to bolus injection of ET-1, 100 and 300 nanograms/kg IV, during conscious state and during anesthesia were similar, respectively. The present data suggest that ET-1 dilates the systemic vascular bed independent of the animal's state of consciousness. The present data also suggest that when compared to the systemic vascular bed, the pulmonary vascular bed is less responsive to bolus administration of ET-1.

Anesthesia, General↗
PubMedDate not supplied

[Genital sites of giant-cell arteritis].

Temporal arteritis is one of the localisation of the giant cell arteritis. The involvement of the female genital tract had been rarely reported with only 16 cases in the literature. We report 3 cases revealed by a tumor of the genital tract. Histologic features are found in the vessels of ovaries, fallopian tubes and myometrium. Only one patient had symptoms suggestive of temporal arteritis.

Aged↗
PubMedDate not supplied

[Pulmonary metastasis of meningioma of the falx cerebri].

We report the case of a woman who had been operated upon for a recurrent meningioma of the falx cerebri which, 22 years after it was discovered, produced pulmonary metastases. Metastases from meningiomas are extremely rare; they affect the lungs in 60% of the cases or, less frequently, the liver or lymph nodes. The factors predictive of secondary dissemination are the site of the tumour, the quality of excision, the histological type (haemangiopericytic meningioma) and the presence of cell necrosis, hypercellularity and strong mitotic activity.

Adult↗
PubMedDate not supplied

Recent advances in the structure and function of isopenicillin N synthase.

Isopenicillin N synthase is a key enzyme in the biosynthesis of penicillin and cephalosporin antibiotics, catalyzing the oxidative ring closure of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine to form isopenicillin N. Recent advances in our understanding of the unique chemistry of this enzyme have come through the combined application of spectroscopic, molecular genetic and crystallographic approaches and led to important new insights into the structure and function of this enzyme. Here we review new information on the nature of the endogenous ligands that constitute the ferrous iron active site, sequence evidence for a novel structural motif involved in iron binding in this and related non-heme iron dependent dioxygenases, crystal structure studies on the enzyme and its substrate complex and the impact of these and site-directed mutagenesis studies for unraveling the mechanism of the isopenicillin N synthase reaction.

Amino Acid Sequence↗
PubMedDate not supplied

Dose efficiency and the effects of resolution and noise on detail perceptibility in radiographic magnification.

The detail signal-to-noise ratio model of radiographic imaging is quantitatively analyzed in terms of its accuracy in describing observer threshold perceptibility of radiographic detail. The model is found to adequately describe the effects of magnification, scatter radiation, and system resolution on observer threshold perceptibility. However, it is shown that the model does not apply in screen/film radiography for very low contrasts and high scatter conditions due to insufficient optical density contrast. The dose-to-information conversion efficiency of a radiographic imaging system is defined and the effects of magnification, scatter, resolution, image processing, detector efficiency, grids, patient table support, field size, and geometry on the dose efficiency of the imaging system are investigated.

Models, Theoretical↗
PubMedDate not supplied

Contrast-detail-dose and dose efficiency analysis of a scanning digital and a screen-film-grid radiographic system.

The purpose of this study is to examine the diagnostic potential of a scanning digital radiography (SDR) system currently used clinically as a CT localization device. The technique of contrast-detail-dose analysis is used to compare the low-contrast sensitivity and dose efficiency of an SDR unit with standard radiography (SR). The theory of threshold perceptibility in both digital radiography and SR is described, including the effects of scattered radiation and antiscatter devices, object attenuation, geometry, system image processing, and recorder quantum efficiency. The concept of dose efficiency is defined and derived from the contrast-detail-dose data. The SDR system is shown to operate with a threshold signal-to-noise ratio of 7.3 +/- 1.2 for large area detection (d greater than or equal to 2 mm); to be relatively scatter-free; and to be as much a 100x more dose efficient than SR for visualization of large low contrast objects (C less than or equal to 0.04, d greater than or equal to 2 mm).

Contrast Media↗
PubMedDate not supplied

Resolution in radiographic magnification.

Radiographic resolution and image sharpness are analyzed as a function of magnification for a few screen/film systems and a microfocal spot x-ray tube. Resolution and sharpness are described in terms of both MTF and effective aperture. The analysis demonstrates advantages of magnification for any combination of radiographic screen/film system and x-ray focal spot, and, in addition, allows one to compare different screen/film systems each used at different magnifications. Such an analysis is applicable to any radiographic system and may serve as a guide in selecting screen/film systems for use in magnification procedures.

Radiographic Magnification↗
PubMedDate not supplied

Scatter in 240-kVp mobile chest radiography.

The effects of scatter radiation on signal-to-noise ratio and optical density contrast are quantitatively compared for three tissue interfaces at 85, 110, and 240 kVp in mobile chest techniques. It is shown that scatter in the mediastinal portion of the radiograph is virtually independent of energy, while it substantially increases with energy in the lung fields.

Humans↗
PubMedDate not supplied

Relative dose efficiencies of antiscatter grids and air gaps in pediatric radiography.

The relative dose efficiencies (RDE) of various antiscatter grids and air gaps were determined for conditions simulating those found in pediatric radiography, using phantoms representing a newborn child, a 5-yr-old and a 10-yr-old child. Our data indicate than an air gap is best for the newborn, due to the low levels of scatter. The 8:1 fiber grid or 15.2-cm air gap without a grid can improve dose efficiency (DE) for the 5-yr-old child by 20%-25% relative to the 3.3-cm air gap and no-grid technique, while for the 10-yr-old child, DE can be improved by 40% with an 8:1 fiber grid.

Child↗
PubMedDate not supplied

Analysis of variations in contrast-detail experiments.

Three sources of variability in a contrast-detail (CD) experiment have been quantitated: within-observer variance, between-observer variance, and sample variance. It is concluded that (1) it is more efficient to increase the numbers of replicated images and observers than to increase the number of readings; (2) sampling and between-observer variations are approximately equal; (3) one can expect approximately 10% standard errors in the measured value of threshold detail or threshold contrast in a CD experiment which employs four observers, four replicate image samples, and one reading per observer.

Models, Structural↗
PubMedDate not supplied

Nerve terminal damage in cerebral ischemia: greater susceptibility of catecholamine nerve terminals relative to serotonin nerve terminals.

The energy-dependent uptake of (3H)-dopamine (DA), (3H)-norepinephrine (NE) and (3H)-serotonin (5-HT) was measured in synaptosomes isolated from either the whole cerebral hemispheres or the striata of gerbils after cerebral ischemia. Ischemic stroke was induced in the Mongolian gerbil by left common carotid ligation. Uptake values in the affected hemisphere (expressed as a percent of the corresponding control hemisphere) were 32.6% for DA, 35.1% for NE, and 52.0% for 5-HT, 16 hours after stroke. The differential reduction in uptake of the catecholamines relative to 5-HT was significant (p less than 0.005). This differential persisted when measures were made on isolated striata from the ischemic and control hemispheres. In the latter measurements, uptake of DA was 20.7% of control and uptake of 5-HT was 44.7% of control. Uptake of both DA and NE were significantly reduced in animals exhibiting milder circling behavior, while uptake of 5-HT was not. There was no significant reduction of uptake in animals subjected to left common carotid ligation not exhibiting signs of stroke. These studies indicate a selective sensitivity of catecholamine nerve terminals to damage in ischemic stroke.

Animals↗
PubMedDate not supplied

Nerve terminal damage in cerebral ischemia: protective effect of alpha-methyl-para-tyrosine.

Mongolian gerbils were treated with alpha-methyl-para-tyrosine methyl ester (AMPT, a tyrosine hydroxylase inhibitor), in order to decrease brain levels of catecholamines. Six hours later, unilateral ischemic stroke was induced by ligation of the left common carotid artery. The delayed degeneration of nerve terminals was studied sixteen hours later by measuring the high-affinity uptake of radiolabeled transmitters by isolated synaptosomes. Dopamine, serotonin and glutamate terminals were studied. AMPT-treated gerbils were compared to untreated (no AMPT) animals; 220 gerbils were studied. AMPT pretreatment (100, 250 and 400 mg/kg) produced a dose-dependent protection of all three types of nerve terminals. In the absence of AMPT pretreatment, the uptake of radiolabeled transmitters by the ischemic hemisphere, expressed as a percentage of that seen in the contralateral (unaffected) side of the brain, was as follows (mean +/- SEM): 27.3 +/- 5.2% for dopamine terminals, 49.5 +/- 6.2% for serotonin terminals, and 42.7 +/- 5.3% for glutamate terminals. Protection was essentially complete at a dose of 400 mg AMPT per kg. The number of animals with significant damage to nerve terminals was reduced from 38.5% in untreated animals to 11.1% in animals treated with AMPT 400 mg/kg. Although the nerve terminals were protected, gerbils still showed the behavioral signs of unilateral stroke due to the permanent occlusion of the left carotid. These results indicate that endogenous dopamine may play a significant role in ischemic damage to nerve terminals in the cerebrum.

Animals↗