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Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 325 records · Page 18Linked to original sources

Prevention of cecitis in hamsters by certain prostaglandins.

Acute inflammation of the colon (cecitis) was produced in hamsters by daily subcutaneous administration of an antibiotic for 3 days. The following prostaglandins completely prevented the cecitis: 16,16-dimethyl-PGE2, 15(R)-15-methyl-PGE2, and 2-acetyl-2-decarboxy-15(S)-15-methyl-PGF2 alpha. PGF2 beta was less active. The synthesis of 2-acetyl-2-decarboxy-15(S)-methyl-PGF2 alpha is described. Castor oil also prevented the cecitis and peanut oil exerted partial protection. Since these oils contain linoleic acid, a precursor of PGE1, protection may have been due to endogenous formation of that prostaglandin. A partial block of the protective effect of castor oil by treatment with indomethacin supports such mechanism. The tissue level of endogenous prostaglandins seems to exert protection since administration of cyclooxygenase inhibitors, indomethacin and aspirin, markedly increased the incidence of cecitis. Magnesium sulfate given orally and sodium salicylate given subcutaneously reduced the incidence of cecitis only partially. The following agents were inactive: loperamide, an antidiarrheic agent; carbachol, a cholinergic and diarrheogenic agent, atropine, an anticholinergic agent; and acetazolamide, a carbonic anhydrase inhibitor. These results, show that certain prostaglandins, which have been shown earlier to be cytoprotective for the stomach and the small intestine, are cytoprotective for the large intestine as well.

Animals↗

The endosomal compartment of rat hepatocytes. Its characterization in the course of [125I]insulin internalization.

When freshly isolated hepatocytes are incubated with [125I]insulin in the presence of the microtubule-disrupting agent colchicine, internalization of the labelled hormone is not significantly altered. However, the drug limits the endocytosis of the labelled material to a peripheral band of cytoplasm extending 1 micron beyond the plasma membrane. Both in the presence and absence of colchicine, internalized [125I]insulin preferentially associates with clear vesicles (endosomes) and lysosome-like structures, but the relative amount of labelled material associated with clear vesicles is higher in the presence of the drug than in its absence. An inverse pattern is observed for the lysosome-like structures. As demonstrated by cytochemical methods, clear vesicles do not contain the lysosomal enzyme aryl sulfatase. Moreover, colchicine induces an increase of the clear vesicle diameter without affecting their frequency, while it perturbs multivesicular bodies and dense bodies in an opposite way by increasing their frequency without affecting their size. By reducing and/or delaying the fusion between internalized endocytotic vesicles and lysosomes, colchicine allows better characterization of the endosomal compartment of isolated rat hepatocytes and allows it to be distinguished from other compartments, such as multivesicular bodies and the Golgi apparatus.

Animals↗

Cytoprotection by prostaglandin occurs in spite of penetration of absolute ethanol into the gastric mucosa.

Several prostaglandins are cytoprotective for the stomach; they prevent mucosal necrosis and hemorrhages produced by noxious agents, such as absolute ethanol. One possible mechanism of cytoprotection would be that the prostaglandin may prevent penetration of the necrotizing agent into the gastric mucosa. To test this hypothesis, 2 ml of 100% ethanol containing tracer amounts of 14C at carbon 1 was given orally to rats, after ligating the pylorus. [14C]Ethanol was measured in the gastric mucosa and in plasma from 2.5 to 60 min after ethanol administration. 16,16-Dimethyl prostaglandin E2 was given orally at a cytoprotective dose (10 micrograms/kg) 15 min before 100% ethanol. The level of [14C]ethanol (disintegrations per minute per gram of tissue) in the gastric mucosa of 16,16-dimethyl prostaglandin E2-treated animals were not different from those of control animals. The plasma levels were slightly lower during the first 10 min, but the area under the curve for the entire 60 min was the same in both groups. We conclude that (a) 16,16-dimethyl prostaglandin E2 does not prevent entry of ethanol into the gastric mucosa; (b) 16,16-dimethyl prostaglandin E2 protects the cells located deep in the gastric mucosa from necrosis, in spite of the fact that these cells are in contact with as much ethanol as cells of untreated animals; (c) gastric cytoprotection is probably due to a defense mechanism at the cellular level. These findings minimize the importance of luminal factors, such as an increase in mucus or bicarbonate, in the mechanism of cytoprotection.

16,16-Dimethylprostaglandin E2↗

[Postoperative analgesic effect of pethidine injected epidurally].

Postoperative pain was treated by epidural administration of 30 to 50 mg pethidine (5 mg X ml-1) in a group of 36 patients who had undergone retropubic prostatectomy. Surgery was carried out under epidural anaesthesia with lidocaine. Pain was assessed by means of the visual analogue scale. A general study of the effects of injections and reinjections showed that analgesia thus obtained was excellent at the first hour after injection and lasted 3 to 5 h. The effect of the first postoperative injection on spontaneous pain was studied in 14 patients. Statistical analysis (Wilcoxon test) demonstrated that the fall in pain score was significant at the first and third hours after injection, but not significant at the fifth hour. The analgesia to that pain produced by coughing was studied in 11 patients. There was a significant decrease in pain at the first hour after injection; differences in pain scores at the third hour were not significant. No noticeable side-effect was observed. It was concluded that low doses of epidural pethidine were efficient on postoperative pelvic abdominal pain, but that doses should be increased if painless coughing was required.

Aged↗

Diagnostic value of computerized exercise testing in men without previous myocardial infarction. A multivariate, compartmental and probabilistic approach.

The value of exercise testing for the diagnosis of coronary artery disease is disputed but very few studies have taken advantage of all recent improvements, namely computer averaging of the ECG signals, multivariate analysis of the data, a compartmental diagnostic approach and probabilistic interpretation of the results. These methods were tested in a group of 387 men who had a computer-assisted multistage maximal exercise test; none had a history of myocardial infarction. In 284 symptomatic patients, the diagnosis was made by arteriography; 103 ostensibly healthy men were also included. The computer-averaged ECG signals (X, Y, Z) recorded at maximal exercise, maximal heart rate, blood pressure and workload, and the onset of angina pectoris during exercise were submitted to a multivariate stepwise discriminant analysis. The pretest likelihood for CAD was calculated from age and history; the post-test likelihood was calculated from Bayes' theorem and the average information content of several diagnostic methods was assessed in categorical and compartmental models. By multivariate analysis, 5 variables collected at maximal exercise were selected, namely the heart-rate, the ST60 segment level, the onset of angina during the test, the workload and the slope of the ST segment in lead X. The average information content of the analysis using 5 variables was 44% in a categorical model versus 55% in a compartmental model (P less than 0.001). For comparison, the information content of the analysis using the ST60 segment level alone was only 16% in the categorical model and 27% in the compartmental model. The clinical value of these diagnostic methods (categorical versus compartmental, univariate versus multivariate) was assessed by a probabilistic classification of the patients. The classification provided by the analysis of the ST60 segment changes was barely better than that one provided by the simple history. The probabilistic use of a multivariate and compartmental analysis of the data led to a significantly better and more accurate classification of the patients (83% of correct classification).

Adult↗

Alternative diagnostic strategies for coronary artery disease in women: demonstration of the usefulness and efficiency of probability analysis.

Alternative strategies using conditional probability analysis for the diagnosis of coronary artery disease (CAD) were examined in 93 infarct-free women presenting with chest pain. Another group of 42 consecutive female patients was prospectively analyzed. For this latter group, the physician had access to the pretest and posttest probability of CAD before coronary angiography. These 135 women all underwent stress electrocardiographic, thallium scintigraphic, and coronary angiographic examination. The pretest and posttest probabilities of coronary disease were derived from a computerized Bayesian algorithm. Probability estimates were calculated by the four following hypothetical strategies: SO, in which history, including risk factors, was considered; S1, in which history and stress electrocardiographic results were considered; S2, in which history and stress electrocardiographic and stress thallium scintigraphic results were considered; and S3, in which history and stress electrocardiographic results were used, but in which stress scintigraphic results were considered only if the poststress probability of CAD was between 10% and 90%, i.e., if a sufficient level of diagnostic certainty could not be obtained with the electrocardiographic results alone. The strategies were compared with respect to accuracy with the coronary angiogram as the standard. For both groups of women, S2 and S3 were found to be the most accurate in predicting the presence or absence of coronary disease (p less than .05). However, it was found with use of S3 that more than one-third of the thallium scintigrams could have been avoided without loss of accuracy. It was also found that diagnostic catheterization performed to exclude CAD as a diagnosis could have been avoided in half of the patients without loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prostaglandin cytoprotection: role of microcirculatory changes.

Both the fluorescent in vivo microscopic study and the hydrogen-gas-clearance study revealed complete absence of blood flow in the areas of gross ethanol damage. PG pretreatment prevented this cessation of flow. However, the hydrogen-gas-clearance study demonstrated that PG administered in a cytoprotective dose did not increase blood flow. It maintained blood flow by some other mechanism. The final in vivo microscopic studies demonstrated a marked leak of albumin from microvessels and slowing and then cessation of flow very shortly after topical ethanol application. This suggests that an increase in blood viscosity due to plasma leak may be the mechanism of the ethanol-induced flow stasis. PG prevented this leak. PG cytoprotection, by preventing this permeability change, maintains mucosal blood flow and may thus protect the mucosa against the deeper and more severe ethanol injury.

16,16-Dimethylprostaglandin E2↗

Human circulating monocytes internalize 125I-insulin in a similar fashion to rat hepatocytes: relevance to receptor regulation in target and nontarget tissues.

Circulating monocytes bind 125I-insulin in a specific fashion and have been used to analyze the ambient receptor status in humans. When freshly isolated circulating monocytes are incubated with 125I-insulin and examined by electron microscopic autoradiography, approximately 18% of the labeled material is internalized after 15 minutes at 37 degrees C. By 2 hours at 37 degrees C, approximately one half of the 125I-insulin is internalized. Internalization occurs also at 15 degrees C but at a slower rate. Furthermore, the monocytes bind and internalize 125I-insulin in a manner that mirrors that of major target tissues, such as rat hepatocytes. These data suggest that the insulin receptor of the circulating monocyte might be regulated by adsorptive endocytosis in a manner analogous to that of target tissue, such as the liver.

Animals↗

Validation of radionuclide cardiac output measurements during exercise.

A nongeometric radionuclide technique with correction for attenuation was used for the determination of cardiac output and stroke volume during exercise in nine normal subjects and in ten hypertensive patients. Simultaneous reference stroke volume (range 48-159 ml) and cardiac output (range 3.6-23.8 l/min) measurements were obtained by the Fick method. Data were collected at rest and during 60 degrees upright exercise, at two or three levels of increasing severity. Three statistical measurements were used for the comparison of both methods: correlation, precision, and accuracy. Radionuclide and Fick cardiac output measurements (n = 67, rest and exercise data) correlated well (r = 0.90). For stroke volume, the correlation was less (r = 0.64); however, the precision or random variability of both methods was similar for stroke volume (radionuclide: 8 ml or 9%; Fick: 16 ml or 16%). The accuracy or systematic error was defined as the mean difference between radionuclide and Fick measurements. The radionuclide method underestimated the Fick measurements. The systematic error was 18 +/- 18 ml for stroke volume and 2.4 +/- 2.4 l/m for cardiac output. A similar comparison of both methods was made on the absolute changes of stroke volume (r = 0.61; range -19 + 70 ml) and cardiac output (r = 0.82; range +1.6 + 16.4 l/m) between rest and exercise. The precision of the two methods was similar; the systematic error was 1.9 +/- 2.2 l/m for cardiac output and 6 +/- 17 ml for stroke volume. Thus, in these two groups of patients, although radionuclide and Fick cardiac output measurements at rest and during exercise correlated well, the radionuclide values were systematically and significantly lower.

Adult↗

[Effect of the presence of females on the concentration of androgens in the male guinea pig at puberty].

At weaning (21 days), male guinea-pigs were assigned to three groups: A: two or three males with females in separate cages but in the same room; B: two males with one pubertal female in each cage; C: males without female in the environment. Animals were sacrificed on 50th day. Testosterone and androstenedione concentrations in the blood plasma and the testis were estimated by gas chromatography. The body and testicular weights of group C were lower than those of other groups. Testosterone and androstenedione levels in the plasma were lower in group C; testicular concentration of testosterone was similar in group A and C whereas level was weak in group B. Testicular concentration of androstenedione was increased with animals isolated of female. The results showed that, in guinea-pig at puberty, the presence or the lack of female, modify testicular weight and androgen concentration.

Androstenedione↗

Role of exercise testing and stress thallium scintigraphy in the management of old men with suspected or documented coronary artery disease.

From 217 old men submitted to a symptom-limited maximal exercise test, 145 had also an exercise thallium scintigraphy; 44 of those patients were submitted to an angiography. The decision to perform angiography in these aged patients was based mostly on their history and their complaints. This decision was likely influenced by the results of the exercise test; even in symptomatic patients, angiography was rarely performed when the exercise data were normal (normal ECG, no angina during the test). The thallium scintigraphy was not a major element in the overall clinical decision making: when the scintigraphy was available, it contributed, however, to refine the decision whether or not to perform an angiography.

Aged↗

Role of glutathione in gastric mucosal cytoprotection.

Exogenous thiol compounds have been reported to protect the stomach from ethanol-induced necrotic lesions. The gastric mucosa contains high levels of an endogenous thiol, glutathion (GSH). Because of the known role of glutathione in protecting against hepatic injury, its role in gastric mucosal cytoprotection was of interest. By use of an animal model for acute gastric injury from ethanol, a close parallel relation between depletion of endogenous mucosal GSH and induction of mucosal protection was demonstrated. Surprisingly, mucosal protection varied inversely with the level of mucosal GSH obtained after treatment with specific GSH-depleting agents (diethyl maleate and cyclohexene-1-one). Depletion of gastric mucosal GSH was associated with an increase in the mucosal content of prostaglandins 6-keto F1 alpha and F2 alpha but not E2. The protective effect induced by GSH-depleting agents was partially reversed by indomethacin in some but not all studies. Although GSH depletors increased gastric juice volume, protection with these agents persisted after the volume and mucosal GSH had returned to control levels and also was not reversed by increasing the dose of ethanol threefold to overcome a possible dilutional effect. We conclude that, contrary to apparent predictions, depletion of endogenous gastric GSH protects the stomach from acute ethanol-induced injury. Although the mechanism of this protection is unknown, a mediation by endogenous release of prostaglandins seems to play a minor role since diethyl maleate was protective even in indomethacin-treated animals.

6-Ketoprostaglandin F1 alpha↗