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Biomedical subjects

A Chiari

Publications and source records attributed to A Chiari.

At least 37 records · Page 2Linked to original sources

Stress response to tracheal intubation: direct laryngoscopy compared with blind oral intubation.

Haemodynamic and hormonal responses to tracheal intubation can be profound and associated with serious cardiovascular and cerebral side effects. The Augustine Guide, a device enabling blind oral intubation, has been introduced recently. The aim of our study was to compare the haemodynamic and hormonal stress response of this method with direct laryngoscopy. Thirty five patients (ASA 1 and 2) were randomly assigned to undergo either direct laryngoscopy (n = 17), or blind oral intubation (n = 18). Haemodynamic responses and concentrations of adrenaline, noradrenaline and prolactin were determined prior to induction, before intubation and 5 min after intubation. The median duration of intubation was 22s for direct laryngoscopy vs 46s for blind oral intubation (p < 0.05). Between the groups, no significant differences were observed for heart rate, systolic or mean arterial blood pressure. Serum levels of adrenaline decreased slightly after induction and remained unaltered after intubation in both groups. Noradrenaline (1.01 vs 0.66 nmol.l-1) and prolactin (5.2 vs 2.9 nmol.l-1) levels were significantly higher after direct laryngoscopy compared to blind oral intubation. Although blind oral intubation took significantly longer to perform than direct laryngoscopy, hormonal stress response was less pronounced. Blind oral intubation should therefore not be withheld from patients with impaired cardiovascular reserve.

Adolescent↗

[Urethrovesical morphology in continent women in spinal anesthesia].

OBJECTIVE: To assess the influence of spinal anesthesia on bladder neck position and a clinical stress test in continent women. METHODS: In a prospective investigation, 14 women underwent urodynamic, sonographic and clinical assessment during spinal anesthesia. Results were compared to those obtained immediately preoperatively in the same patient. RESULTS: During spinal anesthesia, the bladder neck was found to be located significantly lower and more posterior, and in 4/7 parous patients (0/7 nullipara) the clinical stress test was positive. CONCLUSION: These data provide additional evidence for the importance of neuromuscular function in the etiology of pelvic floor dysfunction and genuine stress incontinence.

Adult↗

Imidazolylbenzopyrane derivatives: a new class of acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors.

Inhibitors of the enzyme Acyl-CoA: Cholesterol Acyltransferase are regarded as potentially useful agents in the treatment of hypercholesterolemia and atherosclerosis. We report here a novel series of 2, 6-disubstituted-3-imidazolylbenzopyrane derivatives with significant in vitro ACAT inhibitory activity (IC50 range 0.05-0.5 microM). Compounds of this series such as 26 are examples of a new, structurally distinct class of potent ACAT inhibitors with high specificity for the aortic subtype of the enzyme. The structure-activity relationships of the 3-imidazolylbenzopyrane ACAT inhibitors were investigated by systematic manipulation of two regions of the parent compound 1 and the inhibitory activity resulted linked to the substituent in position 6 of the benzopyrane ring and modulated by the size of lipophilic substituents in position 2. Investigation of the mechanism of the inhibitory effect leads to the conclusion that these compounds act in a non-competitive fashion.

Animals↗

Anticoagulation with prostacyclin and heparin during continuous venovenous hemofiltration.

OBJECTIVES: To investigate anticoagulation with prostacyclin (prostaglandin I2 [PGI2]) and/or heparin during continuous venovenous hemofiltration, and the role of in vitro tests of primary hemostasis in controlling anticoagulation. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive care unit. PATIENTS: Forty-six consecutive, critically ill, mechanically ventilated patients with postoperative acute renal failure. INTERVENTIONS: Anticoagulation of the patient's blood was accomplished using heparin (6.0 +/- 0.3 IU/kg/hr for group 1), PGI2 (7.7 +/- 0.7 ng/kg/min for group 2), or both PGI2 and heparin (6.4 +/- 0.3 ng/kg/min, 5.0 +/- 0.4 IU/kg/hr, respectively, for group 3), administered into the extracorporeal line before the hemofilter during continuous venovenous hemofiltration. MEASUREMENTS AND MAIN RESULTS: After Ethics Committee approval and informed consent were obtained, tests of primary and secondary hemostasis, plasma concentrations of 6-ketoprostaglandin F1 alpha (by radioimmunoassay), and hemodynamic measurements were performed before hemofiltration and 24 hrs after hemofiltration. In groups 1 and 3, hemodynamic parameters remained stable, whereas in group 2 (the PGI2 group), there were significant reductions in systemic and pulmonary vascular resistances and mean arterial pressure. Platelet function was unchanged in group 1, and was inhibited in groups 2 and 3. Corresponding with the prolongation of in vitro bleeding time, the 6-ketoprostaglandin F1 alpha concentration was increased, indicating an effective inhibition of platelet aggregation within the hemofilter. Platelet counts remained stable in all patients. Plasma coagulation tests were stable in groups 2 and 3, and were prolonged in group 1. In all patients, no major bleeding complications were observed and there was no clinically important bleeding. Mean hemofilter duration lasted longest in group 3. Blood urea nitrogen and circulating creatinine concentrations decreased significantly in groups 2 and 3 within the study period. CONCLUSIONS: Patients receiving both PGI2 and heparin showed better hemodynamic profiles and enhanced hemofilter duration compared with the other groups and no bleeding complications were observed. Therefore, we recommend anticoagulation with PGI2 and heparin during continuous venovenous hemofiltration with close monitoring of platelet function, coagulation profile, and overall hemodynamics.

6-Ketoprostaglandin F1 alpha↗

Results and implications of high-resolution surface dosimetry of ruthenium-106 eye applicators.

The dosimetry of 106Ru/106Rh beta-emitting eye applicators is still inadequate. Manufacturer's specifications of absolute dose rates are loaded with a +/- 30% error, and the relative distribution of activity on the surface is measured on a few points only, using a 3-mm plastic scintillation probe. While reducing the absolute error of dose rate measurements to +/- 15% by a method published earlier, we now present a phantom using small thermoluminescent dosimetry crystals for refined assessment of its distribution over the surface. Evaluation of two applicators revealed a 50% increase in activity in the midperiphery in one and a steep falloff of activity 1 mm within the margin of both specimens. The method and findings are demonstrated in detail and compared to those reported by other authors.

Brachytherapy↗

Ethyl 2-([5,6-dihydro-7-(1H-imidazol-1-yl)-2-naphthalenyl]oxy)- 2-methylpropanoate as a new potent oxyisobutyrate hypolipidaemic with unusual features.

Some compounds containing the N-imidazolyl and the ethyl oxy-isobutyrate groups linked to a naphthalene ring structure and some related analogues were synthesized and tested for hypolipidaemic activity. Ethyl 2-([5,6- dihydro-7-(1H-imidazol-1-yl)-2-naphthalenyl]oxy)- 2-methylpropanoate (V) proved to be a strong hypolipidaemic agent, several times more potent than clofibrate. Structural requirements for activity and differences from clofibrate analogues are discussed.

Animals↗

N-imidazolylchroman-4-ones, N-imidazolyl-1-tetralones, and their alcohols as hypolipemic agents raising high-density lipoproteins.

A series of 3-(1-imidazolyl)chroman-4-ones and 2-(1-imidazolyl)-1-tetralones II, some of their alcohols, and some related compounds were synthesized and tested for hypolipidemic activity. Compounds II, bearing appropriate lipophilic substituents on the phenyl ring, strongly reduced total serum cholesterol while raising high-density lipoprotein cholesterol in diet-induced hypercholesterolemic rats. 3-(1-Imidazolyl)chroman-4-ols and 2-(1-imidazolyl)-1-tetralols corresponding to II retained the hypolipidemic activity while removal of the carbonyl or hydroxy group adjacent to imidazole gave inactive compounds. Although many of the active compounds significantly increased liver weight, the one studied as a model, 6-chloro-3-(1-imidazolyl)-2,3-dihydro-4H-1-benzopyran-4-one (5), caused no peroxisome proliferation. Compound 5 and the corresponding alcohol 40, as representatives of the ketone and alcohol series, showed significant hypolipidemic activity in normolipemic rats. Some of the compounds assayed in cholesterol biosynthesis inhibited acetate incorporation but none inhibited HMG-CoA reductase. 5-Bromo-6-hydroxy-2-(1-imidazolyl)-3,4-dihydro-1(2H)-naphthalenone (38), which showed strong activity but caused little hepatomegaly in the rat, was chosen for further pharmacological evaluation.

Alcohols↗

Effect of the antilipolytic compound acipimox on peroxisome marker enzymes, lipid pattern and biotransformation related functions in rat liver.

The antilipolytic drug acipimox (5-methylpyrazine-2-carboxylic acid 4-oxide) was given to male rats for 1 week at 500, 1000 and 2000 mg/kg/day and for 2, 6 and 7 months at 20, 100 and 500 mg/kg/day. The peroxisome proliferative effect was evaluated determining the activity of catalase and carnitine acetyltransferase, the rate of cyanide-insensitive palmitoyl CoA oxidation and the electrophoretic profile of liver polypeptides. Hepatic lipid content and distribution were evaluated after 2 and 6 months' treatment. The effect on liver detoxificating function was evaluated by assaying glutathione, cytochrome P-450, glutathione-S-transferase and glutathione-reductase activities after 7 months' treatment. Sub-acute and chronic treatment with a wide range of acipimox doses did not cause hepatomegaly, liver peroxisome proliferation or liver steatosis and did not change some important biochemical variables related to detoxification and biotransformation mechanisms. Acipimox given to rats does not have the negative side-effects of other compounds and seems a safe blood lipid lowering drug.

Animals↗

In vivo imaging of the spinal cord cholinergic system with PET.

PURPOSE: Our goal was to demonstrate the feasibility of an in vivo noninvasive method for imaging spinal cord cholinergic terminals using (+)-4-[18F]fluorobenzyltrozamicol ([18F]FBT) and PET. METHOD: In vitro and in vivo experiments in rats were conducted to demonstrate the specific binding characteristics, localization, and time course of [3H]FBT binding in the spinal cord. PET imaging was then performed on seven rhesus monkeys. RESULTS: The rat studies demonstrate high specific binding in the spinal cord with a distribution coinciding with the known distribution of cholinergic terminals. In vivo tracer concentrations in the spinal cord and basal ganglia were of the same magnitude. With use of [18F]FBT and PET in the rhesus monkey, the spinal cord was clearly visualized, with tracer concentration in the spinal cord being approximately one-fourth of that seen in the basal ganglia. CONCLUSION: This work demonstrates the feasibility of imaging cholinergic terminals in vivo in the spinal cord using [18F]FBT and PET.

Animals↗

Peritoneal macrophage cholesteryl ester content as a function of plasma cholesterol in rats.

Cholesterol accumulation in macrophages that have migrated in the subintimal space leads to foam cell formation, which is believed to be one of the initiating events in atherosclerosis. In this study we investigated the effect of cholesterol feeding on peritoneal monocyte/macrophage cholesterol content and peritoneal cavity lipoprotein composition in rats. A cholesterol (2%) and cholic acid (1%) diet caused significant hypercholesterolemia in plasma, and at the same time the cholesterol content of peritoneal monocytes/macrophages was increased. At day 7, the cellular cholesteryl ester content had risen to 30.1 micrograms/mg cellular protein from a baseline value of 9.2 micrograms/mg. The unesterified cholesterol content also increased by 56%. At this time, acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was doubled, whereas neutral and acidic cholesteryl ester hydrolase activities were unchanged. Reversal to the regular chow diet after 7 days of the cholesterol-enriched diet normalized plasma cholesterol levels as well as peritoneal monocyte/macrophage cholesteryl ester content. ACAT activity also decreased toward normal levels. Analysis of the d less than 1.21 g/ml peritoneal lipoproteins isolated by ultracentrifugation revealed the presence, in both normal and hypercholesterolemic rats, of apolipoprotein A-I-rich lipid complexes with pre-beta mobility on agarose gel electrophoresis. The size of the peritoneal lipoproteins was smaller than that of plasmatic high density lipoproteins, and their chemical composition was also different from that of the major plasma lipoproteins. The cholesteryl ester content of peritoneal lipoproteins increased after feeding of the cholesterol-enriched diet. In conclusion, our results show that cholesterol feeding leads to rapid accumulation of cholesteryl esters in monocytes/macrophages. As soon as plasma cholesterol levels are returned to normal, cellular cholesterol content is also normalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗