Sickling crisis, fat embolism, and coma after steroids.
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Acute Disease↗
Biomedical subjects
R Gay
Publications and source records attributed to R Gay.
Gas gangrene and purulent pericarditis during Clostridium septicemia revealing a cecal carcinoma.
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Adenocarcinoma↗
Pharmacokinetics and dosage regimens of amikacin in intensive care unit patients.
The pharmacokinetics of amikacin have been studied in 40 intensive care unit (ICU) patients using a two-compartment model and the Bayesian estimation method implemented in the USC PC-PACK program of Jelliffe et al. The volume of the central compartment was significantly higher in these patients (0.36 l.kg-1) than in the reference population (0.20 l.kg-1). A method has been designed to compute dosage regimens in order to maintain a constant steady-state average plasma concentration of 8 mg.l-1 for repeated i.v. infusions. The regimen calculated for the 'average' ICU patient varies between 11 mg.kg-1 three times per day for the patient with normal renal function and 6 mg.kg-1 every 2 days for the anuric patient. This regimen is intended to begin amikacin therapy in an ICU patient, while the population pharmacokinetic parameters would allow the individualization of the regimen by means of the Bayesian method.
Amikacin↗
The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase II) oil/water emulsions.
The Cosmetic, Toiletry and Fragrance Association (CTFA) Evaluation of Alternatives Program is an evaluation of the relationship between Draize ocular safety test data and comparable data from a selection of in vitro tests. In Phase II, 18 representative oil/water-based personal-care formulations were subjected to the Draize primary eye safety test and 30 in vitro assay protocols (14 different types of in vitro endpoints were evaluated; the remainder were protocol variations). Correlation of in vitro with in vivo data was evaluated using analysis of sensitivity/specificity and statistical analysis of the relationship between maximum average Draize score (MAS) and in vitro endpoint. Regression modelling is the primary approach adopted in the CTFA Program for evaluating in vitro assay performance. The objective of regression analysis is to predict MAS for a given test material (and to place upper and lower prediction interval bounds on the range in which the MAS is anticipated to fall with high probability) conditional on observing an in vitro assay score for that material. The degree of confidence in prediction is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curves: the narrower the prediction interval, the more predictive of the Draize score is the in vitro test result. 16 assays were shown to have the greatest agreement with the Draize procedure and were therefore selected for regression analysis. Based on the magnitude of the 95% prediction bounds of each of the 16 selected assays over the range of test data, it may be inferred that prediction of MAS values from experimentally determined in vitro scores is more accurate for oil/water-based formulations with lower rather than higher irritancy potential. The assays selected for modelling in Phase II generally exhibited weaker relationships with MAS than those selected in Phase I (evaluated using hydroalcoholic formulations), even though several assays were common to both Phases.
3T3 Cells↗
Population pharmacokinetic parameters for Bayesian monitoring of amikacin therapy in intensive care unit patients.
The pharmacokinetics of amikacin has been studied in 40 intensive care unit patients using the bayesian estimation method implemented in the USC PC PACK program of Jelliffe. The volume of the central compartment was significantly higher in these patients than in the reference population, while other pharmacokinetic parameters did not differ significantly from the reference values. The population values may be employed, in addition to those supplied with the software, to adapt dosage regimens of amikacin in ICU patients.
Adolescent↗
Absorption and metabolism of topically applied testosterone in an organotypic skin culture.
The Living Skin Equivalent (LSE) is an organotypic coculture of human dermal fibroblasts in a collagen-containing matrix and a stratified epidermis composed of human epidermal keratinocytes. In order to establish the feasibility of using this in vitro system as a model for cutaneous biotransformation, the metabolic fate of topically applied testosterone (T) was monitored in the LSE. After a 24-hour exposure period (37 degrees C) to radiolabelled T, LSE extracts analyzed by high-performance thin-layer chromatography showed that approximately 50% of the applied T had been metabolized. Identified metabolites included bands which comigrated with polar metabolites and products of T 5 alpha-reductase. The general distribution of the observed metabolites was similar to that obtained using biopsied human skin. The rates of T penetration (32 degrees C) through the LSE were monitored after application of T in two vehicles (water and petrolatum) and yielded permeability constants (Kps) of 29 and 1.6 x 10(-3) cm/h, respectively. These Kp values were 4- to 6-fold higher than those reported for human abdominal skin, and reflect the vehicle-related shift in penetration seen in human skin. The Kp values for two additional steroids, estradiol and hydrocortisone, and for T were also determined at 22 degrees C and compared to published Kp values. These Kp values in the LSE were, respectively, 63-, 187- and 35-fold higher than those reported for human skin. The data suggest that compared to human skin the LSE has only a partial barrier function to the passage of test chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdomen↗
[History of mechanical ventilation].
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History, 16th Century↗
Mercuric reductase activity in the adaptation to cationic mercury, phenyl mercuric acetate and multiple antibiotics of a gram-negative population isolated from an aerobic fixed-bed reactor.
Eighty-eight strains, isolated from an aerobic fixed-bed reactor and identified to the genus level, were examined for resistance to 21 antibiotics, cationic mercury and phenylmercuric acetate. All except three were able to grow on Mueller-Hinton agar plates containing 8 micrograms/ml mercuric chloride, but only 42 exhibited a mercuric reductase and an organomercurial lyase activity. Furthermore, 82 of them were multiply-antibiotic resistant, whereas no positive correlation between this property and cationic mercury volatilization capacity was found. It was concluded that this bacterial community-adapted response to these selective agents, which has been most often shown to be mediated by R plasmids, was the result of two independent phenomena. Moreover, the high percentage of multiple antibiotic and mercury resistance found in this population suggested that simultaneous selections occurred on filters of bacteria which exhibited mucoid colonies and tolerance to these two categories of stress agents.
Anti-Bacterial Agents↗
Recipes for reconstituting skin.
Reconstituted Living Skin Equivalent (LSE) is made up of a dermal equivalent (DE) on which keratinocytes are plated where they give rise to a multilayered differentiated epidermis. The dermal equivalent develops through interactions between fibroblasts and collagen fibrils that begin to form after the cell-matrix precursor is cast. The gel that forms as a result of collagen polymerization and fluid trapping is contracted uniformly in all dimensions. By securing it at ends and edges in the mold in which it is cast, the final dimensions, strength and morphology of the forming tissue are altered. The same phenomena are seen in casting tubular tissues for the fabrication of small caliber blood vessel equivalents. The cells of the dermal equivalent are biosynthetically active and enrich the matrix to different degrees with secretory products, depending on how the cells are stimulated and on the presence or absence of an epidermis. Collagen biosynthesis by dermal cells in the DE is sensitive to growth factors, ascorbate concentrations and amino acid pools. Both ascorbate and TGF beta 1 increase total collagen biosynthesis at least two-fold by one week after tissue formation. With TGF beta 1 present, the capacity of cells in the DE to synthesize collagen increases with time, over a two-week period. If ascorbate (200 micrograms/ml) is added just after the tissue is cast and daily thereafter, contraction lattice is blocked, and collagen biosynthesis is enhanced relative to contracted controls that had received 200 micrograms/ml ascorbate once. The increase was nearly an order of magnitude over that of controls and was coordinate with a comparable increase in hyaluronate and sulfated glycosaminoglycan (GAG) production as shown by TCA-precipitable glucosamine in the intercellular matrix of the DE. Both the LSE and the Living Dermal Equivalent (LDE) exhibit complex responses to UV radiation and to various chemicals that are greatly different from responses given by monolayered cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acids↗
Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure.
Abnormalities in vasomotor tone, including enhanced vasoconstriction at rest and diminished vasodilation in response to various stimuli, develop as a consequence of chronic heart failure. This study was undertaken to evaluate whether a specific local mechanism, namely endothelium-derived relaxing factor (EDRF) activity, might be impaired in an experimental model of chronic heart failure. Segments of thoracic aorta (TA) and pulmonary artery (PA) were isolated from a group of rats that had hemodynamic evidence of heart failure 10 weeks after ligation of the left coronary artery (n = 25) and from a group of sham-operated control rats (n = 18). Both endothelium-dependent and endothelium-independent vascular responses were assessed by exposing arterial segments to increasing concentrations of agonists. All studies were performed in the presence of 10 microM indomethacin to avoid the influence of vasoactive prostanoids. The dose-response curve for EDRF-mediated relaxation to acetylcholine was shifted rightward in rats with heart failure, and the concentrations of acetylcholine required to achieve 50% maximal relaxation (EC50) were increased compared with those of control rats in both TA and PA segments. Additionally, the dose-response curve for relaxation to ADP was shifted rightward with significantly increased EC50 in PA segments from rats with heart failure. In contrast, EDRF-mediated relaxation to the calcium ionophore A23187 was similar in the groups. Endothelium-independent relaxation to nitroglycerin was slightly increased in TA but not PA segments in the heart-failure group. Basal EDRF activity, as assessed by the increase in force after exposure to hemoglobin, was diminished in PA segments from rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Increased expression of the gene for the pro alpha 1(IV) chain of basement-membrane procollagen in cultured skin fibroblasts from two variants of osteogenesis imperfecta.
Fibroblasts from two lethal variants of osteogenesis imperfecta were shown to synthesize increased amounts of type IV procollagen. Previous studies established that one of these variants had a non-functional allele for the pro alpha 2 chain of type I procollagen, whereas the other pro alpha 2(I) allele contained a mutation leading to synthesis of shortened pro alpha 2(I) chains. In the two variants, the relative level of mRNA for pro alpha 1(IV) was 31 and 42% of the level of mRNA for pro alpha 1(I) chains. A value of less than 2% was found for a third lethal and four non-lethal variants of osteogenesis imperfecta. Immunofluorescent staining of fibroblasts from the two variants synthesizing increased amounts of type IV procollagen indicated that a homogeneous population of cells synthesized both type IV and type I procollagen. The results suggest that mutations in the type I procollagen genes that result in osteogenesis imperfecta can be associated with increased expression of the genes for type IV procollagen.
Basement Membrane↗
Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction.
The proportion of cardiac energy derived from fatty acid oxidation decreases and that derived from glucose increases during ischemia. This biochemical profile of cardiac energy production is achieved in rats and mice without ischemia by pharmacological agents such as tetradecylglycidic acid. Chronically this leads to increased cardiac stiffness, and hypertrophy in the rodent models. Elements of human cardiac dysfunction are hypothesized to develop from and/or cause similar changes in substrate utilization for energy production. For some individuals treatment that would prevent or reverse these changes may be appropriate.
Animals↗
Pyruvate fermentation by Clostridium acetobutylicum.
Clostridium acetobutylicum ATCC 824 using pyruvate as the sole carbon source produced mainly acetate and butyrate as end products of fermentation. Acetate and butyrate kinase activities were higher in cells growing in the presence of pyruvate than glucose, whereas the level of the acetoacetate decarboxylase, an enzyme involved in solvent formation, was lower. Similar activities of glyceraldehyde-3-phosphate dehydrogenase were found in cells grown in pyruvate and glucose mediums. The transfer of C. acetobutylicum from pyruvate to glucose medium suggested that pyruvate represses the "solventogenesis."
Acetate Kinase↗
Collagen content and types in the intestinal strictures of Crohn's disease.
The collagen content and the relative amount of collagen types were quantitated in control intestine as well as in both inflamed and strictured intestine resected from patients with Crohn's disease. The major collagen type in control intestine was type I (68%), followed by types III (20%) and V (12%). In strictured intestine both collagen content and the relative amount of type V collagen were significantly increased compared with control intestine. Histologic studies demonstrated that in strictured specimens there was a striking proliferation of smooth muscle cells of the muscularis mucosae associated with an accumulation of collagen in the submucosa. The thickness of the muscularis propria was also increased. Immunohistochemical studies demonstrated small amounts of type V collagen in the submucosa of control bowel. In contrast, large amounts of type V collagen were seen in the fibrotic, expanded submucosa of strictured bowel, particularly in the areas where smooth muscle cells of the muscularis mucosae had proliferated. Intestinal strictures in Crohn's disease are therefore characterized by an accumulation of collagen, a proliferation of smooth muscle cells, and an increase in type V collagen, a collagen type produced in relatively large amounts by smooth muscle cells. These changes appear to result in both a loss of the normal compliance of the intestine and a thickening of the intestine wall, resulting ultimately in the intestinal obstruction so frequently seen in patients with Crohn's disease.
Amino Acids↗
Bone marrow derived cells express human T-cell lymphotropic virus type I (HTLV-I)-related antigens in patients with multiple sclerosis.
Mononuclear cells in peripheral blood (PB) and cerebrospinal fluid (CSF) of seven patients and lymph nodes of three patients with clinically definite multiple sclerosis (MS) expressed antigens that reacted with monoclonal antibodies (MoAb) specific for HTLV-I p19 and p24 gag proteins. The labelled cells were visualized with immunoperoxidase staining and indirect immunofluorescence and identified at the ultrastructural level with immunogold technique. The frequency of these cells was low, ranging from 0.1% to less than 0.01% in blood. In CSF it was approximately 10 times lower. Cells reacting with anti-p19 Ab were found in all MS samples, whereas cells reacting with anti-p24 Ab were found in 3 out of 6 blood samples and in 3 out of 7 CSF samples. All lymph nodes (3/3) obtained from MS patients contained cells that reacted with anti-HTLV-I. p19 and p24 Ab. Cells reacting with the same AB were detected in blood of one out of 12 healthy controls. Stained cells were irregular, distinctly larger than lymphocytes, and had abundant cytoplasm, suggesting that they may be monocytes/macrophages. Immunogold particles were located in vacuole-like structures in the cytoplasm. The presence in MS patients of cells that react with HTLV-I Ab indicates that a human retroviral genome is being expressed, and suggests that a virus may be present. Our data support a role for a human retrovirus in multiple sclerosis.
Antibodies, Monoclonal↗
Unilateral diaphragmatic dysfunction in blunt chest trauma.
This study was undertaken to evaluate unilateral diaphragmatic dysfunction within ten days after blunt chest trauma. Thirty patients with unilateral chest injury, or predominantly one-sided injuries, were investigated in the supine position, under analgesia. Right and left hemidiaphragm displacement (DD) was measured, using digital subtraction radiography, during quiet and forced breathing. The diaphragmatic contribution to breathing was determined by rib cage and abdominal circumference measurement changes. In both breathing modes, DD of the injured side was lower than DD of the uninjured side (p less than 0.01, p less than 0.001). Six patients had complete diaphragmatic motionlessness. The inspired air volume due to diaphragmatic motion (Vab) was reduced when compared to normal subjects and Vab/VT ratio was always found to be less than 0.65. The degree of diaphragmatic dysfunction appeared related to injury location and is most severe in injuries of the lower chest which implies direct diaphragm muscle injury, although other mechanisms may be implicated. Diaphragmatic dysfunction can contribute to respiratory failure in these patients, and should be considered.
Diaphragm↗
Effects of butyric and acetic acids on acetone-butanol formation by Clostridium acetobutylicum.
The actions of butyric and acetic acids on acetone-butanol fermentation are investigated. Production of butyric and acetic acids are controlled by the extracellular concentrations of both acids: acetic acid added to the medium inhibits its own formation but has no effect on butyric acid formation, and added butyric acid inhibits its own formation but not that of acetic acid. The ratio of end metabolites depends upon acetic and butyric acid quantities excreted during the fermentation. In contrast to acetic acid, which specifically increases acetone formation, butyric acid increases both acetone and butanol formations. Acetate and butyrate kinase activities were also examined. Both increase at the start of fermentation and decrease when solvents appear in the medium. Coenzyme A transferase activity is weak in the acidogenic phase and markedly increases in the solvent phase. Acetic and butyric acids appear to be co-substrates. On the basis of these results, a mechanism of acetic and butyric acid pathways, coupled to solvent formation by C. acetobutylicum glucose fermentation is proposed.
Acetate Kinase↗
Radio-carpal and inter-carpal degenerative arthritis in sequellae of scaphoid injuries.
Degenerative arthritis is a frequent pattern after old fractures or rotatory subluxations of the scaphoid. The authors have studied this phenomenon, on 48 wrists. In old scaphoid fractures, the degenerative arthritis begins with an impingement between radial styloid process and proximal pole of the scaphoid, and then reaches the lunocapitate joint. A dorsi flexion by instability is then constant. After a scaphoid subluxation, degenerative arthritis begins between scaphoid and radial epiphysis too, but arthritis in these cases, is earlier and more symptomatic. We found two types of wrists: the sequellae of the post-traumatic scapholunate diastasis and the peri-scaphoid arthritis "primary in appearance", which corresponds to the scapholunate advanced collapsed pattern of A.K. Watson.
Adult↗