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Biomedical subjects

S L Smith

Publications and source records attributed to S L Smith.

At least 163 records · Page 9Linked to original sources

Metrical variation in the thumb, index, and middle finger among four samples of both sexes.

Metrical length and width parameters of the first through third ray metacarpals and phalanges are presented for four samples of adults of both sexes drawn from radiographs of the Ten State Nutrition Survey (1968-1970). Radiographic measurements were obtained with the aid of a digitizer and computer translation program. The establishment of ranges of variation among these samples allows their use in clinical diagnosis, for example of syndromes via pattern profile analysis. Proportional analyses of hand metrics can now be extended to include widths of the first three rays as well as lengths, and data for such a purpose are now available for American blacks. Mexican-Americans, and Oriental-Americans in addition to American white groups. Examples of intersample variation are given; the need to consider such variation in clinical contexts is emphasized.

Adult↗

Application of image analysis to neurological screening through figure-copying tasks.

Approaches to the detection and monitoring of neurological dysfunction are generally resource-intensive and often difficult to evaluate objectively. This paper describes an approach to neurological screening which is based on the on-line analysis of figure copying tasks, and a variety of features are measured to characterise task execution. It is shown how both qualitative and quantitative measures of individual performance can be obtained in real time. A preliminary experimental study is described to identify appropriate performance indicators for a reference asymptomatic population and for a population with a known abnormal clinical history. The results obtained experimentally demonstrate that the approach proposed, while convenient and efficient in terms of the resources required in implementation, nevertheless offers a high degree of robustness and sensitivity which supports an optimistic view of its clinical viability.

Adolescent↗

Acetaldehyde and microtubules.

Acetaldehyde covalently binds to tubulin to form stable and unstable adducts. Although tubulin has numerous lysine residues available to react with acetaldehyde, a key highly reactive lysine (HRL) on the alpha chain appears to be a preferential target for stable binding. The HRL residue is available for selective binding when tubulin is in the free (dimer) state but not when it is in the polymerized (microtubule) state. Stable binding of acetaldehyde to the HRL residue markedly inhibits tubulin assembly into microtubules, whereas stable binding to other residues (bulk adducts) has little influence on assembly. Substoichiometric stable binding of acetaldehyde to the HRL is sufficient to inhibit polymerization, via direct interference of tubulin dimer-dimer interactions, and an HRL adduct on only one out of 20 tubulin molecules can totally inhibit polymerization. These findings, along with our previous studies demonstrating impaired microtubule-dependent protein trafficking pathways in livers of ethanol-fed animals, indicate that low acetaldehyde concentrations, formed during ethanol oxidation in vivo, could generate sufficient amounts of HRL adducts on the alpha chain of tubulin in cellular systems to alter microtubule formation and function. In addition to alpha-tubulin, calmodulin and actin have also been found to have enhanced reactivity toward acetaldehyde. Thus, a general hypothesis to describe cellular injury induced by acetaldehyde adducts can be formulated: during ethanol oxidation, acetaldehyde forms stable adducts via binding to reactive lysine residues of preferential target proteins, resulting in selective functional impairment of these proteins and ultimately leading to cellular injury.

Acetaldehyde↗

In vivo and in vitro characterization of mesothelial lipid inclusions.

The nature of intracytoplasmic lipid inclusions found in cultured rabbit and rat peritoneal mesothelial cells was examined by ultrastructural and biochemical techniques. Transmission electron microscopy also demonstrated extracellular release of these lipid bodies. Differential fixation with tannic acid revealed 2 types of inclusions, lamellated (lamellar bodies) and nonlamellated (homogeneous). The lamellar bodies were found near or in the Golgi apparatus and on the cell surface where occasionally they were observed in exocytotic pouches. The homogeneous inclusions were the predominant species being found primarily intracellularly. Lipid bodies obtained from the culture media over the cells displayed on electron microscopy the same morphological characteristics as those seen intracellularly. Exposure of confluent cultures of mesothelial cells to the vital lipid stain Nile Red caused the appearance of intensely fluorescent droplets in or on the cells at wave lengths consistent with staining for phosphatidylcholine-rich vesicles. Incubation of the cells with (14C)-choline and subsequent analysis of phospholipid formation revealed high rates of (14C)-phosphatidylcholine addition to both intra- and extracellular lipid pools. Taken together, mesothelial cells exhibit lipid bodies similar in ultrastructure to the surfactant containing organelles of Type II pneumocytes.

Animals↗

Comparison of the efficacy of mechanistically different antioxidants in the rat hemorrhagic shock model.

Four pharmacological mechanisms for antagonizing free radical generation or reactions were compared in terms of their efficacy in attenuating hemorrhagic shock in rats. These included opposing superoxide generation by xanthine oxidase (e.g., oxypurinol), inhibiting arachidonic acid oxidation by cyclooxygenase (e.g., ibuprofen), chelating iron (e.g., desferal), and inhibiting lipid peroxidation (e.g., tirilazad mesylate [U-74006F] and U-78517G). Animals were hemorrhaged to a mean arterial pressure (MAP) of 43-45 mmHg where they were held for 2 hr. Five minutes prior to the end of the hemorrhage period, either vehicle, U-74006F (10 mg/kg), U-78517G (10 mg/kg), oxypurinol (10 or 25 mg/kg), desferal (10 or 25 mg/kg), or ibuprofen (10 mg/kg) was administered i.v., followed by the reinfusion of shed blood. In vehicle-treated animals, MAP declined progressively over the 2 hr post-reinfusion. Ibuprofen, desferal, and oxypurinol treatments each failed to attenuate this decline. In contrast, both U-74006F and U-78517G resulted in a significantly improved maintenance of MAP. Evidence of shock-induced lipid peroxidation was observed in terms of a 73.8% depletion in liver vitamin E content at 2 hr post-reinfusion in vehicle-treated rats. This decrease was prevented by both U-74006F and U-78517G. Inhibition of free radical-induced lipid peroxidation appears more effective for attenuating free radical pathophysiology in hemorrhagic shock that attempting to inhibit specific pathways of oxygen radical generation.

Animals↗

U-78517F: a potent inhibitor of lipid peroxidation with activity in experimental brain injury and ischemia.

U-78517F (2-[4-[2,6-di-(1-pyrrolidinyl)-4-pyridinyl)-1-piperazinyl] methyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydrochloride), which combines the antioxidant ring portion of alpha-tocopherol together with the amine of the previously described 21-aminosteroids (e.g., U-74006F), is a novel inhibitor of iron-catalyzed lipid peroxidation. U-78517F was found to have a 50% inhibitory concentration (IC50) of 0.6 microM against 200 microM ferrous chloride-initiated lipid peroxidation in rat brain homogenates, compared to 8 microM for U-74006F, 28 microM for alpha-tocopherol and 43 microM for the ring portion of alpha-tocopherol (i.e., trolox). Both stereoisomers of the racemic U-78517F proved to be equally active antioxidants. Against lipid peroxidation initiated by xanthine/xanthine oxidase, U-78517F was even more potent, with an IC50 of 0.01 microM. U-78517F was also observed to protect cultured mouse spinal neurons against iron-induced damage, with an IC50 of approximately 0.5 microM. When administered to male CF-1 mice i.v. at 5 min after a severe concussive head injury. U-78517F produced a dose-related improvement in the 1-hr neurological recovery. The minimum effective i.v. dose was 1.0 micrograms/kg. Measurement of U-78517 concentrations in the brains of mice after administration of a 10-mg/kg i.v. dose revealed effective antioxidant levels for as long as 2 hr. Evidence of an in vivo antioxidant action was provided by the attenuation of iron-induced blood-brain barrier disruption (i.e., Evans' blue extravasation) in rats pretreated with U-78517F.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Establishing reliability of biomechanical data using univariate and multivariate approaches.

The purpose of this study was to use generalizability theory with both univariate and multivariate approaches to examine reliability of total body center of mass (CM) values calculated from cinematographical data. Twenty-eight college-aged male volunteers were filmed by a LOCAM camera at 100 fps while performing the basic locomotion skill of walking. Film analysis was conducted on each subject using six frames of film depicting a one-stride walking cycle consisting of right heel strike, right foot flat, left toe-off, left heel strike, left foot flat, and right toe-off. Nineteen segmental endpoints and a reference point were digitized by three experienced plotters. The digitizing sequence was replicated three times by each plotter. A FORTRAN program calculated nine CM values (three plotters by three repetitions) for each subject filmed in each of the six positions of the stride. The x- and y-coordinates of the CM values were the dependent variables analyzed by fully crossed 3-way univariate and multivariate ANOVAs (subjects by plotters by repetitions). All measurement facets were considered to be random. Results indicate that there was very little repetition error but considerable interplotter error for most frames. Phi-coefficients for x- and y-coordinates, separately, fluctuated across frames. The univariate values for the x-coordinates were similar but slightly less than the multivariate values. The Phi-coefficients for Y, however, were considerably lower than the multivariate values. The multivariate Phi-coefficients for generalizing over three plotters and three repetitions ranged from .82 to .90.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Strain-gauge fontanometry--an advance in non-invasive intracranial pressure measurement.

The validation of a fontanometer based on the strain-gauge principle is described. Fontanelle pressures correlated well with invasively determined cerebrospinal fluid (CSF) pressures in a group of neonates and infants with hydrocephalus. This device, which can be zeroed in vivo, has the additional advantage of a fast response time and allows reliable measurements of spontaneous pulsations and induced changes in CSF pressure. Unlike previously reported devices, the accuracy of this transducer was shown to be independent of external forces.

Humans↗

Plasmid profiling of members of the family Enterobacteriaceae, lactobacilli, and bifidobacteria to study the transmission of bacteria from mother to infant.

Plasmid profiles of isolates of the family Enterobacteriaceae, lactobacilli, and bifidobacteria cultured from vaginal, oral, and rectal swabs collected from women soon after admission to a maternity hospital were compared with those of strains detected in the feces of their infants. Lactobacilli inhabiting the vaginas of the mothers did not appear to colonize the infant digestive tract, but evidence for the transmission of fecal isolates of the Enterobacteriaceae and bifidobacteria from mother to infant was obtained in four out of five cases. Many of the bifidobacteria isolated were plasmid-free but could be distinguished with biochemical profiles.

Bifidobacterium↗

Factors influencing the presence of faecal lactobacilli in early infancy.

The faecal flora of 46 preterm infants and 52 born at full term was studied at 10 days of age; 46 born at full term and 37 preterm infants were also studied at 30 days. Viable counts of coliforms, lactobacilli, and bifidobacteria were made; gas liquid chromatography was used to identify the anaerobes. Lactobacilli, but not bifidobacteria, were found in high counts in the stools of most of the infants born at full term by 30 days of age. The mode of delivery, but not the method of feeding, had a significant influence on early colonisation. A selective deficiency of lactobacilli compared with coliform organisms was found in preterm infants. Previous treatment with antibiotics and being nursed in an incubator were also significantly associated with a lower rate of early colonisation with lactobacilli. Our findings indicate that lactobacilli may be an important part of the normal stool flora in early infancy, and that modern methods of neonatal care are associated with delayed or deficient colonisation.

Anti-Bacterial Agents↗

Limiting care: the case of organ transplantation.

The technical challenge of performing organ transplants is nearly nonexistent, and great progress has been made in understanding and overcoming the barriers associated with the immune system. The questions are no longer, "Can we perform organ transplants?" and "Which ones?". These questions have been replaced by a much more complex one. "Who should be offered the therapeutic option of transplant?". This article explores the concept of limited access to a vital care option, organ transplantation. The two major factors that limit unrestricted access are the high cost of organ transplantation to the individual and society, and the limited supply of donor organs. These issues are discussed within the framework of, and how they affect, patient selection for transplantation.

Age Factors↗

Postoperative perfusion deficits.

The three keys to successful recovery of the critically ill postoperative patient are: (1) in-depth preoperative assessment and risk evaluation; (2) review of intraoperative course and evaluation of risk for perfusion deficit; and (3) diligent postoperative monitoring for early onset of perfusion deficit. Complications arise when metabolic demands exceed the body's ability to supply essential nutrients. The choice of treatment modality is related to the cause of perfusion deficits. Decreased preload and afterload is treated with fluid and vasopressor therapy. Increased preload is best managed by diuretics and venous dilation. Afterload reduction is accomplished with vasodilator therapy and decreases in sympathetic stimulation. Contraction is enhanced with inotropic therapy and management of preload and afterload within normal ranges. Metabolic demands are best managed with tight control of the patient's hemodynamic profile, oxygen consumption, and environmental stimuli. The challenge of managing the critically ill postoperative patient is great, but the rewards of successful recovery are tremendous.

Cardiac Output, Low↗

Spreadsheet interface for transfer of drug-use data from a mainframe to a personal computer.

The development of spreadsheets and automated instructions for transfer of drug-use data from a hospital's mainframe computer to the pharmacy department computer is described. Drug-use data are down-loaded from the mainframe as an ASCII file on a floppy disk. Instructions within the spreadsheet ("macros") are used to import the data into the first spreadsheet, arrange the data to be compatible with the database portion of the spreadsheet, and transfer the data to another spreadsheet where drug use and cost are calculated and placed in the column for the appropriate month. A series of formulas are used to arrange the imported data to account for items that have not been used. By eliminating the need for manual data input into the spreadsheets, the macros and associated formulas saved pharmacists substantial time.

Clinical Pharmacy Information Systems↗

Regulation of cytochrome P-450 dependent steroid hydroxylase activity in Manduca sexta: evidence for the involvement of a neuroendocrine-endocrine axis during larval-pupal development.

Ecdysone 20-monooxygenase activity and the factors which may regulate this steroid hydroxylase were examined in the midgut of the tobacco hornworm, Manduca sexta, during the last larval stadium. Radioassay experiments revealed that midgut ecdysone 20-monooxygenase undergoes a single 50-fold increase in activity temporally coincident with the onset of the wandering stage. The increase in midgut monooxygenase activity was prevented by actinomycin D and cycloheximide, and could be elicited in head (but not thoracic) ligated animals by a brain-retrocerebral complex factor(s) released at the same time as prothoracicotropic hormone. In contrast, ecdysone or 20-hydroxyecdysone could elicit the increase in enzyme activity in both head and thoracic ligated animals. These data suggest the operation of a neuroendocrine-endocrine axis in the regulation of midgut ecdysone 20-monooxygenase activity.

Animals↗

Stereoselective, strong inhibition of ribonucleotide reductase from E. coli by cisplatin.

Using ribonucleotide reductase (EC 1.17.4.1) purified from E. coli clones with overproducing plasmids for the B1 and B2 subunits, respectively, studies have been carried out of the inhibition of this enzyme by cisplatin. Under anaerobic conditions, using the dithiol, reduced form of the enzyme, it was found that ribonucleotide reductase is extremely sensitive to cisplatin: greater than 90% inhibition was achieved with 2-fold molar excess of platinum reagent even at 10(-8)M enzyme. Inhibition was essentially instantaneous and irreversible to G-25 gel filtration. The site of inhibition was found to be the B1 subunit. Transplatin was much less effective. Inhibition of the enzyme by cisplatin (molar ratio cisplatin:B1 = 4.3) led to a decrease in thiol titre corresponding to approximately 1 thiol group per dimer of B1 subunits under conditions leading to 94% inactivation of the ribonucleotide reductase activity.

Carboplatin↗

Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium.

The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two to three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.

Acetaldehyde↗