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Biomedical subjects

L A Smith

Publications and source records attributed to L A Smith.

At least 73 records · Page 4Linked to original sources

Laboratory test utilization in the diagnosis of hypercoagulability.

OBJECTIVE: To determine the appropriateness and utility of laboratory tests ordered by physicians for evaluation of hypercoagulability. DESIGN: Retrospective review of patient charts was performed to collect information on patient demographics, clinical history, coagulation testing, interpretation of results, and clinical decisions. SETTING/SAMPLE: Subjects included all patients from a 400-bed acute care hospital who had a laboratory workup for hypercoagulability within the most recent 12-month period. Thirty-four patients whose medical records were available and whose clinical history included thrombosis were included in the study. MAIN OUTCOMES/CONCLUSIONS: Eighty-two percent of the patients had a familial and/or acquired risk factor for thrombosis. Over 40% had abnormal coagulation test results. Up to one-third of the tests were ordered and performed while the patient was on anticoagulant therapy. In over 50% of the cases with abnormal results, the physicians' notes did not mention the abnormality or the abnormal result was considered normal. These results indicate that although physicians are selecting the appropriate patients for laboratory test workup for hypercoagulability, the testing is being performed at an inappropriate time after the thrombotic event and the results of laboratory tests are often not utilized in patient diagnosis and management.

Blood Coagulation Tests↗

Impact of interruptions and distractions on dispensing errors in an ambulatory care pharmacy.

A possible association between interruptions and distractions and the occurrence of dispensing errors was investigated. Fourteen pharmacists and 10 technicians in an ambulatory care pharmacy at a general medical-surgical hospital were tested for distractibility by using the group embedded figures test (GEFT) as well as for visual acuity and hearing. They were videotaped as they filled prescriptions during a 23-day period in 1992. A study investigator compared each filled prescription with the physician's written order, noted details of deviations, verified with the pharmacist any errors that occurred, and asked the pharmacist to correct the error if necessary. Interruptions and distractions were detected and characterized by reviewing the videotapes. None of the study participants had significant hearing or visual impairment. There was a significant association between GEFT scores and error rates. A total of 5072 prescriptions were analyzed, and 164 errors were detected, for an overall error rate of 3.23%. Wrong label information was the most common type of error (80% of errors detected). A total of 2022 interruptions (mean +/- S.D. per half hour per subject, 2.99 +/- 2.70) and 2457 distractions (mean +/- S.D. per half hour per subject, 3.80 +/-3.17) were detected. The error rate for sets of prescriptions with one or more interruptions was 6.65% and for sets during which there were one or more distractions, 6.55%. Interruptions and distractions per half hour were both significantly associated with errors. In an ambulatory care pharmacy, interruptions and distractions over a half-hour period were associated with dispensing errors, a majority of which involved incorrect label information.

Ambulatory Care Facilities↗

Geographically diverse Australian isolates of Melissococcus pluton exhibit minimal genotypic diversity by restriction endonuclease analysis.

Melissococcus pluton, the causative agent of European foulbrood is an economically significant disease of honey bees (Apis mellifera) across most regions of the world and is prevalent throughout most states of Australia. 49 Isolates of M. pluton recovered from diseased colonies or honey samples in New South Wales, Queensland, South Australia, Tasmania and Victoria were compared using SDS-PAGE, Western immunoblotting and restriction endonuclease analyses. DNA profiles of all 49 geographically diverse isolates showed remarkably similar AluI profiles although four isolates (one each from Queensland, South Australia, New South Wales and Victoria) displayed minor profile variations compared to AluI patterns of all other isolates. DNA from a subset of the 49 Australian and three isolates from the United Kingdom were digested separately with the restriction endonucleases CfoI, RsaI and DraI. Restriction endonuclease fragment patterns generated using these enzymes were also similar although minor variations were noted. SDS-PAGE of whole cell proteins from 13 of the 49 isolates from different states of Australia, including the four isolates which displayed minor profile variations (AluI) produced indistinguishable patterns. Major immunoreactive proteins of approximate molecular masses of 21, 24, 28, 30, 36, 40, 44, 56, 60, 71, 79 and 95 kDa were observed in immunoblots of whole cell lysates of 22 of the 49 isolates and reacted with rabbit hyperimmune antibodies raised against M. pluton whole cells. Neither SDS-PAGE or immunoblotting was capable of distinguishing differences between geographically diverse isolates of M. pluton. Collectively these data confirm that Australian isolates of M. pluton are genetically homogeneous and that this species may be clonal. Plasmid DNA was not detected in whole cell DNA profiles of any isolate resolved using agarose gel electrophoresis.

Animals↗

High vagal tone is associated with more efficient regulation of homeostasis in low-risk human fetuses.

Homeostasis is maintained primarily by the parasympathetic nervous system and is thought to provide a physiological substrate for the development of complex behaviors. This investigation was undertaken to test the hypothesis that infants with high parasympathetic tone are more efficient regulators of homeostasis than infants with low parasympathetic tone. Respiratory sinus arrhythmia (RSA) was used as a measure of parasympathetic tone, and the efficiency of homeostatic control was quantified, for each infant, by the slope (SRSA) and correlation coefficient (RRSA) of the regression line relating fluctuations in heart period and fluctuations in RSA. To test our hypothesis, we examined the relationship between RSA and both SRSA and RRSA in 34 low-risk human fetuses between 36 and 40 weeks gestation. We found that fetuses who were parasympathetic-dominated had larger SRSA and RRSA values, and hence were more efficient regulators of homeostasis, than fetuses who were sympathetic-dominated. The results of our analyses are important because they establish, very early in development, a physiological basis for the relationship between vagal tone and the development of complex behaviors.

Arousal↗

Behavioral state affects heart rate response to low-intensity sound in human fetuses.

The cardiac orienting reflex is elicited by a low-intensity sound, it consists of a sustained heart rate (HR) deceleration, and it is a specific physiological correlate of cognitive processing. In this study we examined the relationship between behavioral state and the cardiac orienting reflex in 75 human fetuses between 36 and 40 weeks gestation. Each fetus was stimulated with a 30-s speech sound at an average intensity of 83 dB SPL in quiet sleep (QS) and active sleep (AS). The fetal cardiac electrical signal was captured transabdominally at a rate of 1024 Hz and fetal R-waves were extracted using adaptive signal processing. Fetal behavioral states were assigned based on HR pattern and the presence or absence of eye and general body movements. We found that a significant HR deceleration occurred, in both QS and AS, following stimulus onset. However, HR decelerations occurred more often in QS than AS; and for fetuses exhibiting a HR deceleration, the magnitude of the deceleration was greater in AS compared to QS. In addition, in AS female fetuses exhibited a larger, more sustained HR deceleratory response than male fetuses, but the seconds x gender interaction in QS was not significant. Based on these results, we concluded that behavioral state is an important determinant of the HR deceleratory response in human fetuses.

Acoustic Stimulation↗

Vascular reconstruction utilizing artery from an amputated extremity: A case report.

Although infrainguinal arterial reconstruction is best performed with autologous tissue, reconstruction with vein in an infected field has been associated with vein graft disruption and hemorrhage. H.P., a 61-year-old man with peripheral vascular disease, was initially seen with an infected prosthetic right femoral-tibioperoneal artery bypass graft. Because of the presence of purulent drainage from the proximal and distal anastomotic regions and his comorbidities, a right through-knee guillotine amputation was performed, followed by graft excision and groin débridement. Right hip and thigh perfusion was preserved via arterial reconstruction by using a segment of endarterectomized popliteal artery, harvested from the amputated extremity. Arterial reconstruction with autologous tissue from an amputated extremity allowed us to balance our patient's overall risks with life and tissue preservation. This technique may be applied in the settings of lower extremity ischemia, trauma, or malignancy requiring concomitant arterial or venous reconstruction.

Amputation, Surgical↗

Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha subunits.

Dendrotoxin (DTX) homologues are powerful blockers of K+ channels that contain certain subfamily Kv1 (1.1-1.6) alpha- and beta-subunits, in (alpha)4(beta)4 stoichiometry. DTXk inhibits potently Kv1.1-containing channels only, whereas alphaDTX is less discriminating, but exhibits highest affinity for Kv1.2. Herein, the nature of interactions of DTXk with native K+ channels composed of Kv1.1 and 1.2 (plus other) subunits were examined, using 15 site-directed mutants in which amino acids were altered in the 310-helix, beta-turn, alpha-helix and random-coil regions. The mutants' antagonism of high-affinity [125I]DTXk binding to Kv1. 1-possessing channels in rat brain membranes and blockade of the Kv1. 1 current expressed in oocytes were quantified. Also, the levels of inhibition of [125I]alphaDTX binding to brain membranes by the DTXk mutants were used to measure their high- and low-affinity interactions, respectively, with neuronal Kv1.2-containing channels that possess Kv1.1 as a major or minor constituent. Displacement of toxin binding to either of these subtypes was not altered by single substitution with alanine of three basic residues in the random-coil region, or R52 or R53 in the alpha-helix; accordingly, representative mutants (K17A, R53A) blocked the Kv1.1 current with the same potency as the natural toxin. In contrast, competition of the binding of the radiolabelled alphaDTX or DTXk was dramatically reduced by alanine substitution of K26 or W25 in the beta-turn whereas changing nearby residues caused negligible alterations. Consistently, W25A and K26A exhibited diminished functional blockade of the Kv1.1 homo-oligomer. The 310-helical N-terminal region of DTXk was found to be responsible for recognition of Kv1.1 channels because mutation of K3A led to approximately 1246-fold reduction in the inhibitory potency for [125I]DTXk binding and a large decrease in its ability to block the Kv1.1 current; the effect of this substitution on the affinity of DTXk for Kv1.2-possessing oligomers was much less dramatic (approximately 16-fold).

Amino Acid Sequence↗

Sledding injuries in the southeastern United States.

BACKGROUND: Heavy ice and snow accumulation combined with record low temperatures in Chattanooga, Tennessee, from February 2-6, 1996, contributed to many sledding injuries. METHODS: We retrospectively reviewed medical records of emergency visits to seven area hospitals from February 2-6, 1996. We further reviewed sledding injury records. Sledding was defined as sliding on snow or ice using any device except skis. RESULTS: Of 2,134 emergency room visits, 241 patients had 310 sledding injuries. Ages of patients ranged from 3 to 53 years (mean, 18.9; median, 16). One hundred twenty-eight injuries were severe. These included extremity injuries (65), head injuries (28), chest injuries (10), intra-abdominal injuries (10), vertebral column fractures (11), and pelvic fractures (4). Thirty-six patients required inpatient hospitalization; 18 had surgery. The minimum healthcare costs associated with these injuries were estimated at $220,000. CONCLUSIONS: Major trauma potential is associated with sledding, especially where significant winter storms are uncommon. Level I trauma centers should seasonally incorporate sledding safety into community-wide injury prevention programs.

Adolescent↗

Bacteriophage T4 rnh (RNase H) null mutations: effects on spontaneous mutation and epistatic interaction with rII mutations.

The bacteriophage T4 rnh gene encodes T4 RNase H, a relative of a family of flap endonucleases. T4 rnh null mutations reduce burst sizes, increase sensitivity to DNA damage, and increase the frequency of acriflavin resistance (Acr) mutations. Because mutations in the related Saccharomyces cerevisiae RAD27 gene display a remarkable duplication mutator phenotype, we further explored the impact of rnh mutations upon the mutation process. We observed that most Acr mutants in an rnh+ strain contain ac mutations, whereas only roughly half of the Acr mutants detected in an rnhDelta strain bear ac mutations. In contrast to the mutational specificity displayed by most mutators, the DNA alterations of ac mutations arising in rnhDelta and rnh+ backgrounds are indistinguishable. Thus, the increase in Acr mutants in an rnhDelta background is probably not due to a mutator effect. This conclusion is supported by the lack of increase in the frequency of rI mutations in an rnhDelta background. In a screen that detects mutations at both the rI locus and the much larger rII locus, the r frequency was severalfold lower in an rnhDelta background. This decrease was due to the phenotype of rnh rII double mutants, which display an r+ plaque morphology but retain the characteristic inability of rII mutants to grow on lambda lysogens. Finally, we summarize those aspects of T4 forward-mutation systems which are relevant to optimal choices for investigating quantitative and qualitative aspects of the mutation process.

Acriflavine↗

Human fetuses have nonlinear cardiac dynamics.

Approximate entropy (ApEn) is a statistic that quantifies regularity in time series data, and this parameter has several features that make it attractive for analyzing physiological systems. In this study, ApEn was used to detect nonlinearities in the heart rate (HR) patterns of 12 low-risk human fetuses between 38 and 40 wk of gestation. The fetal cardiac electrical signal was sampled at a rate of 1,024 Hz by using Ag-AgCl electrodes positioned across the mother's abdomen, and fetal R waves were extracted by using adaptive signal processing techniques. To test for nonlinearity, ApEn for the original HR time series was compared with ApEn for three dynamic models: temporally uncorrelated noise, linearly correlated noise, and linearly correlated noise with nonlinear distortion. Each model had the same mean and SD in HR as the original time series, and one model also preserved the Fourier power spectrum. We estimated that noise accounted for 17.2-44.5% of the total between-fetus variance in ApEn. Nevertheless, ApEn for the original time series data still differed significantly from ApEn for the three dynamic models for both group comparisons and individual fetuses. We concluded that the HR time series, in low-risk human fetuses, could not be modeled as temporally uncorrelated noise, linearly correlated noise, or static filtering of linearly correlated noise.

Algorithms↗

CGRP activates renal pelvic substance P receptors by retarding substance P metabolism.

Substance P and calcitonin gene-related peptide (CGRP) are colocalized in renal pelvic sensory nerves. Increasing renal pelvic pressure results in an increase in afferent renal nerve activity that is blocked by a substance P receptor antagonist but not by a CGRP receptor antagonist. CGRP potentiates the effects of substance P by preventing the metabolism of substance P. Therefore, we examined whether CGRP enhanced the afferent renal nerve activity responses to substance P and increased renal pelvic pressure, a stimulus known to increase substance P release. Combined administration of substance P and CGRP into the renal pelvis resulted in an increase in afferent renal nerve activity (1392+/-217%. s; area under the curve of afferent renal nerve activity versus time) that was greater (P<0.01) than that produced by substance P (620+/-156%. s) or CGRP (297+/-96%. s) alone. Likewise, CGRP enhanced the afferent renal nerve activity response to increased renal pelvic pressure. During renal pelvic administration of the neutral endopeptidase inhibitor thiorphan, the afferent renal nerve activity response to substance P plus CGRP was similar to that produced by either neuropeptide alone. Because these studies suggested that CGRP potentiated the afferent renal nerve activity responses to substance P, we examined whether the afferent renal nerve activity response to CGRP was blocked by a substance P receptor antagonist, RP67580. RP67580 blocked the afferent renal nerve activity response to CGRP by 85+/-12% (P<0.02). We conclude that CGRP activates renal pelvic sensory nerves by retarding the metabolism of substance P, thereby increasing the amount of substance P available for stimulation of substance P receptors.

Afferent Pathways↗

Effects of recombinant equine somatotropin on wound healing, carbohydrate and lipid metabolism, and endogenous somatotropin responses to secretagogues in geldings.

The primary purpose of this experiment was to assess the possible beneficial effects of recombinant equine somatotropin (reST) administration on wound healing in adult geldings. The effects of the 21-d reST treatment on carbohydrate and lipid metabolism and on endogenous ST characteristics were monitored as well. Single, full-thickness skin incisions (7.62 x 7.62 cm) were made in the pectoral region of all geldings on d 0. Treated geldings received reST at 20 microg/kg BW i.m., and control geldings received vehicle (10 mM sodium borate) at equivalent volumes daily from d 0 (immediately after surgery) through d 20. Tracings of the wounds were made with acetate transparencies, and wound areas were calculated via a digital analyzer. In addition to once-daily blood samples collected at specified days throughout the treatment period, an i.v. glucose tolerance test was performed on d 16, and three assessments of endogenous ST secretion were performed in the 2 d immediately following the end of treatment: epinephrine administration during the morning of d 21, an exercise test during the afternoon of d 21, and i.v. aspartic acid infusion on d 22. There was no effect (P > . 1) of reST treatment on wound healing as assessed by changes in wound areas. Daily plasma ST, IGF-I, glucose, and insulin concentrations were higher (P < .05) and urea-nitrogen concentrations were lower (P < .001) in geldings receiving reST relative to controls. Glucose, NEFA, and insulin concentrations were all higher (P < .01) in reST-treated geldings before glucose infusion on d 16, and the responses to glucose were greater (P < .05) as well. Epinephrine administration increased (P < .02) ST concentrations in control geldings on d 21 but not in reST-treated geldings; a similar suppressive effect of reST treatment was observed for the ST response to exercise (P < .001). After aspartic acid infusion on d 22, reST-treated geldings had a much smaller (P < .001) ST response than did control geldings. In conclusion, reST administered to geldings at 20 microg/kg BW i.m. caused hyperglycemia, hyperinsulinemia, insulin insensitivity, mobilization of fatty acids, and an apparent negative feedback on the pituitary's ST response to various stimuli known to induce ST secretion. However, there was no beneficial effect of reST treatment with the wound model used in this experiment.

Animals↗

Mathematical representations of correlations among yield traits and somatic cell score on test day.

Prediction of lactation yields and accuracies of yields for use in genetic evaluation can be improved by including information from test day correlations, especially for milk recording plans that vary in the numbers of milk weights recorded and component samples taken. Daily milk weights for 658 lactations of Canadian cows and monthly test records of milk, fat, and protein yields and somatic cell scores for 500,000 lactations of US cows were used to estimate phenotypic correlations between test days within herd-year. Correlations between daily yields for a designated interval between test days generally were highest for midlactation and were lowest for early and late lactation. Regression (two linear, two quadratic, and interaction effects) on mean DIM and interval between test days predicted correlations with a squared correlation of 0.94 for daily milk yields. Similar relationships were found for US monthly data. Variation in sampling was reduced, computer memory was minimized, and positive definiteness was guaranteed by fitting regressions on simply defined sources of correlation. An autoregressive matrix represented the within-trait correlations very well. The equations developed could be used to derive covariances and, subsequently, to estimate lactation yields and accuracies from combinations of individual daily milk, fat, and protein yields and somatic cell score.

Animals↗

Selection and mating considering expected inbreeding of future progeny.

Animals most related or least related to current members of their breed were revealed by calculating the expected inbreeding of their future progeny. A sample of potential mates was chosen by randomly selecting 600 females from a recent birth year (1995). Relationships among the sample were computed by the tabular method. Relationships of other animals to the sample population were computed quickly from the relationships of their parents or ancestors. To-Mar Blackstar-ET and Round Oak Rag Apple Elevation were most related to the Holstein breed with expected inbreeding of 7.9 and 7.7%, respectively. Corresponding Jersey bulls were Highland Magic Duncan and Soldierboy Boomer Sooner of CJF with expected inbreeding of 10.9 and 9.5%, respectively. The highest expected inbreeding was 11.1% for Selwood Bettys Commander, 8.6% for Forest Lawn Simon Jetway, 10.1% for Dutch Mill Telestars Fayette, and 7.4% for Korncrest Pacesetter for Ayrshire, Brown Swiss, Guernsey, and Milking Shorthorn breeds, respectively. Regression on inbreeding in the genetic evaluation model removed effects of past inbreeding. Future inbreeding effects could be included for each potential mating or by adjusting breeding values for average inbreeding expected with random mating. The correlation between Holstein breeding values unadjusted and adjusted for inbreeding was 0.9976. The estimated genetic trend was 6% lower with future inbreeding included.

Animals↗

Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys.

Treatment of Parkinson's disease with L-dopa therapy leads to long-term complications, including loss of drug efficacy and the onset of dyskinesia. Adenosine A2A receptors in striatum are selectively localized to GABAergic output neurons of the striato-pallidal pathway and may avoid such problems. The novel adenosine A2A receptor antagonist KW-6002 has been examined for antiparkinsonian activity in MPTP-treated primates. Oral administration of KW-6002 reversed motor disability in MPTP-treated common marmosets in a dose-dependent manner. However, KW-6002 only modestly increased overall locomotor activity and did not cause abnormal movement, such as stereotypy. The ability of KW-6002 to reverse motor disability was maintained on repeated daily administration for 21 days, and no tolerance was observed. KW-6002 induced little or no dyskinesia in MPTP-treated primates previously primed to exhibit dyskinesia by prior exposure to L-dopa. These results suggest that selective adenosine A2A receptor antagonists represent a new class of antiparkinsonian agents that improve disability without producing hyperactivity and without inducing dyskinesia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Production and purification of the heavy-chain fragment C of botulinum neurotoxin, serotype B, expressed in the methylotrophic yeast Pichia pastoris.

A recombinant Hc fragment of botulinum neurotoxin, serotype B (rBoNTB(Hc)), has been successfully expressed in a Mut+ strain of the methylotrophic yeast Pichia pastoris for use as an antigen in a proposed human vaccine. The fermentation process consisted of batch phase on glycerol, followed by glycerol and methanol fed-batch phases yielding a final cell mass of 60 g/L (dcw) and was easily scaled-up to 60 L. A multistep ion-exchange chromatographic purification process was employed to produce 99% pure Hc fragment. The final yield of the purified antigen was 390 mg per kilogram of wet cell mass. The purified Hc fragment of serotype B was stable, elicited an immune response in mice, and protected upon challenge with native botulin.

Amino Acid Sequence↗

Development of recombinant vaccines for botulinum neurotoxin.

Synthetic genes encoding non-toxic, carboxyl-terminal regions (approximately 50 kDa) of botulinum neurotoxin (BoNT) serotypes A and B (referred to as fragment C or HC) were constructed and cloned into the methylotropic yeast, Pichia pastoris. Genes specifying BoNTA(HC) and BoNTB(HC) were expressed as both intracellular and secreted products. Recombinants, expressed intracellularly, yielded products with the expected molecular weight as judged by SDS PAGE and Western blot (immunoblot) analysis, while secreted products were larger due to glycosylation. Gene products were used to vaccinate mice and evaluated for their ability to elicit protective antibody titers in vivo. Mice given three intramuscular vaccinations with yeast supernatant containing glycosylated BoNTA(HC) were protected against an intraperitoneal challenge of 10(6) 50% mouse lethal doses (MLD50) of serotype A neurotoxin, a result not duplicated by its BoNTB(HC) counterpart. Vaccinating mice with cytoplasmically produced BoNTA(HC) and BoNTB(HC) protected animals from a challenge of 10(6) MLD50 of serotype A and B toxins, respectively. Because of the glycosylation encountered with secreted BoNT(HC), our efforts focused on the production and purification of products from intracellular expression.

Animals↗