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Biomedical subjects

D Christensen

Publications and source records attributed to D Christensen.

At least 19 recordsLinked to original sources
PubMed1999

Thrombopoietin (Tpo) in the fetus and neonate: Tpo concentrations in preterm and term neonates, and organ distribution of Tpo and its receptor (c-mpl) during human fetal development.

Little is known about thrombopoietin (Tpo) production in human fetuses and neonates. As a step toward determining whether Tpo is relevant to platelet production in the fetus and neonate, we hypothesized that: (1) like other cytokines, Tpo is present in the cord blood in higher concentrations than in adult plasma; (2) Tpo and its receptor (c-mpl) are expressed in fetuses at, and following, 5-6 weeks post-conception (when platelet production begins); and (3) the sites of Tpo and c-mpl production in the fetus are similar to those of adults. We quantified Tpo, by ELISA, in the plasma of 50 adults, as well as in the umbilical cord plasma of 50 preterm and term infants. We also characterized, by RT-PCR, the organ distribution of Tpo and c-mpl during fetal development (at 8 and 16 weeks). Tpo concentrations were measurable (> or =41 pg/ml) in only two of the 50 adult samples (44 and 46 pg/ml), but in 24 of the 50 cord plasma samples (of the 24 samples, the median was 62 pg/ml; mean+/-SD, 80+/-39 pg/ml). Tpo levels did not correlate with either gestational age or platelet count at birth. Similarly to adults, in the fetal tissues, Tpo transcripts were found in all organs tested, but the most dense bands were from liver. C-mpl transcripts were also predominantly from liver. We conclude that: (1) Tpo is present in higher concentrations in cord plasma than in venous plasma of adults; (2) Tpo and c-mpl transcripts are detected in human fetuses as early as the onset of platelet appearance; and(3) Tpo and c-mpl have a similar organ distribution in fetuses and adults.

Adult↗
PubMed1999

Implementation of serum cardiac troponin I as marker for detection of acute myocardial infarction.

BACKGROUND: The goal of this prospective study was to assess whether cardiac troponin I (cTnI) could replace creatine kinase (CK)-MB mass as the serum biochemical marker for detection of acute myocardial infarction (AMI). METHODS AND RESULTS: Over a 3-month period, 327 nonselected, consecutive patients were evaluated for AMI with the use of modified World Health Organization criteria including serial electrocardiographs and CK-MB mass determinations at admission and 6, 12, and 24 hours after admission. cTnI measurements were also made at all time points. Sixty-two (19%) patients were diagnosed with AMI. Diagnostic sensitivity and specificity for peak concentrations were equivalent or better for cTnI (100%; 96.3%) compared with CK-MB (88. 2%; 93.2%) and total CK (73.5%; 84.6%), respectively. cTnI demonstrated 100% negative predictive accuracy for ruling out AMI. Further, cTnI maintained a high diagnostic sensitivity (>94%) up to 96 hours after onset of chest pain compared with CK-MB and total CK (both 50% sensitive) in patients with AMI. However, patients with documented Q-wave infarctions had a significantly longer clearance compared with non-Q-wave infarctions (dagger(1/2) 24.2 vs 7.3 hours, respectively; P <.01). There was a significant (P <.02) positive correlation (r = 0.89) between increasing CK-MB mass and increasing cTnI for AMI specimens. CONCLUSIONS: These findings have strongly supported our clinical implementation of cTnI, replacing CK-MB mass as the preferred marker for detection of AMI.

Biomarkers↗
PubMed1998

Assessment of left ventricular function using serum cardiac troponin I measurements following myocardial infarction.

The prognosis and extent of injury to the myocardium have previously been assessed by increased serum creatine kinase (CK) MB levels. We report findings from 39 consecutive, acute myocardial infarction (AMI) patients presenting 4.5 h (range, 0.7-12.1 h) after the onset of chest pain. We compared CK MB mass (upper reference limit, 5.0 ng/ml) and cardiac troponin I (cTnI; upper reference limit, 0.8 ng/ml) (Stratus II, Dade International) in serial serum specimens obtained over 36 h after chest pain from AMI patients; within 6 h after onset of chest pain. While the appearance of the kinetics of CK MB and cTnI were similar during the initial 24 h following the onset of chest pain, cTnI was increased significantly (p < 0.05) over CK MB after 9 to 12 h. Half-life determinations (mean+/-S.D.) in 22 of the 39 AMI patients demonstrated a significantly (p < 0.01) shorter half-life in non-Q-wave infarcts [t1/2 6.8 h (+/-5.6)] vs. Q-wave infarcts [t1/2 20.4 h (+/-10.7)]. Further serial time versus marker (mean+/-S.D.) results were significantly correlated (p < 0.001, r = 0.66). Sixteen of twenty patients assessed by echocardiography had an abnormal left ventricular ejection fraction (LVEF); mean 37.6 (S.D. 15.2)%, ranging from 15.4 to 67.6%. LVEF was significantly and inversely correlated to peak CK MB (r = .50, p = 0.03), as well as to peak cTnI (r = 0.46, p = 0.04). Based on these findings, cTnI shows excellent promise as a useful marker of infarct size, for the assessment of left ventricular function, and may potentially replace CK MB as the cardiac-specific marker for AMI detection.

Biomarkers↗
PubMed1998

The selective cholecystokininB receptor antagonist L-365,260 diminishes the expression of naloxone-induced morphine withdrawal symptoms in normal and neuropathic rats.

The ability of a pretreatment with the cholecystokininB-receptor (CCK[B]) antagonist L-365,260 to prevent the development of morphine dependence was studied in normal and neuropathic (unilateral peripheral neuropathy) rats. A 4-day pretreatment regimen with two daily s.c. injections of either saline+saline, saline+morphine (3.0 mg/kg) or L-365,260 (0.2 mg/kg)+morphine was used, and withdrawal was precipitated by an injection of naloxone (1.0 or 2.0 mg/kg i.v.) at 24 h after the last pretreatment injection. After pretreatment with morphine alone, physical dependence developed in both normal and neuropathic rats. However, the incidence of teeth chattering and ptosis was higher in neuropathic rats. Pretreatment with the combination of L-365,260 and morphine prevented the expression of teeth chattering, ptosis, diarrhea, writhing and piloerection, but was devoid of effects on the exploratory activity among both groups of rats. These results suggest that endogenous CCK acting on CCK(B)-receptors may be involved in the development of morphine dependence both in normal and neuropathic rats.

Animals↗
PubMed1998

The antinociceptive effect of combined systemic administration of morphine and the glycine/NMDA receptor antagonist, (+)-HA966 in a rat model of peripheral neuropathy.

1. We evaluated the ability of the functional antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex, (+)-(1-Hydroxy-3-aminopyrrolodine-2-one) ((+)-HA966), to modulate the antinociceptive action of systemic morphine in a rat model of neuropathic pain produced by chronic constriction injury to the sciatic nerve. Mechanical (vocalization threshold to hindpaw pressure) and thermal (struggle latency to hindpaw immersion into a water bath) stimuli were used. 2. In the mechanical test, morphine (0.05, 0.1 and 0.3 mg kg(-1), i.v.) alone produced dose-dependent effects in both neuropathic and uninjured rats. Likewise, morphine (0.1, 0.3 and 1 mg kg(-1), i.v.) dose-dependently increased struggle latencies of the nerve-injured hindpaw in the hot noxious (46 degrees C) test but was ineffective in the non-noxious warm (44 degrees C) and cold (10 degrees C) test. 3. Pretreatment with (+)-HA966 (2.5 mg kg(-1), s.c.) dose-dependently enhanced the effect of morphine in the mechanical test with the relative potency being nerve-injured hindpaw > contralateral hindpaw > uninjured rat. 4. Likewise, (+)-HA966 dose-dependently enhanced the effect of morphine against a hot (46 degrees C) stimulus and produced, in combination with morphine, a dose-dependent effect against a warm (44 degrees C) stimulus. In the cold (10 degrees C) test, (+)-HA966 reversed the ineffectiveness of the highest dose of morphine. 5. Naloxone blocked the effect of the combination of (+)-HA966 with morphine in all tests. The drug combination produced no motor deficits in animals using the rotarod test. 6. These findings suggest that combined administration of antagonists, acting at the glycine site of the NMDA receptor complex and morphine may be a promising approach in the treatment of neuropathic and acute pain.

Analgesics, Opioid↗
PubMed1997

Comprehensive manual handling limits for lowering, pushing, pulling and carrying activities.

The objective of this study was to develop a set of mathematical models for manual lowering, pushing, pulling and carrying activities that would result in establishing load capacity limits to protect the lower back against occupational low-back disorders. In order to establish safe guidelines, a three-stage process was used. First, psychophysical data was used to generate the models' discounting factors and recommended load capacities. Second, biomechanical analysis was used to refine the recommended load capacities. Third, physiological criteria were used to validate the models' discounting factors. Both task and personal factors were considered in the models' development. When compared to the results from prior psychophysical research for these activities, the developed load capacity values are lower than previously established limits. The results of this study allowed the authors to validate the hypothesis proposed and tested by Karwowski (1983) that states that the combination of physiological and biomechanical stresses should lead to the overall measure of task acceptability or the psychophysical stress. This study also found that some of the discounting factors for the task frequency parameters recommended in the prior psychophysical research should not be used as several of the high frequency factors violated physiological limits.

Adult↗
PubMed1997

A comprehensive lifting model: beyond the NIOSH lifting equation.

A comprehensive lifting model (CLM) for the evaluation and design of manual tasks was developed in two stages using 11 task, personal and environmental variables. In the first stage, the model was built using the psychophysical data. In the second stage, discounting factors of various variables were tested and adjusted using the physiological and biomechanical data. Two lifting indices are proposed to evaluate lifting tasks for a group of workers (relative lifting safety index or RLSI) and for an individual worker (personal lifting safety index or PLSI).

Energy Metabolism↗
PubMed1996

Low TSH levels in nursing home residents not taking thyroid hormone.

BACKGROUND: Many practitioners perform a thyroid stimulating hormone (TSH) assay as a screening test in older patients. The introduction of sensitive TSH assays with lower normal limits has created a laboratory abnormality that is often of uncertain significance. Mechanisms include autonomous overproduction of thyroid hormone, nonthyroidal illness including medication effects, and hypothalamic/pituitary dysfunction. OBJECTIVE: To characterize the clinical status and course of nursing home residents with low TSH and normal total T4 levels in the absence of treatment with thyroid hormone. DESIGN: Retrospective chart review was performed to determine participants status at the time of low TSH level, with additional recording of follow-up thyroid hormone levels, cardiac rhythm, and mortality. Mortality was compared with that of a control group matched for age and sex. SETTING: A nursing home for veterans and their spouses. MAIN RESULTS: Forty subjects with low TSH and initially normal total T4 were identified. Only three subjects were subsequently diagnosed as hyperthyroid. TSH levels of 18 subjects subsequently normalized, and four additional subjects had low total T3 levels suggesting a nonthyroidal mechanism. Seven subjects died during the first 4 months of follow-up compared with three in a control group (P < .001). Nine of the 40 subjects had a history of or current atrial fibrillation. No new atrial fibrillation was documented during 388 months of EKG follow-up. CONCLUSIONS: Low total T3 levels, TSH normalization, and excess mortality suggest that nonthyroidal illness plays a role in the pathogenesis of low TSH determinants in the nursing home. Autonomous production of thyroid hormone also plays a role. We believe that the term "subclinical hyperthyroidism" should be used only if the clinician believes that autonomous overproduction of thyroid hormone is the cause of a low TSH level. If subsequent research shows correctable adverse consequences associated with subclinical hyperthyroidism from autonomous overproduction of thyroid hormone, a more aggressive diagnostic approach will be needed to define the mechanism of a low TSH level at the time of its discovery.

Aged↗
PubMed1996

Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km.

This study was undertaken to determine the effects of ingesting either glucose (trial G) or glucose plus branched-chain amino acids (BCAA: trial B), compared with placebo (trial P), during prolonged exercise. Nine well-trained cyclists with a maximal oxygen uptake of 63.1 +/- 1.5 ml O2. min-1.kg-1 performed three laboratory trials consisting of 100 km of cycling separated by 7 days between each trial. During these trials, the subjects were encouraged to complete the 100 km as fast as possible on their own bicycles connected to a magnetic brake. No differences in performance times were observed between the three trials (160.1 +/- 4.1, 157.2 +/- 4.5, and 159.8 +/- 3.7 min, respectively). In trial B, plasma BCAA levels increased from 339 +/- 28 microM at rest to 1,026 +/- 62 microM after exercise (P < 0.01). Plasma ammonia concentrations increased during the entire exercise period for all three trials and were significantly higher in trial B compared with trials G and P (P < 0.05). The respiratory exchange ratio was similar in the three trials during the first 90 min of exercise; thereafter, it tended to drop more in trial P than in trials G and B. These data suggest that neither glucose nor glucose plus BCAA ingestion during 100 km of cycling enhance performance in well-trained cyclists.

Adult↗
PubMed1996

Training case managers in cognitive-behaviour therapy.

Four case managers with a nursing background took part in a 26 week in-service programme aimed at developing basic skills in cognitive-behaviour therapy. The programme occupied about 5 hours each week and included directly supervised therapy with at least 4 patients having serious mental illness. Patients' symptoms improved significantly after an average of less than 12 one hour therapy sessions. After the programme, case managers began treating patients autonomously, although all recognised the need for some continuing supervision and the necessity of referring unusually complex or challenging cases to clinical psychologists or others highly skilled in the area.

Adult↗
PubMed1995

Ranking of static non-neutral postures around the joints of the upper extremity and the spine.

Constrained body postures are usually cited as the major cause of musculoskeletal static loading. Thus, the main goal of the present study was to develop a ranking system for the stressfulness of the non-neutral static postures around the wrist, elbow, shoulder, neck and lower back. This was based on the ratings of perceived discomfort. Sixteen men participated in the study. The results indicated that static postural stresses yielded varying effects on the discomforting rating levels. On the basis of these preliminary findings, a ranking system was developed for the stressfulness of non-neutral postures around the joints of the upper extremity and the spine.

Adult↗
PubMed1995

A cross-validation of the NIOSH limits for manual lifting.

The psychophysical, biomechanical, and physiological criteria used in establishing the NIOSH limits for manual lifting were cross-validated against the data published by different researchers in the subject literature. Assessment of the 1991 NIOSH lifting equation indicated that: (1) NIOSH-based limits are significantly different from the psychophysical limits in the (i) low and high frequencies of lift, and (ii) small and large horizontal distances; (2) NIOSH limits are highly correlated with the data of Snook and Ciriello (1991) in the low frequency range, with the Recommended Weight Limit (RWL) protecting about 85% of the female population and 95% of the male population; (3) the 3.4kN limit for compression on the lumbosacral joint cannot protect the majority of the worker population on the basis of damage load concept; and (4) energy expenditure limits used in development of the RWL index can be sustained by 57 to 99% of worker population when compared to the physiological limits based on previous fatigue studies. Results of the cross-validation for psychophysical criterion confirmed the validity of assumptions made in the 1991 NIOSH revised lifting equation. However, the results of cross-validation for the biomechanical and physiological criteria were not in total agreement with the 1991 NIOSH model.

Adult↗
PubMed1993

Bepridil improves left ventricular performance in patients with angina pectoris.

Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01). Total treadmill exercise time, time to onset of angina, and time to 1-mm ST segment depression increased significantly during bepridil therapy. Cardiac output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and during peak upright bicycle exercise. Peak ejection rate and peak filling rate increased, and time to peak ejection rate and time to peak filling rate decreased at rest and at peak exercise during bepridil therapy. In addition, early diastolic filling fraction increased and atrial filling volume decreased during bepridil treatment. Bepridil is effective as monotherapy for treatment of patients with exertional angina; its use is associated with increased exercise capacity and decreased angina frequency and NTG consumption as well as improved LV systolic and diastolic performance at rest and during peak exercise.

Adult↗
PubMed1990

Biochemical purification and crystallographic characterization of the fiber-forming protein pilin from Neisseria gonorrhoeae.

Pilus fibers are long protein filaments on many pathogenic bacteria that participate in attachment to host cells. Although the self-assembling protein pilin is the major structural component of the Neisseria gonorrhoeae pilus fiber, several other proteins co-purified with pilin through the repeated solubilization-reassociation steps of the biochemical purification. Pilin solubilized in the nondenaturing detergent n-octyl-beta-D-glucopyranoside remained an aggregate of about 100 kDa at pH 9.5, but was reduced to a 40-kDa dimer at pH 10.5, suggesting that assembly involves electrostatic interactions of lysine, tyrosine, or other side chains with high pKa values. Pilin dimers and aggregates of higher molecular mass were partially stable even in the presence of sodium dodecyl sulfate and beta-mercaptoethanol. Removal of pilus-associated proteins and stabilization of pilin multimers permitted the reproducible crystallization of pilin. Three-dimensional needle- and plate-shaped crystals of purified N. gonorrhoeae pilin (strain MS11 variant C30) grew from 36 to 40% polyethylene glycol 400, pH 8.0-9.0, in space group C222, with cell dimensions a = 126.4, b = 121.2, c = 26.7 A and Vm = 2.84 A3/dalton for one molecule per asymmetric unit. The best crystals diffracted to 2.4 A resolution using synchrotron radiation, were stable to x-ray damage, and appear suitable for determination of the atomic structure. This approach of stabilizing and crystallizing an intermediate assembly state may be useful for other fiber-forming proteins, which have previously not been successfully crystallized in forms that diffract to atomic resolution.

Bacterial Outer Membrane Proteins↗
PubMed1989

Effect of 67Cu and 99Mo labeled tetrathiomolybdate on the distribution of 67Cu, Cu, and 99Mo in bile fractions in sheep.

The effect of intravenous administration of 67Cu and 99Mo labeled tetrathiomolybdate (TTM) on the appearance of 67Cu, stable Cu, and 99Mo in gel chromatographic fractions of bile was examined in sheep fed either 5 or 35 mg Cu kg-1 DM. Peak excretory periods of biliary 67Cu, stable Cu, and 99Mo were observed at 30 min-1.25 hr, 2-3 hr, and 11-13 hr after 67Cu and after 99Mo labeled TTM. Sephadex G-75 gel filtration of bile samples collected at 1, 3, and 12 hr after 67Cu administration revealed two major protein peaks of molecular weights of greater than 80,000 (peak I) and 7,000 (peak II) containing both 67Cu and Cu. But the ratio of 67Cu in the two peaks varied with time of bile collection. The ratio of areas of peak I:II 1 hr after 67Cu administration was approximately 0.48; at 3 hr, 0.62, and at 12 hr 1.35. Tetrathiomolybdate administration increased both 67Cu and stable Cu in bile by severalfold and induced a major shift of Cu into the higher molecular weight protein fraction. The experiments confirm the effectiveness of TTM as a "decoppering" agent. Furthermore, TTM not only promoted bile Cu excretion, but it also increased the incorporation of Cu into the macromolecular fraction. This may limit enterohepatic circulation of biliary Cu and thereby cause an overall Cu depletion and a negative Cu balance.

Animals↗
PubMed1989

Detection of bovine herpesvirus-1-specific IgM using a capture enzyme immune assay with isotype-specific monoclonal antibodies.

The detection of virus-specific immunoglobulin M (IgM) antibodies in acute-phase serum samples offers the possibility of making an accurate and rapid serologic diagnosis. We have developed a solid-phase capture assay that uses murine monoclonal antibodies specific for bovine IgM to separate the whole IgM fraction of a bovine serum sample. The IgM specific for bovine herpesvirus-1 (BHV-1) is then detected by the addition of viral antigen, which in turn is detected by BHV-1-specific monoclonal antibodies conjugated to horseradish peroxidase. A BHV-1 IgM antibody response was detected during the early postinfection period (7-40 days PI). Bovine herpesvirus-1 IgM antibody was not detected in sera taken from 3 animals following dexamethasone-induced viral reactivation. This method compares favorably with viral isolation, antigen detection in the clinical samples, and paired serology in the diagnosis of BHV-1 infection at a herd level.

Acute Disease↗