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Biomedical subjects

D Christensen

Publications and source records attributed to D Christensen.

At least 19 recordsLinked to original sources
PubMed2005

HIV infection does not influence clinical outcomes in hospitalized patients with bacterial community-acquired pneumonia: results from the CAPO international cohort study.

In a case-control study, outcomes for 58 human immunodeficiency virus (HIV)-positive patients with community-acquired pneumonia (CAP) were compared with outcomes for 174 HIV-negative patients with CAP. No differences were found in the time to clinical stability, the length of hospitalization, and mortality. Clinical outcomes for hospitalized patients with CAP may not be influenced by HIV infection.

Adult↗
PubMed2004

Evidence of piezoelectric resonance in isolated outer hair cells.

Our results demonstrate high-frequency electrical resonances in outer hair cells (OHCs) exhibiting features analogous to classical piezoelectric transducers. The fundamental (first) resonance frequency averaged f(n) approximately 13 kHz (Q approximately 1.7). Higher-order resonances were also observed. To obtain these results, OHCs were positioned in a custom microchamber and subjected to stimulating electric fields along the axis of the cell (1-100 kHz, 4-16 mV/80 microm). Electrodes embedded in the side walls of the microchamber were used in a voltage-divider configuration to estimate the electrical admittance of the top portion of the cell-loaded chamber (containing the electromotile lateral wall) relative to the lower portion (containing the basal plasma membrane). This ratio exhibited resonance-like electrical tuning. Resonance was also detected independently using a secondary 1-MHz radio-frequency interrogation signal applied transversely across the cell diameter. The radio-frequency interrogation revealed changes in the transverse electric impedance modulated by the axial stimulus. Modulation of the transverse electric impedance was particularly pronounced near the resonant frequencies. OHCs used in our study were isolated from the apical region of the guinea pig cochlea, a region that responds exclusively to low-frequency acoustic stimuli. In this sense, electrical resonances we observed in vitro were at least an order of magnitude higher (ultrasonic) than the best physiological frequency of the same OHCs under acoustic stimuli in vivo. These resonance data further support the piezoelectric theory of OHC function, and implicate piezoelectricity in the broad-band electromechanical behavior of OHCs underlying mammalian cochlear function.

Animals↗
PubMed2001

Uterine rupture during second-trimester abortion associated with misoprostol.

BACKGROUND: Misoprostol use is contraindicated in women at term with a history of a uterine scar. There are limited data regarding the use of this drug in the midtrimester. CASE: A 23-year-old woman with two prior cesareans presented at 23 weeks' gestation for pregnancy termination by dilation and evacuation. She had laminariae placed the day before and was instructed to take 400 microg of misoprostol intravaginally at midnight, then 400 microg buccally at 6:00 AM the day of the procedure. During the evacuation, uterine rupture was diagnosed. She underwent emergency laparotomy, and the uterus was repaired. CONCLUSION: Uterine rupture can occur when misoprostol is used in the second trimester in a woman with a uterine scar.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

The effect of the glycine/NMDA receptor antagonist, (+)-HA966, on morphine dependence in neuropathic rats.

We have previously shown that rats with a painful peripheral neuropathy develop dependence without tolerance after repetitive doses [3mg/kg subcutaneously (s.c.)] of morphine. After injections of a higher dose (10mg/kg s.c.) the animals develop tolerance that can be prevented by the glycine/N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-HA966. This study examined whether (1) dependence develops also after repetitive doses of 10mg/kg of morphine and, if so, (2) whether (+)-HA966 prevents the development of dependence after both the low and the higher morphine pretreatment doses. A 4day pretreatment regimen (post-operative days 12-16) with two daily s.c. injections of saline+saline, saline+morphine (3 or 10mg/kg), (+)-HA966 (2.5 or 5mg/kg)+morphine or (+)-HA966 (5mg/kg)+saline was used, and withdrawal was precipitated by an injection of naloxone [2mg/kg intravenously (i.v.)] at 17h after the last pretreatment injection. Three signs of withdrawal (exploring, writhing, ptosis) appeared after pretreatment with both doses of morphine alone, while other signs (teeth chattering, pilo-erection) developed only after injections at the 3mg/kg dose. One sign (penile grooming/erection) appeared only after the higher morphine dose. Pretreatment with the combination of (+)-HA966 and morphine at 3mg/kg prevented the development of all withdrawal signs. By contrast, except for exploring, (+)-HA966 did not modify the incidence of the withdrawal signs observed after pretreatment with doses of 10mg/kg of morphine. The results suggest that prevention of the development of morphine dependence by glycine/NMDA receptor antagonism depends on the degree of morphine dependence.

Animals↗
PubMed2000

Antinociceptive effect of (S)-N-desmethyl trimebutine against a mechanical stimulus in a rat model of peripheral neuropathy.

Trimebutine (2-dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoate, hydrogen maleate) relieves abdominal pain in humans. In the present study, the antinociceptive action of systemic (S)-N-desmethyl trimebutine, a stereoisomer of N-monodesmethyl trimebutine, the main metabolite of trimebutine in humans, was studied in a rat model of neuropathic pain produced by chronic constriction injury to the sciatic nerve. Mechanical (vocalization threshold to hindpaw pressure) stimulus was used. Experiments were performed two weeks after surgery when the pain-related behaviour has fully developed. (S)-N-desmethyl trimebutine (1, 3, 10 mg/kg s.c.) produced dose-dependent antinociceptive effects on the nerve-injured and the contralateral hindpaw. The effect of the lowest dose (1 mg/kg s.c.) of (S)-N-desmethyl trimebutine on the nerve-injured paw was equal to that seen after a ten time stronger dose on the contralateral paw. The effect of (S)-N-desmethyl trimebutine (1 mg/kg) was not naloxone reversible. The results suggest that systemic (S)-N-desmethyl trimebutine may be useful in the treatment of some aspects of neuropathic pain.

Analgesics↗
PubMed2000

Complete prevention but stimulus-dependent reversion of morphine tolerance by the glycine/NMDA receptor antagonist (+)-HA966 in neuropathic rats.

BACKGROUND: Tolerance to the analgesic effect of morphine complicates the management of chronic pain states. The authors studied the ability of the glycine/N-methyl-D-aspartate receptor antagonist (+)-HA966 to modify morphine tolerance in a rat model of neuropathic pain. METHODS: Mononeuropathy was induced by placing four ligatures around the common sciatic nerve. The 4-day pretreatment regimens with two daily subcutaneous injections of saline and saline, saline and morphine (10 mg/kg), (+)-HA966 (2.5 mg/kg) and morphine, or (+)-HA966 and saline were begun on post-operative day 12 to test the ability of (+)-HA966 to prevent the development of tolerance. Behavioral experiments were performed on postoperative day 16, when the pain-related behavior reached a stable maximum. The effect of an acute dose of morphine (1 mg/kg intravenously) was tested against both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency to hind paw immersion into a 46 degrees C hot-water bath) stimuli. In addition, to test the ability of a single injection of (+)-HA966 to reverse established morphine tolerance, groups of morphine-pretreated rats received injections of either (+)-HA966 (2.5 mg/kg subcutaneously) and morphine (1 mg/kg intravenously), saline and morphine, or (+)-HA966 and saline. RESULTS: Baseline vocalization thresholds and struggle latencies did not differ in the various pretreatment groups, indicating that the pretreatments had no effect on pain-related behavior. Coadministration of (+)-HA966 prevented the reduction of the effect observed with morphine alone in both the mechanical test and the thermal test. (+)-HA966 reversed morphine tolerance in the thermal but not in the mechanical test. CONCLUSION: (+)-HA966 prevented morphine tolerance in both mechanical and thermal tests but reversed established morphine tolerance in the thermal test only.

Analgesics, Opioid↗
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

Macro-ergonomic risk assessment in nuclear remediation industry.

In this study, a macro-ergonomic risk assessment tool was developed based on criteria of scope, simplicity, practicality, usefulness, reliability and job-specificity. A relative stress index 'RSI' was formulated to take into account multiple parameters, such as frequency, duration, repetition, weight, force, travel distance and horizontal distance. This tool was tested in nuclear remediation industry. The results are presented and discussed.

Journal Article↗
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↗