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Biomedical subjects

D B Carr

Publications and source records attributed to D B Carr.

At least 55 records · Page 3Linked to original sources
PubMed1999

Alterations in neuropeptide Y, tyrosine hydroxylase, and Y-receptor subtype distribution following spinal nerve injury to rats.

Recent animal models of experimental nerve injury have proven useful in evaluating potential sympathetic involvement in neuropathic pain syndromes. We have employed a widely adopted unilateral L5/L6 spinal nerve ligation model to compare the development of mechanical allodynia with neurochemical changes both at the site of peripheral nerve injury and in the dorsal root ganglia (DRG). We have focused on the expression of neuropeptide Y (NPY), a well-studied regulatory peptide and phenotypic marker of sympathetic neurons, and functionally related Y-receptor binding sites following nerve injury. In sympathetic neurons, NPY is colocalized and coreleased with norepinephrine (NE) at peripheral sites of action. Furthermore, NPY gene expression is induced within the population of medium- and large-diameter DRG neurons of the A beta-fiber class after experimental nerve injury. We therefore hypothesized that concurrent alterations in NPY and NE expression by sympathetic and sensory neurons may be a contributing factor to sympathetically-maintained neuropathic conditions. Animals with unilateral L5/L6 spinal nerve ligation developed mechanical allodynia of the hind paw ipsilateral to the site of injury that persisted until sacrifice at postoperative day 10. A significant induction of preproneuropeptide Y-encoding (PPNPY) mRNA, as detected by in situ hybridization histochemistry (ISHH), occurred in populations of medium- and large-diameter DRG neurons ipsilateral to the site of injury. Immunohistochemical analysis indicated a marked decline in the number of labeled sympathetic axons positive for tyrosine hydroxylase-like and NPY-like immunoreactivities (TH-LI and NPY-LI, respectively) proximal to the site of nerve injury and almost complete elimination of immunopositive fibers distal to the site of ligation. Whereas, the extent of colocalization of NPY-LI to TH-LI-positive sympathetic axons in unaffected L4 or L5 nerve segments exceeded 80%, this figure declined to approximately 50% in regenerating axons of ligated spinal nerve L5. The portion of NPY-LI that was not colocalized to sympathetic TH-LI-positive fibers was most likely contributed by regenerating sensory axons, consistent with marked de novo synthesis of NPY by DRG neurons. In end bulb axon terminals, i.e. morphological profiles characteristic of neuromas, NPY-LI-positive elements that were not colocalized to TH-LI-positive sympathetic elements appeared to be spatially segregated from those of sympathetic origin with colocalized TH-LI and NPY-LI. Receptor autoradiography indicated that small- and medium-diameter DRG somata of the C-fiber class normally express both Y1 and Y2 receptor subtypes. The pattern of the distribution of Y-receptor binding sites appeared to be relatively unaffected by spinal nerve ligation. In contrast, there was a marked increase in the density of Y2 receptor binding sites in the proximal segment of ligated spinal nerve L5, consistent with previously published data indicating differential transport of the Y2 autoregulatory receptor subtype to nerve terminals. Induction of NPY gene expression in injured DRG neurons is consistent with appearance of NPY-LI-positive end bulbs derived from regenerating sensory axons that are found in developing neuromas containing a relatively high density of transported prejunctional Y2 receptors. Newly established functional interactions of spatially segregated sensory- and sympathetically-derived end bulbs in developing neuromas may enhance neuronal hyperexcitability engendered by aberrant electrical activity at the site of injury. Injury-related alterations in the regulatory activities of NPY released within the DRG at somally-distributed Y-receptors may also contribute to the development and/or persistence of symptoms characteristic of sympathetically-maintained pain. Finally, at later times NPY-mediated modulation of NE release from invading sympathetic axon terminals within the DRG may affect the extent of alpha2 rece

Animals↗
PubMed1999

Toward a canon of the pain and analgesia literature: a citation analysis.

UNLABELLED: The purpose of this study was to use citation analysis to identify major themes and contributors to the pain and analgesia literature over the past two decades. A citation analysis was performed on a database of more than 110,000 articles in the biomedical literature from January 1981 through June 1997, and in the interval from January 1988 through June 1997. Articles and authors related to pain and analgesia research and practice were identified by searching approximately 7,700 journals. The 20 articles and 20 authors with the most citations were then checked by hand to ensure relevance to pain or analgesia. Most of the high-impact articles identified pertained to research on basic pain pathways. Nearly all the articles concerned opioids, nonsteroidal antiinflammatory drugs, and consequences of analgesic use. None of the highest-impact articles address assessment of clinical pain. Few women were first authors of any most frequently cited paper. Citation analysis is a useful tool in identifying important contributions to the biomedical literature. Recent and continuing research trends include the use of nonsteroidal antiinflammatory drugs, opioid mechanisms, and persistent pain disorders. Current trends expected to become stronger include description of pain from the patient's perspective and mechanisms of the transition from acute to chronic pain. IMPLICATIONS: We performed a citation analysis to identify important contributions and contributors to the biomedical literature. Recent pain and analgesia research has been focused on mechanisms of pain, but evidence suggests the importance of understanding the pain experience from the patient's perspective and the transition from acute to chronic pain.

Analgesia↗
PubMed1999

Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain.

UNLABELLED: Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cistemal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. IMPLICATIONS: We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

Chromatography, High Pressure Liquid↗
PubMed1998

Large-scale temporal gene expression mapping of central nervous system development.

We used reverse transcription-coupled PCR to produce a high-resolution temporal map of fluctuations in mRNA expression of 112 genes during rat central nervous system development, focusing on the cervical spinal cord. The data provide a temporal gene expression "fingerprint" of spinal cord development based on major families of inter- and intracellular signaling genes. By using distance matrices for the pair-wise comparison of these 112 temporal gene expression patterns as the basis for a cluster analysis, we found five basic "waves" of expression that characterize distinct phases of development. The results suggest functional relationships among the genes fluctuating in parallel. We found that genes belonging to distinct functional classes and gene families clearly map to particular expression profiles. The concepts and data analysis discussed herein may be useful in objectively identifying coherent patterns and sequences of events in the complex genetic signaling network of development. Functional genomics approaches such as this may have applications in the elucidation of complex developmental and degenerative disorders.

Animals↗
PubMed1998

Callosal terminals in the rat prefrontal cortex: synaptic targets and association with GABA-immunoreactive structures.

The callosal projections of the cerebral cortex play an important role in the functional integration of the two hemispheres, and the anatomy of these connections has been extensively studied in primary sensory and motor regions. In the present investigation, we examined the synaptic targets of callosal terminals in a limbic association area, the prefrontal cortex (PFC) in the rat. In addition, we examined the relationship of callosal afferents to GABA local circuit neurons within the PFC. Callosal terminals were labeled by either anterograde transport of Phaseolus vulgaris leucoagglutinin from superficial or deep layers or by anterograde degeneration following electrolytic lesion of the contralateral PFC. Callosal terminals in either the superficial or deep layers labeled by either method formed primarily asymmetric axo-spinous synapses (approximately 95%), while the remainder formed axo-dendritic synapses. Some of the dendrites postsynaptic to callosal terminals exhibited a morphology characteristic of local circuit neurons. This observation was confirmed in tissue immunolabeled for GABA, in which degenerating callosal terminals sometimes formed asymmetric synapses on GABA-labeled dendrites. In addition, GABA-labeled terminals and callosal afferents were sometimes observed to converge onto common postsynaptic dendritic shafts or spines within the PFC. These results indicate that callosal terminals in limbic association cortex, consistent with sensory and motor cortices, primarily target the spines of pyramidal neurons. In addition, the results suggest that callosal afferents to the PFC interact with GABA local circuit neurons at multiple levels. Specifically, a proportion of callosal terminals appear to provide excitatory drive to GABA cells, while GABA terminals may modulate the excitation from callosal inputs to the distal dendrites and spines of PFC pyramidal neurons.

Afferent Pathways↗
PubMed1998

Music does not reduce alfentanil requirement during patient-controlled analgesia (PCA) use in extracorporeal shock wave lithotripsy for renal stones.

To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia (PCA), we conducted a prospective, blinded, randomized controlled trial. Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music. They were then premedicated with morphine and ketorolac and randomly allocated into two groups. Group 1 (n = 97) had music started 10 min before the procedure and maintained until 10 min after its conclusion. Group 2 (n = 96) had music begun at the conclusion of lithotripsy and continued for 10 min. Pain intensity, alfentanil requirement, side effects, quality of analgesia, patient satisfaction, and acceptance of the technique were evaluated. Demographics, alfentanil requirement, pain levels, side effects, quality of analgesia, and patient satisfaction were similar in both groups. The addition of music did not provide any benefit. This result raises the possibility that some nonpharmacologic therapies have minimal impact in settings where the painful stimulus is moderate to severe and adequate pharmacotherapy is available.

Adolescent↗
PubMed1998

Management of perioperative pain in hospitalized patients: a national survey.

A survey was carried out to provide "benchmark" data on current practices of in-hospital perioperative pain management. The 59-item survey questionnaire incorporated all key points contained in the Agency for Health Care Policy and Research and the American Society of Anesthesiologists published guidelines concerning institutional policies as well as practice patterns. The questionnaire was mailed to designated pain specialists in a sample of 400 hospitals that were systematically stratified by bed size and geographic region. Of the 400 questionnaires mailed, 223 (56%) were returned. Of the 223 respondents, 85% were board-certified anesthesiologists. There was good to excellent overall adherence to most of the guideline recommendations; significant exceptions were the infrequent use of nonpharmacologic techniques for pain control and the relatively high frequency of intramuscular opioid use. In general, large hospitals have a greater adherence to the recommendations of the guidelines than do smaller hospitals. No noteworthy variations in institutional policies or practice patterns were evident. These results provide comprehensive baseline data against which future developments in the field of perioperative pain management can be assessed.

Data Collection↗
PubMed1998

Differentiating drivers with dementia of the Alzheimer type from healthy older persons with a Traffic Sign Naming test.

BACKGROUND: Dementia may contribute significantly to the driving impairment commonly associated with older adults. A brief, reliable, and sensitive screening method to identify drivers who may have cognitive impairment due to Alzheimer's disease or other dementing illnesses is needed for a variety of settings, including driver's license renewal offices. METHODS: Control and demented individuals who participated in the Washington University Alzheimer's Disease Research Center (ADRC) between March 1, 1995, and November 30, 1995, were evaluated for the ability to identify traffic signs correctly. After initially testing 39 traffic signs, 10 signs were selected based on scorer reliability and their ability to discriminate cognitively normal individuals from those with dementia. RESULTS: Sixty-six cognitively normal older people (average age 78 years) and 70 people with dementia (average age 76 years) were tested. Using a cutoff score at or below 9 (out of a possible score of 20), the Traffic Sign Naming test successfully identifies 74% of people with mild or moderate dementia of the Alzheimer type (DAT) from cognitively healthy older persons of comparable age, sex, education, and socioeconomic status; 11% of the healthy drivers were misclassified as demented. CONCLUSIONS: A brief, 2-min or less, easily administered naming test of 10 traffic signs differentiated drivers with mild or moderate DAT from cognitively normal controls. This brief test may be useful to identify older drivers in need of further assessment of driving skill.

Aged↗
PubMed1998

The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials.

UNLABELLED: We performed meta-analyses of randomized, control trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after a variety of procedures: epidural opioid, epidural local anesthetic, epidural opioid with local anesthetic, thoracic versus lumbar epidural opioid, intercostal nerve block, wound infiltration with local anesthetic, and intrapleural local anesthetic. Measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), peak expiratory flow rate (PEFR), PaO2, and incidence of atelectasis, pulmonary infection, and pulmonary complications overall were analyzed. Compared with systemic opioids, epidural opioids decreased the incidence of atelectasis (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.33-0.85) and had a weak tendency to reduce the incidence of pulmonary infections (RR 0.53, 95% CI 0.18-1.53) and pulmonary complications overall (RR 0.51, 95% CI 0.20-1.33). Epidural local anesthetics increased PaO2 (difference 4.56 mm Hg, 95% CI 0.058-9.075) and decreased the incidence of pulmonary infections (RR 0.36, 95% CI 0.21-0.65) and pulmonary complications overall (RR 0.58, 95% CI 0.42-0.80) compared with systemic opioids. Intercostal nerve blockade tends to improve pulmonary outcome measures (incidence of atelectasis: RR 0.65, 95% CI 0.27-1.57, incidence of pulmonary complications overall: RR 0.47, 95% CI 0.18-1.22), but these differences did not achieve statistical significance. There were no clinically or statistically significant differences in the surrogate measures of pulmonary function (FEV1, FVC, and PEFR). These analyses support the utility of epidural analgesia for reducing postoperative pulmonary morbidity but do not support the use of surrogate measures of pulmonary outcome as predictors or determinants of pulmonary morbidity in postoperative patients. IMPLICATIONS: When individual trials are unable to produce significant results, it is often because of insufficient patient numbers. It may be impossible for a single institution to study enough patients. Meta-analysis is a useful tool for combining the data from multiple trials to increase the patient numbers. These meta-analyses confirm that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity.

Administration, Oral↗
PubMed1998

Cluster analysis and data visualization of large-scale gene expression data.

The discovery of any new gene requires an analysis of the expression context for that gene. Now that the cDNA and genomic sequencing projects are progressing at such a rapid rate, high throughput gene expression screening approaches are beginning to appear to take advantage of that data. We present a strategy for the analysis for large-scale quantitative gene expression measurement data from time course experiments. Our approach takes advantage of cluster analysis and graphical visualization methods to reveal correlated patterns of gene expression from time series data. The coherence of these patterns suggests an order that conforms to a notion of shared pathways and control processes that can be experimentally verified.

Base Sequence↗
PubMed1997

Current concepts in the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) affects a large proportion of the increasingly aging population of this country, with prevalence rates as high as 47% for those >85 years old and a total annual cost approaching $70 billion. There is no currently validated test for detection of dementia of the Alzheimer type (DAT). Because of this and the insidious onset of the disease, the diagnosis may be missed by primary care physicians. Cerebral extracellular beta-amyloid deposition as senile plaques and intraneuronal neurofibrillary tangles appear to represent critical processes in the development of AD; however, whether and the extent to which these may also occur in nondemented aging is uncertain. Tangles occur primarily in medial temporal lobe structures (hippocampus, entorhinal cortex, and amygdala), and tangle density correlates with dementia severity. Plaques are diffusely distributed throughout the cerebral cortex, and are the neuropathologic hallmark of the disease. Aging is the primary risk factor for AD. After controlling for differential life expectancy, female sex still appears to be an additional risk factor. There may be a genetic component, in some cases based on family and twin studies. Allelic variation in the apolipoprotein E (Apo E) gene located on chromosome 19 represents another important risk factor. However, the diversity of gene mutations apparently responsible for the various forms of AD suggest that the disease is genetically heterogeneous. AD may be conceptualized as an imbalance between neuronal injury and repair. Oxygen free radicals may be involved in the cross-linking process of beta-amyloid aggregation, and antioxidants may represent a potential intervention. There may be a role for heavy metals in the pathogenesis of AD, but this remains controversial. Work continues toward possibly a cure or prevention, but more likely palliation, of AD, and the results of trials of anti-inflammatory agents, estrogen, and antioxidant therapy are anticipated in the near future.

Aging↗
PubMed1997

Dementia and driving: an attempt at consensus.

The number of older drivers in Sweden will be rapidly increasing during the next decades. A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, a clear-cut policy for evaluating driving competence in demented persons is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to formulate a consensus on the issue of driving and dementia. This consensus document is aimed at providing primary care physicians with practical advice concerning the assessment of cognitive status in relation to driving. Suggestions are based on a review of existing research and discuss the use of general and driving-specific sources of information available to the physician. Consensus was reached on the statement that a diagnosis of moderate to severe dementia precludes driving and that certain individuals with mild dementia should be considered for a specialized assessment of their driving competence.

Aged↗
PubMed1997

Motor vehicle crashes and drivers with DAT.

An increasing number of drivers with dementia is expected over the next few decades. From a public safety standpoint, there is concern that these drivers also will have an increased risk for motor vehicle crashes. This paper examines recent studies on motor vehicle crashes experienced by drivers with dementia and/or dementia of the Alzheimer type (DAT). These studies were analyzed for their common findings, strengths, and limitations. Many studies reveal an increased crash rate for drivers with DAT compared with nondemented older drivers. Studies suggest that 50% of DAT drivers stop driving within 3 years of the onset of disease, the risk for a motor vehicle crash increases with the duration of driving after disease onset, males are at increased risk for crashes, dementia severity does not correlate with risk for a crash, and additional medical conditions may further contribute to crash risk. Areas of focus for future studies in this field are discussed.

Accidents↗
PubMed1997

Hemodynamic effects of intravenous somatostatin administered in the postoperative period.

OBJECTIVE: To evaluate the hemodynamic effects of intravenous somatostatin administration in patients during the early postoperative period. DESIGN: Prospective, case-controlled trial. SETTING: Postanesthesia care unit. PATIENTS: Ten postoperative, noncirrhotic, American Society of Anesthesiologists physical status II patients, after resection of nonsecretory (i.e., non-neuroendocrine) tumors. No patient received any vasoactive medication perioperatively. INTERVENTIONS: Three hours after the end of surgery, normal saline or somatostatin was intravenously administered in two phases: a) in phase 1, patients received a 20-mL bolus of normal saline within 1 min, followed by a continuous infusion of 20 mL of normal saline for the next 30 mins. Patients were left undisturbed for the subsequent 30 mins. b) in phase 2, patients received somatostatin (3.5 micrograms/kg, 20-mL bolus) over 1 min, followed by a continuous infusion of somatostatin (3.5 micrograms/kg/hr) for 72 hrs. MEASUREMENTS AND MAIN RESULTS: Anesthesia was managed according to a prospectively designed protocol. Patients' hemodynamic profiles and pressure waveforms were recorded immediately before the bolus injections of normal saline and somatostatin, and at every minute thereafter for 30 mins. Bolus doses of somatostatin produced a transient, nonsignificant decrease in heart rate, along with short-lived increases in systolic arterial pressure, diastolic arterial pressure, systolic pulmonary arterial pressure, diastolic pulmonary arterial pressure, and central venous pressure. CONCLUSION: Bolus intravenous somatostatin administered postoperatively after tumor resection in patients produced transient cardiovascular changes that were not sustained during a subsequent continuous infusion.

Chemotherapy, Adjuvant↗
PubMed1997

Differential effect of central versus parenteral administration of morphine sulfate on regional concentrations of reduced glutathione in rat brain.

Prior studies in rodents have shown significant depletion of reduced glutathione (GSH) in peripheral organs following acute systemic or central administration of opioids. However, little information exists on whether opioid administration affects concentrations of brain GSH. Recently, clinical observations have indicated acute declines of GSH concentrations in the cerebrospinal fluid of cancer patients after acute intracerebroventricular (ICV) morphine which may contribute to the development of organic behavioral brain syndromes associated with central opioid analgesia. Collectively these data led us to investigate the affect of acute systemic and central morphine on regional concentrations of GSH in rat brain. Systemic morphine had no effect on GSH concentrations in selected brain areas. In contrast, ICV morphine resulted in selective GSH depletion in the caudate nucleus, consistent with concurrent excitatory locomotive behavior. This change may have reflected morphine-induced oxidative stress together with increased metabolic activity within the extrapyramidal system.

Analgesics, Opioid↗