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Biomedical subjects

D B Carr

Publications and source records attributed to D B Carr.

At least 37 records · Page 2Linked to original sources
PubMed2000

The value of informant versus individual's complaints of memory impairment in early dementia.

Self-reported versus informant-reported memory problems in nondemented elderly adults and in individuals with very mild and mild dementia of the Alzheimer type (DAT) were correlated with cognitive outcomes. No significant correlations were found between self-reported memory complaints and cognitive performance or (in controls) later development of dementia. In contrast, informant-reported memory loss distinguished nondemented from demented individuals and predicted future diagnosis of DAT.

Aged↗
PubMed2000

Dopamine terminals synapse on callosal projection neurons in the rat prefrontal cortex.

Dopamine (DA) afferents to the prefrontal cortex (PFC) play an important role in the cognitive functions subserved by this cortical area. Within the PFC, DA terminals synapse onto the distal dendrites of both local circuit neurons and pyramidal projection cells. We have previously demonstrated in the rat PFC that some of the dendrites and spines postsynaptic to DA terminals arise from pyramidal neurons that project to the nucleus accumbens. However, it is not known whether the pyramidal cells that give rise to callosal intercortical connections of the PFC also receive DA synaptic input. To address this question, retrograde tract tracing using an attenuated strain of pseudorabies virus (PRV-Bartha) was combined with immunocytochemistry for tyrosine hydroxylase (TH) to identify DA terminals in the PFC. Thirty-six to 40 hours following injection of PRV into the contralateral PFC, numerous callosal projection neurons were extensively labeled throughout their dendritic trees, with no evidence of PRV trans-synaptic passage. In tissue prepared for electron microscopy, labeling for PRV was distributed throughout pyramidal cell somata and extended into distal dendrites and dendritic spines. Some PRV-labeled dendrites and spines received symmetric synaptic input from terminals containing peroxidase labeling for TH. These results demonstrate that DA terminals synapse onto the distal dendrites of callosally projecting PFC neurons and suggest substrates through which DA may modulate interhemispheric cortical communication.

Animals↗
PubMed2000

A substance P-opioid chimeric peptide as a unique nontolerance-forming analgesic.

To elucidate mechanisms of acute and chronic pain, it is important to understand how spinal excitatory systems influence opioid analgesia. The tachykinin substance P (SP) represents the prototypic spinal excitatory peptide neurotransmitter/neuromodulator, acting in concert with endogenous opioid systems to regulate analgesic responses to nociceptive stimuli. We have synthesized and pharmacologically characterized a chimeric peptide containing overlapping NH(2)- and COOH-terminal functional domains of the endogenous opioid endomorphin-2 (EM-2) and the tachykinin SP, respectively. Repeated administration of the chimeric molecule YPFFGLM-NH(2), designated ESP7, into the rat spinal cord produces opioid-dependent analgesia without loss of potency over 5 days. In contrast, repeated administration of ESP7 with concurrent SP receptor (SPR) blockade results in a progressive loss of analgesic potency, consistent with the development of tolerance. Furthermore, tolerant animals completely regain opioid sensitivity after post hoc administration of ESP7 alone, suggesting that coactivation of SPRs is essential to maintaining opioid responsiveness. Radioligand binding and signaling assays, using recombinant receptors, confirm that ESP7 can coactivate mu-opioid receptors (MOR) and SPRs in vitro. We hypothesize that coincidental activation of the MOR- and SPR-expressing systems in the spinal cord mimics an ongoing state of reciprocal excitation and inhibition, which is normally encountered in nociceptive processing. Due to the ability of ESP7 to interact with both MOR and SPRs, it represents a unique prototypic, anti-tolerance-forming analgesic with future therapeutic potential.

Analgesics↗
PubMed2000

Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons.

Excitatory projections from the prefrontal cortex (PFC) to the ventral tegmental area (VTA) play an important role in regulating the activity of VTA neurons and the extracellular levels of dopamine (DA) within forebrain regions. Previous investigations have demonstrated that PFC terminals synapse on the dendrites of DA and non-DA neurons in the VTA. However, the projection targets of these cells are not known. To address whether PFC afferents innervate different populations of VTA neurons that project to the nucleus accumbens (NAc) or to the PFC, a triple labeling method was used that combined peroxidase markers for anterograde and retrograde tract-tracing with pre-embedding immunogold-silver labeling for either tyrosine hydroxylase (TH) or GABA. Within the VTA, PFC terminals formed asymmetric synapses onto dendritic shafts that were immunoreactive for either TH or GABA. PFC terminals also synapsed on VTA dendrites that were retrogradely labeled from the NAc or the PFC. Dendrites retrogradely labeled from the NAc and postsynaptic to PFC afferents were sometimes immunoreactive for GABA but were never TH-labeled. Conversely, dendrites retrogradely labeled from the PFC and postsynaptic to PFC afferents were sometimes immunoreactive for TH but were never GABA-labeled. These results provide the first demonstration of PFC afferents synapsing on identified cell populations in the VTA and indicate a considerable degree of specificity in the targets of the PFC projection. The unexpected finding of selective PFC synaptic input to GABA-containing mesoaccumbens neurons and DA-containing mesocortical neurons suggests novel mechanisms through which the PFC can influence the activity of ascending DA and GABA projections.

Animals↗
PubMed2000

The older adult driver.

More adults aged 65 and older will be driving in the next few decades. Many older drivers are safe behind the wheel and do not need intensive testing for license renewal. Others, however, have physiologic or cognitive impairments that can affect their mobility and driving safety. When an older patient's driving competency is questioned, a comprehensive, step-by-step assessment is recommended. Many diseases that impair driving ability can be detected and treated effectively by family physicians. Physicians should take an active role in assessing and reducing the risk for injury in a motor vehicle and, when possible, prevent or delay driving cessation in their patients. Referral to other health care professionals, such as an occupational or physical therapist, may be helpful for evaluation and treatment. When an older patient is no longer permitted or able to drive, the physician should counsel the patient about using alternative methods of transportation.

Accidents, Traffic↗
PubMed2000

GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex.

Dopamine-containing projections from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) have been extensively characterized since their discovery over 25 years ago. However, the VTA projection to the PFC also contains a substantial nondopamine component, whose neurochemical phenotype is unknown. To examine if a portion of this nondopamine VTA projection contains GABA, anterograde and retrograde tract-tracing in the rat was combined with GABA immunocytochemistry and electron microscopy. Following injections of Fluoro-Gold (FG) into the PFC, many VTA neurons were retrogradely labeled, as visualized by immunoperoxidase staining for FG. A large portion of FG-labeled somata (58%) and dendrites (33%) within the VTA also contained immunogold-silver labeling for GABA. These dually labeled profiles exhibited a morphology similar to dopamine-containing cells within the VTA. To confirm and extend these findings, anterograde transport of biotinylated dextran amine (BDA) from the VTA was combined with immunogold-silver labeling for GABA within the PFC. Consistent with the results obtained from retrograde tracing, a portion of BDA-labeled terminals in the PFC also contained immunoreactivity for GABA. These dually labeled terminals formed symmetric synapses onto small caliber dendrites and dendritic spines. Some PFC dendrites contacted by GABA-containing VTA terminals were themselves GABA-labeled. The results of this investigation have identified a substantial population of GABA-containing neurons in the VTA that send axons to the PFC where they synapse on the distal processes of both pyramidal and local circuit neurons. This GABA-containing mesocortical pathway may provide substrates for both inhibitory and disinhibitory influences on PFC neuronal activity.

Animals↗
PubMed2000

Maternal hemodynamics and pregnancy outcome in women with prior orthotopic liver transplantation.

The aim of this study is to evaluate the hemodynamics and pregnancy outcome of women with prior orthotopic liver transplantation. Hemodynamic measurements by Doppler technique were performed on pregnant subjects with prior orthotopic liver transplantation. Maternal characteristics, renal function, pregnancy complications, delivery indications, delivery mode, and neonatal outcomes were evaluated. Six pregnancies occurred in 5 women after orthotopic liver transplantation at the University of Washington Medical Center (Seattle, WA) between 1991 and 1999. Four of the 6 pregnancies were complicated by chronic hypertension, fetal growth restriction, and preterm delivery. Two pregnancies had worsening hypertension characterized by vasoconstriction in the second trimester despite antihypertensive therapy. These 2 subjects were administered cyclosporine for maintenance immunosuppression and had greater mean arterial pressures preconception and in the first trimester than the other subjects. One of these pregnancies resulted in fetal demise at 25 weeks' gestation. The other subject was delivered at 28 weeks' gestation for nonreassuring fetal status and superimposed preeclampsia. All pregnancies were complicated by renal insufficiency; however, the 2 subjects with poor obstetric outcome had preconception serum creatinine levels greater than 1.5 mg/dL and creatinine clearances less than 40 mL/min. Pregnancies complicated by second-trimester vasoconstriction and moderate renal insufficiency are at risk for preeclamspia, fetal growth restriction, and fetal demise. Good obstetric outcome can occur in women with mild renal insufficiency and well-controlled chronic hypertension. Improved hypertensive control preconception may decrease the risk for preeclampsia and poor obstetric outcome.

Adolescent↗
PubMed2000

Ultrasonography for cervical length measurement: agreement between transvaginal and translabial techniques.

OBJECTIVE: To assess agreement between transvaginal and translabial ultrasonography for measuring cervical length in the second and third trimesters. METHODS: Eighty-four obstetric patients at 14-40 weeks' gestation were enrolled. Three images of the cervix were obtained by translabial (3.5-MHz curvilinear transducer) and transvaginal (6.5-MHz endovaginal probe) ultrasonography. The mean cervical length obtained by using each method was used for data analysis. The McNemar chi(2) test was used to assess the difference between techniques in their ability to obtain a measurement. The paired t-test was used to evaluate the differences between the measurements. The mean difference and SD for the differences were used to calculate the limits of agreement. An acceptable difference was defined as less than 0.5 cm. RESULTS: Cervical length measurements were obtained in 84 patients (100%) by using the transvaginal technique and in 80 patients (95%) by using the translabial technique (P =.1). Eighty patients had both transvaginal and translabial measurements for comparison. The mean difference in cervical length was 0.37 cm (P <.001; 95% confidence interval [CI] 0. 21, 0.52). The upper and lower limits of agreement were 1.75 cm (95% CI 1.48, 2.02) and -1.01 cm (95% CI -0.74, -1.28), respectively. The differences between the two measurements were within these limits 95% of the time. These limits of agreement were greater than the acceptable difference of 0.5 cm. CONCLUSION: Transvaginal and translabial techniques should not be used interchangeably for clinical assessment of cervical length because agreement between the methods is not within an acceptable range.

Adult↗
PubMed2000

Low-dose, short-acting, angiotensin-converting enzyme inhibitors as rescue therapy in pregnancy.

OBJECTIVE: To assess the risks and potential benefits of low-dose angiotensin-converting enzyme (ACE) inhibitor treatment in pregnancies complicated by severe hypertension. METHODS: A retrospective review of pregnant women treated with ACE inhibitors was conducted. Hemodynamics before and after treatment were assessed by using Doppler technique to measure cardiac output. Data were analyzed by using the Wilcoxon signed-rank test. Maternal and neonatal outcomes were assessed by chart review and phone interview. RESULTS: Ten pregnancies were identified in which ACE inhibitor therapy was initiated in pregnancy for severe, unresponsive vasoconstricted hypertension; three were complicated by severe chronic hypertension, 4 by renal insufficiency, and 3 by severe preeclampsia. Treatment was limited to a low-dose, short-acting ACE inhibitor (captopril, 12.5 to 25 mg/day). Treatment was associated with an increase in cardiac output from 5.7 +/- 1.5 L/minute to 7.4 +/- 1.4 L/minute (P<.01) and a reduction in total peripheral resistance from 1770 +/- 670 to 1222 +/- 271 dyne. sec. cm(-5) (P =.005). No fetal or neonatal complications were observed. The probability of observing one or more adverse neonatal outcome in this sample, based on an assumed true risk of 5% and 10%, was calculated to be 12% and 50%, respectively. CONCLUSION: Low-dose captopril therapy was associated with improvement in maternal hemodynamics and, in cases complicated by severe hypertension and renal insufficiency, successful continuation of pregnancy. Fetal and neonatal complications were not experienced, but complication rates of 5-10% could have been missed because of the small number of exposed pregnancies.

Adult↗
PubMed2000

Using the "TOPS," an outcomes instrument for multidisciplinary outpatient pain treatment.

OBJECTIVE: To assess the reliability of an augmented SF-36 instrument, the Treatment Outcomes in Pain Survey ("TOPS"), in patients treated in two pain management programs, and present norms for initial values and treatment-related improvements. DESIGN: Prospective case series at two sites with longitudinal follow-up. SETTING: Multidisciplinary, comprehensive outpatient pain treatment centers in university hospitals in Salt Lake City and Boston. PATIENTS: Nine hundred and forty seven adult outpatients with a range of socioeconomic, demographic, and ethnic characteristics, all referred for evaluation and treatment of chronic pain. INTERVENTIONS: Usual practice multidisciplinary pain treatment. OUTCOMES MEASURES: TOPS prior to pain treatment and 5-week nominal follow-up. Means and standard deviations of baseline and follow-up results. Psychometric results for reliability (Cronbach alpha), validity (item discriminant validity, validity coefficients), and related statistical precision measures for group and individual designs. RESULTS: Several measures were precise enough to permit following individual patients in standard clinic treatment, of which the Total Pain Experience dimension was the most powerful. Similar psychometrics were observed in the Boston and Salt Lake City sites. The Pain Symptom, Objective Family/Social Disability, Objective Work Disability, and Upper Body Functional Limitations scales were validated. DISCUSSION: The TOPS was designed to satisfy several models of clinical pain treatment. It successfully monitored treatment based on those models. Not all patients improve with treatment, but most do. The TOPS can be administered in a variety of ways, but we found paper and pencil administration with computer scanning of results quick and efficient for making the data available to clinicians as part of treatment. CONCLUSIONS: The accuracy of the TOPS is sufficient to monitor the response of individual patients during multidisciplinary treatment of chronic pain. The TOPS provides needed documentation (e.g., to third-party payors) of the aggregate value of multidisciplinary outpatient treatment of chronic pain as well as its benefit for individual patients.

Journal Article↗
PubMed2000

Assessing individual outcomes during outpatient multidisciplinary chronic pain treatment by means of an augmented SF-36.

OBJECTIVE: To meet the growing demand for objective outcomes measurement during treatment of chronic pain, we developed an instrument to track outcomes of individual patients. METHOD: In a 2-phase study, existing and novel outcomes instruments were applied in an interdisciplinary pain management program. In the initial phase, 408 patients were administered the Short Form 36-item questionnaire and during phase 2, 437 patients (87 of whom were followed) were given an expanded (191-item) questionnaire. RESULTS: When applied to individual patients, the Short Form 26-item questionnaire lacked measurement reliability for assessment of treatment outcomes and sensitivity to upper extremity or facial pathology, and failed to separate limitations of work versus everyday activity. A novel group of scales derived from responses to 61 questions, including the Short Form 36-item questionnaire, proved sufficiently reliable for routine follow-up of individual chronic pain patients. CONCLUSIONS: This new Treatment Outcomes in Pain Survey allows assessment of individual patient outcomes, and aggregate or individual clinician performance, during interdisciplinary treatment of chronic pain.

Journal Article↗
PubMed2000

Characteristics of motor vehicle crashes of drivers with dementia of the Alzheimer type.

OBJECTIVE: To determine whether there is a difference in crash rates and characteristics between drivers with dementia of the Alzheimer type (DAT) and nondemented older persons who were controls. DESIGN: A pilot study using a 5-year retrospective analysis of state-recorded crash data and crash characteristics followed by patient enrollment into a study on road test skills. SETTING: Alzheimer's Disease Research Center at Washington University in St. Louis, Missouri. Subjects were enrolled as volunteers in a longitudinal study of aging and DAT. PARTICIPANTS: One hundred twenty-one subjects (58 nondemented, older drivers and 63 drivers with DAT) with a mean age of 77 years met the inclusion criteria for this study. DAT was diagnosed using validated clinical diagnostic criteria and was staged by the Clinical Dementia Rating (CDR) Scale. All subjects with DAT were in the very mild (CDR = 0.5) or mild (CDR = 1) stages. MAIN OUTCOME MEASURE: State-recorded traffic crashes. Also, a daily driving diary was completed by each subject and used to estimate miles traveled per year. RESULTS: Subjects diagnosed with mild DAT (CDR = 1) reported less roadway exposure (average number of miles driven per year) than did drivers with very mild DAT (CDR = 0.5) or controls. Crashes in both groups were infrequent, with 0.07 state-recorded crashes per driver per year in the nondemented group (CDR = 0), 0.06 in the very mild DAT group (CDR = 0.5), and 0.04 in the mild DAT group (CDR = 1). There was no statistical difference in the crash frequency between groups, even when adjusting for exposure. Drivers with DAT had trends toward more at-fault crashes, crashes with injuries, and crashes in which the officer on the scene cited failure to yield. CONCLUSIONS: In our sample, individuals with very mild or mild DAT who continued to drive seemed to have crash rates similar to those of the controls. There may be significant differences between the causes and the consequences of crashes involving drivers with DAT when compared with cognitively intact age-matched controls, but none were found in this pilot study. Further research on crash characteristics is needed in larger samples of community-based drivers with DAT across wider ranges of dementia severity to address issues such as driving competency and public safety.

Accidents, Traffic↗
PubMed2000

Inhibition of morphine tolerance development by a substance P-opioid peptide chimera.

The neuropeptide substance P (SP), apart from its traditional role in spinal nociceptive processing, is an important regulatory effector of opioid-dependent analgesic processes. The present study stems from our original findings indicating that 1) pharmacologically administered SP mediates a strong inhibitory activity on the development of morphine tolerance in rats, and that 2) a novel SP-opioid peptide chimera YPFFGLM-NH(2), designated ESP7, produces opioid-dependent analgesia without tolerance development. To further examine the effects of simultaneous activation of two distinct opposing spinal systems on opioid tolerance and the mechanisms underlying chimeric peptide function, a second SP-opioid chimera was synthesized. This chimera, designated ESP6 (YPFFPLM-NH(2)), contains overlapping domains of endomorphin-2 and SP, respectively. ESP6 is distinguished from ESP7 by a glycine to proline substitution at position 5. Intrathecal administration of morphine sulfate (MS) with ESP6 leads to a prolongation of MS analgesia over a 5-day period. The analgesia produced by ESP6 and MS is opioid receptor-dependent, due to the ability of naltrexone to block the analgesic response. Furthermore, when ESP6 and MS are administered with concurrent NK-1 receptor blockade, a decay in analgesic potency similar to that seen with MS alone results. The presence of a proline in ESP6 appears to reduce its conformational flexibility, limit its potency at the micro-opioid receptor, and hinder its analgesic effectiveness alone. However, ESP6 represents a novel adjuvant for the maintenance of opioid analgesia over time and provides a means to predict the pharmacological properties of a chimera from its structure.

Analgesics, Opioid↗
PubMed1999

Dopamine terminals in the rat prefrontal cortex synapse on pyramidal cells that project to the nucleus accumbens.

Afferents to the prefrontal cortex (PFC) from dopamine neurons in the ventral tegmental area have been implicated in working memory processes and in the pathogenesis of schizophrenia. Previous anatomical investigations have demonstrated that dopamine terminals synapse on dendritic spines and shafts of pyramidal cells in the PFC. Moreover, neurochemical and physiological studies suggest that dopamine modulates the activity of PFC neurons that project to the nucleus accumbens. However, whether this modulation involves direct synaptic input to cortico-accumbens projection neurons has not been determined. To address this question, retrograde transport of an attenuated strain of pseudorabies virus (PRV) from the nucleus accumbens was combined with immunoperoxidase labeling of tyrosine hydroxylase (TH) to identify dopamine terminals in the PFC. At survival times <48 hr, extensive dendritic distribution of immunogold labeling for PRV was observed in cortico-accumbens neurons. However, evidence consistent with trans-synaptic passage of PRV within this timeframe was observed only rarely. When examined at the electron microscopic level, immunogold labeling for PRV was localized to neuronal somata, proximal and distal dendrites, and dendritic spines. Some of these dendritic processes received symmetric synaptic input from TH-immunoreactive terminals. These data represent the first demonstration of dopamine synaptic contacts onto an identified population of pyramidal cells in the PFC. The findings have important implications for understanding how dopamine modulates cortical outflow to limbic regions in normal brain and pathological states such as schizophrenia.

Animals↗
PubMed1999

Acute pain.

Postanaesthesia care units used to echo with cries of patients in pain after general anaesthesia. Each as-needed dose of analgesia was given only after permission of the surgeon or anaesthesiologist. Once conscious, patients were required to request each subsequent analgesic dose until hospital discharge. Not surprisingly, nearly half the patients who have an operation experience moderate to severe pain after surgery. Acute pain control has advanced dramatically and is now a field with dedicated texts, journals, and research. Despite improved surgical techniques that have transformed many operations into same-day procedures, inadequately controlled pain may still extend the length of hospital stay and predispose to expensive, time-consuming complications such as pneumonia. Recognition of economic and humanitarian benefits of pain control has prompted worldwide attention from professional groups, insurers, and governments. This paper describes the process of acute pain and measures to control it with drugs or non-pharmacological interventions. Even brief intervals of acute pain can induce long-term neuronal remodelling and sensitisation ("plasticity"), chronic pain, and lasting psychologial distress. Hence, acute pain and other types of pain (cancer-related or chronic) that are classified as distinct actually have many similarities.

Acute Disease↗
PubMed1999

Maintenance oral nifedipine for preterm labor: a randomized clinical trial.

OBJECTIVE: This study was undertaken to evaluate the efficacy of maintenance oral nifedipine in patients initially treated with intravenous magnesium sulfate for preterm labor. STUDY DESIGN: Patients with a diagnosis of preterm labor between 24 and 33.9 weeks' gestation were randomly assigned to receive either maintenance tocolytic therapy with oral nifedipine (20 mg every 4-6 hours) or no treatment (control) after discontinuation of magnesium tocolysis. Pregnancy and neonatal outcomes were evaluated. A sample size of 50 patients was required to detect a 10-day difference in mean time gained (beta =.2, alpha =.05). Statistical analyses were based on intent to treat. The t, chi(2), and Fisher exact tests were performed. RESULTS: Seventy-four patients were randomly assigned to receive either oral nifedipine (n = 37) or no treatment (n = 37). There were no statistically significant differences in age, race, parity, preterm delivery risk factors, enrollment gestational age, results of cervical examination, delivery gestational age, time gained, or neonatal complications between the groups. Delivery gestational age (mean +/- SD) was 35.4 +/- 3.2 weeks for patients randomly assigned to receive nifedipine and 35.3 +/- 3.2 weeks for patients who received no treatment (P =.9). Time gained during pregnancy was 37 +/- 23.9 days in the nifedipine group and 32.8 +/- 20.4 days in the control group (P =.4). CONCLUSION: Maintenance therapy with oral nifedipine does not significantly prolong pregnancy in patients initially treated with intravenous magnesium sulfate for preterm labor.

Adult↗