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Biomedical subjects

A Barr

Publications and source records attributed to A Barr.

At least 19 recordsLinked to original sources
PubMed1999

Nocturnal and daytime panic attacks--comparison of sleep architecture, heart rate variability, and response to sodium lactate challenge.

BACKGROUND: The purpose of this study was to determine if nocturnal panic patients have greater autonomic dysregulation than patients with daytime panic. METHODS: Three groups were studied: patients who suffer from panic attacks during sleep (n = 12), those who suffer from daytime panic attacks only (n = 12), and control subjects (n = 12). Each subject underwent 24-hour holter monitoring for heart rate variability (HRV), an overnight sleep recording, and sodium lactate challenge during wakefulness. RESULTS: There was a marked subjective response to the sodium lactate challenge in the panic disorder (PD) patients but not in control subjects. Each group showed changes in HRV in response to sodium lactate challenge. The decrease in HRV measures was more marked in PD patients as a whole than in control subjects. During non-rapid eye movement (REM) sleep the value for total power (TP) was significantly higher in the nocturnal panic patients. The PD patients as a whole had higher values for TP and low-frequency (LF) power during REM sleep than control subjects. There were no significant differences between the two PD groups in sleep architecture. The PD patients as a whole had lower sleep efficiency and less stage 4 sleep than control subjects. CONCLUSIONS: These findings indicate that there are substantial differences between PD and control subjects in autonomic regulation and that there are small differences between patients with daytime panic attacks and those with sleep-related panic attacks.

Adult↗
PubMed1999

A model for multidisciplinary peer review and supervision of behavioral health clinicians.

The authors describe a semi-annual program for multidisciplinary peer review and supervision that is in use at two rural adult and child mental health and drug and alcohol service agencies. The program incorporates semiannual chart reviews and face-to-face discussions held with each clinician by a multidisciplinary supervisory group. Several quality improvement issues addressed by this program are described, including improved communication, improved clinical diagnosis, the establishment of service parameters, more appropriate referrals for psychiatric and other medical care, and improved clinician skills. The program represents an inexpensive approach to peer review and supervision that can incorporate university-based consultants, improve quality of care, improve clinicians' skills, and be readily applied by clinical supervisors to most behavioral health settings.

Adult↗
PubMed1999

Validation of a noninvasive measure of local myocardial repolarization in a conscious human model: adaptation of repolarization to changes in rate.

INTRODUCTION: A commercial pacemaker sensor measure of the unipolar endocardial stimulus to T wave interval may accurately reflect changes in the monophasic action potential duration at 90% repolarization (APD90). This sensor system was used to study the kinetics of adaptation of repolarization duration to changes in heart rate in humans. METHODS AND RESULTS: Patients were studied using an external pacemaker capable of displaying all stimulus to T wave intervals for each paced beat. Right ventricular stimulation was delivered via the pacemaker and compared simultaneously to APD90. Steady-state pacing was simulated by 60 seconds of pacing at cycle lengths (CLs) 350 to 700 msec. Adaptation to a new ventricular rate was analyzed with a sudden 200-msec decrease in CL. The relation between repolarization measure and steady-state CL (n = 16) was linear with a slope of 0.16 and 0.19 for APD90 and stimulus to T wave interval, respectively (P = NS). The adaptation of both repolarization measures to a sudden change in rate were best modeled by a biexponential function. Stimulus to T wave interval exhibited a parallel course to APD90, and an analysis of normalized differences between APD90 and stimulus to T wave interval followed an approximately normal distribution, with 93.5% of the paired differences within 2 SD of the mean. CONCLUSION: A pacemaker sensor measure of stimulus to T wave interval accurately parallels APD90 during both steady-state and sudden changes in rate. Repolarization in human endocardium follows a linear relation to steady-state CL and adapts to a new rate with a biexponential function. This model represents a novel method for studying human cardiac repolarization.

Action Potentials↗
PubMed1998

Neuronal nitric oxide synthase is refractory to mechanism-based inactivation in GH3 pituitary cells.

Nitric oxide formation by GH3 pituitary cells is stimulated by depolarizing concentrations of K+ and by the L-channel Ca2+ agonist Bay kappa 8644 in an additive manner that depends on extracellular Ca2+. Ca(2+)-dependent NO formation at 100 microM arginine was inhibited 50% over a 30-min period by 5 microM NG-amino-L-arginine, 30 microM N6-iminoethyl-L-ornithine (NIO) and 520 microM N5-iminoethyl-L-lysine (NIL) but required concentrations of aminoguanidine (AG) greater than 3 mM. As measured at 100 microM extracellular arginine, intracellular neuronal nitric oxide synthase (nNOS) was inactivated 50% over a 30-min period by 150 microM NG-amino-L-arginine and 1500 microM NIO, but required concentrations of NIL or AG greater than 5 mM. The inactivation of nNOS by these agents occurred only under conditions that mobilized extracellular Ca2+ and was inhibited by increased extracellular arginine. Thus these agents inhibit cellular Ca(2+)-dependent NO formation at concentrations far lower than those required to inactivate the cellular nNOS. Inhibition of NO formation by these agents was not attributable to effects on cellular arginine uptake. In contrast diphenyliodonium chloride produced a rapid and complete inactivation of cellular NO formation and nNOS activity. These inactivations produced by diphenyliodonium chloride occurred with identical kinetics but displayed no requirement for Ca2+. These data support the assertion that neuronal NO synthase is refractory to mechanism-based inactivation in GH3 pituitary cells.

Animals↗
PubMed1998

Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST Segment Monitoring Substudy.

OBJECTIVES: We sought to study the relation between recurrent ST segment shift within 6 to 24 h of initial resolution of ST elevation after thrombolytic therapy and 30-day and 1-year mortality. BACKGROUND: Rapid and stable resolution of ST segment elevation in relation to thrombolytic therapy in patients with an acute myocardial infarction is an indicator of culprit artery patency. Whether recurrence of ST segment shift during continuous ST monitoring after initial resolution is related to poor prognosis has not been studied. METHODS: ST segment monitoring was performed within 30 min after thrombolytic therapy for acute myocardial infarction. The predictive value of a new ST segment shift (assessed as > or = 0.1-mV deviation from the baseline) 6 to 24 h after thrombolytic therapy was studied with respect to 30-day and 1-year mortality. RESULTS: Of 734 patients, 243 had a new ST segment shift (33%). The 30-day mortality rate in patients with an ST shift (7.8%) was significantly higher than that in patients without an ST shift (2.25%, p = 0.001), as was the 1-year mortality rate (10.3% vs. 5.7%, respectively, p = 0.025). Multivariable analysis revealed an independent predictive value of ST shift with respect to 30-day mortality (p = 0.008), even after consideration of multiple clinical risk factors in the overall Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO)-I mortality model (p = 0.0001). Moreover, the duration of the ST shift bore a direct relation with 1-year mortality (p = 0.008). CONCLUSIONS: Detection of ST segment shift early after thrombolytic therapy for acute myocardial infarction is a simple, noninvasive means of identifying patients at high risk and is superior to other commonly assessed clinical risk factors. Thus, patients with a new ST shift after the first 6 h, but within 24 h, represent a high risk group that may benefit from more aggressive intervention, whereas patients without evidence of an ST shift represent a low risk subgroup.

Electrocardiography↗
PubMed1998

Designated driving among college students.

OBJECTIVE: We studied the frequency of designated driver use, predictors of designated driver use, whether designated drivers use alcohol, and barriers to using a designated driver. METHOD: Undergraduates at Arizona State University (N = 544) completed a questionnaire assessing designated driver use. The mean age of participants was 20.6 years old and 52% were male. Criterion for inclusion in the study was that participants had consumed alcohol at least one time. RESULTS: Eighty-six percent (86%) of participants had used a designated driver. Monthly alcohol use and driving to drinking destinations were positively associated with designated driver use. Ninety-four percent of participants indicated that their designated driver occasionally consumed alcohol. The most frequent reason for not using a designated driver was, "I stayed where I was drinking until I was sober" (37%). Less alcohol use among friends was associated with sounder methods of designated driver selection. CONCLUSIONS: Findings suggest those groups at risk for alcohol-related driving accidents tend to use designated drivers at high rates, but these groups tend to choose designated drivers who consume alcohol.

Accidents, Traffic↗
PubMed1997

A population-based method for the estimation of defibrillation energy requirements in humans. Assessment of time-dependent effects with a transvenous defibrillation system.

BACKGROUND: A weighted logistic regression analysis was developed to allow pooling of patient data for the study of the stability of defibrillation energy requirements with a new nonthoracotomy lead defibrillation system. METHODS AND RESULTS: One hundred twenty patients were prospectively studied with a single-model nonthoracotomy implantable cardioverter defibrillator (ICD) system at the time of implant and at 3 months. The pooled data of all shocks delivered to all patients were fitted to a logistic function to construct a defibrillation voltage/energy dose-response relationship. The crude logit curve was weighted in quartiles according to the average shock energy delivered per patient. Shocks at implant (n = 802; 6.6 +/- 2.5 shocks/patient) and follow-up (n = 292; 2.4 +/- 1.2 shocks/patient) were analyzed. The modeled voltage/energy required for 50% successful defibrillation (95% CI) in the pooled data was 367 V (273, 461) and 9.8 J (6.7, 12.9) at implant and 338 V (264, 412) and 10.5 J (8, 13.0) at follow-up. The conventional measure of lowest successful voltage/energy (95% CI) was 430 V (411, 449) and 12.1 J (11, 13.2) at implant and 415 V (391, 439) and 11.3 J (10, 12.6) at follow-up. There were no statistically significant differences between implant and follow-up energy requirements with either method. CONCLUSIONS: The nonthoracotomy lead system used in this study demonstrated stability of defibrillation energy requirements at implant and 3-month follow-up. A new technique for the estimation of the defibrillation energy dose-response relationship was derived by using a weighted logistic regression analysis.

Aged↗
PubMed1997

Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior.

The clinical behavior of growth hormone (GH)-producing pituitary tumors is known to vary greatly; however, the events underlying this variability remain poorly understood. Herein we demonstrate that tumor overexpression of the GH-releasing hormone (GHRH) gene is one prognostically informative event associated with the clinical aggressiveness of somatotroph pituitary tumors. Accumulation of GHRH mRNA transcripts was demonstrated in 91 of a consecutive series of 100 somatotroph tumors by in situ hybridization; these findings were corroborated by Northern analysis and reverse transcriptase polymerase chain reaction, and protein translation was confirmed by Western blotting. By comparison, transcript accumulation was absent or negligibly low in 30 normal pituitary glands. GHRH transcripts were found to preferentially accumulate among clinically aggressive tumors. Specifically, GHRH mRNA signal intensity was 1) linearly correlated with Ki-67 tumor growth fractions (r = 0.71; P < 0.001), 2) linearly correlated with preoperative serum GH levels (r = 0.56; p = 0.01), 3) higher among invasive tumors (P < 0.001), and 4) highest in those tumors in which post-operative remission was not achieved (P < 0.001). Using multivariate logistic regression, a model of postoperative remission likelihood was derived wherein remission was defined by the single criterion of suppressibility of GH levels to less than 2 ng/ml during an oral glucose tolerance test. In this outcome model, GHRH mRNA signal intensity proved to be the most important explanatory variable overall, eclipsing any and all conventional clinicopathological predictors as the single most significant predictor of postoperative remission; increases in GHRH mRNA signal were associated with marked declines in remission likelihood. The generalizability of this outcome model was further validated by the model's significant performance in predicting postoperative remission in a random sample of 30 somatotroph tumors treated at another institution. These data indicate that overexpression of GHRH gene is an event associated with the neoplastic progression and clinical aggressiveness of somatotroph adenomas. More generally, these data merge essential elements of the hypothalamic and pituitary hypotheses of pituitary tumorigenesis, providing for a more unified concept of neoplastic progression in the pituitary.

Acromegaly↗
PubMed1996

Word-list generation deficits in dementia.

To evaluate the specificity of the semantic fluency deficit in Alzheimer's disease (AD), we compared the performances of patients with AD, Huntington's disease (HD), vascular dementia (VD), and healthy control subjects on tasks of category (i.e., semantic) and first-letter (i.e., phonemic/lexical) word list generation. As compared to age-appropriate controls, all three patient groups demonstrated relatively more impaired semantic than phonemic fluency. Dementia severity did not affect this relationship. Thus, the greater vulnerability of semantically guided fluency is not specific to AD but occurs in other dementias as well. Deficits in both the organization of semantic memory and retrieval from long-term storage appear to contribute to the relatively poorer performance on semantic than phonemic fluency tasks observed in patients with AD, VD, and HD.

Adult↗
PubMed1996

Increased cardiac fatty acid uptake with dobutamine infusion in swine is accompanied by a decrease in malonyl CoA levels.

OBJECTIVE: Malonyl CoA is an important regulator of fatty acid oxidation in the heart secondary to its ability to inhibit carnitine palmitoyltransferase 1 (CPT 1). Malonyl CoA is produced from acetyl CoA in a reaction catalyzed by acetyl CoA carboxylase (ACC). In this study we determined if alterations in malonyl CoA regulation of fatty acid metabolism are involved in the increase in energy transduction seen following an increase in cardiac work. METHODS: Anesthetized, open-chest, domestic swine were subjected to a 30 min control period followed by a 30 min treatment period with either dobutamine (15 micrograms.kg-1. min-1 i.v.) (n = 6) or saline (n = 6). RESULTS: Heart rate, left ventricular peak dp/dt, and MVO2, were significantly increased in the dobutamine group compared to the saline group during the treatment period. Free fatty acid and glucose uptake were increased 210 and 248%, respectively, in the dobutamine group during the treatment period. Malonyl CoA content was decreased by 55% (from 0.40 +/- 0.05 to 0.18 +/- 0.12 nmol/g wet wt; P < 0.05) with dobutamine treatment, but was not affected by saline treatment. ACC activity was not significantly different between groups (0.31 +/- 0.02 vs. 0.30 +/- 0.04 nmol. min-1. mg protein-1, respectively). The activity of AMP-dependent protein kinase (AMPK), which phosphorylates and inactivates ACC, was also not significantly different in the dobutamine hearts compared to the saline hearts (322 +/- 26 vs. 338 +/- 39 pmol. min-1. mg protein-1, respectively). CONCLUSION: The increased cardiac work following dobutamine infusion is accompanied by a decrease in malonyl CoA levels and an increase in fatty acid uptake. However, the decrease in malonyl CoA cannot be explained by a decrease in ACC activity.

Animals↗
PubMed1995

A multicentre assessment of the specificity of ten anti-HBc screening tests.

Samples from 1828 donations were screened for anti-HBc at seven sites in the UK using kits supplied by 10 manufacturers. Only 10 (0.55%) donations were considered to have true anti-HBc reactivity and these were detected by all 10 kits. Additional markers of HBV infection were found in nine of these 10 donations. Additional reactives were found by all kits, the number ranging from 1 to 43. In the four more specific kits, the 10 true reactives were clearly distinguished from the 'false reactives' by the strength of the reaction. It is concluded that the reliance on a single ELISA test for anti-HBc diagnosis is unwise. The use of a second test known to be more specific than the screening ELISA is recommended.

Blood Donors↗
PubMed1994

Acetyl-CoA carboxylase involvement in the rapid maturation of fatty acid oxidation in the newborn rabbit heart.

Fatty acid oxidation rapidly increases in the rabbit heart following birth. By inhibiting carnitine palmitoyltransferase 1 (CPT1), malonyl-CoA is a potent regulator of fatty acid oxidation in the heart. We therefore addressed the hypothesis that a decrease in acetyl-CoA carboxylase (ACC) activity and/or malonyl-CoA inhibition of CPT1 could account for the increase in the ability of the heart to oxidize fatty acids following birth. ACC activity and expression, malonyl-CoA levels, and mitochondrial CPT1 activity were measured in hearts from 1-day, 7-day, and 6-week-old rabbits. CPT1 activity and sensitivity to malonyl-CoA inhibition did not differ between 1-day, 7-day, or 6-week hearts (the IC50 for malonyl-CoA was 32.0 +/- 1.5, 36.0 +/- 0.3, and 36.3 nM, respectively). Western blot analysis with streptavidin showed that all hearts expressed similar amounts of both a 265-kDa (ACC-265) and 280-kDa isoform (ACC-280) of ACC. A progressive and significant decrease in malonyl-CoA levels was seen in 1-day, 7-day, and 6-week hearts (47 +/- 2, 40 +/- 2, and 26 +/- 2 nmol/g dry weight, respectively), paralleling a decline in ACC activity. We hypothesized that these developmental changes could be due to changes in hormonal regulation of cardiac ACC in the postnatal period. In isolated hearts from 1-day-old rabbits, the fatty acid oxidation rate was 9.01 +/- 1.10 nmol.g dry weight-1.min-1. Glucagon (1 ng/ml) did not alter this rate (11.03 +/- 1.42 nmol.g dry weight-1.min-1), but insulin (100 microunits/ml) resulted in a significant decrease in rate (4.81 +/- 0.82 nmol.g dry weight-1.min-1). ACC activity was markedly elevated in 1-day-old hearts perfused with insulin compared to control hearts or glucagon perfused hearts (0.415 +/- 0.052, 0.095 +/- 0.018, and 0.133 +/- 0.013 nmol of malonyl-CoA produced.g dry weight-1.min-1, respectively). Malonyl-CoA levels were also markedly elevated in 1-day hearts perfused with insulin (123.0 +/- 8.3, 2.0 +/- 0.4, and 1.8 +/- 0.6 nmol/g dry weight in insulin, control, and glucagon hearts, respectively). In 7-day-old rabbit hearts, the basal fatty acid oxidation rate had increased to 24.5 +/- 4.8 nmol.mg-1.min-1. In contrast to the 1-day-old hearts, insulin had no significant effect on fatty acid oxidation, although glucagon resulted in a significant increase in rates (38.9 +/- 12.2 and 80.7 +/- 9.1 nmol.g dry weight-1.min-1, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Acetyl Coenzyme A↗
PubMed1994

Radial, ulnar, and median nerve palsies caused by a congenital constriction band of the arm: single-stage correction.

Single-stage correction of a congenital constriction band of the arm in an infant with radial, ulnar, and median nerve dysfunction is reported with significant improvement in neurologic function. This was accomplished by thorough preoperative physical examination and neurologic evaluation, circumferential excision of the constricting band, decompression of the involved peripheral nerves, and multiple large Z-plasties for skin closure. Based on the case presented here and a review of the literature, management of patients with congenital constriction rings overlying major nerve trunks should include (1) complete neurologic examination, even in the infant, (2) electromyographic and nerve conduction studies if there is any evidence of nerve dysfunction, (3) early complete excision of the band in one stage if there is no evidence of edema seen with lymphatic or venous obstruction (otherwise, two-stage removal of the band should be planned), and (4) early exploration and decompression of all major peripheral nerves beneath the band if there is any neurologic dysfunction.

Amniotic Band Syndrome↗
PubMed1992

Phosphorylation of the C-terminal domain of the Na+/H+ exchanger by Ca2+/calmodulin-dependent protein kinase II.

The Na+/H+ exchanger is a pH-regulatory protein that extrudes one H+ ion in exchange for one Na+ ion when intracellular pH declines. A number of studies have shown phorbol ester stimulation of activity in intact cells, leading to the idea that the exchanger is regulated by protein kinase C-mediated phosphorylation in vivo. cDNA encoding the protein has been cloned, and a recent model suggests a large internal cytoplasmic C-terminal domain that may be a site of regulation of the exchanger [Sardet, Franchi & Pouyssegur (1989) Cell 56, 271-280]. We examined this region of the protein using a rabbit cardiac Na+/H+ exchanger cDNA clone. cDNA of the Na+/H+ exchanger, coding for the C-terminal 178 amino acid residues, was cloned into the expression vector pEX-1 and expressed as a fusion protein with beta-galactosidase. The fusion protein reacted with an antibody produced against a synthetic peptide of the C-terminal 13 amino acid residues of the Na+/H+ exchanger, confirming the identity of the expressed protein. Control and experimental pEX-1-Na+/H+ exchanger protein was purified on a p-aminophenyl beta-D-thiogalactopyranoside-agarose column. Purified Ca2+/calmodulin-dependent protein kinase II readily phosphorylated the Na+/H+ exchanger protein in a Ca(2+)- and calmodulin-dependent manner in vitro, but this region of the protein was not a substrate for purified protein kinase C or for the catalytic subunit of cyclic AMP-dependent protein kinase. Control-expressed beta-galactosidase was phosphorylated to a maximal level of 0.77 +/- 0.17 mol of Pi/mol (mean +/- S.E.M., n = 6) whereas the fusion protein was phosphorylated to a maximal level of 4.09 +/- 0.39 mol of Pi/mol (n = 6), suggesting one site of phosphorylation in beta-galactosidase and three in the C-terminal domain of the Na+/H+ exchanger. Examination of the deduced amino acid sequence of this part of the exchanger reveals three consensus sequences for Ca2+/calmodulin-dependent protein kinase II. These results suggest that the exchanger may be directly regulated in vivo by calmodulin-dependent protein kinase II but not by protein kinase C or cyclic AMP-dependent protein kinase.

Amino Acid Sequence↗
PubMed1991

Identification of the protein and cDNA of the cardiac Na+/H+ exchanger.

We examined the myocardial form of the Na+/H+ exchanger. A partial length cDNA clone was isolated from a rabbit cardiac library and it encoded for a Na+/H+ exchange protein. In comparison with the human Na+/H+ exchanger, the sequence of the 5' end of the cDNA was highly conserved, much more than the 3' region, while the deduced amino acid sequence was also highly conserved. To further characterize the myocardial Na+/H+ exchange protein, we examined Western blots of isolated sarcolemma with antibody produced against a fusion protein of the Na+/H+ exchanger. The antibodies reacted with a sarcolemma protein of 50 kDa and with a protein of 70 kDa. The results show that the rabbit myocardium does possess a Na+/H+ exchanger protein homologous to the known human Na+/H+ exchanger.

Amino Acid Sequence↗
PubMed1989

D-dimer levels in blood salvage for autotransfusion.

Autotransfusion of operatively salvaged blood is an increasingly attractive and used practice. The fear of precipitating a coagulopathy, however, has retarded the acceptance of autotransfusions and the efficiency and convenience of banked homologous blood has proved too competitive in recent years. The risk of transmitting diseases with bank homologous blood has seen a resurgence in the development of autotransfusion. The current alternatives to pre-operative autologous banking or dilution are the reinfusing of filtered salvaged blood, and of blood which has been further processed by washing which involves the extra cost of time, personnel and equipment. Washing removes possible harmful products, but also removes coagulation factors. D-Dimer levels were estimated by monoclonal antibody techniques in salvaged blood before and after washing in 10 patients undergoing aortic surgery and in 10 u of homologous banked blood. The D-Dimer levels in the unwashed blood were increased 85 times, but were normal in the washed blood. D-Dimers are an indication of activation of the coagulation and fibrinolytic systems and the presence of fibrin degradation products.

Aorta↗