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Biomedical subjects

R Carney

Publications and source records attributed to R Carney.

14 recordsLinked to original sources
PubMed2002

Early spatial memory deficit induced by 2,5-hexanedione in the rat.

2,5-Hexanedione (2,5-HD), the major common neurotoxic metabolite of n-hexane and methyl n-butyl ketone, causes a delayed neuropathy with associated sensorimotor impairments. The question arises as to whether specific cognitive deficits occur even prior to changes in sensorimotor ability. The present experiments examined the effects of 2,5-HD on spatial navigation of rats in a water maze at levels/times that did not affect spontaneous exploratory motor activity in an open field holeboard apparatus. Exposure to 1% 2,5-HD in the drinking water for 2 weeks did not significantly affect escape learning, as measured by latency to find a hidden platform. However, 2,5-HD treated animals were impaired in the use of a spatial strategy during a recall test. A similar impairment in spatial memory was observed after i.p. injection of 500 mg/kg/day 2,5-HD for 4 days, in the absence of significant changes in sensorimotor ability or weight loss. Thus 2,5-HD may mediate some of the cognitive effects of hexacarbons and these changes can occur prior to the development of motor symptoms.

Animals↗
PubMed2002

Analysis of immunohistochemical label of Fos protein in the suprachiasmatic nucleus: comparison of different methods of quantification.

The induction of the proto-oncogene c-fos, and its phosphoprotein product Fos, has been extensively used to study the effects of light on the circadian pacemaker in the suprachiasmatic nucleus (SCN). Experimental approaches to the quantification of Fos induction have mainly been based on immunohistochemistry and subsequent measure of Fos immunoreactivity (IR) in sections of the SCN. In this study, the authors compare several methods of quantification using optical density image analysis or counts of Fos-IR labeled cells. To assess whether optical density measures using image analysis reflect the amount of Fos in brain tissue, the authors developed standards of known concentrations of Fos protein in an agar matrix. The agar standards were sectioned and treated simultaneously with sections of the SCN from animals exposed to different levels of irradiance. Optical density was found to be proportional to the quantity of Fos in the sections, indicating that this measure accurately reflects relative levels of Fos protein induction. Quantification by optical density analysis allows an objective measure in which the various parameters, conditions of illumination, and threshold can be maintained constant throughout the analysis. Counting cells by visual observation is more subjective because threshold values cannot be precisely defined and can vary according to the observer, illumination, degree of label, and other factors. In addition, cell counts involving direct visual observation, automated cell counts, or stereological methods do not take into account the difference in the density of label between cells, thus giving equal weight to lightly or densely stained cells. These measures are more or less weakly correlated with measures of optical density and thus do not accurately reflect the amount of bound Fos protein in the tissue sections. In contrast, labeled surface area as measured by image analysis shows a linear relationship with optical density. The main outcome of this study is that computer-assisted image analysis provides an accurate and rapid method to determine the relative amount of Fos protein in the SCN and the effects of light on intracellular signaling mechanisms involved in the circadian clock.

3,3'-Diaminobenzidine↗
PubMed2000

Comparison of different packing methods for capillary electrochromatography columns.

A study was carried out in which 50 microm I.D. fused-silica capillaries were packed with 3 microm octadecylsilane bonded silica, from the same batch, by four methods; liquid slurry and carbon dioxide supercritical carrier, each with and without the use of an ultrasonic probe. A neutral test mixture was analysed by capillary column in reversed-phase mode, and the reproducibility of the electroosmotic flow and of migration time, column efficiency and retention factors, was determined. Initially results suggested that there was no significant difference between properties of columns packed by different methods, and a more thorough statistical evaluation confirmed this; differences observed in the column performance were attributed to random variations between replicate columns, and not between packing methods. However, the variation was least when applying the ultrasonication during liquid slurry.

Carbon Dioxide↗
PubMed2000

P2Y receptor regulation of PAI-1 expression in vascular smooth muscle cells.

P2Y-type purine and pyrimidine nucleotide receptors play important roles in the regulation of vascular hemostasis. In this article, the regulation of plasminogen activator inhibitor-1 (PAI-1) expression in rat aortic smooth muscle cells (RASMCs) by adenine and uridine nucleotides was examined and compared. Northern analysis revealed that RASMCs express multiple P2Y receptor subtypes, including P2Y(1), P2Y(2), and P2Y(6). Treatment of RASMCs with UTP increased PAI-1 mRNA expression and extracellular PAI-1 protein levels by 21-fold (P<0.001) and 7-fold (P<0.001), respectively. The ED(50) for the effect of UTP on PAI-1 expression was approximately 1 micromol/L, and its maximal effect occurred at 3 hours. UDP stimulated a 5-fold increase (P<0.005) in PAI-1 expression. In contrast to these potent stimulatory effects of uridine nucleotides, ATP and 2-methylthioadenosine triphosphate (2-MeSATP) caused a small and transient increase in PAI-1 mRNA at 1 hour, followed by a rapid decrease to baseline levels. ADP produced only an inhibitory effect, reducing PAI-1 mRNA levels by 63% (P<0.05) at 3 hours. The relative nucleotide potency in stimulating PAI-1 expression is UTP>UDP>ATP=2-MeSATP, consistent with a predominant role of the P2Y(6) receptor. Further studies revealed that exposure of RASMCs to either ATP or ADP for 3 hours inhibited both UTP- and angiotensin II-stimulated PAI-1 expression by up to 90% (P<0.001). Thus, ATP induced a small and transient upregulation of PAI-1 that was followed by a strong inhibition of PAI-1 expression. These results show that extracellular adenine and uridine nucleotides exert potent and opposing effects on vascular PAI-1 expression.

Adenosine Triphosphate↗
PubMed1999

Low hot pain threshold predicts shorter time to exercise-induced angina: results from the psychophysiological investigations of myocardial ischemia (PIMI) study.

OBJECTIVES: The purpose of this study was to test whether cutaneous thermal pain thresholds are related to anginal pain perception. BACKGROUND: Few ischemic episodes are associated with angina; symptoms have been related to pain perception thresholds. METHODS: A total of 196 patients with documented coronary artery disease underwent bicycle exercise testing and thermal pain testing. The Marstock test of cutaneous sensory perception was administered at baseline after 30 min of rest on two days and after exercise and mental stress. Resting hot pain thresholds (HPTs) were averaged for the two baseline visits and divided into two groups: 1) average HPT <41 degrees C, and 2) average HPT > or =41 degrees C, to be clearly indicative of abnormal hypersensitivity to noxious heat. RESULTS: Patients with HPT <41 degrees C had significantly shorter time to angina onset on exercise testing than patients with HPT > or =41 degrees C (p < 0.04, log-rank test). Heart rates, systolic blood pressure and rate-pressure product at peak exercise were not different for the two groups. Resting plasma beta-endorphin levels were significantly higher in the HPT <41 degrees C group (5.9+/-3.7 pmol/liter vs. 4.7+/-2.8 pmol/liter, p = 0.02). Using a Cox proportional hazards model, patients with HPT <41 degrees C had an increased risk of angina (p = 0.03, rate ratio = 2.0). These differences persisted after adjustment for age, gender, depression, anxiety and history of diabetes or hypertension (p < 0.01). CONCLUSIONS: Occurrence of angina and timing of angina onset on an exercise test are related to overall hot pain sensory perception. The mechanism of this relationship requires further study.

Adult↗
PubMed1996

Reading skills in children with Turner's syndrome: an analysis of hyperplexia.

Most neuropsychological studies of cases of chromosomal abnormalities report associations with disorders or disabilities. Studies of Turner's Syndrome (TS), in which their is functional absence of the information carried on the short arm of the second X chromosome, have emphasised disorders of spatial skill and potential abnormality of the parietal lobes or right hemisphere. In contrast, language skills have received little investigation despite suggestions by Shaffer (1962) of considerable verbal skill. This paper reports on an analysis of reading skill, in girls with TS. The girls with TS attained reading levels higher than those predicted on the basis of their age and intelligence. Moreover, they attained significantly higher reading levels than controls. Unlike many previous studies of hyperlexia, reading comprehension was also better than controls. The hyperlexia of the girls with TS was characterised by strength in both lexical reading systems, as assessed by the ability to read irregular words, and strength in alphabetical or phonological reading skills, as assessed by the ability to read long unfamiliar regular words. Hyperlexia need not therefore co-occur with comprehension difficulties nor need it reflect strength in only part of the reading system. In TS it appears to represent a genuine hyperdevelopment of a skill. The strength of reading skill counterbalances the spatial difficulties of a comparable sample of girls with TS (Temple and Carney, 1995), and with other verbal skills may potentially be exploited in remedial enterprises.

Child↗
PubMed1995

Neonatal seizures: long-term outcome and cognitive development among 'normal' survivors.

The authors report the long-term outcome and cognitive development in the late-teenage years of 'normal' survivors of neonatal seizures. The outcome of the children was good, and normal in that they had attended normal schools and had normal overall intelligence test scores as adults. However, all of the sample displayed abnormal neuropsychological development in terms of intelligence test profile and subtest scatter, or development of spelling, or development of memory. This was independent of social and behavioural difficulties, which may also be increased. Neonatal seizures may be indicative of a subtle neurodevelopmental vulnerability which may manifest later in life as specific learning difficulties or poor social adjustment.

Adolescent↗
PubMed1994

A randomized trial of intravenous heparin in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex) in acute myocardial infarction: the Duke University Clinical Cardiology Study (DUCCS) 1.

OBJECTIVES: We designed a randomized trial to evaluate the effects of heparin administration in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) on arterial patency and clinical end points. BACKGROUND: The role of conjunctive intravenous heparin therapy with APSAC has not been tested despite the recommendations that intravenous heparin should be used. METHODS: Four hours after APSAC administration, 250 patients with acute myocardial infarction were randomly assigned to receive 325 mg of either aspirin alone or aspirin and a continuous infusion of heparin (15 IU/kg body weight per h). Clinical ischemic events and bleeding complications were monitored. On hospital day 5, coronary arteriography and left ventriculography were performed. RESULTS: The primary end point of the trial (the combined outcome of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery) occurred in 42% of the heparin-treated group versus 43% of the group treated without heparin (p = 0.94). A patent infarct-related artery was present in 80% of the patients treated with heparin and in 73% of those treated without heparin (p = 0.26). Left ventricular function, as measured by ejection fraction, was well preserved in both groups (52% vs. 50.5%, respectively, p = 0.29). The overall bleeding rate was higher in patients with (32%) than without (17.2%) heparin (p = 0.006). CONCLUSIONS: Weight-adjusted intravenous heparin therapy after APSAC in acute myocardial infarction does not reduce the combined incidence of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery. Furthermore, withholding intravenous heparin therapy is associated with a 46% reduction in bleeding complications. Our findings do not support the addition of intravenous heparin after APSAC therapy, as currently recommended, and suggest that a strategy of withholding heparin is simpler and safer and does not place the patient at increased risk for ischemic complications after myocardial infarction.

Aged↗
PubMed1992

Outpatient protocol for biofeedback therapy of pelvic floor outlet obstruction.

Pelvic floor outlet obstruction is a rare cause of severe constipation. Anal myectomy, subtotal colectomy, and medical therapy have limited success. The purpose of this study was to develop a short outpatient treatment using biofeedback techniques. Nine patients with severe constipation and straining resulting from pelvic floor outlet obstruction underwent complete investigation of the pelvic floor musculature and anal sphincter mechanism. Patients were unable to expel a 60-cc rectal balloon and had nonrelaxing puborectalis on defecography. The treatment protocol utilized anal surface electromyography to document improper straining and retrain pelvic floor muscles to relax during defecation. Sensory retraining with a rectal balloon, behavioral relaxation techniques, and defecation of simulated stool using a 120-cc Metamucil (Procter & Gamble, Cincinnati, OH) slurry in the rectum allowed re-establishment of normal defecation in all nine patients. Repeat training was required in three patients during follow-up. Treatment of pelvic floor outlet obstruction with outpatient retraining techniques is possible.

Adult↗
PubMed1983

Regression of thyroid hormone induced cardiac hypertrophy: effect on cardiac beta receptors and adenyl cyclase activity.

Adrenergic mechanisms may be important in the symptomatic manifestations of hyperthyroidism. The chronic administration of thyroid hormone also results in cardiac hypertrophy and increased numbers of beta-adrenergic receptors in cardiac membranes. The roles of adrenergic mechanisms in the initiation and perpetuation of this hypertrophy has been open to speculation. Rats treated chronically with L-thyroxin were sacrificed after 7 days of treatment and 1-4 days after cessation of treatment. Hearts were removed and weighed and norepinephrine measured. In other groups of identically treated rats, membranes were prepared from the left ventricle for in vitro measurements of beta-adrenergic receptor characteristics and adenyl cyclase activity. Regression of cardiac hypertrophy with a decrease in receptor number to control values was seen as early as 2 days after stopping thyroxine. Cardiac norepinephrine concentrations had also returned to control values at this time. Displacement of bound [H3] dihydroalprenolol by isoproterenol was not changed from control. Basal and isoproterenol stimulated adenyl cyclase activity was not changed by thyroxine administration or its cessation. The rapid reversal of the increased beta-adrenergic receptor number and cardiac hypertrophy raises the possibility that thyroid hormone may play a regulatory role in cardiac function. Although the enhancement of myocardial contractility by thyroid hormone may be mediated through cardiac hypertrophy this effect of thyroid hormone is independent of the catecholamine sensitive adenyl cyclase system.

Adenylyl Cyclases↗
PubMed1975

Bias against genetic hypotheses in adoption studies.

Genetic factors are implicated in the cause of psychopathological disorders whenever the incidence of disorder is greater among the adopted-away offspring of affected parents than among those of control (unaffected) parents. The lack of information about most parents who give their children up for adoption could result in the inclusion of a substantial number of high-risk parents in the control groups. This could bias an adoption study against a genetic hypothesis. The Minnesota Multiphasic Personality inventory scores of two groups of pregnant unwed mothers were compared to those of two other groups: married pregnant women and 18-year-old women. Comparisons disclosed that the unwed mothers had significant elevations on five to the nine clinical scales. Elevations on psychopathic deviancy and schizophrenia were particularly substantial. These results indicate a requirement to select control group parents who are representative of the general population.

Adoption↗