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Biomedical subjects

R A Cohen

Publications and source records attributed to R A Cohen.

At least 37 records · Page 2Linked to original sources

Neurocognitive and psychological contributions to quality of life in HIV-1-infected women.

OBJECTIVES: The purpose of this study was to examine the impact of neurocognitive and emotional distress and immune system dysfunction on quality of life in women with HIV. METHODS: Thirty-six HIV-seropositive women were administered measures of mood status (Profile of Mood States), quality of life (Multidimensional Quality of Life Questionnaire for Persons with HIV) and cognitive function. CD4 cell counts were obtained as an indicator of immune system status. RESULTS: Regression analyses revealed that independent of severity of emotional distress, neurocognitive deficits on measures of executive control and speed of information processing were associated with reduced quality of life. Emotional status also was associated with quality of life and together with neurocognitive performance accounted for most of the variance associated with quality of life. Reduced CD4 cell count was significantly associated with neurocognitive deficits, but not severity of emotional distress or quality of life. CONCLUSIONS: Quality of life among women who are infected with HIV is strongly influenced by both neurocognitive and emotional status, as women with the greatest neurocognitive impairment and emotional distress report the poorest quality of life.

Adult↗

Distinct effects of N-acetylcysteine and nitric oxide on angiotensin II-induced epidermal growth factor receptor phosphorylation and intracellular Ca(2+) levels.

These studies describe inhibitory effects of N-acetylcysteine on several biochemical events associated with the activation of extracellular signal-regulated kinases (ERK) by angiotensin II in the cardiac fibroblast and compare these effects with those of the nitric oxide donor, S-nitroso-N-acetylpenicillamine, an agent we showed previously to inhibit angiotensin II-induced ERK activation and the concomitant phosphorylation of proline-rich tyrosine kinase 2 (Wang, D., Yu, X., and Brecher, P. (1999) J. Biol. Chem. 274, 24342-24348). The transactivation of the epidermal growth factor receptor by angiotensin II, a process required for the activation of ERK, was inhibited by N-acetylcysteine but not by nitric oxide. The transactivation of the epidermal growth factor receptor by angiotensin II was shown to be independent of intracellular calcium increases. Nitric oxide, but not N-acetylcysteine, inhibited the angiotensin II-induced increase in intracellular Ca(2+). Neither nitric oxide nor N-acetylcysteine inhibited either phospholipase C activation or inositol triphosphate generation in response to angiotensin II. N-Acetylcysteine did inhibit the phosphorylation of the calcium sensitive tyrosine kinases PYK2 and Src, effects that also occurred using nitric oxide. These studies describe a novel effect of N-acetylcysteine on cross-talk between a G protein-linked receptor and a tyrosine kinase receptor and offer additional molecular insight to explain how N-acetylcysteine and nitric oxide act at different sites and might have an additive effect on specific hormonal responses.

Acetylcysteine↗

Fear recognition deficits after focal brain damage: a cautionary note.

OBJECTIVE: To test the hypothesis that fear recognition deficits in neurologic patients reflect damage to an emotion-specific neural network. BACKGROUND: Previous studies have suggested that the perception of fear in facial expressions is mediated by a specialized neural system that includes the amygdala and certain posterior right-hemisphere cortical regions. However, the neuropsychological findings in patients with amygdala damage are inconclusive, and the contribution of distinct cortical regions to fear perception has only been examined in one study. METHODS: We studied the recognition of six basic facial expressions by asking subjects to match these emotions with the appropriate verbal labels. RESULTS: Both normal control subjects (n = 80) and patients with focal brain damage (n = 63) performed significantly worse in recognizing fear than in recognizing any other facial emotion, with errors consisting primarily of mistaking fear for surprise. Although patients were impaired relative to control subjects in recognizing fear, we could not obtain convincing evidence that left, right, or bilateral lesions were associated with disproportionate impairments of fear perception once we adjusted for differences in overall recognition performance for the other five facial emotion categories. The proposed special role of the amygdala and posterior right-hemisphere cortical regions in fear perception was also not supported. CONCLUSIONS: Fear recognition deficits in neurologic patients may be attributable to task difficulty factors rather than damage to putative neural systems dedicated to fear perception.

Adult↗

Electroencephalographic, volumetric, and neuropsychological indicators of seizure focus lateralization in temporal lobe epilepsy.

CONTEXT: Anterior temporal lobectomy is an effective treatment for medically intractable temporal lobe seizures. Identification of seizure focus is essential to surgical success. OBJECTIVE: To examine the usefulness of presurgical electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological data in the lateralization of seizure focus. DESIGN: Presurgical EEG, MRI, and neuropsychological data were entered, independently and in combination, as indicators of seizure focus lateralization in discriminant function analyses, yielding correct seizure lateralization rates for each set of indicators. SETTING: Comprehensive Epilepsy Program, Shands Teaching Hospital, University of Florida, Gainesville. PATIENTS: Forty-four right-handed adult patients who ultimately underwent successful anterior temporal lobectomy. Left-handed patients, those with less-than-optimal surgical outcome, and any patients with a history of neurological insult unrelated to seizure disorder were excluded from this study. MAIN OUTCOME MEASURES: For each patient presurgical EEG was represented as a seizure lateralization index reflecting the numbers of seizures originating in the left hemisphere, right hemisphere, and those unable to be lateralized. Magnetic resonance imaging data were represented as left-right difference in hippocampal volume. Neuropsychological data consisted of mean scores in each of 5 cognitive domains. RESULTS: The EEG was a better indicator of lateralization (89% correct) than MRI (86%), although not significantly. The EEG and MRI were significantly superior to neuropsychological data (66%) (P=.02 and .04, respectively). Combining EEG and MRI yielded a significantly higher lateralization rate (93%) than EEG alone (P<.01). Adding neuropsychological data improved this slightly (95%). CONCLUSIONS: The EEG and MRI were of high lateralization value, while neuropsychological data were of limited use in this regard. Combining EEG, MRI, and neuropsychological improved focus lateralization relative to using these data independently.

Adult↗

Fatigue and its impact on patients with myasthenia gravis.

We have examined fatigue in myasthenia gravis (MG) by administering a measure of cognitive and physical fatigue to patients and control subjects before and after administration of a lengthy cognitive battery. Subjects also completed a scale that assessed the impact of fatigue on physical, social, and cognitive function. Results of the study revealed that MG patients experience significantly more cognitive and physical fatigue than do control subjects, and the patients' perceptions of both cognitive and physical fatigue increased significantly following completion of demanding cognitive work. Control subjects reported no significant change in fatigue. Furthermore, MG patients reported that fatigue produced mild to moderate effects on cognitive and social function and moderate effects on physical function. Results from this study indicate that cognitive fatigue is an important symptom of MG and that fatigue produces pervasive impairments in important aspects of patients' lives. Additional studies are needed to understand the neurobehavioral determinants of cognitive fatigue in this population.

Adult↗

Resolution of ST-segment elevation after streptokinase therapy in anterior versus inferior wall myocardial infarction.

BACKGROUND: Resolution of ST-segment elevation is the best bedside predictor of myocardial reperfusion. HYPOTHESIS: This study was conducted to examine the resolution of ST-segment elevation after streptokinase therapy in anterior versus inferior acute myocardial infarction (MI) and to corroborate it with echocardiographic and coronary angiographic data. METHODS: The study population consisted of 70 patients, 35 each in the anterior and inferior MI groups. The electrocardiograms (ECGs) were recorded before, on completion of, and on Days 1 and 2 post streptokinase therapy. The resolution of ST segment determined from post-streptokinase ECGs was compared between the two groups and correlated with echocardiographic and coronary angiographic data. RESULTS: On completion of and on Day 1 post streptokinase therapy, ST-segment resolution in both groups was not significantly different. On Day 2 post streptokinase therapy, resolution of the ST segment per lead was significantly lower in anterior than that in inferior MI (61 +/- 21% anterior vs. 77 +/- 21% inferior, p 0.003). The number of patients with akinesis of infarct-related ventricular wall was significantly higher (17 anterior vs. 7 inferior, p 0.02), and left ventricular ejection fraction was significantly lower in anterior MI (39 +/- 7% anterior vs. 48 +/- 8% inferior, p < 0.01). There was no significant difference in coronary angiographic data. One patient in each group demonstrated normal coronary arteries. CONCLUSIONS: The resolution of ST-segment elevation on the completion of and on Day 1 post streptokinase therapy was comparable between anterior and inferior MI. The significantly less frequent resolution of ST-segment elevation in anterior MI on Day 2 post streptokinase could be due to more akinesis, larger infarct size, and worse systolic function rather than due to failure to open the infarct-related vessel.

Coronary Angiography↗

Data acquisition for pediatric CT angiography: problems and solutions.

With appropriate attention to the technical aspects, excellent CT angiography can be obtained even in young infants. In this article, we will present the problems inherent with pediatric CT angiography and offer solutions that minimize or eliminate these difficulties. In addition, a literature review of specific pediatric applications is provided.

Angiography↗

Alternative transcript initiation and novel post-transcriptional processing of a leucine-rich repeat receptor-like protein kinase gene that responds to short-day photoperiodic floral induction in morning glory (Ipomoea nil).

A gene (inrpk1) encoding a putative receptor-like protein kinase was isolated from the Japanese morning glory, Ipo-moea (Pharbitis) nil Roth. cv. Violet. The receptor-like portion of the largest derived polypeptide contains 26 direct leucine-rich repeats (LRRs) in a single block, and the catalytic portion has all the conserved amino acid residues characteristic of Ser/Thr protein kinases. RNA blot analysis detected multiple transcripts in cotyledons. The largest (4.4 kb) transcript encodes the predicted full length polypeptide (INRPK1), whereas a 1.6 kb transcript apparently originates from a secondary transcription initiation site within the gene and potentially encodes a protein kinase identical to INRPK1 but lacking most of the LRRs. Two transcripts (ca. 2.7 and 2.6 kb) are created by alternative 3'-splicing of a large (ca. 1.4-1.5 kb) cryptic intron in the LRR region, creating one transcript (2.6 kb) potentially encoding a small, secretable polypeptide. The larger transcript encoding a polypeptide identical to INRPK1, but lacking 21 LRRs, predominates in vegetative roots. Competitive PCR indicates that inrpk1 mRNA increases 20-fold in cotyledons in response to a previously given single floral-inducing short-day (SD). No differences of this magnitude were detected in any other organs examined from plants similarly treated. This pattern of expression and differential processing suggests a role for inrpk1 in some aspect of SD photoperiodic-induced flowering in morning glory.

Alternative Splicing↗

Decreased aortic glutathione levels may contribute to impaired nitric oxide-induced relaxation in hypercholesterolaemia.

The aim of this study was to determine if the decrease in aortic total glutathione (GSH) levels in hypercholesterolaemia is related to the impairment of relaxation to acetylcholine (ACh) and exogenous nitric oxide (NO). Isometric tension and vascular GSH levels were measured in thoracic aortic rings from rabbits fed for 12 weeks with 0.5% cholesterol diet. Hypercholesterolaemia decreased aortic GSH levels and impaired relaxation to ACh and NO. To determine if GSH depletion impaired the response to NO, normal rabbit thoracic aorta was incubated with 1,3-bis [2-chloroethyl]-1-nitrosourea (BCNU; 0.2 mmol L(-1)), a GSH reductase inhibitor, or diazine-dicarboxylic acid bis [N, N dimethylamide] (diamide; 1 mmol L(-1)), a thiol oxidizing agent. BCNU or diamide decreased aortic GSH levels and impaired ACh and NO-induced relaxation. The effects of diamide on GSH levels and relaxation were partially prevented by co-incubation with GSH ester (GSE; 2 mmol L(-1)). Increasing GSH with GSE significantly enhanced NO-induced relaxation in aorta from both hypercholesterolaemic and normal rabbits, however relaxation of hypercholesterolaemic rabbit aorta was not restored to normal. These data suggest that other factors, perhaps related to the long-term decrease in GSH levels, are responsible for reduced NO bioactivity in hypercholesterolaemia.

Acetylcholine↗

Dementia rating scale performance: a comparison of vascular and Alzheimer's dementia.

Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.

Aged↗

Attentional dysfunction associated with posttraumatic stress disorder among rape survivors.

Posttraumatic stress disorder (PTSD) is characterized by subjective reports of decreased concentration and an inability to sustain attention. Some empirical validation of these symptoms has been demonstrated via reduced performance on attentional tests among war veterans with PTSD. However, the significance of such findings is unclear given high co-morbidity with other psychiatric, neurologic, and substance abuse disorders among veterans. The present study examined neuropsychological functioning among rape survivors with PTSD, a patient population with comparatively low rates of psychiatric co-morbidity. Rape survivors with PTSD (PTSD+; n = 15) were compared to rape survivors without PTSD (PTSD-; n = 16) and age- and education-matched nontraumatized controls (CTRL; n = 16) on tests of attention. Performance of the PTSD+ group was significantly worse than the other groups on measures of sustained and divided attention, but not on shifting of visuospatial selective attention. Performance differences were not attributable to co-morbid psychiatric disorders or substance abuse. The implications of these findings regarding the effects of trauma on attentional functions are discussed.

Adult↗

Decreased sensitivity to nitric oxide in the aorta of severely hypercholesterolemic apolipoprotein E-deficient mice.

A normal response to nitric oxide donors has been cited as evidence that impaired endothelium-dependent vasodilation during hypercholesterolemia is due to decreased synthesis of nitric oxide. This tenet was examined by determining responses to nitric oxide gas as well as to acetylcholine and sodium nitroprusside in the isolated aorta of apolipoprotein E-deficient mice fed normal or Western-type cholesterol-rich diet until 21 or 35 weeks of age. In mice fed normal chow, relaxation to all agents remained comparable to that obtained in wild-type mice. In mice fed Western diet, the relaxation to acetylcholine as well as to nitric oxide was decreased at 35 weeks of age. At 21 weeks of age, decreased sensitivity to nitric oxide was observed despite a normal response to acetylcholine. The response to sodium nitroprusside was normal in all groups. A decrease in aortic superoxide dismutase activity as well as an increase in aortic superoxide anion generated in the presence of NADH as measured by lucigenin chemiluminescence was observed in the group fed Western diet at 35 weeks. This provides evidence that altered superoxide anion could contribute to the deterioration in nitric oxide sensitivity that underlies the impaired endothelium-dependent relaxation. These data indicate that decreased sensitivity to nitric oxide may contribute to the development of impaired endothelium-dependent relaxation in hypercholesterolemia. The response to sodium nitroprusside appears not to reflect the decreased sensitivity of vascular smooth muscle to authentic nitric oxide.

Acetylcholine↗

The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis.

Atherosclerosis involves a complex array of factors, including leukocyte adhesion and platelet vasoactive factors. Aspirin, which is used to prevent secondary complications of atherosclerosis, inhibits platelet production of thromboxane (Tx) A(2). The actions of TxA(2) as well as of other arachidonic acid products, such as prostaglandin (PG) H(2), PGF(2alpha), hydroxyeicosatetraenoic acids, and isoprostanes, can be effectively antagonized by blocking thromboxane (TP) receptors. The purpose of this study was to determine the role of platelet-derived TxA(2) in atherosclerotic lesion development by comparing the effects of aspirin and the TP receptor antagonist S18886. The effect of 11 weeks of treatment with aspirin (30 mg. kg(-1). d(-1)) or S18886 (5 mg. kg(-1). d(-1)) on aortic root atherosclerotic lesions, serum levels of intercellular adhesion molecule-1 (ICAM-1), and the TxA(2) metabolite TxB(2) was determined in apolipoprotein E-deficient mice at 21 weeks of age. Both treatments did not affect body or heart weight or serum cholesterol levels. Aspirin, to a greater extent than S18886, significantly decreased serum TxB(2) levels, indicating the greater efficacy of aspirin in preventing platelet synthesis of TxA(2). S18886, but not aspirin, significantly decreased aortic root lesions as well as serum ICAM-1 levels. S18886 also prevented the increased expression of ICAM-1 in cultured human endothelial cells stimulated by the TP receptor agonist U46619. These results indicate that inhibition of platelet TxA(2) synthesis with aspirin has no significant effect on atherogenesis or adhesion molecule levels. The effects of S18886 suggest that blockade of TP receptors inhibits atherosclerosis by a mechanism independent of platelet-derived TxA(2), perhaps by preventing the expression of adhesion molecules whose expression is stimulated by eicosanoids other than TxA(2).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Regulation of adhesion molecules: a new target for the treatment of chronic venous insufficiency.

As more insight into the mechanisms leading to chronic venous insufficiency (CVI) is gained, novel targets for drug treatment of the disease, or of its complications, become available. Studies using chemical entities capable of inhibiting leukocyte adhesion in postcapillary venules have led to the discovery of selective inhibitors of cell adhesion mechanisms. The aim of the current review is to describe the pharmacology, biochemistry, and molecular biology studies performed with some new inhibitors of adhesion molecule expression. Compounds such as hydroxy triallyl farnisine (S 17834) may offer new and efficient treatment of the microcirculatory complications that accompany chronic venous disease.

Animals↗

Rates of receiving HIV test results: data from the U.S. National Health Interview Survey for 1994 and 1995.

OBJECTIVE: To determine the frequency and predictors of receipt of HIV test results. METHODS: Analysis of responses from 19,127 adults in 1994 and 16,848 in 1995 surveyed for the U.S. National Health Interview Survey, using logit models to determine factors independently associated with decreased likelihood of receiving HIV test results. RESULTS: Overall, 12.5% (+/-1.0%) of persons tested in 1994 and 13.3% (+/-0.9%) in 1995 had not received their test results. Those whose test was not self-initiated were significantly less likely (p<.05) to receive their test results. The proportion who did not receive results was lowest among persons who had sought testing (6.1% in 1994 and 4.3% in 1995) and highest among persons whose tests were required for hospitalization or surgery (24.2% in 1994 and 22.9% in 1995). CONCLUSIONS: An estimated 2.3 million of the 17.5 million people tested annually for HIV infection did not receive their test results. Alternative measures to increase the number of persons who receive their results need to be evaluated. These may include enhancing prevention counseling about the importance of receiving test results, telephone notification, or using rapid HIV-screening tests that provide results at the time of testing.

AIDS Serodiagnosis↗

Impairments of attention after cingulotomy.

BACKGROUND: Outcome studies have generally not indicated significant cognitive disturbances after cingulotomy. There is now considerable evidence that the cingulate may play an important role in emotional behavior and attention. OBJECTIVE: To characterize impairments of attention associated with bilateral lesions of the anterior cingulate cortex produced by cingulotomy. METHODS: Twelve patients who underwent cingulotomy for treatment of intractable pain were administered tests of attention, executive functions, response intention and production, and a broad range of other neurocognitive functions before surgery and again 3 and 12 months after surgery. Data from this within-subjects repeated-measures design were analyzed by multivariate analysis of variance procedures. RESULTS: After cingulotomy, patients initially had executive and attentional impairments. By 12 months, these had resolved into more circumscribed deficits, with greatest impairments on tasks requiring intention and spontaneous response production, and milder impairments of focused and sustained attention. Other aspects of attention and other cognitive functions were generally unaffected. CONCLUSION: The anterior cingulate cortex modulates response intention and focused attention.

Adult↗

Ebstein's anomaly of the tricuspid valve associated with congenital deafmutism.

Ebstein's anomaly is the most common congenital abnormality of the tricuspid valve and accounts for about 0.5% of cases of the congenital heart diseases. It has occasionally been associated with other syndromes but not with the congenital deafmutism. The first case of Ebstein's anomaly associated with the congenital deafmutism is reported. The patient remained asymptomatic until the age of 35 years and presented with palpitations and dizzy spells. This patient also manifested mitral valve prolapse and Wolff-Parkinson-White syndrome with right-sided accessory conduction pathway.

Adult↗