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Biomedical subjects

R A Cohen

Publications and source records attributed to R A Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide.

1. The role of cyclic GMP in the ability of nitric oxide (NO) to decrease intracellular free calcium concentration [Ca2+]i and divalent cation influx was studied in rabbit aortic smooth muscle cells in primary culture. In cells stimulated with angiotensin II (AII, 10(-1) M), NO (10(-10) - 10(-6) M) increased cyclic GMP levels measured by radioimmunoassay and decreased [Ca2+]i and cation influx as indicated by fura-2 fluorimetry. 2. Zaprinast (10(-4) M), increased NO-stimulated levels of cyclic GMP by 3-20 fold. Although the phosphodiesterase inhibitor lowered the level of [Ca2+]i reached after administration of NO, the initial decreases in [Ca2+]i initiated by NO were not significantly different in magnitude or duration from those that occurred in the absence of zaprinast. 3. The guanylyl cyclase inhibitor, H-(1,2,4) oxadiazolo(4,3-a) quinoxallin-1-one (ODQ, 10(-5) M), blocked cyclic GMP accumulation and activation of protein kinase G, as measured by back phosphorylation of the inositol trisphosphate receptor. ODQ and Rp-8-Br-cyclic GMPS, a protein kinase G inhibitor, decreased the effects of NO, 10(-10) - 10(-8) M, but the decrease in [Ca2+]i or cation influx caused by higher concentrations of NO (10(-7) - 10(-6) M) were unaffected. Relaxation of intact rabbit aorta rings to NO (10(-7) - 10(-5) M) also persisted in the presence of ODQ without a significant increase in cyclic GMP. Rp-8-Br-cyclic GMPS blocked the decreases in cation influx caused by a cell permeable cyclic GMP analog, but ODQ and/or the protein kinase G inhibitor had no significant effect on the decrease caused by NO. 4. Although inhibitors of cyclic GMP, protein kinase G and phosphodiesterase can be shown to affect the decrease in [Ca2+]i and cation influx via protein kinase G, these studies indicate that when these mechanisms are blocked, cyclic GMP-independent mechanisms also contribute significantly to the decrease in [Ca2+]i and smooth muscle relaxation to NO.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Diagnosis of pulmonary tuberculosis using PCR assays on sputum collected within 24 hours of hospital admission.

There have been few studies evaluating the efficacy of polymerase chain reaction (PCR) testing in front-line clinical practice. We assessed the diagnostic yield of PCR prospectively in a blinded study of patients admitted to rule out tuberculosis and compared PCR results to a culture and clinical diagnosis of tuberculosis. Specimens were sent for routine smear, culture, and PCR analysis. Sputum sediments were submitted for PCR amplification of IS6110 sequences by an in-house assay and also the Roche Amplicor PCR assay targeting 16s ribosomal RNA genes. Eighty-five patients were enrolled: 27 patients had cultures positive for tuberculosis; 12 were smear-positive. PCR by both assays on the first specimen picked up all patients smear-positive on any specimen. A positive PCR on at least one of two specimens collected in the first 24 h was 85 and 74% sensitive and 88 and 93% specific for tuberculosis by the in-house and Roche techniques, respectively. Sensitivity in smear-negative patients was 73 and 53%, respectively. The in-house PCR detected 100% and Roche detected 95% of patients with more than paucibacillary (greater than 20 colonies) tuberculosis. We conclude that PCR may be a useful tool to evaluate patients for tuberculosis within the first hospital day.

Female↗
PubMed1998

Reduplicative paramnesia: longitudinal neurobehavioral and neuroimaging analysis.

Reduplicative paramnesia (RP) is a delusion in which the patient perceives familiar places, objects, or events to have been duplicated. The current case describes the development of RP in an 81-year-old male following a large right frontal lobe infarction. As the patient had been hospitalized previously with hemorrhagic contusions, neurologic, neuropsychological, and neuroimaging data were obtained both prior to and following RP onset. Psychophysiologic data were obtained following the development of the delusion. Both premorbidly and at follow-up, neuropsychological functioning was characterized by significant impairments of learning and memory and frontal-executive functions. Language and visuospatial skills and motor speed were intact both before and after RP onset. The case is described within the context of preexisting theories of RP, and it is surmised that the delusion is secondary to temporal-limbic-frontal dysfunction giving rise to a distorted sense of familiarity and impaired ability to resolve the delusion via reasoning.

Accidental Falls↗
PubMed1997

Nitric oxide is the mediator of both endothelium-dependent relaxation and hyperpolarization of the rabbit carotid artery.

It is controversial whether the endothelial cell release of nitric oxide (NO) or a different factor(s) accounts for endothelium-dependent hyperpolarization, because in many arteries endothelium-dependent relaxation and hyperpolarization resists inhibitors of NO synthase. The contribution of NO to acetylcholine-induced endothelium-dependent hyperpolarization and relaxation of the rabbit carotid artery was determined by measuring NO with electrochemical and chemiluminescence techniques. In the presence of phenylephrine to depolarize and contract the smooth muscle cells, acetylcholine caused concentration-dependent hyperpolarization and relaxation which were closely correlated to the release of NO. N(omega)-nitro-L-arginine methyl ester (30 microM) partially reduced the release of NO and caused a similar reduction in smooth muscle cell relaxation and hyperpolarization. To determine if the residual responses were mediated by another endothelium-derived mediator or NO released despite treatment with N(omega)-nitro-L-arginine methyl ester, N(omega)-nitro-L-arginine (300 microM) was added. The combined inhibitors further reduced, but did not eliminate, NO release, smooth muscle relaxation, and hyperpolarization. Hyperpolarization and relaxation to acetylcholine remained closely correlated with the release of NO in the presence of the inhibitors. In addition, the NO donor, SIN-1, caused hyperpolarization and relaxation which correlated with the concentrations of NO that it released. These studies indicate that (i) the release of NO by acetylcholine is only partially inhibited by these inhibitors of NO synthase when used even at high concentrations, and (ii) NO rather than another factor accounts fully for endothelium-dependent responses of the rabbit carotid artery.

Animals↗
PubMed1997

Reduced responsiveness of hypercholesterolemic rabbit aortic smooth muscle cells to nitric oxide.

The response to nitric oxide of intracellular free Ca2+ levels, measured by fura 2 fluorimetry, and cyclic GMP, measured by RIA, was evaluated on smooth muscle cells of the thoracic aorta in primary culture from normal and cholesterol-fed rabbits. Relaxation to acetylcholine and nitric oxide was also determined in isolated rings of aorta. After 10 weeks of high-cholesterol diet, the intact aorta relaxed less to both acetylcholine and nitric oxide. In cultured cells from hypercholesterolemic rabbits, intracellular Ca2+ oscillated, and the mean Ca2+ levels were approximately twofold greater than in normal aortic cells. Nitric oxide failed to affect basal Ca2+ in either cell type. The peak and sustained rise in intracellular Ca2+ induced by angiotensin II (10(-7) mol/L) were similar in the two cell types. However, nitric oxide (10(-10) to 10(-6) mol/L) decreased the sustained Ca2+ levels to a significantly smaller extent in cells from cholesterol-fed rabbits. In addition, in cells from hypercholesterolemic rabbits, nitric oxide added before angiotensin II inhibited to a smaller degree the transient increase in intracellular free Ca2+ caused by angiotensin II in the nominal absence of extracellular Ca2+, as well as the increase in Ca2+ associated with the addition of extracellular Ca2+. Measurements of fura 2 quenching caused by Mn2+ influx confirmed that nitric oxide inhibited the entry of extracellular divalent cations significantly less in cells from hypercholesterolemic rabbits. Basal levels of cyclic GMP were significantly less than normal, and nitric oxide increased levels of cyclic GMP to a significantly smaller degree in cells from cholesterol-fed rabbits. These data indicate a substantial resistance to nitric oxide action in aortic smooth muscle cells of cholesterol-fed rabbits. This observation is consistent with the notion that resistance of smooth muscle cells to nitric oxide contributes to abnormal endothelium-dependent vasodilation during hypercholesterolemia and can play a role in the pathogenesis of atherosclerosis.

Animals↗
PubMed1997

Disruption of short-duration timing associated with damage to the suprachiasmatic region of the hypothalamus.

The neural bases of circadian rhythmicity have been demonstrated in a variety of animal species, including primates. Yet, the brain mechanisms underlying time experience and the timing of behaviors of shorter duration are still not well understood. In the present study, we demonstrate disruption of short-duration timing capacity in AH, a patient with damage to the suprachiasmatic (SCN) region of the hypothalamus. AH exhibited extreme inconsistency in her rate of tapping production on a motor continuation paradigm. Her inter-response intervals (IRIs) were extremely large compared with normal control subjects and were similar to those previously reported in patients with cerebellar dysfunction. Increased variability of both central timing and motor implementation processes was evident compared with both age-matched and elderly normal control subjects. Severe impairment of time perception was also evident on duration discrimination, whereas auditory loudness discrimination was intact. These findings suggest that a hierarchic relationship between long-duration (circadian) and short-duration timing exists, and that in addition to the cerebellum, intact hypothalamic functioning is necessary for short-duration timing.

Adult↗
PubMed1997

Access to health care. Part 3: Older adults.

OBJECTIVES: This report examines access to health care for older adults, 65 years of age and over. In the United States for 1993. Access indicators include having a regular source of care, place of care, main reason for no regular source of care, unmet health care needs, and use of clinical and preventive services. Sociodemographic characteristics include sex, age, race, income, health status, and health insurance coverage. METHODS: Data are from the 1993 Access to Care, Health insurance, and Year 2000 Surveys of the National Health interview Survey (NHIS), a continuing household survey of the civilian noninstitutionalized population of the United States. The sample for the Access to Care and Health insurance surveys contained 61,287 persons in 24,071 households. The sample for the Year 2000 survey was 21,028 persons. RESULTS: Persons with Medicare and private or Medicare and public coverage were more likely to have a regular source of medical care than elderly persons with Medicare only. Over 3.3 million elderly persons had at least one unmet need in 1993. Older adults on Medicare and public or Medicare only coverage were twice as likely to have unmet medical needs than those with Medicare and private coverage. Persons with Medicare and private coverage were more likely to receive immunizations than elderly persons with Medicare and public coverage or Medicare only. CONCLUSIONS: Although the majority of older adults have Medicare, this only provides a basic level of access to the health care system. Older adults who do not supplement Medicare with private coverage are at the greatest risk of having unmet health care needs.

Black or African American↗
PubMed1997

Access to health care. Part 1: Children.

OBJECTIVES: This report presents national estimates of access to medical care and unmet health care needs for children through 17 years of age by selected sociodemographic variables including sex, age, race and/or ethnicity, family income, family structure, place of residence, and health status. In addition, the impact of children's health insurance status on access to care is described. METHODS: Data from the 1993 Access to Care and Health Insurance questionnaires of the National Health Interview Survey (NHIS) are analyzed to examine access indicators. The NHIS is a continuing household survey of the civilian noninstitutionalized population of the United States. The sample included 16,907 children from infants through 17 years of age from 24,071 households. RESULTS: In 1993, over 7.3 million U.S. children had at least one unmet health care need or had medical care delayed because of worry about the cost of care. These health care needs included medical care, dental care, prescription medicine, glasses, and mental health care. In addition, almost 4.2 million children lacked a regular source of health care. Factors related to access indicators included health insurance, family income, race and/or ethnicity, family structure, and place of residence. The lack of health insurance or inability to afford care was the main reason given by respondents for children lacking a regular source of medical care. CONCLUSIONS: In the United States, millions of children do not receive needed health care services. Uninsured children and those in families with low income are at the greatest risk of having unmet health needs.

Adolescent↗
PubMed1997

Access to health care. Part 2: Working-age adults.

OBJECTIVES: This report presents data on access to health care for U.S. working-age adults, 18-64 years old. Access indicators are examined by selected sociodemographic characteristics including sex, age, race and/or ethnicity, place of residence, employment status, income, health status, and health insurance status. METHODS: Data are from the 1993 Access to Care and 1993 Health Insurance Surveys of the National Health Interview Survey (NHIS), a continuing household survey of the civilian noninstitutionalized population of the United States. The sample contained 61,287 persons in 24,071 households. RESULTS: In 1993, approximately 3 out of 4 working-age adults had a regular source of medical care. Nine out of 10 adults with health insurance had a regular source of care compared with 6 out of 10 adults without health insurance. For adults with a regular source of care, 86 percent received care in a private doctor's office, 9 percent in a clinic, and 2 percent in a hospital emergency room. The two main reasons given for not having a regular source of care were "do not need a doctor" (49 percent), and "no insurance can't afford it" (22 percent). Persons in the highest income group were more likely to report no need for a doctor (59 percent) than persons in the lowest income group (35 percent). About 40 percent of uninsured persons and 16 percent of insured persons reported an unmet medical need. CONCLUSIONS: Health insurance plays a key role in the access to medical care services. Persons who are uninsured or have low incomes are at the greatest risk of having unmet medical needs.

Adolescent↗
PubMed1996

British pioneer?

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Adult↗
PubMed1996

Positional effects on maternal cardiac output during labor with epidural analgesia.

OBJECTIVE: Our purpose was to test the hypothesis that the supine versus the lateral position is associated with a greater decrement in cardiac output after epidural analgesia in labor. STUDY DESIGN: Twenty-one normal term subjects were randomized to the left lateral or supine position in early labor. Cardiac output measured by the acetylene rebreathing method, stroke volume, heart rate, mean arterial pressure, and systemic vascular resistance were obtained at 5-minute intervals, beginning before a 500 ml intravenous fluid bolus (baseline) and ending 45 minutes after epidural injection. RESULTS: Mean baseline supine versus lateral group differences were significant for 21% lower cardiac output, 21% lower stroke volume, 19% higher mean arterial pressure, 50% higher systemic vascular resistance, and equivalent heart rate. In the supine group fluid bolus resulted in significantly increased cardiac output and stroke volume, decreased mean arterial pressure and systemic vascular resistance, and unchanged heart rate. In the supine group cardiac output and stroke volume decreased significantly after epidural injection. The lateral position group exhibited no hemodynamic alterations after fluid bolus or epidural. CONCLUSIONS: In contrast to the lateral position, the supine position is associated with a significant postepidural decrement in cardiac output, not identified by a change in heart rate. This likely reflects an inability to maintain stable preload volume in the supine position.

Adult↗
PubMed1996

Positive tuberculin skin test reactions among house staff at a public hospital in the era of resurgent tuberculosis.

BACKGROUND: The number and significance of tuberculin skin test reactions were compared with self-reported baseline values among house staff working in a public hospital. High-risk medical specialties, locations, and infection control practices were examined. METHODS: House staff interviews, tuberculin skin test applications, review of employee health service records, and environmental monitoring of high-risk areas were performed. RESULTS: Among house staff self-reported as having negative tuberculin skin test status, 46.2% (95% CI 27.0% to 65.4%) of internal medicine house staff, compared with 4.8% (95% CI 4.3% to 13.9%) of house staff from other areas (p < 0.005), had positive results on a repeat tuberculin skin testing before graduation. These differences were not entirely explained by the use of surgical masks, year of training, or previous vaccination with bacille Calmette-Guérin. Most skin test reactions (69%) occurred among house staff who had not been vaccinated with bacille Calmette-Guérin. Increased skin reactivity probably represented excess conversions from unprotected exposure. Tuberculosis transmission was facilitated by delays in diagnosis, inadequate isolation facilities, and suboptimal ventilation. House staff did not comply with recommended tuberculosis surveillance because of time constraints, fear, and misunderstandings about tuberculin skin test interpretations in light of previous bacille Calmette-Guérin vaccination. CONCLUSIONS: House staff in high-exposure settings with suboptimal environmental controls are at increased risk for tuberculosis infection. Participation in surveillance programs can be increased by enlisting the participation and advocacy of respected medical colleagues, screening house staff differentially according to exposure and job classifications, and more accurately interpreting subsequent test results from baseline two-step testing.

BCG Vaccine↗
PubMed1996

Altered contractility of urinary bladder in diabetic rabbits: relationship to reduced Na+ pump activity.

We studied the effect of alloxan-induced diabetes on Na+ pump activity in isolated rabbit bladder strips. In addition, the effects of diabetes and the Na+ pump inhibitor ouabain on contractions induced by carbachol (CCh) and KCl were studied. In bladder strips from diabetic rabbits, ouabain-sensitive 86Rb+ uptake (a measure of Na+ pump activity) was approximately 50% less compared with strips from normal bladder. Diabetes also reduced the maximum contractions induced by CCh and KCl. Treatment of bladder strips with ouabain alone caused an acute concentration-dependent increase in tone. In contrast, longer incubation with ouabain inhibited CCh- and KCl-induced contractions in normal and diabetic bladders. Furthermore, differences in agonist-mediated contractions observed between normal and diabetic bladders were abolished in the presence of the maximally effective concentration of ouabain (10 microM). The ability of CCh to cause contraction in normal and diabetic rabbit bladders was also significantly inhibited by the Na+ ionophore monensin but not by the Ca2+ ionophore A-23187 or by depolarization with KCl. Monensin also inhibited KCl-induced contractions in normal bladder strips. These results indicate that 1) Na+ pump activity is an important modulator of bladder smooth muscle tone, 2) diabetes diminishes Na+ pump activity and inhibits agonist-induced contractions in bladder, and 3) an increase in intracellular Na+ concentration, secondary to inhibition of bladder smooth muscle Na+ pump activity, is associated with reduced responsiveness to contractile agonists. Diminished Na+ pump activity in diabetes may, in part, contribute to the development of bladder cystopathy.

Animals↗
PubMed1996

Oxidative stress increases glyceraldehyde-3-phosphate dehydrogenase mRNA levels in isolated rabbit aorta.

We have recently shown that inhibition of endogenous Cu,Zn superoxide dismutase (SOD) by diethyldithiocarbamate (DDC) increased superoxide anion levels in isolated rabbit aortic rings, describing a useful experimental model to examine the effects of oxidative stress on the vessel wall. The present study examined the effects of oxidative stress on the steady-state mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). Aortic rings were incubated in physiological salt solution at 37 degrees C for up to 6 h. DDC (2 mM) decreased total SOD activity to < 5% of control levels and increased superoxide anion level ninefold. Steady-state mRNA levels of GAPDH were increased under comparable conditions. Although decreased biological activity of endothelium-derived nitric oxide was indicated by lower basal guanosine 3',5'-cyclic monophosphate levels in aortic rings treated with DDC compared with those in control rings (1.2 +/- 0.1 vs. 1.9 +/- 0.3 fmol/microgram protein, P < 0.05), neither endothelium denudation nor NG-nitro-L-arginine methyl ester had any effects on the steady-state mRNA levels of GAPDH. The cell.permeable iron chelator 1,10-phenanthroline completely prevented the increases in GAPDH mRNA levels induced by DDC. These results suggest that oxidative stress resulting from inhibition of endogenous Cu,Zn SOD causes induction of GAPDH gene expression and that the hydroxyl radical, produced through the iron-catalyzed Haber-Weiss reaction, is the intracellular reactive oxygen species responsible for the DDC-stimulated increase in GAPDH mRNA.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1996

Vasodilator responses in the forearm skin of patients with insulin-dependent diabetes mellitus.

The integrity of endothelium-dependent vasodilation in the skin of patients with insulin-dependent diabetes mellitus (IDDM) is unclear, especially with respect to the role of nitric oxide. To examine this, forearm skin blood flow by laser Doppler flowmetry and total blood flow by venous occlusion plethysmography was measured in response to brachial artery infusions of an endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilator. Peak hyperemic forearm blood flow, following 5 min of arterial occlusion, was also determined. Responses were compared in 11 control subjects and 16 patients with insulin-dependent diabetes mellitus. In ten normal subjects, co-infusion of NG-monomethyl-L-arginine with methacholine produced a significant reduction in total forearm blood flow response to methacholine (p < 0.002), measured by venous occlusion plethysmography, as well as vascular conductance (p < 0.001), confirming that nitric oxide contributes to this response. In contrast, NG-monomethyl-L-arginine had no significant effect on the methacholine-induced increase in forearm skin blood flow measured by laser Doppler flowmetry indicating that factors other than nitric oxide may be involved. Increases in forearm skin blood flow in response to methacholine, sodium nitroprusside and to an ischemic stimulus were not significantly different between the normal subjects and patients with IDDM. Dose-related increases in total forearm blood flow and vascular conductance were not significantly different between control subjects and diabetic patients during infusions of methacholine. The increases in these parameters during infusions of sodium nitroprusside, however, were significantly less in the diabetic group than in the control group (p < 0.05) as was the peak reactive hyperemic blood flow (p < 0.05). Since skin blood flow was not affected, the reduced vasodilator responses to sodium nitroprusside and an ischemic stimulus in the diabetic group are in forearm skeletal muscle. The reduced muscle blood flow does not reflect a decreased vasodilatory capacity, but rather a functional impairment in response to nitric oxide and ischemia since the methacholine dilation was normal. The normal vasodilator responses in the forearm skin, which is predominantly capillary as opposed to arteriovenous anastomatic blood flow, indicate that the response to nitric oxide and an ischemic stimulus in this vascular bed is intact in patients with IDDM. This is, therefore, an unlikely cause of diabetic skin, complications in these areas.

Adult↗
PubMed1995

Human mammary artery endothelial sparing with fibrous jaw clamping.

BACKGROUND: Temporary clamping of the internal mammary artery pedicle is required for visualization during coronary artery bypass grafting. A nylon fibril jaw surface has been developed for these clamps that exerts pressure only at discrete sites on the pedicle surface. The effect of this new jaw surface on endothelial cell function and integrity after compression is investigated in this study. METHODS: Internal mammary artery specimens from 10 patients each were divided into three separate rings, and two of these rings were clamped for 30 minutes with either a smooth or fibrous jaw clamp. Isometric tensions were measured in organ chambers after contraction by relaxing the rings with the endothelium-dependent agent acetylcholine followed by the endothelium-independent agent sodium nitroprusside. The intimal surfaces of similar rings were silver stained to assess the percentage of intact endothelium. RESULTS: Endothelium-dependent relaxation was spared after fibrous jaw clamping (75% versus 89%) but significantly impaired after smooth jaw clamping (25% versus 89%; p < 0.001). Endothelium-independent relaxation was unaffected by either intervention. The percentage of remaining intact endothelium upon silver staining was significantly less after smooth than after fibrous jaw clamping (24% versus 48%; p < 0.01). CONCLUSIONS: Foam silicone with nylon fibrils on the jaw surface of internal mammary artery clamps preserves endothelial cell function and integrity. The remaining undamaged cells also may facilitate the subsequent regeneration of a confluent endothelial cell layer.

Acetylcholine↗