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PubMed2006

Effects of neuromuscular block on systemic and cerebral hemodynamics and bispectral index during moderate or deep sedation in critically ill patients.

OBJECTIVE: To investigate whether neuromuscular block can affect bispectral index (BIS) or cerebral hemodynamics under moderate or deep sedation produced by propofol. DESIGN AND SETTING: Prospective, controlled study in a university hospital affiliated intensive care unit. PATIENTS: Seventeen surgical patients undergoing elective esophagectomy. INTERVENTIONS: After stabilization with either light or deep sedation we investigated whether the BIS, electromyographic activity (EMG), or cerebral and systemic hemodynamic parameters were affected by administration of muscle relaxant. MEASUREMENTS AND MAIN RESULTS: Neuromuscular block reduced the BIS during moderate sedation but not during deep sedation although the EMG at both levels of sedation was significantly reduced. No positive effects of neuromuscular block on cerebral hemodynamics were obtained with monitoring of regional cerebral oxygen saturation and middle cerebral artery blood velocity; however, significant effects on systemic hemodynamic parameters were observed only at moderate propofol sedation. The values of BIS and systemic hemodynamic variables with moderate sedation were also very similar to those with deep sedation and neuromuscular block although these values differed without neuromuscular block. CONCLUSIONS: Neuromuscular block altered the BIS score in moderately sedated patients but not in deeply sedated patients although cerebral hemodynamics was not affected by neuromuscular block during either moderate or deep sedation. Muscular relaxant also enhanced cardiovascular stability with moderate sedation. These results suggest that level of consciousness may be decreased by neuromuscular block during moderate sedation but not affected during deep sedation.

Aged↗

PubMed2005

Transient impairment of flow-mediated vasodilation in patients with metabolic syndrome at moderate altitude (1,700 m).

BACKGROUND: The influence of moderate altitude on the cardiovascular system in patients with metabolic syndrome has not been investigated sufficiently, yet. The aim of this study was to assess the effect of acute and mid-term exposure to moderate altitude (1,700 m) on endothelial function in patients with metabolic syndrome. METHODS: Flow-mediated (FMD) and nitroglycerin-mediated vasodilation (NMD) were assessed in 18 patients with coronary risk factors on 5 occasions: (1) at location A (576 m), (2) on the first day at moderate altitude (location B, 1,700 m), (3) after 3 weeks at moderate altitude, (4) and (5) again at location A (6 and 16 weeks after the stay at moderate altitude, respectively). In addition, markers of lipid metabolism, serum erythropoietin and endothelin were measured. RESULTS: FMD on the first day at moderate altitude was similar compared to baseline FMD at location A (7.0 +/- 3.3 vs. 7.4 +/- 4.6%; NS). A 3-week stay at moderate altitude was associated with a significant reduction in FMD (7.4 +/- 4.6 vs. 3.8 +/- 2.5%; p < 0.05) despite a decrease in baseline diameter (4.5 +/- 0.3 vs. 4.3 +/- 0.4 mm; p < 0.05). Six weeks after returning to location A, FMD was still reduced compared to baseline (4.3 +/- 2.8%; p < 0.05) and after further 16 weeks, FMD returned to baseline values (5.5 +/- 3.5%). However, metabolic parameters improved significantly. In contrast, NMD and endothelin levels remained unchanged. CONCLUSION: In patients with metabolic syndrome, a sojourn of 3 weeks at moderate altitude leads to a prolonged, but reversible impairment of FMD. The discrepancy to improvement of other cardiovascular and metabolic parameters requires further investigation.

Adult↗

PubMed2005

Tc-99m HMPAO brain SPECT findings in mild and moderate Alzheimer's disease: correlation with event related potentials.

We investigated whether brain SPECT findings show any differences between patients with mild and moderate Alzheimer's disease (AD) and to compare results with event related potentials (ERPs). Twenty-two patients with mild to moderate AD diagnosed according to NINCDS-ADRDA criteria and 10 age-matched control subjects were included in this prospective study. All subjects underwent ERP recordings and Tc-99m HMPAO brain SPECT study. Cortical perfusion index (CPI) was calculated as the ratio of cortical activity to the cerebellum activity. CPI was found to be statistically lower in bilaterally posterolateral temporal cortex and precuneus in the moderate AD compared to the control group. There was no statistically significant difference between the mild AD and control groups for CPI in any cortical areas. The mean P300 latency was statistically prolonged in the mild and moderate AD compared to the control group. In addition, in moderate AD P300 latency was longer than in mild AD. While the mean P300 amplitude was statistically reduced in moderate AD compared to the control and mild AD, there was no statistically significant difference between the mild AD and control groups. There was a strong negative correlation between P300 latency and CPI in the right and left precuneus in the moderate AD group. The present study suggested that Tc-99m HMPAO SPECT study is the more appropriate technique for patients with moderate AD rather than mild AD. Our results indicated that alterations in ERPs, especially prolongation of P300 latency could be a finding that occurred earlier than the deterioration in cerebral blood flow. We thought that precuneus is closely related to cognitive function and may have an important role in the pathophysiology of AD.

Aged↗

PubMed2003

Natural history and predictors of moderate mitral regurgitation following balloon mitral valvuloplasty using Inoue balloon.

BACKGROUND: We studied the predictors and natural history of moderate mitral regurgitation following valvuloplasty using Inoue balloon since it has not been well documented in a large series. METHODS: Balloon mitral valvuloplasty was performed in 590 consecutive patients with severe mitral stenosis with mitral regurgitation of mild or lesser grade. Echocardiography and haemodynamics of patients who developed moderate mitral regurgitation were compared with those who did not. They were followed-up. Factors that predicted the development of moderate regurgitation were studied. RESULTS: 21 patients (3.5%) developed moderate regurgitation (identified by auscultation, haemodynamics, angiography and colour flow mapping). They were managed conservatively. At 3 months, regurgitation decreased in severity to mild grade in 12 patients. At 1 year, it was trivial in 5, mild in 11 and remained moderate in 5. There was progressive symptomatic improvement. No clinical, echocardiographic, hemodynamic or procedural variables could predict the development of moderate mitral regurgitation. CONCLUSIONS: Patients with moderate regurgitation after mitral valvuloplasty show gradual improvement in regurgitation and symptoms. There were no factors-clinical, echocardiographic, hemodynamic or procedural-that predicted the occurrence of moderate MR after BMV.

Adolescent↗

PubMed1997

Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm?

OBJECTIVES: This study sought to examine the hemodynamic and autonomic dose response to digoxin. BACKGROUND: Previous studies have demonstrated an increase in contractility and heart rate variability with digitalis preparations. However, little is known about the dose-response to digoxin, which has a narrow therapeutic window. METHODS: Nineteen patients with moderate heart failure and a left ventricular ejection fraction < 0.45 were studied hemodynamically using echocardiography and blood pressure at baseline and after 2 weeks of low dose (0.125 mg daily) and 2 weeks of moderate dose digoxin (0.25 mg daily). Loading conditions were altered with nitroprusside at each study. Autonomic function was studied by assessing heart rate variability on 24-h Holter monitoring and plasma norepinephrine levels during supine rest. RESULTS: Low dose digoxin provided a significant increase in ventricular performance, but no further increase was seen with the moderate dose. Low dose digoxin reduced heart rate and increased heart rate variability. Moderate dose digoxin produced no additional increase in heart rate variability or reduction in sympathetic activity, as manifested by heart rate, plasma norepinephrine or low frequency/high frequency power ratio. In addition, we did not find that either low or moderate dose digoxin increased parasympathetic activity. CONCLUSIONS: We conclude that moderate dose digoxin provides no additional hemodynamic or autonomic benefit for patients with mild to moderate heart failure over low dose digoxin. Because higher doses of digoxin may predispose to arrhythmogenesis, lower dose digoxin should be considered in patients with mild to moderate heart failure.

Cardiotonic Agents↗

PubMed1996

Gastric emptying, pulmonary function, gas exchange, and respiratory quotient after feeding a moderate versus high fat enteral formula meal in chronic obstructive pulmonary disease patients.

High fat enteral formulas have been advocated for the nutritional support of chronic obstructive pulmonary disease (COPD) patients because dietary fat utilization under ideal conditions produces less CO2 per O2 consumed than carbohydrate. No data exist for these patients comparing the effects of a moderate fat vs. a high fat enteral formula on gastric emptying times (GE) and subsequent CO2 production (VCO2), oxygen consumption (VO2), respiratory quotient (RQ), and pulmonary function. Our double-blind crossover study compared these parameters after feeding a 355 mL (530 kcal) meal with either 41% fat calories (Respalor) or 55% fat calories (Pulmocare). Thirty-six COPD outpatients with a forced expiratory volume in 1 s (FEV1) < 60% of predicted were studied after an overnight fast. Gastric emptying half-time (GE t1/2) was measured using the 99MTc-radionuclide technique; VCO2, VO2, RQ, and other pulmonary functions were measured at 0, 30, 90, and 150 min postprandial using the Canopy Mode of the Deltatrac Metabolic Monitor and the Renaissance Spirometry System. We observed a significantly (p = 0.0001) longer GE t1/2 of the high fat meal when compared to the moderate fat meal (134.1 vs. 108.6 min) At 30 and 90, but not at 150 min postprandial, the VCO2 and VO2 for patients fed the moderate-fat formula were significantly (p = 0.05) higher than for those fed the high-fat formula; no differences were observed for the other pulmonary functions. Although RQ increased significantly (p = 0.01) after both meals, no differences between formulas were noted at all postprandial times tested. Compared to the high-fat meal, the moderate-fat meal significantly enhanced gastric emptying. The earlier rise in VCO2 and VO2 after the moderate-fat meal did not impact pulmonary function and reflected the earlier utilization of the moderate-fat meal. The fact that RQ was not different between the two meals at all postprandial times tested suggest that the higher rise in VCO2 and VO2 after the moderate-fat meal was most likely due to earlier gastric emptying of the moderate-fat meal rather than the difference of the fat-to-carbohydrate ratio between the two tested meals. The impact of these findings on long-term management of COPD patients awaits long-term prospective studies.

Adult↗

PubMed2001

Public opinion on the health benefits of moderate drinking: results from a Canadian National Population Health Survey.

AIMS: To explore beliefs about the health benefits of drinking alcohol in the Canadian population. DESIGN: Secondary analysis of data from a national population health survey. PARTICIPANTS: Canadians age 12 or older (weighted n = 72375) in all provinces but Alberta excluding those living in remote regions, native reserves and armed forces bases. MEASURES: Responses to questions concerning the definition of moderate drinking and the belief that moderate drinking can be good for health. Self-reports of age, gender, province of residence, quantity and frequency of drinking, health problems and indicators of alcohol dependence. FINDINGS: Fifty-seven per cent of respondents believed that moderate drinking has health benefits. Forty-seven per cent defined moderate drinking as drinking less than one drink a day and believed this to be good for health. Twelve per cent defined moderate drinking as one or more drinks a day and believed this is good for health. Belief in the health benefits of moderate drinking was more common among men, those age 45 or older, residents of Ontario and Quebec, more frequent drinkers and those with ischaemic heart disease. Those who believed in the health benefits of at least one drink a day were more often males, older persons and frequent, heavy drinkers. CONCLUSIONS: Belief in the health benefits of moderate drinking is generally associated with a conservative definition of moderate drinking. However, some drinkers at risk for alcohol problems may be influenced to drink by the belief that this can have health benefits or use this belief as an excuse for drinking.

Adolescent↗

PubMed1998

Severe haemorrhage partially reverses moderate haemorrhage-induced decrease in intestinal vascular capacitance.

The purpose of the present study was to compare the effect of severe haemorrhage with moderate haemorrhage on intestinal vascular capacitance. In 12 chloralose-anaesthetized pigs, moderate and subsequent severe haemorrhage was induced by removal of 15 and 25% of blood volume, respectively. Six of the animals were vagotomized prior to induction of haemorrhage. The portal vein pressure/intestinal blood volume (P-V) relationship was measured by using blood pool scintigraphy and varying portal vein pressure. Moderate haemorrhage resulted in a leftward shift of the P-V relationship towards the pressure axis with decreases in cardiac output, portal blood flow and arterial pressure, and an increase in heart rate. Severe haemorrhage shifted the P-V relationship back towards the volume axis compared with moderate haemorrhage, with further decreases in cardiac output, portal blood flow and arterial pressure. While moderate haemorrhage reduced intestinal blood volume at a portal vein pressure of 7 mmHg (Vp7) to 81 +/- 3% of the control value (P < 0.01), severe haemorrhage increased Vp7 to 88 +/- 1% of the control value (P < 0.05 compared with moderate haemorrhage). After vagotomy, moderate haemorrhage decreased Vp7 to 84 +/- 4% of the control value (P < 0.01), whereas Vp7 did not change significantly after severe haemorrhage (Vp7 increased to 86 +/- 1% of the control value). Thus, severe haemorrhage is associated with an increase in intestinal vascular capacity compared with moderate haemorrhage. This increase is mediated in part via the cardiac vagal reflex. The attenuation of intestinal venoconstriction during severe haemorrhage probably contributes to further decreases in cardiac output and arterial pressure by redistribution of blood to the peripheral circulation.

Animals↗

PubMed2004

Effects of moderate-fat (from monounsaturated fat) and low-fat weight-loss diets on the serum lipid profile in overweight and obese men and women.

BACKGROUND: Little evidence of the effects of moderate-fat (from monounsaturated fat) weight-loss diets on risk factors for cardiovascular disease exists because low-fat diets are typically recommended. Previous studies in weight-stable persons showed that a moderate-fat diet results in a more favorable lipid and lipoprotein profile (ie, lower serum triacylglycerol and higher HDL cholesterol) than does a low-fat diet. OBJECTIVE: We evaluated the effects of energy-controlled, low-fat and moderate-fat diets on changes in lipids and lipoproteins during weight loss and subsequent weight maintenance. DESIGN: We conducted a parallel-arm study design in overweight and obese [body mass index (in kg/m(2)): 29.8 +/- 2.4] healthy men and women (n = 53) assigned to consume a low-fat (18% of energy) or moderate-fat (33% of energy) diet for 6 wk to achieve weight loss, which was followed by 4 wk of weight maintenance. All foods were provided and body weight was monitored to ensure equal weight loss between groups. RESULTS: The moderate-fat diet elicited favorable changes in the lipoprotein profile. Compared with baseline, HDL cholesterol was unchanged, whereas triacylglycerol and the ratios of total and non-HDL cholesterol to HDL cholesterol were lower at the end of the weight-maintenance period in the moderate-fat diet group. Despite similar weight loss, triacylglycerol rebounded, HDL cholesterol decreased, and the ratios of total and non-HDL cholesterol to HDL cholesterol did not change during the 10-wk interval in the low-fat diet group. CONCLUSIONS: A moderate-fat weight-loss and weight-maintenance diet improves the cardiovascular disease risk profile on the basis of favorable changes in lipids and lipoproteins. There is merit in recommending a moderate-fat weight-loss diet.

Adult↗

PubMed1997

Moderate alcohol feeding attenuates postinjury vascular cell proliferation in rabbit angioplasty model.

Our studies in the cholesterol-fed rabbit model indicate that moderate alcohol consumption reduces the risk of restenosis by preventing low-density lipoprotein (LDL) oxidation. Eighteen hypercholesterolemic rabbits underwent arterial injury by Fogerty balloon endothelial denudation of iliac arteries. Two weeks later, balloon angioplasty of atherogenic or atherosclerotic arterial segments was performed. Nine rabbits (control) received water ad lib, whereas nine rabbits (moderate alcohol treated) received an average of 2.5 ml alcohol per 500 ml water daily, from the day of feeding hypercholesterolemic diet until they were killed, 10 weeks later. There was a 26% increase in lumen size of the moderate alcohol-treated group compared with the control group. The percentage neointima formation (NI) values of the moderate alcohol-treated and control groups were 77 +/- 2.1 and 61 +/- 1.9, respectively (p < 0.001). The lumen/neointima (L/NI) ratio of the moderate alcohol-treated group was 0.71 +/- 0.07 compared with the control group, 0.33 +/- 0.04 (p < 0.001). The number of foam cells in the moderate alcohol-treated group was threefold less than the control group [i.e., 1.4 +/- 0.4 and 3.9 +/- 0.8, respectively (p = 0.005)]. The arterial lesion malondialdehyde (MDA) values of the control and the moderate alcohol-treated groups were 13.6 +/- 2.8 and 4.4 +/- 0.5 (p = 0.004), respectively. By radioimmunoassay, the moderate alcohol-treated group had less macrophage chemotactic protein-1 (MCP-1; 3,277 cpm/microg protein) and platelet-derived growth factor (PDGF; 2,261 cpm/microg protein) compared with the controls (MCP-1, 4,529 cpm/microg protein; PDGF, 3,583 cpm/microg protein). Thus we conclude that low concentrations of alcohol reduce neointimal formation, and the extent of lipid oxidation, the number of foam cells in the neointimal area and may decrease the expression of MCP-1 and PDGF by reducing LDL oxidation in an animal model of postangioplasty restenosis.

Angioplasty, Balloon↗

PubMed2003

Galantamine provides sustained benefits in patients with 'advanced moderate' Alzheimer's disease for at least 12 months.

Galantamine (Reminyl), a novel agent with a dual mode of action, modulates nicotinic acetylcholine receptors and inhibits acetylcholinesterase. Galantamine has consistently demonstrated a broad range of beneficial effects and has shown sustained benefits in cognitive and functional abilities for at least 12 months in patients with mild-to-moderate Alzheimer's disease (AD). As pivotal studies demonstrating the efficacy of cholinergic drugs were designed to exclude patients with severer AD, many patients with the advanced stage of this condition are currently not treated due to the lack of demonstrated efficacy in clinical trials. We aimed to investigate whether there was any evidence for the benefits of galantamine in patients with severer disease, by performing a post hoc analysis using data extracted from the population of the two long-term galantamine studies. We evaluated the efficacy of galantamine in patients with 'advanced moderate' AD. 'Advanced moderate' patients were those with baseline Mini Mental State Examination (MMSE) scores </=14 or Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) scores >30. These patients were compared with matched controls who received placebo in a different historical study. Cognitive abilities (assessed using the ADAS-cog scale) of 'advanced moderate' AD patients receiving galantamine for 12 months were maintained at baseline levels after 12 months, and significantly improved over those of placebo patients (p < 0.001). Of the 'advanced moderate' patients receiving galantamine, 51% with baseline ADAS-cog of >30 maintained or improved their ADAS-cog scores over baseline values, compared with 13% receiving placebo (p < 0.001). In the subgroup of 'advanced moderate' patients with baseline MMSE </=14, 48% of those receiving galantamine and 4% of those receiving placebo maintained or improved their ADAS-cog scores at 12 months (p = 0.001). In both subgroups, the treatment difference (galantamine vs. historical placebo) amounted to approximately 10 points on the ADAS-cog scale. Functional abilities, as assessed using the Disability Assessment for Dementia scale, remained significantly superior in galantamine-treated patients compared with historical placebo-treated patients at 12 months (p < 0.001). In conclusion, galantamine offered sustained efficacy to patients with 'advanced moderate' AD, confirming the benefits seen in published studies of patients with mild-to-moderate AD. This drug has potential for broader use in clinical practice.

Aged↗

PubMed2004

Moderate-intensity exercise suppresses platelet activation and polymorphonuclear leukocyte interaction with surface-adherent platelets under shear flow in men.

The reciprocal modulation of platelet and polymorphonuclear leukocyte (PMN) activities is important in the pathogenesis of thrombosis and inflammation. This study investigated how moderate exercise affects shear-induced platelet activation and subsequent PMNs interaction with platelet-related thrombi under shear flow. Sixteen sedentary healthy men engaged in moderate exercise (about 60% VO(2max)) on a bicycle ergometer. Platelet activation, PMNs interaction with surface-adherent platelets, and PMN-dependent inhibition of platelet activation under shear flow were measured both before and immediately after exercise. The results of this study can be summarized as follows: (1) moderate exercise was associated with lower extents of shear-induced platelet adhesion and aggregation, binding of von Willbrand factor (vWF) to platelets, and glyco-protein IIb/IIIa activation and P-selectin expression on platelet than at rest; (2) the velocity and percentage of rolling PMNs increased while the number of PMNs remaining bound to surface-adherent platelets decreased after moderate exercise; (3) although treating the PMNs with oxidized-low density lipoprotein (Ox-LDL) enhanced PMNs interaction with surface-adherent platelets, moderate exercise suppressed the enhancement of platelet-PMN interaction by Ox-LDL; (4) moderate exercise decreased platelet [Ca (2+)](i) elevation induced by ADP and platelet [Ca(2+)](i) levels mediated by PMN and Ox-LDL-treated PMN; and (5) plasma and PMN-derived nitric oxide metabolites and plasma vWF antigen and activity increased after moderate exercise, whereas plasma and platelet-derived soluble P-selectin levels remained unchanged in response to exercise. Therefore, we conclude that moderate-intensity exercise suppresses shear-induced platelet activation and subsequent PMNs adhesion to platelets deposited at sites of vascular injury under flow, thereby reducing the risks of vascular thrombosis and inflammation.

Blood Platelets↗

PubMed1982

Moderate head injury: completing the clinical spectrum of brain trauma.

We have divided head injury into three categories based on the Glasgow Coma Scale (GCS) (severe, 3-8; moderate, 9-12; and minor, 13-15). In a previous report, we described significant disability after minor head injury. The present report describes 199 patients with moderate head injury, 159 of whom underwent follow-up examinations at 3 months. In contrast to patients with minor head injury, half as many were students (17%) and twice as many were intoxicated (53%). Seventy-five patients were studied with computed tomographic (CT) scanning; 30% of the scans were negative and 31% showed a space-occupying mass. As reported by Gennarelli et al. in patients with severe head injuries, those with moderate head injury and subdural hematoma had a very poor outcome: 65% died or were severely disabled and none made a good recovery as measured by the Glasgow Outcome Scale. At 3 months, 38% of the moderate head injury patients had made a good recovery compared with 75% of the minor head injury patients. Within the good recovery category, however, there was much disability (headache, 93%; memory difficulties, 90%; difficulties with activities of daily living, 87%), and only 7% of the patients were asymptomatic. The Halstead-Reitan Neuropsychological Battery in an unselected subset (n = 32) showed significant deficits on all test measures. Sixty-six per cent of the patients previously employed had not returned to work, compared to 33% of the minor head injury patients. The major predictors of unemployment after minor head injury were premorbid characteristics (age, education, and socio-economic status). In contrast, all predictors in moderate head injury were measures of the severity of injury (length of coma, CT diagnosis, GCS on discharge). We conclude that: (a) moderate head injury, not described previously in the literature, results in mortality and substantial morbidity intermediate between those of severe and minor head injury; (b) unlike minor head injury, the principal predictors of outcome after moderate head injury are measures of the severity of injury; and (c) more attention should be directed to patients with moderate head injury than to those with the most severe injuries, in whom brain damage is probably irreversible and all forms of management have demonstrated little success.

Accidents, Traffic↗

PubMed1995

Alterations in striatal dopamine release and reuptake under conditions of mild, moderate, and severe cerebral ischemia.

Cerebral ischemia can result in varying degrees of tissue damage. Conditions of severe ischemia can produce extensive areas of irreversible injury, whereas in conditions of moderate ischemia, tissue damage may be reversible, as in the region of the ischemic penumbra. The reversibility of tissue damage in the penumbral region is of clinical interest, because the characterization of conditions underlying this reversible state may provide information needed for the development of new therapeutic approaches for treatment. Our previous studies demonstrated neurochemical alterations in the levels of dopamine (DA) within the striatum after cerebral ischemia. In the present study, we postulate that these changes may be caused, in part, by alterations in transmitter release and reuptake. To test this hypothesis, forebrain ischemia was induced in Sprague-Dawley rats (Harlan, Indianapolis, IN) by means of bilateral common carotid artery occlusion and hemorrhagic hypotension. Cerebral blood flow (CBF) in the striatum was measured by the method of hydrogen clearance, and the extracellular DA ([DA]e) levels were measured by in vivo microdialysis. Varied reductions of CBF were induced and maintained for 5 hours. Three subgroups were established retrospectively according to the degree of CBF reduction: 67.7, 35.6, and 13.2% of normal CBF in the mild, moderate, and severe ischemic groups, respectively. The induction of ischemia resulted in 1.9-, 9.3-, and 122.3-fold increases in [DA]e above baseline in the mild, moderate, and severe ischemia groups, respectively. At 3 hours after the induction of ischemia, high potassium (100 mmol/L) or Nomifensin (Sigma, St. Louis, MO) (10 mmol/L), a DA uptake blocker, was administrated via a microdialysis probe to stimulate DA release while reductions in CBF were maintained continuously. Thirteen rats were used in the study of the release of DA by potassium or Nomifensin in nonischemic conditions. The administration of high potassium or Nomifensin stimulated DA release in conditions of mild and moderate ischemia. The increase in DA release by potassium stimulation was higher in rats with mild ischemia (106.6-fold) than that in normal rats (22.3-fold). This suggests a hyperexcitability of DA terminals under mild ischemia, as compared with nonischemic conditions. On the other hand, Nomifensin increased [DA]e levels more in moderately ischemic brains than in control brains, suggesting that DA uptake is up-regulated in the former case. The increased release of DA by potassium and Nomifensin was sustained after stimulation in conditions of mild and moderate ischemia. The high level of [DA]e with severe ischemia after ischemic induction was sustained throughout the period of study and was not stimulated by potassium or Nomifensin. We conclude that under conditions of mild and moderate ischemia, DA terminals become highly excitable and reuptake mechanisms are compromised. These changes of DA metabolism during mild and moderate ischemia may explain the sustainability of neurons in the "penumbra" condition of cerebral ischemia and the transformation of the ischemic penumbra to a necrotic core.

Animals↗

PubMed2005

Mild and moderate-to-severe COPD in nonsmokers: distinct demographic profiles.

STUDY OBJECTIVE: To investigate the risk of COPD among nonsmokers. DESIGN: Case-control study, logistic regression analysis. SETTING: Third National Health and Nutrition Examination Survey, from 1988 to 1994. PARTICIPANTS: Community residents 18 to 80 years of age, of white, black, or Mexican-American ethnicity. Nonsmokers included never-smokers and former smokers with a < 5 pack-year smoking history who had never smoked cigars or pipes. MEASUREMENTS: COPD (FEV1/FVC < 70%) was classified as mild (FEV1 > or = 80% predicted) or moderate to severe (FEV1 23 to 79% predicted). RESULTS: Among 13,995 examinees, 51.3 +/- 0.4% were female, mean age was 42.2 +/- 0.4 years, 48.7 +/- 0.9% were nonsmokers, 8.8 +/- 0.3% had mild COPD, and 4.1 +/- 0.3% had moderate-to-severe COPD [+/- SE]. One fourth of mild and moderate-to-severe cases were nonsmokers. Among 7,526 nonsmokers, 4.7 +/- 0.3% had mild COPD (n = 403; age, 60.9 +/- 1.3 years) and were mostly female (82.5%), while 1.9 +/- 0.3% had moderate-to-severe COPD (n = 92, age 39.3 +/- 1.3) and were mostly male (88.1%). Few nonsmokers with COPD (12.1 +/- 2.4%) had a previous diagnosis of chronic bronchitis or emphysema. Among nonsmokers, physician-diagnosed asthma increased the risk of mild and especially of moderate-to-severe COPD. Independently of asthma, risk of mild COPD in nonsmokers increased with age (doubling every 12 years), before age 60 was lower among men than women, and was inversely associated with current exposure to tobacco smoke at home and at work. In contrast, the risk of moderate-to-severe COPD in nonsmokers was markedly associated with male gender, peaked in middle age, and was inversely associated with nonwhite ethnicity. COPD risks did not vary by minimal smoking history, longest-held occupation, urban residence, income, allergies, thyroid disease, or Helicobacter pylori antibody. CONCLUSIONS: Among nonsmokers, mild and moderate-to-severe COPD are associated with asthma but otherwise have distinct demographic profiles, suggesting that moderate-to-severe disease is not a mere progression of mild COPD.

Adult↗

PubMed1998

Long-term survival in patients with mild or moderate impairment of left ventricular contractility during routine diagnostic left ventriculography.

Long-term survival in patients with mild to moderate impairment of left ventricular contractility in the absence of coronary artery disease has not been studied extensively but the prognosis is assumed to be good. One hundred sixty-eight patients with angiographic evidence of mild or moderate impairment of left ventricular contractility and no other significant cardiac disease at the time of routine diagnostic cardiac catheterization were studied to determine long-term survival and event-free survival. Clinical characteristics, electrocardiograms, chest X-rays, laboratory data, and hemodynamics including end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and regional wall motion at the time of catheterization were examined. Patients with moderate impairment were more likely to have dyspnea (P = 0.005) and an abnormal electrocardiogram (P = 0.006) than patients with mild impairment. Mean ejection fraction was 57% (P = 0.0001 vs. normal) in patients with mild impairment and was 47% (P = 0.0001 vs. normal) in patients with moderate impairment. Wall motion studies showed impairment to be generalized and more significantly abnormal in patients with moderate impairment. Survival at a mean of 138 months could be determined in 162 of the 168 patients (96%). Fourteen year actuarial survival was 92% for patients with mild impairment compared to 75% for patients with moderate impairment (P = 0.01). Long-term prognosis is good in patients found to have mild generalized impairment at the time of routine diagnostic cardiac catheterization. In patients with moderate impairment, closer follow-up to prevent arrhythmia and the onset of congestive heart failure appears to be warranted.

Adult↗

PubMed2002

Clock drawing test in mild and moderate dementia of the Alzheimer's type: a comparative and correlation study.

OBJECTIVES: (a) To compare two different clock drawing tests (CDTs) in mild and moderate dementia of the Alzheimer's type (DAT); (b) To examine presumed correlation between these CDTs and some demographic, cognitive and activities of daily living (ADL) variables in mild and moderate DAT. METHODS: Cross-sectional study. Psychogeriatric outpatient clinic. 49 DAT patients, total; 26-mild, 23-moderate, mean age 77.8 and 80.6, respectively. Evaluations included the Mini-Mental State Examination (MMSE), the Cambridge Cognitive Examination (CAMCOG), the Instrumental Activities of Daily Living Scale (IADL), and a Basic Activities of Daily Living (BADL)-dressing subscale. Severity of dementia was determined with the Clinical Dementia Rating (CDR). Each clock was blindly scored by the same investigator, according to Shulman's and Freedman's methods. RESULTS: Mild and moderate DAT groups were similar in age, gender and education. Performance on Shulman's clock was similar between groups while moderate DAT subjects performed significantly worse on Freedman's clock compared to mild DAT patients. Both clocks correlated highly in mild and moderate DAT. CDT scores correlated significantly with age and education only in mild DAT. Neither clock correlated with ADLs in either stage of dementia severity. CDTs correlated with the MMSE score, and the CAMCOG score in mild DAT, and only with the CAMCOG score in moderate DAT. These correlations were still significant after controlling for age and education. CONCLUSIONS: Different aspects of cognition and dementia severity are reflected depending on how a clock drawing is scored. Some scoring systems may have greater sensitivity than others in monitoring progression of cognitive deterioration. Correlation between different CDTs and the variables studied (demographic, cognitive, ADLs), when present, is not ubiqitous and changes with the dementia severity.

Activities of Daily Living↗

PubMed1990

An experimental study of the moderator assembly for a low-energy proton accelerator neutron irradiation facility for BNCT.

An accelerator-based neutron irradiation facility (ANIF), which has been proposed for BNCT, is based on a 2.5-MeV proton beam bombarding a thick lithium target. Neutrons which are emitted from the lithium target are too energetic for BNCT and must be moderated. A calculational study, which was done previously on the moderator assembly for an ANIF, shows that, with an optimized moderator assembly, an ANIF can produce a neutron flux which has quality and intensity sufficient for BNCT. In order to verify our previous calculational study, a lithium target and a non-optimized moderator assembly (a cylindrical tank of D2O) have been constructed and tested at the Ohio State University Van de Graaff proton accelerator. The neutron spectrum was measured for neutrons emerging from the moderator assembly. The measured neutron spectrum agrees reasonably well with that obtained from Monte Carlo calculations, except for neutrons with energies above 100 keV. For those neutrons, the measured spectrum is lower by a factor of two than the calculated one. In addition to the neutron spectrum measurement, the boron-10 absorbed dose was measured on the axis of the neutron field in a 20 cm x 20 cm x 20 cm water phantom, and the result agrees quite well with that obtained from calculation. This experiment confirms that the calculated optimized moderator assembly, consisting of a 22.5-cm thick, 25-cm diameter cylinder of beryllia (BeO) surrounded by a 30-cm thick jacket of alumina (Al2O3), produces an epithermal neutron flux of 3.12 x 10(7) n/cm2-s per mA of protons. For an accelerator delivering 30 mA of 2.5-MeV protons, the irradiation time for a single-session treatment can be as short as 50 minutes. The calculated ratio of absorbed neutron dose to fluence for the optimized moderator assembly is 4.9 x 10(-11) cGy-cm2/n, which is equal to that of a 5-keV neutron beam. Our experimental measurements indicate that the ratio of absorbed neutron dose to fluence may in fact be lower (better) than calculated.

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