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Biomedical subjects

R Greene

Publications and source records attributed to R Greene.

At least 37 records · Page 2Linked to original sources

Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction.

OBJECTIVES: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.

Angioplasty, Balloon, Coronary↗

Up-regulation of vascular endothelial growth factor mRNA and angiogenesis after transmyocardial laser revascularization.

BACKGROUND: Angiogenesis has been proposed as a potential mechanism whereby transmyocardial laser revascularization (TMLR) has provided clinical relief of angina. Experimental work has found histologic evidence supporting this, as well as an improved response when angiogenic growth factors have been added to TMLR. The purpose of this study was to demonstrate that the molecular response to TMLR was an increase in the production of endogenous vascular endothelial growth factor to promote angiogenesis. METHODS: Ameroid constrictors were placed on the proximal circumflex artery in 12 domestic pigs. After a chronic ischemic zone was established the animals were randomly divided into two groups. In the TMLR group the ischemic zone was treated with carbon dioxide laser. In the control group the ischemic zone was untreated. Six weeks later the animals were sacrificed, and sections from the ischemic zone and the nonischemic zone were submitted for immunohistochemical, histologic, and molecular analysis. Messenger RNA was obtained from northern blot analysis after being probed with vascular endothelial growth factor. RESULTS: There was a twofold increase in the vascular endothelial growth factor messenger RNA in the ischemic zone of the TMLR group compared with the control group. Additionally, there was a threefold increase in the number of new blood vessels in the ischemic zone of the TMLR group compared with the control group. CONCLUSIONS: Transmyocardial laser revascularization promotes angiogenesis by upregulation of vascular endothelial growth factor. The resulting angiogenesis could be the principle mechanism for the clinical efficacy of TMLR.

Animals↗

Subcutaneous fat in the fetal abdomen as a predictor of growth restriction.

OBJECTIVE: To determine if measuring fetal abdominal fat antenatally using ultrasound can predict fetal growth restriction (FGR). METHODS: One hundred thirty-seven unselected women with singleton pregnancies had serial ultrasound scans at 20, 26, 31, and 38 weeks' gestation. Subcutaneous fat in the fetal abdomen was measured using the same section as the abdominal circumference (AC). Outcome measures were birth weight, neonatal morbidity, and ponderal index. RESULTS: Infants with subcutaneous fat less than 5 mm at 38 weeks (n = 51) were almost five times more likely to have a birth weight below the 10th centile than those with subcutaneous fat of 5 mm or more (n = 75). The incidence of neonatal morbidity was significantly higher in infants with subcutaneous fat less than 5 mm, compared with those with subcutaneous fat of 5 mm or more (20% versus 8%, P < .05). Decreased subcutaneous fat was also associated with a high prevalence of low ponderal index, regardless of birth weight category. CONCLUSION: Measurement of fat in the abdominal wall is a simple technique with a sensitivity for predicting low birth weight similar to that of conventional sonography and might potentially predict FGR irrespective of fetal weight.

Abdomen↗

In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement.

OBJECTIVES: The purpose of this study was to target acoustically reflective liposomes to atherosclerotic plaques in vivo for ultrasound image enhancement. BACKGROUND: We have previously demonstrated the development of acoustically reflective liposomes that can be conjugated for site-specific acoustic enhancement. This study evaluates the ability of liposomes coupled to antibodies specific for different components of atherosclerotic plaques and thrombi to target and enhance ultrasonic images in vivo. METHODS: Liposomes were prepared with phospholipids and cholesterol using a dehydration/ rehydration method. Antibodies were thiolated for liposome conjugation with N-succinimidyl 3-(2-pyridyldithio) propionate resulting in a thioether linkage between the protein and the phospholipid. Liposomes were conjugated to antifibrinogen or anti-intercellular adhesion molecule-1 (anti-ICAM-1). In a Yucatan miniswine model, atherosclerosis was developed by crush injury of one carotid and one femoral artery and ingestion of a hypercholesterolemic diet. After full plaque development the arteries were imaged (20-MHz intravascular ultrasound catheter and 7.5-MHz transvascular linear probe) after injection of saline, unconjugated liposomes and antibody conjugated liposomes. RESULTS: Conjugated liposomes retained their acoustically reflective properties and provided ultrasonic image enhancement of their targeted structures. Liposomes conjugated to antifibrinogen attached to thrombi and fibrous portions of the atheroma, whereas liposomes conjugated to anti-ICAM-1 attached to early atheroma. CONCLUSIONS: Our data demonstrate that this novel acoustic agent can provide varying targeting with different antibodies with retention of intravascular and transvascular acoustic properties.

Animals↗

Longitudinal patterns of risk for depression in dementia caregivers: objective and subjective primary stress as predictors.

The present study examined how patterns of risk for depression over 1 year in 188 dementia caregivers (consistently asymptomatic, n = 88; consistently symptomatic, n = 40; changing risk, n = 60) could be predicted by objective (behavior problems of the relative) and subjective (role captivity and overload) primary stress. Results reveal that all primary stressors differentiated caregivers who remained at low levels of symptomatology over the course of 1 year from those who were at risk for experiencing a depressive disorder. In addition, caregivers' subjective experience of role captivity predicted the chronicity of risk. Findings extend prior caregiving research on patterns of depressive symptomatology by highlighting the relationship between subjective primary stressors and stability and change in caregivers' mental health.

Activities of Daily Living↗

Trends from 1987 to 1991 in alcohol, tobacco, and other drug (ATOD) use among adolescents exposed to a school district-wide prevention intervention.

This study involved a school-based prevention program initiated to reduce alcohol, tobacco, and other drug (ATOD) use among adolescents in the Troy School District in the Detroit area. One purpose was to describe the current ATOD situation by investigating changes in reported ATOD use from 1987 to 1991. Another purpose was to explore and identify the most salient risk and protective factors present. In 1987, 1,490 students (comprising grades 8 and 11) and in 1991, 3,171 students (comprising grades 8 to 12) completed questionnaires. Significant decreases were found for use of most drugs with the exception of alcohol. Involvement in problem behaviors was identified as the most salient risk factor, while having a member of a non-using peer group was the most salient protective factor. Implications for the design of subsequent intervention programs are discussed.

Adolescent↗

Failure of the canine principal ascending epicardial lymphatic to regenerate after transection.

We transected the principal ascending anterior epicardial cardiac lymphatic in 10 dogs, and after varying time intervals reoperated to look for lymphatic regeneration using dye injection. Photographs and sketches were made to record the findings, and in six dogs serial histologic sections were also examined. In none of the 10 dogs was regeneration of the transected principal cardiac lymphatic detected although small lymphatic collaterals from the distal side of the lymphatic developed in 2 dogs. Further studies are merited to assess the role of lymphatic insufficiency in the development of coronary vasculopathy and chronic rejection after cardiac transplantation and other heart operations (e.g., coronary artery bypass) that may injure lymphatic drainage capacity.

Animals↗

Left ventricular functional improvement after transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization has been used to treat patients with end-stage coronary artery disease that is not amenable to standard revascularization. Although there is evidence of angina relief and quality of life enhancement, there is little information concerning improvement in myocardial contractility. The purpose of this study was to determine whether transmyocardial laser revascularization improves myocardial function in chronically ischemic myocardium. METHODS: In a model of chronic ischemia by Ameroid occlusion of the circumflex artery, domestic pigs (n = 8) were treated with transmyocardial laser revascularization. Before laser treatment, segmental contraction was assessed at rest and with dobutamine stress echocardiography. Myocardium subtended by the occlusion was compared with that remote from the occlusion. Six weeks after transmyocardial laser revascularization, the animals were restudied at rest and with stress, and then sacrificed. Sham-treated control animals (n = 4) underwent the same procedures but were not treated with transmyocardial laser revascularization. Control animals did not demonstrate significant recovery of function. RESULTS: Transmyocardial laser revascularization improved resting function in chronically ischemic myocardium by 100%. CONCLUSIONS: Transmyocardial laser revascularization significantly improves the function of chronically ischemic myocardium. These data may help explain the mechanisms by which transmyocardial laser revascularization is clinically effective.

Animals↗

Cardiovascular autonomic modulation and activity of carotid baroreceptors at altitude.

1. To assess the effects of acute exposure to high altitude on baroreceptor function in man we evaluated the effects of baroreceptor activation on R-R interval and blood pressure control at high altitude. We measured the low-frequency (LF) and high-frequency (HF) components in R-R, non-invasive blood pressure and skin blood flow, and the effect of baroreceptor modulation by 0. 1-Hz sinusoidal neck suction. Ten healthy sea-level natives and three high-altitude native, long-term sea-level residents were evaluated at sea level, upon arrival at 4970 m and 1 week later.2. Compared with sea level, acute high altitude decreased R-R and increased blood pressure in all subjects [sea-level natives: R-R from 1002+/-45 to 775+/-57 ms, systolic blood pressure from 130+/-3 to 150+/-8 mmHg; high-altitude natives: R-R from 809+/-116 to 749+/-47 ms, systolic blood pressure from 110+/-12 to 125+/-11 mmHg (P<0.05 for all)]. One week later systolic blood pressure was similar to values at sea level in all subjects, whereas R-R remained elevated in sea-level natives. The low-frequency power in R-R and systolic blood pressure increased in sea-level natives [R-R-LF from 47+/-8 to 65+/-10% (P<0.05), systolic blood pressure-LF from 1.7+/-0. 3 to 2.6+/-0.4 ln-mmHg2 (P<0.05)], but not in high-altitude natives (R-R-LF from 32+/-13 to 38+/-19%, systolic blood pressure-LF from 1. 9+/-0.5 to 1.7+/-0.8 ln-mmHg2). The R-R-HF decreased in sea-level natives but not in high-altitude natives, and no changes occurred in systolic blood pressure-HF. These changes remained evident 1 week later. Skin blood flow variability and its spectral components decreased markedly at high altitude in sea-level natives but showed no changes in high-altitude natives. Neck suction significantly increased the R-R- and systolic blood pressure-LF in all subjects at both sea level and high altitude.3. High altitude induces sympathetic activation in sea-level natives which is partially counteracted by active baroreflex. Despite long-term acclimatization at sea level, high-altitude natives also maintain active baroreflex at high altitude but with lower sympathetic activation, indicating a persisting high-altitude adaptation which may be genetic or due to baroreflex activity not completely lost by at least 1 year's sea-level residence.

Adult↗

Stress reduction for family caregivers: effects of adult day care use.

OBJECTIVES: This study reports the findings of an evaluation of the psychological benefits of use of adult day care by family caregivers assisting a relative with dementia. METHODS: The study used a quasi-experimental design in which caregivers in the treatment group used substantial amounts of services, whereas caregivers in a control group did not use day care at any point during the evaluation and only small amounts of other respite services. The evaluation was guided by the stress process model of caregiving which distinguishes between appraisals of primary stressors and well-being. RESULTS: Results after 3 months of day care use showed that the treatment group had significantly lower scores than the control group on two of the three measures of primary appraisals (overload and strain) and two of the three measures of well-being (depression and anger). Findings at one year showed that the treatment group had significantly lower scores on overload and depression than the control group. DISCUSSION: These results demonstrate that use of adult day care by caregivers of dementia patients results in lower levels of caregiving-related stress and better psychological well-being when compared to that of controls.

Aged↗

Gas tensions in cardiac lymph as a reflection of the interstitial space of the heart.

The purpose of this study was to determine the feasibility of measuring partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and pH in cardiac lymph and to evaluate the relationship of these parameters to comparable measurements in arterial and coronary sinus blood in the normal heart under various respiratory conditions. In four anesthetized open-chest dogs, the principal cardiac lymphatic as well as the femoral artery and coronary sinus were cannulated. Ventilation was varied by changing oxygen concentration, tidal volume, and respiratory rate. PO2, pCO2, and pH were measured in the cardiac lymph, arterial blood, and coronary sinus blood after each change in ventilation. For pH and pCO2, good correlations were observed between the arterial blood and cardiac lymph, arterial blood and coronary sinus blood, and coronary sinus blood and cardiac lymph. The correlation between the pO2 measured in the arterial blood and the pO2 measured in the cardiac lymph was not as strong, and this may have been related to difficulty achieving a steady state. Gas tensions (pO2, pCO2, and pH) can be measured in cardiac lymph and may provide a window to the interstitial compartment of the heart. This is an additional tool for the laboratory study of ischemia and other forms of heart disease.

Animals↗

Arginine vasopressin inhibition of cytochrome P450c17 and testosterone production in mouse Leydig cells.

The mechanism of arginine vasopressin (AVP) action in Leydig cells was investigated, and compared to the effects of phorbol-13-myristate-12-acetate (PMA) and interleukin-1 beta (IL-1 beta). Previous reports suggested that AVP inhibits Leydig cell testosterone production at the level of 17 alpha-hydroxylase/C17-lyase activity. The present study confirms and extends these observations, and contrasts the effects of AVP to IL-1. In all experiments, macrophage-depleted Leydig cells were isolated from mice and maintained in primary culture for 5 d prior to initiation of treatments. Leydig cells were treated with 8-Br-cAMP plus increasing concentrations of AVP or IL-1 beta. AVP caused a significant and dose-dependent inhibition of cAMP-stimulated testosterone production and P450c17 mRNA expression. IL-1 beta completely inhibited cAMP-stimulated testosterone production and P450c17 mRNA expression. PMA is a known activator of protein kinase C (PKC) and has been reported to inhibit Leydig cell steroidogenesis. Leydig cells express type V1 vasopressin receptors, which are coupled to PKC activation. The mechanism of IL-1 action in Leydig cells is not understood, but activation of the PKC pathway has been suggested for IL-1 action in other systems. Therefore, the effects of PMA on cAMP-stimulated steroidogenesis were compared to AVP and IL-1. Similar to the effects of AVP, PMA inhibited cAMP-stimulated testosterone production and P450c17 mRNA expression. To assess the possible involvement of PKC in AVP and IL-1 action in Leydig cells, the PKC inhibitor Calphostin C was tested. cAMP-stimulated testosterone production and P450c17 mRNA expression were significantly inhibited by 10 nM AVP (p < 0.05), and this inhibition was reversed by treatment with Calphostin C. Analogous experiments were performed to assess the role of PKC in IL-1 action. In contrast to the results for AVP, Calphostin C did not reverse the inhibitory effects of IL-1 on cAMP-stimulated P450c17 mRNA expression. To assess further PKC activation, myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation was analyzed. Only AVP and PMA, but not IL-1 beta, caused an increase in MARCKS phosphorylation. These results confirm that AVP and PMA activate PKC and indicate that IL-1 likely does not activate PKC in Leydig cells. The implications of AVP-mediated inhibition of steroidogenesis and potential role of MARCKS phosphorylation are discussed.

8-Bromo Cyclic Adenosine Monophosphate↗

The lymphatic drainage of the left ventricle in the Yucatan minipig.

The gross anatomy of the cardiac lymphatic system draining the left ventricle was studied in 15 Yucatan minipigs and 2 regular swine. The findings confirm that the drainage pathways are similar to those of man and dog. After a coloring marker is injected near the apex of the left ventricle, one or more lymphatics are seen to ascend towards the left atrial appendage. Where there is more than one ascending lymphatic, they typically join before or at the left atrial appendage. This principal lymphatic then passes beneath the appendage and travels behind (dorsal to) the pulmonary artery and aorta to the right side of the mediastinum. From here, the lymphatic passes cephalad along the left border of the superior vena cava to enter the cardiac lymph node between the superior vena cava and the trachea.

Animals↗