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Biomedical subjects

D Waters

Publications and source records attributed to D Waters.

At least 109 records · Page 6Linked to original sources
PubMed1993

Methylene blue inhibits the antithrombotic effect of nitroglycerin.

OBJECTIVES: The aim of this study was to examine whether cyclic guanosine monophosphate (GMP) may be involved in the antithrombotic action of nitroglycerin. BACKGROUND: Nitroglycerin has been shown to inhibit platelet function in vitro by stimulating prostacyclin or inhibiting thromboxane A2 production, or both. Nitroglycerin has also been shown to possess potent antithrombotic properties in vivo. However, the mechanism of this antithrombotic effect is unclear. METHODS: Nitroglycerin was infused to produce a 10% decrease in mean arterial pressure in 27 normal pigs by exposing their circulating arterial blood to porcine aortic media in an ex vivo perfusion chamber. Eight pigs received an infusion of nitroglycerin alone; eight received an infusion of methylene blue, a guanylate cyclase inhibitor, followed by nitroglycerin infusion and five pigs received an infusion of nitroglycerin followed by methylene blue and subsequent infusion of cyclic GMP. RESULTS: With nitroglycerin alone, quantitative autologous indium-111-labeled platelet deposition (x10(6) on the aortic media was decreased to 63.9 +/- 10.4% (p = 0.01) of the baseline control platelet deposition. Methylene blue given before nitroglycerin tended to increase platelet deposition relative to baseline and platelet deposition after nitroglycerin was 142 +/- 35% (p = NS) of baseline value. In pigs that received all three agents, nitroglycerin reduced platelet deposition to 42.3 +/- 12.2% of baseline value; this decrease was then attenuated by subsequent methylene blue infusion but was enhanced by cyclic GMP infusion to 16.4 +/- 3.8% of baseline value (p = 0.006 vs. baseline control and p = 0.02 versus methylene blue infusion). CONCLUSIONS: Guanylate cyclase inhibition with methylene blue abolishes the antithrombotic effect of nitroglycerin, which can be enhanced by cyclic GMP.

Animals↗
PubMed1993

The prevalence of antibodies to the human T lymphotropic virus (HTLV) in Ghana, West Africa.

We conducted a population-based serosurvey of urban areas and rural regions of southern Ghana, West Africa. Subjects (3763) of all ages were enrolled from 25 city and village sites and in studies of groups of special interest. "Positive" results were difficult to define because of a high frequency of results that were indeterminate on immunoblotting, the current standard for confirmation of HTLV-I. However, polymerase chain reaction results and HTLV type-specific discriminatory tests proved HTLV-I was present in Ghana. No HTLV-2 positivity was observed. By using strict criteria that considered indeterminate results as negative, the overall prevalence was found to be between 1 and 2% in all areas, with no difference by geographic location. Prevalence rose with age and was higher in adult women than men. However, in substudies of selected populations, we found HTLV prevalence among 124 persons with lymphomas and hematological malignancies was not different from that in the general population. Furthermore, the prevalence in prostitutes was similar to that in the general population and in pregnant women. HTLV-I is present in West Africa, but we were unable to associate HTLV-I seropositivity with malignancy or with prostitution.

Adolescent↗
PubMed1993

Effects of thrombocytopenia and shear rate on neutrophil and platelet deposition on endothelial and medial arterial surfaces.

Both platelets and neutrophils interact with the injured vessel wall and may contribute to thrombosis and vasospasm. The effect of platelets on neutrophil interactions with the vessel wall was studied in normal and thrombocytopenic pigs. 51Cr-labeled platelet deposition (x10(6)) and 111In-labeled neutrophil deposition (x10(3)) on undamaged aortic strips with intact endothelium or damaged aortic strips with exposed media were quantified in superfusion flow chambers before and after platelet depletion by specific rabbit antisera. Arterial blood was drawn at a constant flow rate through the superfusion chambers at 37 degrees C. Under basal conditions, platelets did not adhere to the uninjured vessel wall with intact endothelium, whereas neutrophil interaction with the endothelium was low and constant at shear rates of 427, 853, and 1280 s-1 and did not change significantly after thrombocytopenia. On exposed aortic media simulating deep arterial injury, platelet deposition increased over these shear rates from 14.0 +/- 3.4 to 37.5 +/- 12.0 (P < .05) to 68.0 +/- 9.0, respectively (P < .05). Similarly, neutrophil deposition on the media increased from 48.7 +/- 8.7 to 73.7 +/- 14.3 (P < .05) to 118.3 +/- 22.9, respectively (P < .05). Platelet deposition on the media did not occur after thrombocytopenia (80% reduction in platelet count); however, neutrophil deposition persisted, but was less intense and was now independent of shear rates (23.3 +/- 5.2 at 427 s-1, 18.7 +/- 3.2 at 853 s-1, and 24.1 +/- 3.9 at 1280 s-1; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prognostic significance of progression of coronary atherosclerosis.

BACKGROUND: Angiographic progression of coronary atherosclerosis is frequently observed in clinical practice and is used as an end point in clinical trials; however, its prognostic significance is unclear. METHODS AND RESULTS: Progression defined as an increase in diameter stenosis by > or = 15% of at least one coronary lesion was seen in 141 (42%) of 335 patients who underwent repeat coronary arteriography after a 2-year interval as part of clinical trial. Coronary lesions were measured quantitatively from comparable end-diastolic frames selected by a radiologist viewing each pair of films together. During a mean follow-up of 44 +/- 10 months after the second arteriogram, cardiac death occurred in 19 patients (5.7%), cardiac death or nonfatal infarction was seen in 40 cases (11.9%), and 90 patients (26.9%) underwent coronary revascularization. At least one end point event occurred in 112 of the 335 patients. Sixteen of the 19 cardiac deaths were in progressors, a relative risk of 7.3 (95% CI, 2.2-24.7; p < 0.001). The relative risk of cardiac death or nonfatal infarction for progressors was 2.3 (1.3-4.2, p = 0.009) and of any cardiac event was 1.7 (1.3-2.3, p < 0.001). A stepwise multivariable Cox regression model of time to event was used to assess the relative contribution of progression as a predictor of coronary events. Low ejection fraction (p = 0.001), progression (p = 0.001), and hypertension (p = 0.011) were retained as predictors of cardiac death. Angina and the number of diseased vessels were the strongest predictors of revascularization. CONCLUSIONS: Coronary progression is a strong, independent predictor of future coronary events, particularly cardiac death, and its use as a surrogate end point in clinical trials is justified.

Coronary Angiography↗
PubMed1993

Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina.

BACKGROUND: Antiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina; however, no definitive data exist on the relative clinical efficacy of the two drugs. METHODS AND RESULTS: Aspirin (325 mg bid) or heparin (5000-U intravenous bolus followed by a perfusion titrated to the APTT) were compared in a double-blind randomized trial of 484 patients in two cohorts enrolled sequentially. The study was initiated at admission to hospital at a mean of 8.3 +/- 7.8 hours after the last episode of pain. End points were assessed 5.7 +/- 3.3 days later, when the decision for long-term management was made. Myocardial infarction occurred in 2 (0.8%) of the 240 patients randomized to heparin and in 9 (3.7%) of the 244 randomized to aspirin (P = .035), an odds ratio of 0.22 and a risk difference of 2.9% (95% confidence limits, 0.3% to 5.6%) with heparin. The only death resulted from a myocardial infarction in an aspirin patient. Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infarction with heparin (P = .035) was independent of other baseline characteristics. CONCLUSIONS: This study documents that heparin prevents myocardial infarction better than aspirin during the acute phase of unstable angina.

Acute Disease↗
PubMed1993

Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events.

BACKGROUND: There is considerable evidence that remnants of triglyceride-rich lipoproteins may be particularly atherogenic. METHODS AND RESULTS: Levels of lipoprotein lipids and of apolipoprotein B in low-density lipoproteins were measured in 335 men and women enrolled in a study in which quantitative coronary angiography was carried out at 2-year intervals. Clinical events related to coronary disease occurred in 129 patients during the trial and in the subsequent follow-up period of 4 to 6 years. In multivariate analysis controlled for a number of nonlipid risk factors, high-density lipoprotein cholesterol was inversely related to the mean percentage increase in coronary artery stenosis in both men and women. Neither plasma triglycerides nor low-density lipoprotein cholesterol, triglycerides, or apolipoprotein B was related to change in stenosis, but a measure of remnants of triglyceride-rich lipoproteins, which included cholesterol in intermediate-density lipoproteins, was directly related to lesion progression. The same relations for these measures of plasma lipoprotein concentrations were found to hold for clinical events related to coronary artery atherosclerosis. CONCLUSIONS: In patients with established coronary heart disease, increased levels of remnants of triglyceride-rich lipoproteins and decreased levels of high-density lipoproteins appear to promote progression of coronary artery atherosclerosis, which in turn may lead to an untoward clinical event. No such relation could be shown for the level of components of low-density lipoproteins. These and other observations call for reevaluation of relations between particular species of lipoproteins containing apolipoprotein B and the pathogenesis of coronary artery atherosclerosis and coronary heart disease.

Adult↗
PubMed1993

Advantages and limitations of serial coronary arteriography for the assessment of progression and regression of coronary atherosclerosis. Implications for clinical trials.

BACKGROUND: Clinical trials with angiographic end points have been used to assess whether interventions influence the evolution of coronary atherosclerosis because sample size requirements are much smaller than for trials with hard clinical end points. Further studies of the variability of the computer-assisted quantitative measurement techniques used in such studies would be useful to establish better standardized criteria for defining significant change. METHODS AND RESULTS: In 21 patients who had two arteriograms 3-189 days apart, we assessed the reproducibility of repeat quantitative measurements of 54 target lesions under four conditions: 1) same film, same frame; 2) same film, different frame; 3) same view from films obtained within 1 month; and 4) same view from films 1-6 months apart. Quantitative measurements of 2,544 stenoses were also compared with an experienced radiologist's interpretation. The standard deviation of repeat measurements of minimum diameter from the same frame was very low (0.088 mm) but increased to 0.141 mm for measurements from different frames. It did not increase further for films within 1 month but increased to 0.197 mm for films 1-6 months apart. Diameter stenosis measurements were somewhat more variable. Measurement variability for minimum diameter was independent of vessel size and stenosis severity. Experienced radiologists did not systematically overestimate or underestimate lesion severity except for mild overestimation (mean 3.3%) for stenoses > or = 70%. However, the variability between visual and quantitative measurements was two to three times higher than the variability of paired quantitative measurements from the same frame. CONCLUSIONS: Changes of 0.4 mm or more for minimum diameter and 15% or more for stenosis diameter (e.g., 30-45%), measured quantitatively, are recommended as criteria to define progression and regression. Approaches to data analysis for coronary arteriographic trials are discussed.

Clinical Trials as Topic↗
PubMed1992

Reactivation of unstable angina after the discontinuation of heparin.

BACKGROUND: Heparin is an effective, widely used treatment for unstable angina. Among patients enrolled in a double-blind, randomized, placebo-controlled trial comparing intravenous heparin, aspirin, both treatments, and neither during the acute phase of unstable angina, we encountered patients in whom unstable angina was reactivated after heparin was discontinued. METHODS: The study population included 403 of the original 479 patients in the trial who had completed six days of blinded therapy without refractory angina or myocardial infarction. After the discontinuation of therapy, clinical events, including reactivation of unstable angina and myocardial infarction occurring within 96 hours after hospitalization, were closely monitored. RESULTS: Early reactivation occurred in 14 of the 107 patients who received heparin alone, as compared with only 5 patients in each of the other three study groups (P less than 0.01). These reactivations required urgent intervention (thrombolysis, angioplasty, or coronary-bypass surgery) in 11 patients treated with heparin alone, but in only 2 patients in the other groups combined (P less than 0.01). Four of the six patients who had a myocardial infarction during a reactivation of their disease were in the heparin group. Reactivations in this group occurred in a cluster a mean (+/- SD) of 9.5 +/- 5 hours after the discontinuation of the study drug but were randomly distributed over the initial 96 hours in the other three groups. CONCLUSIONS: Although heparin is beneficial in treating unstable angina, the disease process may be reactivated within hours of the discontinuation of this drug. Concomitant therapy with aspirin may prevent this withdrawal phenomenon.

Acute Disease↗
PubMed1992

Preoperative coronary artery disease risk stratification based on dipyridamole imaging and a simple three-step, three-segment model for patients undergoing noncardiac vascular surgery or major general surgery.

A 3-step, 3-segment scintigraphic model was developed to improve the accuracy of dipyridamole-thallium imaging for preoperative cardiac risk assessment and to simplify the prognostic interpretation of the images. The model was developed in a pilot study of 60 patients and validated in a group of 355 patients referred for vascular and major general surgery. Study end points included myocardial infarction and cardiac death. Step 1: The postoperative cardiac event rate was 1.3% in 225 patients with normal anterior, inferio- and posterolateral segment perfusion and without transient left ventricular dipyridamole-induced cavitary dilation. Step 2: The physiologic rationale for step 2 consists of identifying patients who are most likely to have left main, 3-vessel or high-risk 2-vessel coronary artery disease or a significant amount of jeopardized myocardium in the territory of a critical coronary stenosis. Of 29 patients with either reversible defects of all 3 segments, transient cavitary dilation, or at least 1 severe grade 3/3 reversible defect, 52% (15 of 29) sustained a postoperative cardiac event. Step 3: The remaining 101 patients were stratified according to age greater than 70 years (p = 0.01), presence of diabetes (p = 0.0004) and the number of segments displaying reversible defects (1 or 2) with cardiac event rates ranging from 5 to 36%. The 3-step, 3-segment model is a useful alternative to the conventional interpretation of dipyridamole myocardial perfusion images for the purpose of quick and efficient preoperative risk stratification based on the rationale of correlating surgical risk with the amount of potentially ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effect of diltiazem slow-release formulation on silent myocardial ischemia in stable coronary artery disease. The Canadian Multicenter Diltiazem Study Group.

Silent myocardial ischemia is associated with adverse outcome in several subsets of coronary artery disease patients. This article presents results of a placebo-controlled, randomized, double-blind study of the effects of sustained-release diltiazem (180 mg twice daily) on ischemic episodes in 60 patients with documented coronary artery disease. The mean age of the study population was 60 years and 93% were male. The mean number of episodes of silent ischemia per patient was 5.6 (placebo) and 2.8 (diltiazem), a 50% reduction (p less than 0.0001). Duration of ST-segment depression was 119 minutes (placebo) and 67 minutes (diltiazem), a 44% reduction (p less than 0.001). This study demonstrates that sustained-release diltiazem can significantly reduce the frequency and total duration of silent ischemic episodes.

Adult↗
PubMed1992

Measuring progression and regression of coronary atherosclerosis in clinical trials: problems and progress.

Interventions that may influence the evolution of coronary atherosclerosis can be evaluated more rapidly and efficiently in clinical trials with angiographic endpoints as opposed to using coronary events as endpoints. Quantitative coronary arteriography provides precise and reproducible measurements of coronary artery dimensions for this purpose. The variability of 2 quantitative systems was assessed in 54 lesions under 4 different conditions: same film, same frame; same film, same view; different frame; same view from different films obtained within one month; and same view from different films obtained one to 6 months apart. With the Cardiovascular Angiographic Analysis System (CAAS), variability of repeat measurement of minimum diameter, expressed as 1 standard deviation of the mean, increased from 0.088 mm (same frame) to 0.197 mm (films 1 to 6 months apart) as conditions decreased from optimal to those encountered in clinical studies. With the Cardiovascular Measurement System (CMS), 1 standard deviation for repeat measurements of minimum diameter increased from 0.087 mm (same frame to 0.240 mm (films one to 6 months apart). The differences between the two systems for measurements of minimum diameter were not statistically significant and CMS tracked the arterial edge more meticulously than did CAAS. A change in minimum diameter greater than or equal to 0.4 mm for CAAS or greater than or equal to 0.48 mm for CMS is more than 2 standard deviations of the mid-term variability and therefore represents a true change, either progression or regression, with greater than 95% probability. Quantitative coronary arteriography is an essential tool in clinical trials to assess the effect of an intervention upon the evolution of coronary atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗
PubMed1992

Prognostic implications of a negative dipyridamole-thallium scan: results in 360 patients.

PATIENTS AND METHODS: A total of 360 patients with either normal perfusion (314) or fixed defects (46) on dipyridamole-thallium scans were followed over an average period of 16 months. Of the 360 patients, 194 subsequently underwent major noncardiac surgery. RESULTS: There were a total of eight cardiac events including two postoperative complications (one fatal and one nonfatal myocardial infarction) and six cardiac events during long-term follow-up (one sudden death and five nonfatal infarctions). During the follow-up period, three patients underwent coronary artery bypass surgery. The low cardiac event rate could not be explained by a low pretest likelihood of coronary artery disease: 77% of the 360 patients had either typical angina pectoris, a previous myocardial infarction, or peripheral vascular disease, which is associated with a high prevalence of coronary artery disease. CONCLUSIONS: In patients with a high pretest likelihood of coronary artery disease, the absence of thallium redistribution on a dipyridamole-thallium scan denotes a very low (1%) cardiac risk for major noncardiac surgery as well as low long-term cardiac mortality (0.3%) and morbidity (1.4%) rates. The coronary death rate is comparable to that of patients with minimal (less than 50%) coronary stenoses.

Clinical Protocols↗
PubMed1992

Impacts of afforestation on water quality trends in two catchments in mid-Wales.

The impact of afforestation on stream-water chemistry for two catchments in central Wales is investigated. Trends in water chemistry are evaluated with forest age progressing at 8-15 years and 20-27 years. To assess the possible exacerbating effect of afforestation on surface-water acidification two moorland catchments are used as controls. Absolute differences in inter-catchment streamwater chemistry are evident. Differences in acidity between the moorland and the young forest site reflect site preparation and modifications to water pathways. Differences in the observed present day chemistry between the young and old forest result from past interactions between deposition changes during forest development. An estimate of the future impact of forest growth was attained from model predictions. The model was calibrated to present day stream-water chemistry and incorporates, cation uptake, evapotranspiration/ concentration effect and increased scavenging of occult and dry deposition. Predictions suggest the pH will decline to 5.3 when the young forest progresses to 20 years of age, which is still much higher than the pH recorded at the older forest site at the age of 20 years.

Journal Article↗
PubMed1992

Symptom-limited versus low level exercise testing before hospital discharge after myocardial infarction.

OBJECTIVE: This study was undertaken to compare a low level and a symptom-limited test performed before hospital discharge after an uncomplicated myocardial infarction. BACKGROUND: Exercise testing after myocardial infarction provides useful prognostic information. Usually either a low level test is performed before hospital discharge or a symptom-limited test is performed at 3 weeks. METHODS: The study group comprised 202 patients with an uncomplicated myocardial infarction; 58 patients had a non-Q wave infarction and 115 patients had received thrombolytic therapy. Both a low level and a symptom-limited exercise test were performed in 200 of the 202 study patients in randomized order on consecutive days, a mean of 7.4 +/- 2.3 days after infarction. RESULTS: The symptom-limited test required a considerably greater effort than the low level test: exercise duration was 554 +/- 209 versus 389 +/- 125 s (p less than 0.0001), and peak work load was 5.7 +/- 1.8 versus 4.2 +/- 1.1 METs (p less than 0.0001). The peak heart rate was higher during the symptom-limited test (121 +/- 20 vs. 108 +/- 14 beats/min, p less than 0.0001), as was the rate-pressure product. The number of patients who developed ST segment depression greater than or equal to 1 mm increased from 56 during the low level test to 89 during the symptom-limited test (p less than 0.0001). ST segment depression greater than or equal to 2 mm occurred in 22 patients during the low level test and in 41 patients during the symptom-limited test, an 86% increase (p less than 0.0001). The number of patients with either angina or ST depression greater than or equal to 1 mm increased from 66 to 105 (p less than 0.0001) with the symptom-limited test. Exercise test results were similar for patients with a Q wave or a non-Q wave infarction. Exercise duration was longer and exercise-induced ST depression less frequent in patients who had received thrombolytic therapy. CONCLUSIONS: A symptom-limited exercise test performed before hospital discharge after uncomplicated myocardial infarction provides a significantly greater cardiovascular stress than does a low level test and is associated with an ischemic response nearly twice as frequently. The prognostic significance of a positive response at higher work loads has not been defined.

Angina Pectoris↗
PubMed1992

Nucleotide sequence analysis of an HTLV-I isolate from a Chilean patient with HAM/TSP.

Isolates of HTLV-I have been characterized from a number of different regions of the world; however, there has not been a nucleotide sequence analysis of an HTLV-I isolate from a South American country. Reported here is an individual from Chile identified with the HTLV-I-associated neurological disease HAM/TSP. The sera and the nucleic acid sequence of the HTLV-I present in peripheral blood lymphocytes from this Chilean HAM/TSP patient over a two year period are characterized. During this time, the patient's condition grew progressively worse. While the serological profile of this patient was unremarkable in comparison with other HAM/TSP patients previously described, nucleic acid sequence analysis identified two nucleotide positions which contained nucleotides unique to this Chilean isolate. The nucleotide sequence analysis also indicates that the Chilean HTLV-I isolate is more closely related to Caribbean and Japanese isolates of HTLV-I than to the African and U.S. isolates described so far.

Base Sequence↗
PubMed1992

Preoperative and long-term cardiac risk assessment. Predictive value of 23 clinical descriptors, 7 multivariate scoring systems, and quantitative dipyridamole imaging in 360 patients.

A total of 360 patients underwent preoperative cardiac risk assessment using 23 clinical parameters, seven multivariate clinical scoring systems, and quantitative dipyridamole-thallium imaging to predict postoperative and long-term myocardial infarction and cardiac death after noncardiac surgery. There were 30 postoperative and an additional 13 cumulative long-term cardiac events after an average follow-up of 15 months. Clinical descriptors were not useful in predicting the outcome of individual patients. The postoperative and long-term cardiac event rates were 1% and 3.5%, respectively, in patients with normal scans or fixed perfusion defects, and 17.5% and 22% in patients with reversible defects. Using quantitative indices reflecting the amount of jeopardized myocardium, patients could be stratified by dipyridamole imaging into multiple scintigraphic subsets, with corresponding postoperative and 1-year coronary morbidity and mortality rates ranging from 0.5% to 100% (p = 0.0001). Thus, postoperative and long-term cardiac events cannot be predicted clinically, whereas quantitative dipyridamole imaging accurately identifies high-risk patients who require preoperative coronary angiography.

Aged↗
PubMed1992

Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion.

BACKGROUND: Coronary angiography in acute myocardial infarction has revealed complicated atherosclerotic plaque and a high rate of thrombotic occlusion. However, the characteristics of lesions at high risk of subsequent occlusion are not well known. METHODS AND RESULTS: In the present study, the qualitative and quantitative angiographic features of 38 coronary artery lesions that occluded within 3 years to cause an acute myocardial infarction were compared with 64 control segments from the same patients that did not occlude. Compared with control lesions, the lesions that occluded were more likely to have a division branch originating within the stenosis (76% versus 52%, p less than 0.05). The percent lumen diameter reduction was more severe (47.5 +/- 17.8% versus 41 +/- 12.5%, p less than 0.05) and the inflow (21 +/- 10 degrees versus 16 +/- 7 degrees, p less than 0.05) and outflow (20 +/- 10 degrees versus 16 +/- 8 degrees, p less than 0.05) angles of the stenosis were steeper. Time to myocardial infarction after the angiogram interacted with the importance of these features (p less than 0.02). Thus, paired analysis of the lesions that occluded within 3 months and of the most severe control lesion from each patient showed percent lumen diameter reduction of 62.1 +/- 11.5% and 46.4 +/- 11.4%, respectively (p less than 0.001). The length of the stenosis, its asymmetry, and the irregularity of the contours did not help differentiate occlusive from control segments. CONCLUSIONS: Coronary artery lesions at high risk of thrombotic occlusion share common characteristics that favor higher shear stress and flow separation.

Adult↗