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Biomedical subjects

D Waters

Publications and source records attributed to D Waters.

At least 91 records · Page 5Linked to original sources
PubMed1995

Delayed diagnosis of cystic fibrosis in children with a rare genotype (delta F508/R117H).

OBJECTIVE: In neonatal screening for cystic fibrosis (CF), infants recognised as delta F508 heterozygotes require a sweat test to confirm the diagnosis. However, compound heterozygotes with delta F508 and the R117H mutation are known to have non-diagnostic sweat chlorides (< 60 mmol/L) at an early age. As genotyping for rare mutations is not readily available in Australia, there is a need to determine whether quantitative pancreatic stimulation tests could facilitate the diagnosis of CF in three infants with the delta F508/R117H mutation. METHODOLOGY: Formal sweat testing, genotyping and pancreatic stimulation tests were performed in three subjects heterozygous for delta F508 who initially had non-diagnostic sweat chloride results (40-60 mmol/L) but presented later with persisting chest symptoms and/or signs consistent with CF. RESULTS: All three patients were shown to have the delta F508/R117H genotype with initial sweat chloride results ranging from 40 to 58 mmol/L. Pancreatic stimulation tests demonstrated reduced enzyme secretion in two and decreased fluid, bicarbonate and chloride secretion in all three patients. CONCLUSIONS: In infants recognized as delta F508 heterozygotes by the newborn screening programme, the presence of an equivocal sweat chloride does not exclude the diagnosis of CF. If such patients with an initially equivocal sweat chloride subsequently develop symptoms suggestive of CF and have a persisting non-diagnostic sweat chloride then the diagnosis of CF can be confirmed by more extensive genotyping if available or by pancreatic stimulation testing.

Child, Preschool↗
PubMed1995

Feasibility of radiofrequency powered, thermal balloon ablation of atrioventricular bypass tracts via the coronary sinus: in vivo canine studies.

Radiofrequency catheter ablation of left-sided accessory pathways is technically demanding and usually requires left heart catheterization. The feasibility of creating lesions from within the coronary sinus of sufficient size to ablate accessory pathways in humans using a thermal balloon catheter was studied in 20 dogs. In group 1 (n = 14), 17 thermal inflations were performed in 12 dogs at either 70 degrees, 80 degrees, or 90 degrees C each for 30 or 60 seconds (in 2 dogs two non-thermal control inflations were performed). Animals were sacrificed 6.3 +/- 1.6 days later. In group 2 (n = 6), seven thermal inflations were performed at 90 degrees C each for 180, 300, or 360 seconds. Group 2 animals received antiplatelet and anticoagulant therapy for 1 week and were sacrificed at 13 +/- 10.7 days. In both groups, hemodynamic, angiographic, and electrocardiographic studies were performed at baseline, 1 hour after inflation, and prior to sacrifice. All dogs remained clinically stable throughout the procedure and no complications were attributed to the effect of thermal inflation. Thermal lesions measured 14.4 +/- 4.4 mm in length and extended from the coronary sinus intima to a mean depth of 2.9 +/- 1.2 mm (range 1.4-6.5 mm). Group 2 lesions were significantly deeper than group 1 lesions (P = 0.03). Of the 24 thermal lesions created, atrial necrosis was present in 23 and ventricular necrosis in 11. In all lesions there was some degree of either atrial necrosis, ventricular necrosis, or both. A variable degree of coronary sinus thrombus was present in 18 dogs without clinical sequelae. It is concluded that radiofrequency balloon heating via the coronary sinus can create thermal lesions in the atrioventricular sulcus of dogs that may be of sufficient size to ablate accessory left-sided pathways in humans.

Animals↗
PubMed1994

Efficacy of high dose intravenous heparin for treatment of left ventricular thrombi with high embolic risk.

OBJECTIVES: This study was performed to assess the efficacy of high dose intravenous heparin to treat mobile or protruding left ventricular thrombi as detected by serial echocardiography. BACKGROUND: The presence of mobile and protruding left ventricular thrombi greatly increases the risk of arterial embolization, yet optimal therapy, be it thrombolysis, anticoagulation or surgical removal, has not been defined. METHODS: Full dose heparin, 31,291 +/- 7,980 (mean +/- SD) IU/day, to prolong partial thromboplastin time to at least twice normal, was administered intravenously to 23 consecutive patients with 25 mobile and protruding thrombi. Patients were prospectively evaluated for hemorrhagic complications and embolic events during therapy. The presence or absence of thrombi and their size and characteristics were assessed by serial echocardiography. RESULTS: In all 23 patients left ventricular thrombi decreased in size, with disappearance of the high risk features. The duration of high dose heparin infusion was 7 to 22 days (mean 14 +/- 4). Thrombus size was reduced from 3.9 +/- 2.6 to 0.16 +/- 0.38 cm2, and thrombus disappeared entirely in 19 (83%) of 23 patients. No embolic events were detected during treatment, and the only complication was an upper gastrointestinal hemorrhage that was successfully treated medically. CONCLUSION: High dose intravenous heparin is a highly effective and safe treatment for completely resolving left ventricular thrombi with high risk features for embolization. Most such thrombi disappear completely within 1 to 3 weeks of this treatment without embolic or hemorrhagic complications.

Echocardiography↗
PubMed1994

Platelet aggregation, coronary artery disease progression and future coronary events.

The platelet-aggregatory response, platelet-release factors and markers of thrombin generation in vivo were studied prospectively in 53 patients participating in a randomized clinical trial evaluating the influence of nicardipine on the progression of coronary atherosclerosis. Coronary lesions were measured quantitatively and progression was defined as a decrease in minimum diameter by > or = 0.4 mm. At repeat angiography 24 months after study entry, 20 of the 53 patients had progression of 28 coronary narrowings. Only thrombin-induced enhanced platelet aggregation differentiated patients with from those without coronary disease progression, with an estimated odds ratio of 2.49 (95% confidence interval 1.10 to 5.66). The aggregatory response to adenosine diphosphate, collagen, epinephrine and platelet-activating factor were not different in the 2 groups of patients, nor were measurements of platelet factor 4, beta-thromboglobulin, thromboxane B2, 6-keto-prostaglandin F1 alpha and fibrinopeptide A. During 46.8 months of follow-up after repeat angiography, coronary events occurred in 11 of the 20 with and 6 of the 33 without progression (difference 37%, p = 0.013, confidence interval 11 to 63%). Those with coronary disease progression and an enhanced thrombin-induced platelet aggregation had a worse prognosis than those with no disease progression and a low thrombin-induced platelet aggregation. Thus, patients with coronary disease progression and future coronary events have an enhanced thrombin-induced platelet aggregation. This platelet abnormality may be a marker of increased risk and may play a causative role in the development of coronary events.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

A new look at coronary angiograms: plaque morphology as a help to diagnosis and to evaluate outcome.

Characterization of plaque morphology can provide useful information beyond those generally yielded by the more traditional methods of interpretation of coronary angiograms based on assessment of severity of stenoses and number of diseased vessels. Focus on the culprit coronary lesion in acute myocardial infarction and in unstable angina allows recognition of the complex plaque and of presence of endoluminal thrombi that are closely associated to the mechanisms of the disease. Response to treatment in these clinical situations, and the healing process can be assessed by repeated opacifications of the lesion. The presence of a residual thrombus is associated with a worse clinical outcome and also a higher risk of complication if coronary angioplasty is performed. The prognostic information derived from the morphologic analysis extends to the chronic phase of the disease. The extent score of disease, defined as the sum of coronary artery segments showing a narrowing of any severity marks more severe disease and predicts future progression. Severity of stenosis is also a predictor. More severe lesions will occlude more frequently but most often without clinical consequences. Occlusion of less severe stenosis, on the other hand, leads to acute myocardial infarction or to the other manifestations of acute coronary syndromes. Other morphologic features are also associated with a higher risk of myocardial infarction. These include a geometry favoring blood flow separation and turbulence such as acute inflow and outflow angles of the stenosis and presence of a division within its vicinity. This new look at coronary angiograms may help orient therapy. Patients with angina and a significant stenosis will profit from a corrective intervention. Others with a high extent score should receive a comprehensive program for control of risk factors. Patients with a lesion of borderline significance at risk of activation should be closely monitored, and when clinical symptoms evolve, receive more intensive antithrombotic therapy. Quantification of the morphologic characteristics of the plaque, coupled to new techniques for endovascular imaging should lead in the future to better diagnostic and better risk stratification.

Angina, Unstable↗
PubMed1994

Calcium channel blockers and coronary atherosclerosis: from the rabbit to the real world.

Many calcium channel blockers have been shown to retard the development of atherosclerosis in cholesterol-fed rabbits. The mechanisms that may contribute to this effect include stimulation of cholesteryl ester hydrolase activity in smooth muscle cells, amelioration of hypercholesterolemic-induced endothelial dysfunction, or inhibition of smooth muscle cell proliferation and migration. The effect of calcium channel blockers on the evolution of coronary atherosclerosis in humans has been assessed in three clinical trials. In the Montreal Heart Institute trial, nicardipine did not influence the overall rate of progression and regression; however, patients treated with nicardipine experienced significantly less progression of minimal lesions, defined as stenoses of less than or equal to 20% severity. In the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT), nifedipine had no effect on overall progression and regression but, by one method of analysis, reduced the rate of appearance of new coronary lesions. In a preliminary report, diltiazem prevented the development of coronary atherosclerosis in heart transplant recipients. These studies indicate that calcium channel blockers retard the development of early atherosclerosis not only in animal models but also in human coronary arteries. Other studies recently completed or now under way will help to clarify the clinical role of calcium channel blockers in antiatherosclerotic therapy.

Animals↗
PubMed1994

Development of a 10-day chorioallantoic membrane vascular assay as an alternative to the Draize rabbit eye irritation test.

The chorioallantoic membrane (CAM) of a fertilized hen's egg has been studied extensively as a promising alternative model for predicting eye irritation potential. The specific methodology used with this model has varied among investigators but the basic premise of applying test material to the membrane surface and evaluating changes in the vasculature is relatively consistent. The CAM vascular assay (CAMVA) has shown high correlation with in vivo rabbit eye irritation data. This method uses the CAM of a 14-day-old egg and the response at 30 min after treatment as the endpoint. The primary CAM methods being evaluated in Europe use 9-10-day-old eggs because older eggs are considered 'live animals'; the possibility of using 10-day-old eggs to make the method more globally acceptable as a non-animal test was therefore investigated. By keeping the original CAMVA dosing and evaluation procedures the same, and only altering the age of the eggs from 14-day to 10-day, the results were found to be nearly identical for the two methods and both produce equivalent correlations to the in vivo eye irritation test results. Maintaining the original CAMVA methodology but using a younger egg, therefore, provides a good alternative method for predicting eye irritation potential that is more globally acceptable as a non-animal test.

Allantois↗
PubMed1994

Localized intramural drug delivery during balloon angioplasty using hydrogel-coated balloons and pressure-augmented diffusion.

OBJECTIVES: This study was designed to assess the feasibility of using hydrogel-coated balloons to deliver biologically active agents to the blood vessel wall. BACKGROUND: The local intramural delivery of therapeutic agents during balloon angioplasty has been proposed as an adjunctive technique for preventing early intracoronary thrombosis and late restenosis. METHODS: To assess the efficacy of delivery and depth of penetration in vitro, local delivery of horseradish peroxidase was performed in 40 porcine peripheral arteries, and delivery of fluoresceinated heparin was performed in 20 porcine peripheral arteries and 7 human atheromatous arteries. To determine the persistence of these agents in the vessel wall in vivo, horseradish peroxidase was delivered to 18 porcine peripheral arteries that were harvested at intervals of 45 min to 48 h. Fluoresceinated heparin was delivered to 22 porcine peripheral arteries, 14 with the use of a protective sleeve, harvested at intervals of 30 s to 24 h. RESULTS: In vitro agent delivery was successful in all specimens. The depth of penetration of horseradish peroxidase was directly related to both balloon pressure (p < 0.04) and duration of inflation (p < 0.01). In vivo peroxidase staining was evident at 45 and 90 min but not thereafter. With the use of a protective sleeve, heparin was present in all arteries harvested at 30 s, with marked dissipation at 1 and 24 h. Without a sleeve, no fluorescein staining was detected in any artery. With both agents, delivery occurred consistently over broad regions of the vessel wall that were free of architectural disruption. CONCLUSIONS: Hydrogel-coated balloons can deliver biologically active agents to the vessel wall without gross tissue disruption and may provide an atraumatic method for the local delivery of therapeutic agents during balloon angioplasty.

Angioplasty, Balloon↗
PubMed1994

Viral variability and serum antibody response in a laboratory worker infected with HIV type 1 (HTLV type IIIB).

Molecular clones of HIV-1 were obtained from isolates cultured from peripheral blood mononuclear cells (PBMCs) and directly from uncultured PBMCs from a laboratory worker accidentally infected with the HIV-1 laboratory strain, HIV-1(HTLV-IIIB). Envelope sequences corresponding to the first 752 amino acids of HIV-1(HTLV-IIIB) clone BH10 were obtained from clones of cultured virus and sequenced. Three env clones obtained shortly after infection differed among themselves at only seven nucleotide positions, resulting in one amino acid substitution and one frameshift mutation. These envelope sequences were as similar to the envelope sequences of various IIIB clones as the latter were to each other. env divergence increased over the course of infection. However, the overall diversity in env clones obtained two or more years after infection was still comparable to that among IIIB env clones from the original IIIB culture. Multiple clones of partial env gene sequences containing the V3 loop were also obtained directly from uncultured PBMCs by polymerase chain reaction amplification. The env sequences of these clones were generally similar to those of the cultured viruses. Within the V3 region, the earliest isolates retained the sequence of the HXB2 clone from IIIB. Clones obtained later showed a progressive divergence in V3. An A-to-T substitution within the GPGRAF sequence at the tip of the V3 loop was observed within 1 year after infection, and this mutation predominated in all subsequent isolates. Antibodies against the V3 loops of IIIB and divergent 1987 and 1990 LW isolates appeared simultaneously in laboratory worker serum and persisted with no significant differences in titer. Furthermore, neutralization studies with autologous sequential sera suggested selection for the A-to-T change in V3 was not due to V3-directed antibodies. These results demonstrate a surprising homogeneity among env sequences of HIV-1 from an infected laboratory worker, perhaps because the initial infection originated from a relatively homogeneous population of tissue culture-adapted virus.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on eIF-4 gamma.

Many picornaviruses cause a dramatic decrease in the translation of cellular mRNAs in the infected cell, without affecting the translation of their own RNA. Specific proteolysis of protein synthesis initiation factor eIF-4 gamma occurs during infection with rhinoviruses, enteroviruses, and aphthoviruses, apparently leading to an inability of the ribosomes to bind capped mRNAs. Cleavage of eIF-4 gamma in human rhinoviruses and enteroviruses is carried out by the viral 2A proteinase; in aphthoviruses (i.e., foot-and-mouth disease viruses), the leader proteinase is responsible for this reaction. We describe here the purification to homogeneity of the Lb form of the leader proteinase expressed in Escherichia coli. The primary cleavage products of eIF-4 gamma obtained in vitro with purified leader or 2A proteinase are electrophoretically indistinguishable from those found during infection in vivo. However, additional proteolysis products of eIF-4 gamma are observed with the leader proteinase and the human rhinovirus type 2 2A proteinase in vitro. The cleavage site of the leader proteinase in eIF-4 gamma from rabbit reticulocyte was determined by sequencing the purified C-terminal cleavage product by automated Edman degradation. The cleavage site is between Gly-479 and Arg-480 and thus differs from that of rhinovirus and enterovirus 2A proteinases, which cleave between Arg-486 and Gly-487.

Amino Acid Sequence↗
PubMed1994

Endothelium-derived nitric oxide attenuates neutrophil adhesion to endothelium under arterial flow conditions.

Nitric oxide (NO) synthesized from cultured endothelial cells inhibits platelet aggregation and adhesion to subendothelial extracellular matrix and may contribute to the thromboresistance of the endothelium. NO has also been shown to inhibit neutrophil aggregation and adherence to postcapillary venules. Whether NO derived from the intact endothelium of an arterial wall can influence platelet and neutrophil adhesion under whole-blood arterial flow conditions was evaluated in this study. Porcine aortic segments with intact endothelium were exposed to flowing porcine arterial blood for 5 minutes at a shear rate of 424 sec-1. Pretreatment of the endothelium with the physiological precursor of NO, L-arginine (2 mmol/L), reduced 111In-labeled neutrophil adhesion by 32% from 10.2 +/- 1.6 to 6.9 +/- 1.3 x 10(3)/cm2 (P < .05), relative to control. This effect was reversed by the inhibitor of NO synthesis, N omega-nitro-L-arginine methyl ester (L-NAME, 5 mmol/L) (8.2 +/- 3.0 versus 8.6 +/- 3.2 x 10(3)/cm2 for control; P = NS). Pretreatment of the endothelium with D-arginine (2 mmol/L) did not influence neutrophil adhesion (8.7 +/- 2.0 versus 8.6 +/- 2.0 x 10(3)/cm2 for control; P = NS). The intact endothelium, which is normally thromboresistant, shows a low basal level of 51Cr activity, corresponding to a platelet adhesion less than 0.5 x 10(6)/cm2, and this thromboresistance was not significantly influenced by L-arginine. These results indicate that NO derived from an intact arterial endothelium under whole-blood arterial flow conditions may be an important modulator of neutrophil interaction with the intact endothelium.

Animals↗
PubMed1994

Oral verapamil inhibits platelet thrombus formation in humans.

BACKGROUND: Calcium antagonists such as verapamil are potent coronary and systemic vasodilators that are used in the treatment of coronary disease. They have also been shown to inhibit platelet aggregation in vitro, but whether they have beneficial antithrombotic effects in humans is unclear, and whether they can potentiate the antithrombotic effects of aspirin is unknown. METHODS AND RESULTS: Platelet thrombus formation and whole blood platelet aggregation were measured in 18 stable coronary patients on three separate occasions: at baseline when receiving no active medications, after 7 days of receiving oral verapamil SR (240 mg/d), and after 7 days of receiving a combination of oral verapamil SR and aspirin (325 mg/d). Thrombus formation on porcine aortic media that were placed into cylindrical flow chambers and exposed to flowing antecubital venous blood for 3 minutes was assessed morphometrically at a shear rate of 2546 s-1, which is typical of arterial flow at sites of stenoses. Thrombus formation under basal conditions was 7.0 +/- 1.6 microns 2, and this was decreased to 3.1 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil SR and to 2.6 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil and aspirin. Whole blood platelet aggregation levels in response to 0.050 and 0.075 U of thrombin at baseline were 10.8 +/- 1.0 and 11.9 +/- 1.0 omega; aggregation was inhibited after 7 days of treatment with verapamil to 6.5 +/- 1.1 and 7.8 +/- 0.9 omega (P < .05 versus baseline) and after 7 days of treatment with verapamil and aspirin to 6.1 +/- 1.1 and 7.2 +/- 1.0 omega (P < .05), respectively. CONCLUSIONS: The present study demonstrates that part of the benefit of verapamil in ischemic heart disease may occur by inhibition of platelet aggregation and thrombus formation. This beneficial antithrombotic effect may be important in preventing acute coronary ischemic events resulting from thrombus formation at sites of plaque rupture.

Administration, Oral↗
PubMed1994

Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined. METHODS AND RESULTS: To address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after 2 years. In 299 patients (90%), 3858 coronary segments containing 2309 stenoses were measured blindly on pairs of films with an automated computerized quantitative system. Total and LDL cholesterol decreased by 21 +/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but changed by < 2% in placebo patients. The primary end point, coronary change score, defined as the per-patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01). Progression (a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm) with no regression at other sites occurred in 48 of 146 lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New coronary lesions developed in 23 lovastatin and 49 placebo patients (P = .001). The beneficial effect of treatment was most pronounced in the more numerous, milder lesions and in patients whose baseline total or LDL cholesterol levels were above the group median. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and inhibits the development of new coronary lesions.

Canada↗
PubMed1993

Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus.

The rate-limiting step of eukaryotic protein synthesis is the binding of mRNA to the 40 S ribosomal subunit, a step which is catalyzed by initiation factors of the eIF-4 (eukaryotic initiation factor 4) group: eIF-4A, eIF-4B, eIF-4E, and eIF-4 gamma. Infection of cells with picornaviruses of the rhino- and enterovirus groups causes a shut-off in translation of cellular mRNAs but permits viral RNA translation to proceed. This change in translational specificity is thought to be mediated by proteolytic cleavage of eIF-4 gamma, which is catalyzed, directly or indirectly, by the picornaviral 2A protease. In this report we have used highly purified recombinant 2A protease from either human Coxsackievirus serotype B4 or rhinovirus serotype 2 to cleave eIF-4 gamma in vitro in the eIF-4 complex purified from rabbit reticulocytes. Neither the rate of cleavage nor fragment sizes were affected by addition of eIF-3. The NH2- and COOH-terminal fragments of eIF-4 gamma were separated by reverse phase HPLC and identified with specific antibodies, and the NH2-terminal sequence of the COOH-terminal fragment was determined by automated Edman degradation. The cleavage site for both proteases is 479GRPALSSR decreases GPPRGGPG494 in rabbit eIF-4 gamma, corresponding to 478GRTTLSTR decreases GPPRGGPG493 in human eIF-4 gamma.

Amino Acid Sequence↗
PubMed1993

A dose-response study of clentiazem, a chloro-derivative of diltiazem, in patients with stable angina. CAMCAT Study Group.

OBJECTIVES: The efficacy and safety of clentiazem were assessed in 199 patients with stable angina in a dose-ranging, placebo-controlled, double-blind, parallel design study. BACKGROUND: To date, this is the first large efficacy and safety study of clentiazem in patients with stable angina. METHODS: After washout and a 1-week placebo run-in period, patients received 20, 40, 80 or 120 mg/day of clentiazem tablets or placebo as a twice-daily dosage for 1 week of treatment after 1 week of dose titration. A symptom-limited exercise tolerance test was performed 4 and 12 h after dosing at the end of treatment and results were compared with baseline measurements. RESULTS: At 4 h after dosing, improvement of exercise duration from baseline value was significantly greater with clentiazem at doses of 40 mg/day (63 +/- 11 s), 80 mg/day (99 +/- 10 s) and 120 mg/day (70 +/- 11 s) than with placebo (34 +/- 10 s). Moreover, clentiazem (80 and 120 mg/day) increased the time to onset of angina and to > or = 1 mm of ST segment depression significantly more than did placebo. At submaximal exercise, clentiazem (40, 80 and 120 mg/day) decreased rate-pressure product, mainly as a result of a decrease in heart rate. At 12 h after dosing, improvement of exercise duration from baseline was significantly greater with clentiazem in doses of 80 mg/day (77 +/- 9 s) and 120 mg/day (70 +/- 10 s) than with placebo (42 +/- 9 s). The incidence of treatment-related adverse events with placebo (27%) and clentiazem (29%) was similar. The most frequently reported treatment-related adverse events with clentiazem were asthenia, headache (both 7.9%), first-degree atrioventricular block and dizziness (both 4.4%). CONCLUSIONS: The results of this short-term study suggest that clentiazem given twice daily in doses of 80 or 120 mg/day is safe and effective monotherapy in the treatment of stable angina.

Aged↗
PubMed1993

Design features of a controlled clinical trial to assess the effect of an HMG CoA reductase inhibitor on the progression of coronary artery disease. Canadian Coronary Atherosclerosis Intervention Trial Investigators Montreal, Ottawa, and Toronto, Canada.

This report describes the design and methodological features of a double-masked, randomized, placebo-controlled trial to determine whether administration of the HMG CoA reductase inhibitor lovastatin retards the progression or facilitates the regression of coronary atherosclerosis. The study population consists of coronary patients with a recent arteriogram that characterizes them as being at high risk for coronary progression and a baseline fasting total serum cholesterol > or = 5.7 mmol/L and < or = 7.8 mmol/L. Lovastatin, or matching placebo, are up-titrated from 20 mg to 40 mg to 80 mg/day during the first 16 weeks of the study in an attempt to attain a fasting serum LDL cholesterol level of 3.4 mmol/L; patients and study personnel remain masked as to cholesterol levels throughout the trial. Coronary arteriography is repeated at 2 years, or earlier if necessitated by worsening symptoms, and all segments are measured quantitatively using a computer-based system. The primary outcome of the trial is a comparison between the lovastatin and placebo groups for coronary change score, defined as the mean of the minimum lumen diameter changes for all lesions (follow-up minus baseline arteriogram) per patient. The advantages and limitations of coronary arteriographic trials and some of the issues related to outcome measurements are discussed. The question posed by this study is of clinical relevance because the consequences of progression of coronary disease, angina, myocardial infarction, and sudden cardiac death are leading causes of morbidity and mortality.

Adult↗
PubMed1993

Effect of a standardized meal on the threshold of exercise-induced myocardial ischemia in patients with stable angina.

OBJECTIVES: This study was undertaken to determine the effect of a standardized meal on the ischemic threshold and exercise capacity in a series of 20 patients with stable angina, exercise-induced ischemia and reversible exercise-induced perfusion defects. BACKGROUND: It is generally accepted that exercise tolerance in patients with angina is reduced after a meal. However, studies that have addressed this phenomenon have yielded results that are contradictory and inconclusive. METHODS: Two exercise tests using the Bruce protocol with technetium-99m (99mTc)-sestamibi were performed on consecutive days in a randomized order. One test was performed in the fasting state and the other 30 min after a 1,000-calorie meal. RESULTS: In the postprandial state, exercise time to ischemia was reduced by 20% from 248 +/- 93 s to 197 +/- 87 s (p = 0.0007), time to angina by 15% from 340 +/- 82 s to 287 +/- 94 s (p = 0.002) and exercise tolerance by 9% from 376 +/- 65 s to 344 +/- 86 s (p = 0.002). Rate-pressure products at these exercise test end points were not significantly different in the fasting and postprandial tests, and the quantitative 99mTc-sestamibi ischemia score was unchanged. CONCLUSIONS: In patients with stable angina, a 1,000-calorie meal significantly reduced time to ischemia, time to angina and exercise tolerance because of a more rapid increase in myocardial oxygen demand with exercise. The extent and severity of exercise-induced ischemia were unchanged.

Aged↗