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Biomedical subjects

X Q Zhao

Publications and source records attributed to X Q Zhao.

18 recordsLinked to original sources
PubMed1996

Effectiveness of revascularization in the Emory angioplasty versus surgery trial. A randomized comparison of coronary angioplasty with bypass surgery.

BACKGROUND: The Emory Angioplasty Versus Surgery Trial (EAST) was designed to determine whether percutaneous transluminal coronary angioplasty (PTCA) is as effective as coronary artery bypass graft surgery (CABG) in restoring arterial perfusion capacity in eligible patients with multivessel disease. METHODS AND RESULTS: Of 392 patients in EAST, 198 were randomized to PTCA and 194 to CABG. Index lesions (2.7 +/- 1.0 per patient) were those with > or = 50% stenosis judged treatable by both angioplasty and surgery. Coronary segments jeopardized by these index lesions were designated as index segments (4.4 +/- 1.4 per patient). Percent stenosis was measured by quantitative angiography at the point of greatest obstruction in the main perfusion path of each index segment. The EAST primary arteriographic end point was the percent of a patient's index segments with < 50% stenosis in the main perfusion pathways at 1 and 3 years. At baseline, the percent of index segments for which revascularization was attempted was 85% for PTCA and 98% for CABG (P < .0001). At 1 year, PTCA patients had a smaller percentage of successfully revascularized index segments than CABG patients (59% versus 88%, P < .001). At 3 years, the findings were similar but less striking (70% versus 87%, P < .001). When only "high-priority" index segments (2.1 +/- 1.6 per patient) were considered, baseline attempts were comparable (96% versus 99%, P = NS); despite this, CABG remained more successful at 1 (64% versus 93%, P < .001) and 3 (76% versus 89%, P < .01) years. However, the mean percent of index segments free of severe stenosis (> or = 70%) did not differ between PTCA and CABG patients at 3 years (93% versus 95%, P = NS). Furthermore, the frequency of patients with all index segments free of severe stenosis did not differ between the two groups at 1 (76% versus 83%, P = NS) or 3 (82% for both PTCA and CABG) years. CONCLUSIONS: In patients with multivessel disease, index segment revascularization was more complete with CABG than PTCA at both 1 and 3 years. However, when the physiological priority of the target lesion and the measured severity of the residual stenosis are taken into account, the advantage of CABG becomes less significant or nonsignificant. This may, in part, explain why these two strategies did not differ in terms of the EAST primary clinical end points over 3 years.

Aged↗
PubMed1996

The influence of dietary fibre and environmental temperature on the development of the gastrointestinal tract, digestibility, degree of fermentation in the hind-gut and energy metabolism in pigs.

The present study was undertaken to provide detailed information about the effect of dietary fibre (DF) level on the development of the digestive tract, on nutrient digestibility and on energy and protein metabolism of pigs housed in low (13 degrees) or high (23 degrees) thermal environments. Low- and high-fibre diets (59 v. 268 g DF/kg DM) were studied in three balance periods with fistulated pigs in the weight range 45-120 kg. Heat production was measured using open-circuit respiration chambers. Pea fibre and pectin were used to adjust the DF level in the high-fibre diet. Per kg empty body weight the stomach, caecum and colon and the length of colon were significantly greater in pigs consuming the high-fibre diet than in those on the low-fibre diet. Pigs kept at low temperature had significantly heavier caecums than those kept at the high temperature. Digestibilities of protein, DM and energy were lowest for the high-fibre diet. Only minor amounts of NSP and its constituent sugars were degraded anterior to the ileum, whereas in the hind-gut the fermentation of the total NSP fraction was high, being 0.77 for the high-fibre diet and 0.59 for the low-fibre diet. Feeding the high-fibre diet increased the flow of digesta through the terminal ileum 5-6-fold and an extra 460 g organic matter was fermented daily in the hind-gut compared with pigs fed on the low-fibre diet. The amount of retained energy as a proportion of metabolizable energy decreased in relation to the amount of energy fermented in the hind-gut. Based on the present data it was estimated that the relative value of energy derived from hind-gut fermentation was 0.73 in comparison with energy enzymically digested in the small intestine. There was negligible effect of the temperature--fibre interaction on energy metabolism. However, it could be calculated that the decrease in temperature from 23 degrees to 13 degrees was associated with an increase in heat production by 2.9 MJ/pig per d.

Animals↗
PubMed1996

The influence of dietary fibre source and level on the development of the gastrointestinal tract, digestibility and energy metabolism in broiler chickens.

The present study was undertaken to provide detailed information about the effect of fibre source (pea fibre, wheat bran or oat bran) at inclusion levels of 0, 187 and 375 g/kg diet on the development of the digestive tract, nutrient digestibility and energy and protein metabolism in broiler chickens. Heat production was measured using open-air-circuit respiration chambers. Diets with increasing levels of pea fibre decreased the DM in droppings and increased excreta output (2.5-fold) relative to DM intake. Adaptation to increased dietary fibre levels included increases in the size of the digestive system, with pea fibre exerting a stronger impact than wheat bran or oat bran. The length of the intestine, and particularly the length and weight of the caecum, increased with the fibre level. The digestibility of all nutrients also decreased with increasing fibre level. The decrease in the digestibility in relation to NSP for the three fibre sources was bigger for oat bran (0.0020 per g dietary NSP) than for pea fibre and wheat bran (0.0014 and 0.0016 per g dietary NSP) indicating that the cell walls in oat bran (aleurone and subaleurone) had a significant negative effect on the digestibility of cellular nutrients, i.e. protein and fat. The degradation of the NSP constituents was far lower in chickens than found in other animal species such as pigs and rats, thus supporting the view that chickens do not ferment fibre polymers to a great extent. Excretion of organic acids (mainly lactic acid and acetic acid) accounted for up to 2% of metabolizable energy (ME) intake with the highest excretion for the high-fibre diets. H2 excretion was related to the amount of NSP degraded and indicated higher microbial fermentation with increasing fibre levels. The chickens' feed intake responded to a great extent to dietary ME concentration but expressed in terms of metabolic body size (W0.75) ME intake was depressed at the high fibre levels. Dietary NSP was able to explain between 86% (oat bran) and 96% (pea fibre) of the variation in ME concentration. The amount of energy available from fermentation of NSP appears to reach a maximum of 42 kJ/d independent of fibre source and level. Expressed in relation to ME intake the NSP fermentation contributed 3-4%. With increasing fibre intake the partitioning of retained energy between body protein and body fat changed in favour of protein.

Animals↗
PubMed1996

Energy metabolism and protein balance in growing rats housed in 18 degree C or 28 degree C environments and fed different levels of dietary protein.

A study was performed to investigate the effect of environmental temperature and increasing levels of protein in the diet on visceral organ size, digestibility, protein balance and energy metabolism in rats. Thirty-six male Wistar rats, initial body weight 77-80 g, were used in a factorial design consisting of three levels of dietary protein and two environmental temperatures of either 18 or 28 degrees C. Three fish meal-based diets were prepared to contain 91, 171 and 262 g protein (N X 6.25/kg diet). Gas-exchange measurements were made and urine and feces were quantitatively collected. The weights of the visceral organs from rats housed at 18 degrees C were greater (P < 0.05) than those of rats housed at 28 degrees C. The digestibilities of dry matter and protein were not affected by environmental temperature, whereas fat and energy digestibilities were higher (P < 0.05) at 18 degrees C than at 28 degrees C. As the level of protein was increased, the digestibilities of protein, energy and fat increased (P < 0.05). Protein intake and protein retention were higher at 18 degrees C (P < 0.05) than at 28 degrees C and increased (P < 0.05) as dietary protein concentration increased. Apparent biological value was lower (P < 0.05) at 18 degrees C than at 28 degrees C and decreased (P < 0.05) as dietary protein level increased. Heat production as a percentage of metabolizable energy was higher (P < 0.05) for the low protein diet than for the medium and high protein diets. The efficiency of energy utilization was depressed (P < 0.05) for the high protein diet when rats were kept at 28 degrees C. The results suggest that thermogenesis was induced when low protein was fed. The increase in thermogenesis may have been important in regulating energy balance and maintaining a constant body temperature in a cold environment.

Animals↗
PubMed1995

Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a).

OBJECTIVE: To determine if lowering elevated low-density lipoprotein cholesterol (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels on coronary artery disease (CAC) in men. DESIGN: Randomized, double-blind, placebo-controlled trial of lipid lowering for CAD. SETTING: Post hoc analysis of the Familial Atherosclerosis Treatment Study. PARTICIPANTS: A total of 146 men aged 62 years or younger with CAD and apolipoprotein B levels of at least 125 mg/dL. INTERVENTION: Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C > 90th percentile) for 2.5 years. They were grouped by their LDL-C responses: "minimal" if LDL-C decreased by 10% or less from baseline (mean [SD] change, +6% [13%]) and "substantial" if LDL-C decreased more than 10% (mean [SD] change, -40% [16%]). MAIN OUTCOME MEASURE: Impact of lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction, and revascularization for refractory ischemia) and CAD change associated with elevated Lp(a). RESULTS: In multivariate analyses, the best correlate of baseline CAD severity was Lp(a) (r = 0.30; P < .001). For 36 patients with minimal LDL-C reduction, CAD progression correlated only with in-treatment Lp(a) levels (r = 0.45; P < .01), but for 84 patients with substantial LDL-C reduction, disease regressed and its change correlated with in-treatment LDL-C (r = 0.24; P < .05) but not with Lp(a) (r = -0.05). Lipoprotein(a) levels were not significantly altered in either group. For 40 patients with Lp(a) at the 90th percentile or higher, events were frequent (39%) if reduction of LDL-C was minimal, but were few (9%) if reduction was substantial (relative risk, 0.23; 95% confidence interval, 0.06 to 0.99). CONCLUSIONS: In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years. However, with substantial LDL-C reductions, persistent elevations of Lp(a) were no longer atherogenic or clinically threatening. This provides a possible direction for treatment in such patients with elevated Lp(a) and LDL-C.

Adult↗
PubMed1995

What benefit can be derived from treating normocholesterolemic patients with coronary artery disease?

Controversy still remains regarding the possible clinical or arteriographic benefit of intensive lipid-altering therapy in patients who have coronary artery disease and apparently normal lipid levels. Resolution of this controversy appears to depend on an improved understanding of the role of variables other than total or low density lipoprotein cholesterol levels. A comparison of the "normolipidemic" subgroup of The Familial Atherosclerosis Treatment Study patients and The Harvard Atherosclerosis Reversibility Project patients indicates that low levels of high density lipoprotein cholesterol and elevated levels of apolipoprotein B appear to increase considerably the likelihood of benefit from intensive lipid-altering therapy. Other risk-related variables such as systolic blood pressure and lipoprotein(a) further contribute to the prediction of risk and possibly to the potential for treatment benefit.

Adult↗
PubMed1994

A randomized trial comparing coronary angioplasty with coronary bypass surgery. Emory Angioplasty versus Surgery Trial (EAST)

BACKGROUND: The clinical benefit of percutaneous transluminal coronary angioplasty (PTCA) as compared with coronary-artery bypass grafting (CABG) for patients with multivessel coronary artery disease has not been established. To determine the outcomes of these treatments in patients referred for the first time for coronary revascularization, we conducted a three-year prospective, randomized trial comparing the two procedures. METHODS: Revascularization was performed by accepted methods. Follow-up clinical information was collected every six months, and coronary arteriography and thallium stress scanning were performed at one and three years. The primary end point was a composite of death, Q-wave myocardial infarction, and a large ischemic defect identified on thallium scanning at three years. Secondary end points included clinical and angiographic status and the need for additional revascularization procedures. Data were analyzed according to the intention-to-treat principle. RESULTS: Of the 5118 patients screened for the trial, 842 (16.5 percent) were eligible for enrollment, and 392 (7.7 percent) agreed to participate. A total of 194 patients were randomly assigned to the CABG group, and 198 to the PTCA group. The primary end point occurred in 27.3 percent of the CABG group and 28.8 percent of the PTCA group (P = 0.81). Death occurred in 6.2 percent of the CABG group and 7.1 percent of the PTCA group (P = 0.73 by log-rank test). At three years, the proportions of patients in the CABG group who required repeated bypass surgery (1 percent) or angioplasty (13 percent) were significantly lower than the proportions in the PTCA group (22 and 41 percent, respectively; P < 0.001). Angiographic studies at three years showed a greater degree of revascularization in the CABG group. Angina was more frequent in the PTCA group (20 percent) than in the CABG group (12 percent). CONCLUSIONS: We found that CABG and PTCA did not differ significantly with respect to the occurrence of the composite primary end point. Consequently, the selection of one procedure over the other should be guided by patients' preferences regarding the quality of life and the possible need for subsequent procedures.

Angioplasty, Balloon, Coronary↗
PubMed1994

Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol.

OBJECTIVES: Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol? BACKGROUND: The merits of the present LDL cholesterol treatment goal of < or = 100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels. METHODS: Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographic comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B > or = 125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (delta %SProx) among nine standard proximal segments. RESULTS: Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol < 90th percentile (mean LDL cholesterol 152 mg/dl) and 60 > 90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels < 160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 > 160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol < 90th percentile benefited angiographically from therapy (delta %SProx = -1.5% diameter stenosis [regression] during intensive therapy vs. +2.3% diameter stenosis [progression] during conventional therapy, p < 0.01), as did patients with LDL cholesterol < 160 mg/dl (delta %SProx = -4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographic benefit was less pronounced among those entering with very high LDL cholesterol (delta %SProx = -0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol > or = 160 mg/dl (delta %SProx = +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups. CONCLUSIONS: Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy.

Adult↗
PubMed1993

Arteriographic view of treatment to achieve regression of coronary atherosclerosis and to prevent plaque disruption and clinical cardiovascular events.

Lipid-lowering therapy, as assessed by angiography, clearly benefits the arterial disease process. For example, among intensively treated patients in FATS the frequency of definite progression per lesion at risk was reduced by 75% among mild and moderate lesions, which form the great preponderance of the lesion population. Regression frequency per lesion was more than doubled by intensive therapy in mild and moderate subgroups and quadrupled in the subgroup with severe lesions. Clinical events were reduced by 73%. This was clearly due to a 15-fold reduction in the likelihood that a mildly or moderately diseased arterial segment would undergo abrupt and substantial progression to a severe lesion at the time of the clinical event. It has been shown that the process of plaque fissuring, leading to plaque disruption, thrombosis, and clinical coronary events, is predicted by the size of the plaque core lipid pool and the abundance of lipid-laden macrophages in its fibrous cap. Experimentally, lipid lowering therapy decreases the number of lipid-laden intimal macrophages and more slowly depletes core cholesteryl ester deposits. Thus the composite of new and previously published data presented here supports the idea that lipid-lowering therapy selectively lipid-depletes (causes regression of) those fatty lesions containing a large lipid core and abundant intimal foam cells. By doing so, these lesions, which are most vulnerable to fissuring, are rendered much more stable and the clinical event rate is accordingly decreased.

Clinical Trials as Topic↗
PubMed1993

Atherosclerosis regression, plaque disruption, and cardiovascular events: a rationale for lipid lowering in coronary artery disease.

In the Familial Atherosclerosis Treatment Study (FATS), the reduction in clinical events (75%) far outweighed the modest frequency and magnitude of lesion regression observed among those receiving intensive lipid-lowering therapy. To understand this result, the disruptive changes in plaque that trigger clinical events (cardiac death, myocardial infarction, unstable angina) are described. Data are presented in support of the idea that the clinical benefits of lipid-lowering therapy are best explained by stabilization, by depletion of lipid, of the "dangerous" subpopulation of lipid-rich plaques that are often associated with only mild or moderate coronary narrowing.

Coronary Artery Disease↗
PubMed1993

Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease.

The consensus of evidence from angiographic trials demonstrates both coronary artery and clinical benefits from lowering of lipids by a variety of regimens. The findings of reduced arterial disease progression and increased regression have been convincing but, at best, modest in their magnitude. For example, among those treated intensively in FATS, the mean improvement in proximal stenosis severity per patient was < 1% stenosis, and only 12% of all lesions showed convincing regression. In view of these modest arterial benefits, the associated reductions in cardiovascular events have been surprisingly great. For example, coronary events were reduced 75% in FATS; this was entirely a result of a 93% reduction in the likelihood that a mildly or moderately diseased arterial segment would experience substantial progression to a severe lesion at the time of a clinical event. We believe that the magnitude of the clinical benefit is best explained in terms of this observation, according to the following lines of reasoning. Clinical events most commonly spring from lesions that are initially of mild or moderate severity and then abruptly undergo a disruptive transformation to a severe culprit lesion. The process of plaque fissuring, leading to plaque disruption and thrombosis, triggers most clinical coronary events. Fissuring is predicted by a large accumulation of core lipid in the plaque and by a high density of lipid-laden macrophages in its thinned fibrous cap. Lesions with these characteristics constitute only 10-20% of the overall lesion population but account for 80-90% of the acute clinical events. In the experimental setting, normalization of an atherogenic lipid profile substantially decreases the number of lipid-laden intimal macrophages (foam cells) and depletes cholesterol from the core lipid pool. In the clinical setting, intensive lipid lowering virtually halts the progression of mild and moderate lesions to clinical events. Thus, the reduction in clinical events observed in these trials appears to be best explained by the relation of the lipid and foam cell content of the plaque to its likelihood of fissuring and by the effects of lipid-lowering therapy on these "high-risk" features of plaque morphology. The composite of data presented here supports the hypothesis that lipid-lowering therapy selectively depletes (regresses) that relatively small but dangerous subgroup of fatty lesions containing a large lipid core and dense clusters of intimal macrophages. By doing so, these lesions are effectively stabilized and clinical event rate is accordingly decreased.

Coronary Angiography↗
PubMed1993

Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B.

BACKGROUND: Do the benefits of intensive lipid-lowering therapy seen in symptomatic patients extend to high-risk subjects who have never had symptoms? METHODS AND RESULTS: Of 120 men completing the FATS trial, 91 were symptomatic and 29 asymptomatic. All had apolipoprotein B > or = 125 mg/dL, a positive family history, and coronary atherosclerosis. All were counseled in diet and randomized to intensive therapy: colestipol 10 g TID plus either niacin 1 g QID or lovastatin 20 mg BID or to conventional therapy: placebos, or colestipol if low-density lipoprotein cholesterol was elevated. End points included quantitative arteriographic disease change and clinical events over a 2.5-year interval. At baseline, symptomatic and asymptomatic patients had comparable risk profiles, but proximal stenosis severity averaged 36% for symptomatic and 23% for asymptomatic patients (P < .001). Among the 91 symptomatic patients, those in the intensive group experienced definite (> or = 10%S) proximal lesion progression less frequently than conventional (24% of intensive versus 48% of conventional) and definite regression more frequently (36% of intensive versus 15% of conventional) (P = .009). Similarly, among the 29 asymptomatic patients, 19% of intensive versus 38% of conventional had progression and 31% of intensive versus 0% of conventional, regression (P = .04). Ischemia on baseline exercise tolerance testing was associated with significantly greater proximal disease progression among the asymptomatic patients. Clinical cardiovascular events (death, infarction, or revascularization) occurred in 10 of 38 symptomatic patients originally assigned to conventional therapy, compared with 5 of 76 symptomatic patients assigned to intensive (P < .01); no asymptomatic patient had an event. CONCLUSIONS: Asymptomatic subjects with this high-risk profile have less coronary disease at baseline than comparable symptomatic patients, and they have an excellent short-term clinical prognosis. However, asymptomatic subjects are indistinguishable from symptomatic patients in terms of their arterial disease progression with conventional therapy and their regression with intensive. These findings may justify an active treatment strategy in such subjects, particularly those with provokable ischemia.

Adult↗
PubMed1993

A maximum confidence approach for measuring progression and regression of coronary artery disease in clinical trials.

BACKGROUND: Imaging trials using arteriography have been shown to be effective alternatives to clinical end point studies of atherosclerotic vascular disease progression and the effect of therapy on it. However, lack of consensus on what end point measures constitute meaningful change presents a problem for quantitative coronary arteriographic (QCA) approaches. Furthermore, standardized approaches to QCA studies have yet to be established. To address these issues, two different arteriographic approaches were compared in a clinical trial, and the degree of concordance between disease change measured by these two approaches and clinical outcomes was assessed. METHODS AND RESULTS: In the Familial Atherosclerosis Treatment Study (FATS) of three different lipid-lowering strategies in 120 patients, disease progression/regression was assessed by two arteriographic approaches: QCA and a semiquantitative visual approach (SQ-VIS). Lesions classified with SQ-VIS as "not," "possibly," or "definitely" changed were measured by QCA to change by 10% stenosis in 0.3%, 11%, and 81% of cases, respectively. The "best" measured value for distinguishing definite from no change was identified as 9.3% stenosis by logistic regression analysis. The primary outcome analysis of the FATS trial, using a continuous variable estimate of percent stenosis change, gave almost the same favorable result whether by QCA or SQ-VIS. CONCLUSIONS: The excellent agreement between these two fundamentally different methods of disease change assessment and the concordance between disease change and clinical outcomes greatly strengthens confidence both in these measurement techniques and in the overall findings of the study. These observations have important implications for the design of clinical trials with arteriographic end points.

Clinical Trials as Topic↗
PubMed1990

Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.

BACKGROUND AND METHODS: The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). RESULTS: The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent). In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent. By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; P less than 0.005). Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions. Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77). CONCLUSIONS: In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events.

Adult↗
PubMedDate not supplied

Decrease in hepatotoxicity by lead exposure is not explained by its mitogenic response.

The present research was conducted to evaluate the effect of mitogen pre-exposure on CCl4-induced hepatotoxicity. Male Wistar rats were administered a single i.p. injection of CCl4 (0.3 ml kg-1 in corn oil) 48 h following either a single dose of lead nitrate (0.33 mg kg-1) or distilled water via i.v. injection. Hepatotoxicity, as measured by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was monitored 6, 24, 48, 72 and 120 h after CCl4 exposure. The lead nitrate-pretreated rats displayed markedly lower serum ALT and AST levels at 24, 48 and 72 h than rats pretreated with distilled water. However, treatment with the antimitotic agent colchicine did not alter the lead-induced protection. These findings suggest that the lead-induced protection is not associated with the major mitogenic response of lead, despite its strong temporal association. A critical review of the available toxicological data also argues against the lead protection being a function of its capacity to inhibit cytochrome P-450.

Alanine Transaminase↗
PubMedDate not supplied

Potency ranking of methemoglobin-forming agents.

This study represents the first systematic attempt to rank methemoglobin-forming agents. It is a quantitative potency ranking study utilizing linear regression analysis of dose-response data for comparative purposes. Six agents that are direct-acting and eight that require bioactivation were tested for their ability to induce methemoglobin formation in Dorset sheep erythrocytes under defined in vitro conditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected to induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol l-1 of the agent. The direct-acting agents, ranked from most to least potent inducers of methemoglobin formation, are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite > chlorate. The ranking from most to least potent inducers of the bioactivated agents are: alpha-naphthol > p-nitroaniline > m-nitroaniline, o-nitroaniline > p-nitrotoluene = aniline > m-nitrotoluene = o-nitrotoluene. The ranking procedures are discussed and issues of interindividual variation and agent-specific sensitivities are addressed.

Analysis of Variance↗