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Biomedical subjects

W J Mack

Publications and source records attributed to W J Mack.

At least 55 records · Page 3Linked to original sources

Physical aggression is associated with preservation of substantia nigra pars compacta in Alzheimer disease.

OBJECTIVE: To investigate specific neuropathologic correlates of agitation and physical aggression in Alzheimer disease (AD). DESIGN: Neuronal counts in the nucleus basalis, locus ceruleus, and substantia nigra were compared in the brains of patients with pathologically definite AD with or without histories of agitation or interpersonal violence. SETTING: Alzheimer disease center of a university department of neurology. MAIN OUTCOME MEASURES: Neuron densities in the nucleus basalis and absolute neuron counts in the locus ceruleus and substantia nigra pars compacta. RESULTS: The patients with AD who had histories of unequivocal interpersonal violence had significantly greater neuron counts in the substantia nigra pars compacta than did the nonviolent patients with AD. This finding remained significant after multiple clinical and neuropathologic variables were adjusted for. Neuropathologic findings in the nucleus basalis and locus ceruleus were not different between violent and nonviolent patients. CONCLUSION: Preservation of pigmented substantia nigra neurons may be a risk factor for physical aggression in AD.

Aged↗

Probucol suppresses oxidant stress in hypertensive arteries. Immunohistochemical evidence.

Oxy-free radicals may be involved in the pathogenesis of accelerated atherosclerosis in hypertension. We evaluated the direct antioxidant potential of probucol in hypertensive arteries by studying the spatial immunohistochemical distribution of three primary antioxidant enzymes (AEs). Nineteen normocholesterolemic New Zealand White rabbits were divided into two groups: normotensive controls (NT; n = 6) and 13 animals rendered hypertensive by surgical coarctation of abdominal aorta. The hypertensive group was subdivided into hypertensive alone (HT; n = 8) and hypertensive treated with 1% probucol (PO) for 9 weeks (HT-P; n = 5). Blood pressure rose significantly in both hypertensive groups (P < .005). At autopsy, both hypertensive groups showed similarly significant increases in mean arterial intima-media thickness (IMT) whether or not they were treated with probucol. However, only HT rabbits revealed significant increases in the intima-media depth penetration of glutathione peroxidase, superoxide dismutase, and catalase AEs. By contrast, in HT-P animals probucol produced significant reductions of immunostaining of all three AEs compared to the HT group (P < .05). Additionally, specific macrophage immunostaining revealed that the arterial wall of HT rabbits had numerous (10 to 12 per high power field) subintimal and medial macrophages as compared to the HT-P animals (1 to 2 per high power field). The blood pressure level correlated significantly with IMT in all three groups, but with depth penetration of the three AEs only in the NT and HT groups. Probucol, therefore, appears to act in concert with the native arterial antioxidant enzymes as a potent free radical scavenger to reduce oxidative stress and thus attenuate the macrophage invasive response in hypertensive arteries.

Animals↗

Efficacy of interventions designed to inhibit the progression of coronary atherosclerosis.

This paper reviews the design and results of published randomized coronary angiographic trials and estimates treatment effect sizes for these trials to clearly demonstrate that antiatherosclerosis interventions are effective in inhibiting the progression of coronary artery disease (CAD). Furthermore, these interventions show differential treatment benefit on particular lesion populations defined by initial lesion severity. The efficacy of such interventions have been virtually unstudied in diabetic populations. Ancillary analyses of these trials implicate certain risk factors for the continued progression of CAD assessed by coronary angiography; although standard lipids such as total cholesterol and LDL-cholesterol are important risk factors, recent evidence suggests that triglycride-rich lipoproteins are also important contributors to progression of CAD, both in treated and untreated trial subjects. Recent reports demonstrating an association between progression of coronary disease assessed by coronary angiography and the risk of clinical events provide critical validation for the use of serial coronary angiography as a surrogate endpoint measure in controlled clinical trials. Finally, the advent of noninvasive ultrasonographic measures of carotid intima-media thickness may provide an important avenue for future testing of antiatherosclerosis interventions.

Carotid Arteries↗

Concurrent validity of Spanish-language versions of the Mini-Mental State Examination, Mental Status Questionnaire, Information-Memory-Concentration test, and Orientation-Memory-Concentration test: Alzheimer's disease patients and nondemented elderly comparison subjects.

One-hundred fifty-eight elderly Spanish-speaking U.S. residents (81 patients diagnosed with Alzheimer's disease and 77 subjects without dementia) were tested with Spanish-language versions of four brief cognitive assessment instruments: the Mini-Mental State Examination (S-MMSE), the Mental Status Questionnaire (S-MSQ), the Information-Memory-Concentration test (S-IMC), and the Orientation-Memory-Concentration test (S-OMC). Within-group performances were highly correlated for all four instruments. All tests distinguished between the demented and nondemented groups, but best discrimination was achieved with the S-IMC, which correctly classified 98% of subjects. This version was also the best predictor of functional disability, as measured by impairments in instrumental activities of daily living. Within the normal comparison group, neither gender nor a subject's monolingual/bilingual status affected test performance. These four Spanish-language cognitive screening tasks may aid in the evaluation of dementia among Spanish-speaking patients.

Adult↗

Lipoprotein subclasses in the Monitored Atherosclerosis Regression Study (MARS). Treatment effects and relation to coronary angiographic progression.

Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease. Using data from the Monitored Atherosclerosis Regression Study, an angiographic trial of middle-aged men and women randomized to lovastatin or placebo, we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis. Coronary artery lesion progression was determined by quantitative coronary angiography in low-grade ( < 50% diameter stenosis), high-grade ( > or = 50% diameter stenosis), and all coronary artery lesions in 220 baseline/2-year angiogram pairs. Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis. All low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) masses were significantly lowered and all high density lipoprotein (HDL) masses were significantly raised with lovastatin therapy. The mass of smallest LDL (Svedberg flotation rate [Sf] 0 to 3), IDL (Sf 12 to 20), all VLDL subclasses (Sf 20 to 60, Sf 60 to 100, and Sf 100 to 400), and peak LDL flotation rate were significantly related to the progression of coronary artery lesions, specifically low-grade lesions. Greater baseline levels of HDL3, were related to a lower likelihood of coronary artery lesion progression. In multivariate analyses, small VLDL (Sf 20 to 60) and HDL3 mass were the most important correlates of coronary artery lesion progression. These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease. In addition, these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions. More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins.

Adult↗

Compensatory vascular changes of remote coronary segments in response to lesion progression as observed by sequential angiography from a controlled clinical trial.

BACKGROUND: Local coronary artery enlargement to compensate for atherosclerotic plaques preserves the vessel lumen. The extent to which coronary segments remote from progressing lesions enlarge is unknown. This is clinically relevant since compensatory enlargement may be important in determining whether clinical complications result from progression of coronary artery disease (CAD). Additionally, compensatory change has implications for quantitative coronary angiographic (QCA) trials, since the effect of progression on diameter means may be mitigated by compensatory changes in remote coronary segments when QCA change is averaged over all lesions. METHODS AND RESULTS: Serial QCA data from 78 subjects in the Monitored Atherosclerosis Regression Study were used to demonstrate compensatory changes in coronary segments remote from progressing or regressing lesions. Coronary segments were first classified as progressing (regressing) if percent diameter stenosis (PS) increased or decreased by > 10 with a concurrent decrease or increase in minimum lumen diameter (MLD) of either > 0.32 mm or > 10% of the normal baseline reference diameter (DNORM). Segments not meeting these criteria were labeled stenosis stable. Stenosis-stable segments opposite progressing lesions showed increases in MLD (P = .0006), DNORM (P = .001), and average diameter (P = .001). On-trial apolipoprotein (apo) B, apo C-III, and blood pressure levels inversely correlated with these compensatory changes. CONCLUSIONS: Lesion progression in one coronary segment is associated with significant increases in segmental diameter of remote parts of the coronary tree. We hypothesize these increases to be vascular compensatory changes in response to progression of CAD. Vascular compensatory change is enhanced by LDL cholesterol and triglyceride-rich lipoprotein reduction and appears to be part of the treatment effect itself.

Adult↗

Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis.

OBJECTIVE: To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease. DESIGN: A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression. SETTING: Community- and university-based cardiac catheterization laboratories. SUBJECTS: A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery. INTERVENTION: Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized). OUTCOME: Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary angiography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S). RESULTS: Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS: These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed.

Adult↗

A case-control study of maternal risk factors for thyroid cancer in young women (California, United States).

A population-based case-control interview study investigated whether reproductive factors are related to the striking female-over-male excess of thyroid cancer among women of reproductive age in Los Angeles County, CA (United States). As a separate component of that study, mothers of 153 cases and 140 controls who were age 40 or younger at diagnosis or reference date were interviewed by telephone to determine the significance of family and maternal risk factors in the subsequent development of thyroid cancer among the daughters. More case than control mothers experienced miscarriage prior to the index pregnancy (odds ratio [OR] = 2.0, 95 percent confidence interval [CI] = 1.1-3.5). Increased risk was associated with family history of thyroid cancer or other thyroid disease (OR = 2.1, CI = 1.2-3.6). More control than case mothers smoked during the index pregnancy (OR = 0.6, CI = 0.4-1.0); however, among mothers who smoked, case mothers smoked more. Case mothers experienced a greater increase in weight from minimum adult weight to weight at index pregnancy (P for trend = 0.01). Reports from mothers also confirmed the risk associated with the daughter's exposure to ionizing radiation from birth through adolescence; ionizing radiation remains the best-established risk factor for thyroid cancer.

Adolescent↗

Triglyceride-rich lipoproteins and the progression of coronary artery disease.

A growing body of evidence from serial coronary angiographic studies indicates that triglyceride-rich lipoproteins are an important factor in the progression of coronary artery disease. Compelling evidence also suggests that triglyceride-rich lipoproteins may be most important in the progression of mild-moderate lesions, the very lesions that are likely to be responsible for clinical coronary events.

Apolipoproteins B↗

Multicenter clinicopathological correlation in dementia.

OBJECTIVE: The aim of the present study was to determine the accuracy of clinical diagnoses of dementia in a large group of patients evaluated in a multicenter, university-based, Alzheimer's disease diagnostic and treatment program. METHOD: Clinical diagnoses and neuropathological results from seven collaborating Alzheimer's disease research centers were compared for 196 cases of dementia. RESULTS: When diagnoses of probable Alzheimer's disease, possible Alzheimer's disease, and Alzheimer's disease plus another condition were combined, 163 (83%) of the patients were clinically regarded as likely to have had Alzheimer's disease. Of those patients, 134 (82%) were found to have neuropathological changes diagnostic of Alzheimer's disease or Alzheimer's disease plus another condition. A total of 116 patients were diagnosed as having probable Alzheimer's disease; 100 (86%) of those were found to have pathological diagnoses of Alzheimer's disease or Alzheimer's disease plus another condition. Cerebral infarcts were found in 17% of the patients clinically diagnosed with probable Alzheimer's disease. Lewy bodies with variable Alzheimer's disease-type pathological changes were found in 7% of the patients with clinical diagnoses of probable Alzheimer's disease. Conversely, significant Alzheimer's disease-type pathological changes were found in 55% of the patients clinically diagnosed as having vascular dementia. CONCLUSIONS: Clinicians accurately predict Alzheimer's disease-type neuropathological findings in a high proportion of cases of dementia but may not predict cerebrovascular pathology and Lewy bodies in some patients with apparent clinical Alzheimer's disease and may often fail to predict Alzheimer's disease-type pathological findings in patients with apparent vascular dementia. With the emergence of effective treatments for Alzheimer's disease, there is an increasing need to optimize methods for ante-mortem diagnosis of dementia.

Aged↗

Evaluation of computerized edge tracking for quantifying intima-media thickness of the common carotid artery from B-mode ultrasound images.

A new method to measure carotid intima-media thickness (IMT) from B-mode ultrasound images was developed that utilizes automatic tracking of the lumen-intima and media-adventitia echoes. Phantom studies and human replicate studies under typical clinical protocols for common carotid IMT measurement were carried out to assist in evaluation of the method. A lucite step wedge phantom was used to show that incorporation of sub-pixel interpolation to locate echo boundaries allowed detection of changes in the echo separation that were 5-10 times smaller than the axial resolution of the ultrasound transducer. For average IMT measured in the distal common carotid artery (CCA) wall in 24 subjects scanned twice within 60 days, mean absolute difference was 0.036 mm with a standard deviation of 0.045 mm. Replicate scans obtained 1 week apart of eight subjects by three sonographers showed the intersonographer variability was 5.4%. In another study of 12 subjects scanned every 4 months for 48 months, the root mean square deviation of the IMT measurements from a linear regression line was 0.030 mm. These data indicate that the method is equally precise over short intervals (60 days) and over long intervals (48 months). The new automated computerized edge tracking method presented in this paper represents an advance for image analysis of B-mode ultrasound images of common carotid IMT with measurement variability substantially reduced (2 to 4 times) compared with currently available manual methods.

Adult↗

Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS).

To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

BACKGROUND: The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets. METHODS AND RESULTS: Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor. CONCLUSIONS: These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.

Adult↗

A method to improve interrater reliability of visual inspection of brain MRI scans in dementia.

MR scanning is used in the clinical evaluation of patients with dementia but lacks a reliable method of visual inspection. Two neurologists conducted multiple pilot trials of alternate methods for visual inspection of MRIs, including methods that produced at least 75% interrater agreement in repeat trials, and selected a final method for rating ventricular:brain ratio (VBR), cortical atrophy, and white matter changes. Two other neurologists, new to the method, tested interrater reliability for each component of the method after a brief training session. The correlation of VBR measurement was 0.884 (p = 0.0001). The weighted kappa scores were 0.68 for overall frontal lobe atrophy, 0.38 for right temporal lobe atrophy, 0.20 for left temporal lobe atrophy, and 0.54 for parietal lobe atrophy. The weighted kappa scores were 0.77 for overall periventricular white matter hyperintensities and 0.72 for centrum semiovale hyperintensities. The proposed method may provide a rapid and reliable way to assess VBR, frontal lobe atrophy, parietal lobe atrophy, and white matter changes on brain MRIs in the evaluation of dementia, but it was less reliable for the assessment of temporal lobe atrophy.

Alzheimer Disease↗

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

Adult↗

A bivariate genetic analysis of HDL- and LDL-cholesterol incorporating measured covariates: a Gibbs sampling application.

We analyzed HDL- and LDL-cholesterol levels as a bivariate phenotype in 27 families as a function of major genes, polygenes, and measured covariates using a Monte Carlo sampling technique called Gibbs sampling. Major genes and polygenes exhibited strong effects, when considered separately. While a major gene versus polygene model could not be clearly differentiated for HDL-C, polygenes appeared to play a stronger role than a major gene for LDL-C. There was no evidence of linkage between the two major genes for HDL- and LDL-C, and the correlation in polygenes was negative. The analysis illustrate the potential applicability of Gibbs sampling to such complex problems as the multivariate analysis of continuous phenotypes.

Cholesterol, HDL↗

A case-control study of thyroid cancer in women under age 55 in Shanghai (People's Republic of China).

A population-based interview study of 207 case-control pairs investigated reproductive, dietary, and other factors thought likely to increase thyroid cancer risk among women of reproductive age in Shanghai. Of particular interest were factors that might help explain the striking female over male excess in this age group. Risk was strongly associated with prior goiter or benign nodules (odds ratio [OR] = 7.0, 95 percent confidence interval [CI] = 2.5-27.5) and miscarriage as outcome of first pregnancy (OR = 9.9, CI = 2.0-48.4). Weaker associations were seen for women who were ever-pregnant (OR = 2.1, CI = 1.1-4.2), ever had an induced abortion (OR = 1.6, CI = 0.9-2.9), and ever used oral contraceptives (OR = 1.7, CI = 1.0-3.1). Compared with controls, cases gained significantly more weight from menarche to highest nonpregnant weight (P trend < 0.01). Overall, cases ate more fish and shellfish, but there was no trend with level of consumption. More cases had a parent, sibling, or child with thyroid disease (OR = 5.2, CI = 2.5-12.1). Our findings relating to goiter and benign nodules and various reproductive factors support earlier studies. Consumption of seafood was difficult to evaluate; more detailed dietary data are needed to assess iodine intake.

Abortion, Spontaneous↗