Biomedical subjects
Publications and source records attributed to G Howard.
The diagnosis and management of orbital disease often requires the interaction of several specialties. The authors have reviewed the concepts in orbital reconstruction from an ophthalmologic, oculoplastic, otolaryngologic, and plastic surgical approach. Careful attention is given to the clinical examination, radiologic studies, surgical indications, and surgical techniques for orbital disease.
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Phenobarbital (PB) is a potent inducer of cytochrome P450 enzymes, particularly CYP2B1/2B2. Although the mechanism(s) of PB induction of CYP2B1/2B2 is not fully understood, current research is focusing on the role PB may play in altering the binding of nuclear proteins to critical DNA response elements in the 5'-flanking region of these genes. In this study, rat liver nuclear proteins were analyzed for DNA binding ability using both a general consensus and a CYP2B2 sequence-specific AP-1 oligonucleotide. We demonstrate that in vivo PB treatment enhances protein binding activity to the consensus AP-1 oligonucleotide. Likewise, a putative AP-1 site, identified at -1441 in the CYP2B2 5'-flanking region, also formed a sequence specific DNA/protein complex which was enhanced after PB exposure. These data may support a role of AP-1 in the PB induction mechanism of CYP2B1/2B2.
OBJECTIVE: To describe the distribution of hypertension and its association with subclinical atherosclerosis in blacks and whites. DESIGN: Population-based survey of 15,587 middle-aged adults from the Atherosclerosis Risk in Communities Study. Ultrasound-measured carotid artery intima media thickness (IMT) was used to estimate atherosclerosis. Hypertension was defined by the revised fifth Joint National Committee categories. Continuous systolic and diastolic blood pressure measurements also were evaluated. RESULTS: Among participants not reporting use of antihypertensive medication, 43% to 52% of black and 68% to 78% of white participants had optimal to high-normal blood pressure across the 4 study centers; 11% to 22% of black and 6% to 9% of white participants had stage I or higher hypertension. Use of antihypertensive medications was reported by 34% to 45% of blacks and 20% of whites; 11% to 17% of blacks had stage I or higher hypertension compared with 4% to 7% of whites when treated. Higher hypertension categories were associated with thicker intima medias in all ethnic and gender groups, in participants who did and did not use medications. In participants who did not use medications, multiple linear regression models adjusted for diastolic blood pressure and other risk factors found that systolic blood pressure was positively associated with IMT except in black men; diastolic blood pressure was not related to IMT in blacks and had a negative relation with IMT in white men and a J-shaped relation with IMT in white women. Results of similar direction and magnitude were found in participants who used medications. CONCLUSIONS: Hypertension was higher in blacks than whites and was associated with subclinical atherosclerosis. The association of atherosclerosis with hypertension is accounted for predominantly by systolic blood pressure. The intriguing negative association of diastolic blood pressure and atherosclerosis implies that pulse pressure may be an important correlate of atherosclerosis.
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BACKGROUND: Reduced insulin sensitivity has been proposed as an important risk factor in the development of atherosclerosis. However, insulin sensitivity is related to many other cardiovascular risk factors, including plasma insulin levels, and it is unclear whether an independent role of insulin sensitivity exists. Large epidemiological studies that measure insulin sensitivity directly have not been conducted. METHODS AND RESULTS: The Insulin Resistance Atherosclerosis Study (IRAS) evaluated insulin sensitivity (SI) by the frequently sampled intravenous glucose tolerance test with analysis by the minimal model of Bergman. IRAS measured intimal-medial thickness (IMT) of the carotid artery as an index of atherosclerosis by use of noninvasive B-mode ultrasonography. These measures, as well as factors that may potentially confound or mediate the relationship between insulin sensitivity and atherosclerosis, were available in relation to 398 black, 457 Hispanic, and 542 non-Hispanic white IRAS participants. There was a significant negative association between SI and the IMT of the carotid artery both in Hispanics and in non-Hispanic whites. This effect was reduced but not totally explained by adjustment for traditional cardiovascular disease risk factors, glucose tolerance, measures of adiposity, and fasting insulin levels. There was no association between SI and the IMT of the carotid artery in blacks. The association between SI and the IMT was stronger for the internal carotid artery than for the common carotid artery in all ethnic groups. CONCLUSIONS: Higher levels of insulin sensitivity are associated with less atherosclerosis in Hispanics and non-Hispanic whites but not in blacks. This effect is partially mediated by traditional cardiovascular risk factors.
Characterization and regulation of angiotensin II (AII) receptor binding sites was performed in rat membrane preparations from nonadipose (liver, lung) and adipose (interscapular (ISBAT) and periaortic (PA) brown adipose tissue; epididymal (EF) and retroperitoneal (RPF) white adipose tissue). In membrane preparations from brown and white adipose sources, [125I]AII saturation binding revealed a single, high affinity (Kd range of 0.3 -0.6 nM) binding site with a modest AII receptor density (Bmax range of 17-120 fmol/mg protein) comparable to rat lung (130 fmol/mg protein). White adipose tissue contained a greater number of AII receptor sites than brown adipose tissue. Competition displacement studies demonstrated the AT1 receptor is the only angiotensin receptor subtype localized in adipose tissue, with the rank order for competition of [125I]AII binding in all adipose tissues examined AIII > AII > losartan > angiotensin I (AI) > PD123319. The AT2 specific receptor antagonist, PD123319, was ineffective at displacing [125I]AII binding in all adipose tissues examined. Since components of the renin-angiotensin system are regulated in adipose tissue, we determined if the AII receptor is also regulated in the obese state. AII receptor binding characteristics were determined in liver, lung, ISBAT and EF membrane preparations from adult Zucker obese (fa/fa) and lean (Fa/?) rats. AII receptor density was decreased in liver from obese rats. In contrast, the affinity for [125I]AII binding was not altered in tissues from obese rats. In a separate group of obese and lean rats, regulation of the AII receptor by phenobarbital (PB) was examined. Administration of PB restored AII receptor density in liver from obese rats to levels obtained in lean rats. In summary, these results demonstrate the presence of AT1 receptor sites in brown and white adipose tissue. Moreover, AII receptor density is decreased in tissues from obese rats, with restoration of receptor density by administration of PB. Future studies will determine if PB regulates the AT1 receptor at the level of gene expression.
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Litigation has become a major weapon in the conflict between those who seek to control tobacco and the tobacco industry. Apart from the cases arising from the high proportion of fires caused by cigarettes (including, in the UK, the disastrous fire at the Bradford football stadium and the fire at Kings Cross railway station, both of which were caused by discarded cigarette butts), in the last few years there have been and are continuing major lawsuits against the tobacco manufacturers both in the USA and in the UK. In Australia, a Court has ruled that the tobacco industry's claims that passive smoke had not been proven to cause a variety of diseases were false and misleading. A Quebec judge ruled as unconstitutional a Canadian law which had banned tobacco advertising. A product liability suit was filed against cigarette manufacturers by airline flight attendants whose health, they alleged, was impaired by exposure to passive smoke. To date, attempts to win damages from the manufacturers for injuries caused by smoking have failed, but several group actions are pending in the courts in England and the USA. The cases to date demonstrate the range and importance of tobacco control issues now being considered by the Courts.
OBJECTIVE: To assess the knowledge, attitudes, and behaviours of tobacco growers and allotment owners in the southeastern United States. DESIGN: Cross-sectional telephone survey. PARTICIPANTS: Tobacco growers (n = 529) and tobacco allotment owners (n = 417) were interviewed by telephone in March 1995. SETTING: Tobacco growing states in the southeastern US. MAIN OUTCOME MEASURES: Attitudes of tobacco growers and tobacco allotment owners towards, and experience with, diversification; and attitudes towards an increase in the federal excise tax on tobacco. RESULTS: Half of the respondents had done something to learn about on-farm alternatives to tobacco, had an interest in trying other on-farm ventures to supplement tobacco income, and found alternatives that were profitable. There was a strong, negative linear trend between age and being interested in or trying alternative enterprises. Structural and economic impediments to diversification were noted by respondents (especially younger respondents), but 73% supported an increase in the federal excise tax on tobacco if the money was used to help farmers overcome these barriers. CONCLUSIONS: These data suggest that farmers and health professionals have reason to establish dialogue around diversification and using excise tax increases to fund diversification and to promote health. Tobacco companies have been successful in mobilising farmers against tax increases, but efforts must be made to show farmers that tax increases can be beneficial both to their diversification efforts and to public health. The outcome of this dialogue may well affect the economic infrastructure of thousands of rural communities, the livelihood of tens of thousands of tobacco farmers and their families, and the health of millions of tobacco users.
BACKGROUND AND PURPOSE: Ethnic differences in cardiovascular disease (CVD) morbidity and mortality have been observed in US adults. However, little data exist on differences in indices of preclinical atherosclerosis such as carotid wall intima-media thickness (IMT) for US non-Hispanic whites, Hispanics, and blacks. This study was undertaken to determine whether there were ethnic differences in carotid wall IMT. METHODS: Internal carotid artery (ICA) IMT and common carotid artery (CCA) IMT, indices of atherosclerosis, were assessed with the use of B-mode ultrasound in 1020 nondiabetic participants in the Insulin Resistance Atherosclerosis Study, a multicenter study designed to examine the association between insulin resistance and carotid atherosclerosis. The study included 281 blacks, 329 Hispanics, and 410 non-Hispanic whites aged 40 to 69 years. RESULTS: Blacks had significantly greater CCA IMT than non-Hispanic whites (865 versus 808 microns); this remained significant after adjustment for major CVD risk factors and insulin sensitivity (864 versus 823 microns). There were no significant differences in ICA IMT between blacks and non-Hispanic whites. Hispanics had significantly lesser CCA IMT than non-Hispanic whites (749 versus 776 microns), and these differences remained significant after adjustment for traditional cardiovascular risk factors and insulin sensitivity (750 versus 778 microns). There were no significant differences in ICA IMT between non-Hispanic whites and Hispanics. CONCLUSIONS: We conclude that ethnic differences exist in CCA but not in ICA IMT in nondiabetic subjects. These differences in IMT, which are indicators of atherosclerosis, are a non-invasive measure that is consistent with some of the data on clinical end points. These differences may be associated with the observed differences in CVD morbidity and mortality among major ethnic groups in the United States.
BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) polymorphism affects plasma cholesterol and may influence risk of atherosclerosis. We investigated the association of apoE with carotid artery wall thickening (an index of atherosclerosis) in individuals with and without coronary artery disease (CAD). METHODS: ApoE phenotypes were resolved in 260 individuals equally represented by angiographically determined CAD case subjects and disease-free control subjects. Carotid artery intima-media thickening (IMT) was evaluated by B-mode ultrasound. Associations of apoE (E2, E3, or E4) with risk factors and IMT were evaluated in general linear models adjusted for age, sex, and CAD status with and without other traditional risk factors. RESULTS: Total cholesterol (TC) and LDL cholesterol were associated with apoE isoforms. Mean TC and LDL cholesterol were lower in E2 (n = 33) carriers than E3 (n = 155) and E4 (n = 66) carriers (each P < .001). IMT also varied by apoE. E2 carriers had less common carotid IMT than E3 and E4 carriers (P < .01), while internal carotid IMT was less in E2 and E3 carriers than in E4 carriers (P < .02). Bifurcation IMT was not associated with apoE (P = .24). ApoE polymorphism remained associated with common (P < .01) and internal (P < .04) IMT, and the association of apoE with mean IMT of all sites reached significance (P < .04) after adjustment for age, sex, CAD status, TC, LDL cholesterol, HDL cholesterol, triglycerides, diabetes, hypertension, and smoking. CONCLUSIONS: ApoE polymorphism is associated with segment specific carotid IMT. The association of apoE with carotid IMT was statistically independent of apoE-associated variation in LDL cholesterol levels.
BACKGROUND AND PURPOSE: The Asymptomatic Carotid Atherosclerosis Study (ACAS) Doppler validation study assessed the performance of individual Doppler machines across a spectrum of laboratories. We attempted to establish a threshold specific to individual machines to predict angiographically defined hemodynamic stenosis. The reliability of these Doppler ultrasound criteria was prospectively and independently evaluated among patients screened with ultrasound in the ACAS trial. METHODS: Regression techniques were used to establish the relationship between Doppler velocity and percent stenosis by angiography for 63 specific Doppler machines. This relationship was used to establish a Doppler threshold to provide a 90% positive predictive value (PPV) of a 60% stenosis by angiography. The sensitivity of each Doppler machine to detect a 60% stenosis (at the 90% PPV threshold) was estimated. The efficacy of these Doppler thresholds was then prospectively evaluated by calculating the PPV among ACAS participants eligible by ultrasound. RESULTS: Of the 63 machines, 13 (21%) had an excellent sensitivity (80%+) at 90% PPV. In 32 devices (51%) only a marginal sensitivity (50% to 80%) could be achieved. In 9 devices (14%) the sensitivity was poor (0% to 50%), and in 9 (14%) no threshold could be established. Despite the heterogeneity of Doppler performance, the standardization program worked as designed in the ACAS trial. Of 825 surgical patients, 399 were eligible by Doppler and 395 subsequently underwent angiography. Of these, 32 (8.1%; 95% confidence interval, 5.4% to 10.8%) did not have hemodynamically significant stenosis by arteriography, a proportion nonsignificantly lower than the planned 10% by the PPV. CONCLUSIONS: The performance of Doppler ultrasound was highly variable. This suggests that Doppler performance is likely overstated in the literature, but specific devices may perform satisfactorily to detect individuals with hemodynamically significant stenosis. Because performance differs substantially among devices, local investigators are strongly urged to maintain local standardization series. With such standardization, ultrasound performance is sufficient for admission to clinical trials and as the is sufficient for admission to clinical trials and as the basis for carotid surgery. However, without quality control many ultrasound machines are not adequate to accurately predict the degree of carotid stenosis and should not be the only test to decide whether surgery is warranted.
The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.
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