Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites.

BACKGROUND: Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms. METHODS: In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models. RESULTS: Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005-0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0-2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11-122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3-0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2-2.5] and 1.4 [1.0-1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0-2.0]). CONCLUSION: Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor that plays a key role in the differentiation of adipocytes. Activation of this receptor in liposarcomas and breast and colon cancer cells also induces cell growth inhibition and differentiation. In the present study, we show that PPARgamma is expressed in human prostate adenocarcinomas and cell lines derived from these tumors. Activation of this receptor with specific ligands exerts an inhibitory effect on the growth of prostate cancer cell lines. Further, we show that prostate cancer and cell lines do not have intragenic mutations in the PPARgamma gene, although 40% of the informative tumors have hemizygous deletions of this gene. Based on our preclinical data, we conducted a phase II clinical study in patients with advanced prostate cancer using troglitazone, a PPARgamma ligand used for the treatment of type 2 diabetes. Forty-one men with histologically confirmed prostate cancer and no symptomatic metastatic disease were treated orally with troglitazone. An unexpectedly high incidence of prolonged stabilization of prostate-specific antigen was seen in patients treated with troglitazone. In addition, one patient had a dramatic decrease in serum prostate-specific antigen to nearly undetectable levels. These data suggest that PPARgamma may serve as a biological modifier in human prostate cancer and its therapeutic potential in this disease should be further investigated.

Visual outcome after contact lens and intraocular lens correction of neonatal monocular aphakia in monkeys.

PURPOSE: A monkey model was used to evaluate intraocular lenses (IOLs) and extended-wear contact lenses (EWCLs) for the optical treatment of infantile aphakia in humans. Specifically, the relative effectiveness of EWCLs used alone and IOLs used in combination with EWCLs in preventing amblyopia was assessed. METHODS: A total of 33 rhesus monkeys was studied in this project, 24 assigned to experimental treatment groups and 9 to normal controls. Contact lenses made from a diffusing material or dyed opaque were placed on one eye at birth to simulate an infantile cataract. A unilateral lensectomy was then performed on the same eye within 2.5 weeks after birth. In 15 monkeys this was combined with implantation of an IOL. The eyes were left aphakic in the remaining 9 animals. EWCLs were used to adjust the optical correction of both aphakic and pseudophakic eyes to a near point (3-5 D). Opaque lenses were used to maintain daily part-time (approximately 70%) occlusion of the fellow eye. The primary outcome measure was grating acuity assessed with behavioral methods. Some animals were also assessed for acuity with sweep visually evoked potentials (VEPs) and for optotype acuity (Landolt C) with behavioral methods. RESULTS: Two of the animals with IOLs developed complications in the eye that precluded completion of the behavioral assessment protocol. Only behavioral outcomes obtained before or in the absence of surgical complications are presented. There was a developmental delay in the maturation of grating acuity in both eyes of both treatment groups. Normal adult levels of grating acuity were eventually achieved in the group treated with IOLs combined with EWCLs. Grating acuity was significantly poorer than normal in aphakic eyes treated only with EWCLs. Comparison of the two treatment groups revealed that pseudophakic eyes treated with multifocal IOLs had significantly better gating acuity than aphakic eyes. Assessments of optotype acuity and sweep VEP acuity revealed amblyopic deficits in both pseudophakic and aphakic eyes. CONCLUSIONS: Given an absence of serious postoperative complications, neonatal correction of aphakia with IOLs combined with EWCLs can lead to normal grating acuity in a primate model. Correction with EWCLs alone was not sufficient to produce normal grating acuity. Multifocal IOL treatments combined with EWCL provided a significantly better outcome than EWCL methods alone. However, neither IOL nor EWCL methods were able to prevent amblyopia as evaluated using behavioral testing with optotypes or with sweep VEPs.

Infantile lensectomy and intraocular lens implantation with long-term follow-up in a monkey model.

PURPOSE: To report the long-term clinical and histopathologic findings in infant monkeys following a lensectomy and intraocular lens (IOL) implantation using two different surgical techniques. METHODS: A lensectomy and IOL implantation was performed on the right eye of 10 infant monkeys. A posterior capsulotomy was performed using a limbal approach in 5 monkeys (Group 1), and a pars plana approach in 5 other monkeys (Group 2). The residual refractive error in the pseudophakic eye was then corrected with a contact lens and the fellow eye was occluded for 70% of the daylight hours. The monkeys were then examined at regular intervals for 2 to 4 years. Visual acuity was assessed using operant testing and sweep visual evoked potentials (VEPs). At the end of the study, the pseudophakic eyes were studied histopathologically. RESULTS: The only complications that required reoperation were diaphanous fibrin membranes on the lens optic (n=10) and lens reproliferation into the pupillary space (n=5). The visual outcome was similar in Groups 1 and 2, with better acuities in the phakic eyes compared with the pseudophakic eyes. A higher percentage of both haptics were found in the capsular bag for the monkeys in Group 2 (n=3) than in Group 1 (n=1). CONCLUSIONS: Although haptic placement was superior using a pars plana approach to perform the primary posterior capsulotomy, no clinically discernable difference was noted in IOL centration between the monkeys undergoing a limbal versus a pars plana posterior capsulotomy and no difference was noted in the visual outcome.

Asymmetric responses in cortical visually evoked potentials to motion are not derived from eye movements.

PURPOSE: Normal neonates and many adults after abnormal visual development have directional preferences for visual stimulus motions; i.e., they give better responses for optokinetic nystagmus (OKN) and visually evoked potentials (VEPs) in one direction than to those in the opposite direction. The authors tested whether the VEP responses were asymmetrical because of abnormal eye movements. METHODS: VEPs were recorded from the visual cortices of five macaque monkeys: one normal, one neonate, and three reared with alternating monocular occlusion (AMO). They were lightly anesthetized, followed by paralysis to prevent eye movements. They then had "jittered" vertical grating patterns presented in their visual fields. The steady state VEPs were analyzed with discrete Fourier transforms to obtain the amplitudes and phases of the asymmetries. RESULTS: The normal, control monkey had small, insignificant amplitudes of its asymmetrical Fourier component and random phases that were not 180 degrees out of phase across the left and right eyes. The neonatal monkey and the AMO monkeys all had large, significant asymmetries that were approximately 180 degrees out of phase between the left and right eyes. CONCLUSIONS: The neonate and abnormally reared monkeys continued to have asymmetrical responses even after their eyes were paralyzed. Therefore, eye movements cannot be the source of the asymmetrical amplitudes of the VEPs, and the visual cortex is at least one source responsible for asymmetries observed in neonates and adults reared under abnormal visual inputs.

Influence of physician attitudes on willingness to perform abortion.

OBJECTIVE: To survey attitudes about abortion in a sample of physicians practicing in the Bronx, New York, identify factors associated with those attitudes, and investigate how attitudes about abortion influence willingness to do it. METHODS: A questionnaire mailed to obstetricians and gynecologists affiliated with a medical school in the Bronx elicited information on attitudes about abortion and the willingness to do it. Attitude scores were measured on a Likert scale ranging from 1 to 5, with 5 indicating a proponent attitude about abortion. The practice score ranged from 0 to 2, with 2 indicating proponent attitude about practicing abortion. RESULTS: The median attitude score was 3.8. Physicians were receptive to reasons for abortion that were medically indicated. A proponent attitude was found in non-Catholics and those who were trained in residency programs that required observing abortions. The median practice score was 1.2. The most important personal factors influencing a physician's decision not to perform abortions included lack of proper training and ethical and religious beliefs. There was a significant positive correlation between the attitude score and practice score (r = .42, P < .001). CONCLUSION: Personal beliefs and past experience with abortion are associated with attitudes about abortion that, besides competence doing them, influence physicians' willingness to do them. Offering training in abortion might benefit physicians who are proponents and willing to perform abortions.