Lessons learned from community-based minority health care serving system participation in an NIH clinical trial

To address the historically low rate of minority participation in clinical trials, the NIH and others have provided incentives to increase the diversity of patients and study sites involved in NIH-funded research. An example of the efforts to achieve this aim was the creation of the Partnerships Program to Reduce Cardiovascular Health Disparities," whereby a health care system that serves a predominantly minority patient population partners with a research-intensive medical center that has a track record of NIH-supported research. In the city of Baltimore, Maryland, the Bon Secours Baltimore Health System partnered with the University of Maryland and was awarded 1 of 7 U01 partnerships within cardiovascular health. This commentary describes the qualitative experiences of the participating physicians and not a quantitative analysis of the study data or findings. It describes the lessons learned by Bon Secours that can address patient and physician barriers to clinical trial participation. Based upon the views of participating physicians, it is easiest to engage physicians when there is a supportive principal investigator and appropriate infrastructure to do research. Patient recruitment requires cultural competence and sensitivity, and using minority physicians, nurses, and staff may greatly assist in building the trust that is necessary for patients to be willing to participate in research. Clarity of the study's purpose and aims at the outset is critical, and reinforcement with educational sessions helped with physician and patient retention throughout the study.     

The role of preexisting pathology in the development of neointimal hyperplasia in coronary artery bypass grafts

OBJECTIVE: Saphenous vein grafts (SVG) used for coronary artery bypass surgery (CABG) often develop a gradual luminal narrowing over the first year due to neointimal hyperplasia (NH). Although the basic science of NH is well studied, our clinical understanding of this issue is limited. The purpose of this cohort study was to investigate clinical risk factors for NH by monitoring luminal narrowing within SVG using multichannel CT angiography (CTA). METHODS: Thirty patients underwent CABG involving SVG (N = 44) and arterial grafts (N = 36). Patient variables were recorded and the baseline quality of each conduit determined intraoperatively by analyzing surplus segments for intima-media thickness ratio (IMT) by histology and matrix metalloproteinase-2 by enzyme-linked immunosorbent assay. Percent luminal narrowing (%LN) was calculated for each patent graft by comparing the CTA appearance on day 5 to a repeat study at 1 y. RESULTS: Compared with arterial grafts, SVG showed significantly higher IMT at baseline (0.9 +/- 0.65 versus 0.22 +/- 0.17, P < 0.0001) and more %LN over the first year (6.9 +/- 7.5 versus 25.3 +/- 13.3% LN, P< 0.0001). Of all of the measured variables, the only significant predictors of %LN included baseline IMT (r = 0.58, P = 0.002) and matrix metalloproteinase-2 levels (r = 0.60, P = 0.002) in SVG. CONCLUSIONS: The degree of NH at baseline, a phenomenon exclusive to SVG and not found in arterial grafts, was significantly related to the development of lumen loss in the conduit over the first year after CABG. The study of SVG using serial CTA may provide unique insights into the natural history of SVG remodeling and to identify factors that influence the long-term function of this conduit.     

Neuroprotection in glaucoma using calpain-1 inhibitors: regional differences in calpain-1 activity in the trabecular meshwork, optic nerve and implications for therapeutics

Glaucoma is a group of irreversible blinding eye diseases affecting over 70 million people worldwide. Systemic delivery of calpain-1 inhibitors was proposed as a neuroprotection strategy for the prevention of progressive optic nerve damage in glaucoma. We present a general review of calpain-1 and an account of vast differences in processing of calpain-1 in the trabecular meshwork (trade mark) and the optic nerve. Calpain-1 accumulates in the glaucomatous trade mark tissues in vivo. However, calpain-1 activity is substantially lower in the glaucomatous trade mark compared to controls, apparently owing to partial degradation, and modification by lipid oxidation products such as iso [4]levuglandin E2 (iso [4]LGE(2)). Treatment of calpain-1 with iso [4]LGE(2) in vitro results in covalent modification, inactivation, and resistance to protease digestion. Iso [4]LGE(2)-modified calpain-1 appeared to undergo ubiquitination in the trade mark by cellular degradation machinery mediated by ubch1-2, ubch5,6 and E6-AP, E2 and E3 enzymes respectively. In the trade mark, iso [4]LGE(2)-modified calpain-1 loading impairs the cellular proteasome activity consistent with competitive inhibition and formation of suicidal high molecular weight aggregates. In contrast, higher calpain-1 activity, that appears to be under translational control, was observed in glaucomatous optic nerve compared to control. Therapeutic neuroprotection strategies using calpain-1 inhibitors will require consideration of such anatomic differences in its activity and biosynthesis.     

Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole.

The effectiveness of metronidazole (Flagyl) and nimorazole (Naxogin) has been compared by using these drugs in the recommended dosage in alternate patients in a series of 218 consecutive cases of vaginal trichomoniasis. Follow-up tests in 100 patients treated with metronidazole and 97 treated with nimorazole indicated cure-rates of 95 and 82 per cent. respectively. Male consorts were examined and given treatment on epidemiological grounds in about 70 per cent. of both treatment groups. Both drugs were free from significant side-effects. The causes of treatment failure in trichomoniasis are discussed and the desirability of relating dosage to the patient's body-weight is suggested. This factor may be especially important in deciding the dosage given on epidemiological grounds to the male consorts. It may also be an important advantage in the current trend of treating trichomoniasis in both sexes with larger doses over a much shorter time.     

Isolation and structure elucidation by LC-MS-SPE/NMR: PR toxin- and cuspidatol-related eremophilane sesquiterpenes from Penicillium roqueforti

Three eremophilane sesquiterpenes (1, 2, and 3) were isolated from Penicillium roqueforti DAOM 232127, and their structures were established. The new (3S)-3-acetoxyeremophil-1(2),7(11),9(10)-trien-8-one (3) is a likely biosynthetic precursor of PR toxin. 1-Hydroxyeremophil-7(11),9(10)-dien-8-one (1) is related to the immunosuppressant cuspidatol. The application of semihyphenated LC-MS-SPE/NMR to rapidly identify, purify, and elucidate the structures of 1, 2, and 3 is described.     

Two Automated Techniques for Carotid Lumen Diameter Measurement: Regional versus Boundary Approaches

The degree of stenosis in the carotid artery can be predicted using automated carotid lumen diameter (LD) measured from B-mode ultrasound images. Systolic velocity-based methods for measurement of LD are subjective. With the advancement of high resolution imaging, image-based methods have started to emerge. However, they require robust image analysis for accurate LD measurement. This paper presents two different algorithms for automated segmentation of the lumen borders in carotid ultrasound images. Both algorithms are modeled as a two stage process. Stage one consists of a global-based model using scale-space framework for the extraction of the region of interest. This stage is common to both algorithms. Stage two is modeled using a local-based strategy that extracts the lumen interfaces. At this stage, the algorithm-1 is modeled as a region-based strategy using a classification framework, whereas the algorithm-2 is modeled as a boundary-based approach that uses the level set framework. Two sets of databases (DB), Japan DB (JDB) (202 patients, 404 images) and Hong Kong DB (HKDB) (50 patients, 300 images) were used in this study. Two trained neuroradiologists performed manual LD tracings. The mean automated LD measured was 6.35 ± 0.95 mm for JDB and 6.20 ± 1.35 mm for HKDB. The precision-of-merit was: 97.4 % and 98.0 % w.r.t to two manual tracings for JDB and 99.7 % and 97.9 % w.r.t to two manual tracings for HKDB. Statistical tests such as ANOVA, Chi-Squared, T-test, and Mann-Whitney test were conducted to show the stability and reliability of the automated techniques.