Faculty Bibliography

Rapid diagnostic tests for tuberculosis (TB) are needed to facilitate early treatment of TB and prevention of Mycobacterium tuberculosis transmission. The ICT Tuberculosis test is a rapid, card-based immunochromatographic test for detection of antibodies directed against M. tuberculosis antigens. The objective of the study was to evaluate the performance of the ICT Tuberculosis test for the diagnosis of active pulmonary TB (PTB) with whole blood, plasma, and serum from patients suspected of having PTB and from asymptomatic controls in a setting with a high prevalence of PTB. Seventy patients suspected of having PTB (and who were later confirmed to have or not to have PTB by use of M. tuberculosis culture as the "gold standard") and 42 controls were studied. Twenty-one controls were neither vaccinated with Mycobacterium bovis bacillus Calmette-Guérin (BCG) nor tuberculin skin test (TST) positive (group A controls), and 21 controls were TST positive and/or had previously been vaccinated with BCG (group B controls). Study subjects were drawn from one hospital and one primary health care unit in Rio de Janeiro City, Brazil. One version of the test (ICT-1) was evaluated by using whole blood, plasma, and serum samples. Sera obtained for this study were frozen and later tested with a manufacturer-modified version of the test (ICT-2). Among the patients suspected of having PTB, the sensitivities of the ICT-1 with whole blood, serum, and plasma were 83, 65, and 70%, respectively, and the specificities were 46, 67, and 56%, respectively. Among the group A controls, the specificities of ICT-1 with the three specimen types were 95, 100, and 95%, respectively. Among the group B controls, the specificities of ICT-1 with the three specimen types were 71, 86, and 86%, respectively. Among the patients suspected of having PTB, the sensitivity of ICT-2 was 70% and the specificity was 65%. Among the group A controls, the specificity of ICT-2 was 95%, and among the group B controls, the specificity of ICT-2 was 81%. With a 29% observed prevalence of PTB among patients suspected of having PTB, the positive predictive values of the ICT tests ranged from 39 to 50% and the negative predictive values ranged from 82 to 87%. The ICT Tuberculosis tests were not sufficiently predictive to warrant their widespread use as routine diagnostic tests for PTB in this setting. However, further evaluation of these tests in specific epidemiologic settings may be warranted.

Particle classification is an important component of multivariate statistical analysis methods that has been used extensively to extract information from electron micrographs of single particles. Here we describe a new Bayesian Gibbs sampling algorithm for the classification of such images. This algorithm, which is applied after dimension reduction by correspondence analysis or by principal components analysis, dynamically learns the parameters of the multivariate Gaussian distributions that characterize each class. These distributions describe tilted ellipsoidal clusters that adaptively adjust shape to capture differences in the variances of factors and the correlations of factors within classes. A novel Bayesian procedure to objectively select factors for inclusion in the classification models is a component of this procedure. A comparison of this algorithm with hierarchical ascendant classification of simulated data sets shows improved classification over a broad range of signal-to-noise ratios

Secretory non-pancreatic phospholipase A(2) (sPLA(2)) has been implicated in inflammation and has been found in human atherosclerotic lesions. To test the effect of sPLA(2) deficiency on atherosclerosis, C57BL/Ks mice (apoE(+/+) and PLA(2)(++) were bred with C57BL/6 apoE knockout mice which are sPLA(2)(--) due to a spontaneous mutation. Sibling pairs of mice (apoE(--)/sPLA(2)(++) and apoE(--)/sPLA(2)(--)) on high fat Western diets were dissected at 22 weeks. In vitro enzyme assays confirmed higher serum sPLA(2) activity in the sPLA(2)(++) compared to sPLA(2)(--) for both sexes, while sPLA(2)(--) males had slightly higher serum cholesterol and phospholipids. Analysis of lipoprotein profiles by FPLC showed no effect of sPLA(2) genotype on any measured parameters. Atherosclerosis was quantitated by assaying cholesterol in aortic extracts. Male sPLA(2) trended slightly higher than sPLA(2)(++) with no statistical significance. Female sPLA(2)(++) and sPLA(2)(--) mice showed no significant differences in any of the measured parameters. These results suggest that the endogenous mouse sPLA(2) gene does not significantly affect HDL or atherosclerosis in mice.

So when the last of 3,000 reports was presented at the annual meeting of the American Society of Clinical Oncology here with no apparent major breakthroughs in any of the four most common forms of the disease -- lung, breast, prostate and colorectal -- few researchers were disappointed. While the gains reported were incremental, measured in percentage points and weeks of added survival, the experts said the gains could change the standard of medical practice for certain cancers. The drug and biotechnology industries want to market new drugs and therapies as fast as possible to recoup the big development costs. The industry boasts of significant advances to encourage doctors to prescribe their drugs and to encourage investors. Companies and leading cancer centers pay squadrons of public relations workers to flock around reporters to offer interviews with major researchers. So gains that seem merely incremental may disappoint industry executives and investment analysts. As Dr. [William Gradishar] of Northwestern said, summing up the modest gains reported for ''smart bomb'' drugs and other new therapies, ''Unfortunately, chemotherapy, surgery and radiation are not going to go away.''

Women at high risk for inherited breast and ovarian cancer can sharply reduce the chances of developing either disease by having surgery..

*The drug Gleevec was found to be much more effective and better tolerated than a combination of two other drugs in treating the early stages of chronic myelogenous leukemia. Gleevec was highly effective in preventing blast crisis, the most lethal form of the disease. The drug, marketed last year to treat the most advanced form of the blood cancer, should be standard therapy for new cases of the leukemia in its early stage and may substantially reduce the need for bone marrow transplants, the study's authors said. Of the 101 women who chose prophylactic surgery, 3 had early ovarian cancer that was found at the time of the operation. After a two-year follow-up period, 4 cancers (3 breast and 1 peritoneal, a type that resembles ovarian) developed among the remaining 98 women who had preventive surgery. This compared with the 13 cancers (8 breast, 4 ovarian and 1 peritoneal) that developed among 72 women who chose intensive surveillance for cancer instead of prophylactic ovarian surgery. In the largest study of malignant mesothelioma, the group that took Alimta combined with cisplatin (a standard cancer drug) survived a year on average, compared with nine months for those who took only cisplatin. The mesothelioma shrank in 41 percent of the Alimta group that took Alimta compared with 17 percent in the cisplatin group. There were 456 patients in the study

Some medical groups recommend yearly PSA tests for men 50 and older. But the role of prostate screening tests is controversial. Proof that such testing improves survival is lacking, and many men choose not to be tested. The researchers recommended increased vigilance for men with normal levels of 2 or higher. For men with initial levels of 2 to 2.9, the level rose to 4 over a five-year period in 34 percent of those tested. For those with an initial level of 3 to 3.9, the level rose to 4 in 83 percent.If less frequent testing intervals became standard practice, the number of PSA tests performed each year in the United States would drop by 55 percent, producing a saving of $500 million to $1 billion, Dr. [E. David Crawford] said. And, he added, it would reduce anxiety among men

Some medical groups recommend yearly PSA tests for men 50 and older. But the role of prostate screening tests is controversial. Proof that such testing improves survival is lacking, and many men choose not to be tested

The drug Gleevec was found to be much more effective and better tolerated than a combination of two other drugs in treating the early stages of chronic myelogenous leukemia. Gleevec was highly effective in preventing blast crisis, the most lethal form of the disease. The drug, marketed last year to treat the most advanced form of the blood cancer, should be standard therapy for newly diagnosed cases of the leukemia in its early stage, and it may substantially reduce the need for bone marrow transplants, the study's authors said. Of the 101 women who chose prophylactic surgery, three had early ovarian cancer that was found at the time of the operation. After a two-year follow-up period, four cancers (three breast and one peritoneal, a type that resembles ovarian) developed among the remaining 98 women who had preventive surgery. This compared to the 13 cancers (eight breast, four ovarian and one peritoneal) that developed among 72 women who chose intensive surveillance for cancer instead of prophylactic ovarian surgery. The study indicates that prophylactic ovarian surgery can be delayed until the completion of childbearing because the greatest risk for ovarian cancer is after age 40. The surgery provides women with hereditary risk for breast cancer an additional option beyond prophylactic removal of the breasts in preventing breast cancer and may allow ovarian cancer to be detected at an early stage when it can be cured, said Dr. Olufunmilayo Olopade of the University of Chicago