Faculty Bibliography

CONTEXT: The traditional teaching that pulmonary tuberculosis characterized by lymphadenopathy, effusions, and lower or mid lung zone infiltrates on chest radiography represents 'primary' disease from recently acquired infection, whereas upper lobe infiltrates and cavities represent secondary or reactivation disease acquired in the more distant past, is not based on well-established clinical evidence. Furthermore, it is not known whether the atypical radiograph common in human immunodeficiency virus (HIV)-associated tuberculosis is due to a preponderance of primary progressive disease or altered immunity. OBJECTIVE: To analyze the relationship between recently acquired and remotely acquired pulmonary tuberculosis, clinical and demographic variables, and radiographic features by using molecular fingerprinting and conventional epidemiology. DESIGN, SETTING, AND POPULATION: A retrospective, hospital-based series of 456 patients treated at a New York City medical center between 1990 and 1999. Eligible patients had to have had at least 1 positive respiratory culture for Mycobacterium tuberculosis and available radiographic data. MAIN OUTCOME MEASURES: Radiographic appearance as measured by the presence or absence of 6 features: upper lobe infiltrate, cavitary lesion, adenopathy, effusions, lower or mid lung zone infiltrate, and miliary pattern. Radiographs were considered typical if they had an upper lobe infiltrate or cavity whether or not other features were present. Atypical radiographs were those that had adenopathy, effusion, or mid lower lung zone infiltrates or had none of the above features. RESULTS: Human immunodeficiency virus infection was most commonly associated with an atypical radiographic appearance on chest radiograph with an odds ratio of 0.20 (95% confidence interval, 0.13-0.31). Although a clustered fingerprint, representing recently acquired disease, was associated with typical radiograph in univariate analysis (odds ratio, 0.68; 95% confidence interval, 0.47-0.99), the association was lost when adjusted for HIV status. CONCLUSIONS: Time from acquisition of infection to development of clinical disease does not reliably predict the radiographic appearance of tuberculosis. Human immunodeficiency virus status, a probable surrogate for the integrity of the host immune response, is the only independent predictor of radiographic appearance. The altered radiographic appearance of pulmonary tuberculosis in HIV is due to altered immunity rather than recent acquisition of infection and progression to active disease

Dr. Peter Piot, who directs the United Nations AIDS program, said: ''The epidemic has yet to display a natural saturation point. In Swaziland, the country most affected by AIDS in the world, adult prevalence continues to climb; 42.6 percent of pregnant women there tested positive for H.I.V. in 2004. ''In East Africa, for example, in every big city'' there had been declines in the rates for young people, ''and particularly among women and girls,'' Dr. Piot said in an interview. He cited Addis Ababa, Kigali, Lusaka and Nairobi -- the capitals of Ethiopia, Rwanda, Zambia and Kenya -- largely because they are the places with the most extensive AIDS education and prevention programs, particularly for young people. For the first time, truly comprehensive responses to AIDS, including prevention and treatment, are emerging, Dr. Piot said. ''Iran has one of the best AIDS programs,'' he added, citing in particular its needle-exchange efforts

Surgeons can generally learn the on-pump operation faster than the off-pump technique because it is technically less demanding. Also, the report said, surgeons can generally perform more grafts, if necessary, in an on-pump bypass, and the grafts may stay open longer. A controversy has developed over some evidence that a small but significant number of on-pump bypass patients suffer a degree of cognitive impairment like memory and attention deficits and language problems. Such problems tended to occur less among patients whose bypasses were performed with the beating-heart technique compared with the stopped-heart technique, the team said. The extent of the decrease was not detailed. The most conclusive benefit of off-pump over on-pump operations was for patients who had deposits of calcium in their aortas, the body's main artery. When surgeons clamp the aorta in the on-pump technique, small pieces can break off to cause disabling and fatal strokes

The scientists analyzed the genetic makeup of patients taking warfarin in clinics at the University of Washington in Seattle and Washington University in St. Louis and found that they fell into three dosing groups -- low, intermediate and high. The genetic variations identified in the study correlated with the grouping, suggesting the findings hold promise for simplifying warfarin therapy, the scientists reported in The New England Journal of Medicine. The scientists identified genetic variations, matched them to the doses warfarin patients were taking, and found that patients with a particular variation of the gene usually took similar doses of warfarin. The VKORC1 gene accounted for 25 percent of the overall variation in warfarin doses in the studies -- what Dr. [Mark J. Rieder] said he believes is the largest genetic variation affecting warfarin

A novel series of selective ligands for the human glucocorticoid receptor is described. Structure-activity studies focused on variation of B-ring size, ketal ring size, and ketal substitution. These analogs were found to be potent and selective ligands for GR and have partial agonist profiles in functional assays for transactivation (TAT, GS) and transrepression (IL-6). Of these compounds, 27, 28, and 35 were evaluated further in a mouse LPS-induced TNF-alpha secretion model. Compound 28 had an ED(50) of 14.1 mg/kg compared with 0.5 mg/kg for prednisolone in the same assay.

A patient with newly diagnosed end-stage renal disease (ESRD) received a femoral catheter for hemodialysis (HD). Shortly thereafter he developed fever, and blood cultures grew methicillin-resistant Staphylococcus aureus. The catheter was removed and the patient was treated with both vancomycin and rifampin; however, blood culture positivity persisted. The cerebrospinal fluid showed sterile meningitis. Subsequent imaging studies demonstrated aortic valve endocarditis and multiple mycotic aneurysms that appeared to include the intra- and extracranial vessels. The patient eventually died from sepsis. This case illustrates the aggressive and invasive nature of systemic infection with S. aureus and underscores the high morbidity and mortality associated with infections related to HD catheters.

OBJECTIVES: Over time, quarantine has become a classic public health intervention and has been used repeatedly when newly emerging infectious diseases have threatened to spread throughout a population. Here, we weigh the economic costs and benefits associated with implementing widespread quarantine in Toronto during the SARS outbreaks of 2003. METHODS: We compared the costs of two outbreak scenarios: in Scenario A, SARS is able to transmit itself throughout a population without any significant public health interventions. In Scenario B, quarantine is implemented early on in an attempt to contain the virus. By evaluating these situations, we can investigate whether or not the use of quarantine is justified by being either cost-saving, life saving, or both. RESULTS: Our results indicate that quarantine is effective in containing newly emerging infectious diseases, and also cost saving when compared to not implementing a widespread containment mechanism. CONCLUSIONS: This paper illustrates that it is not only in our humanitarian interest for public health and healthcare officials to remain aggressive in their response to newly emerging infections, but also in our collective economic interest. Despite somewhat daunting initial costs, quarantine saves both lives and money.

Combining prescription drugs has advantages, but various combinations can have conceptual differences. When 2 medications are combined in 1 pill, as in 2 new statin combos, a doctor may not be able to identify which drug is causing a side effect. Packaging 2 drugs physically separate but together in a blister pack makes the most sense for initial therapy

How the Food and Drug Administration (FDA) responds to criticism of its drug safety process will determine whether drug safety actually improves. Propping up the Office of Drug Safety with more bureaucratic prominence or adding new requirements to the preapproval process will add to the cost of drug development and not make drugs safer. New information tools can dramatically improve postmarketing surveillance and collection of data on safety. This information could then be used to reach more definitive regulatory conclusions sooner. New incentives will be needed to entice payers and product developers to work on building a broader, more robust system for collecting data on drug safety