Faculty Bibliography

We describe a case of immune reconstitution inflammatory syndrome (IRIS) secondary to reactivation of Mycobacterium tuberculosis in an HIV-infected patient with a high CD4+ cell count, who presented with a generalized seizure 6 weeks after starting antiretroviral therapy (ART). In our patient, the inflammatory response resulted in radiological features of neurological, pulmonary, and lymph node (LN) tuberculosis- (TB) IRIS, without the typical symptoms. Diagnosis was confirmed by LN biopsy and acid-fast bacilli (AFB) culture of LN and sputum. Treatment with isoniazid, rifabutin, ethambutol, and pyrazinamide was started in addition to continuation of ART. To our knowledge, we describe the first case of an atypical clinical presentation of an unmasking reaction of disseminated TB-IRIS in an HIV infected patient without acquired immune deficiency syndrome (AIDS), with restoring immunity during ART. Clinical and radiological predictors of TB-IRIS in co-infected patients starting ART are therefore essential in anticipating complications and facilitating expeditious management and prompt therapy.

BACKGROUND/OBJECTIVES: Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery. METHODS: A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA. RESULTS: MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I. CONCLUSIONS: These results indicate an involvement of MASP-2 in ischemia-related necrotic myocardial injury in humans.

BACKGROUND: Congestive heart failure (CHF) is one of the leading causes of hospital readmissions within 30 days of discharge. Due to the substantial costs associated with these readmissions, several interventions to reduce CHF readmissions have been developed and implemented. METHODS: To reduce CHF readmissions at our community teaching hospital, the Smooth Transitions Equal Less Readmission (STELR) program was developed. Utilizing the Plan-Do-Check-Act cycle for quality improvement, resident physicians tracked patients enrolled in the STELR program. The resident contribution to the program was substantial in that they were able to quantify the improvement in both physician practices and patient readmissions. This provided insight into program areas requiring further modification, which the hospital would not have obtained without resident participation. RESULTS: The readmission rate for patients diagnosed with heart failure decreased from 32% prior to program implementation, to 24% hospital wide (including patients who were not tracked in the STELR program), and 21% among patients tracked by the residents. CONCLUSION: This effective CHF readmission reduction program requires less financial resources compared to government funded programs. The resident involvement in the STELR program helped to assess and improve the program and also allowed the residents to gain an awareness of the resources available to their patients to facilitate their transition home. The program exposed the residents to systems-based practice, a fundamental element of their residency training and, more generally, community care.

BACKGROUND:This study is a comparative epigenetic evaluation of the methylation status of the DLC1 tumor suppressor gene in naturally-occurring canine lymphoma. Canine non-Hodgkin's lymphoma (NHL) has been proposed to be a relevant preclinical model that occurs spontaneously and may share causative factors with human NHL due to a shared home environment. The canine DLC1 mRNA sequence was derived from normal tissue. Using lymphoid samples from 21 dogs with NHL and 7 normal dogs, the methylation status of the promoter CpG island of the gene was defined for each sample using combined bisulfite restriction analysis (COBRA), methylation-specific PCR (MSP), and bisulfite sequencing methods. Relative gene expression was determined using real-time PCR. RESULTS:The mRNA sequence of canine DLC1 is highly similar to the human orthologue and contains all protein functional groups, with 97% or greater similarity in functional regions. Hypermethylation of the 5' and 3' flanking regions of the promoter was statistically significantly associated with the NHL phenotype, but was not associated with silencing of expression or differences in survival. CONCLUSION/CONCLUSIONS:The canine DLC1 is constructed highly similarly to the human gene, which has been shown to be an important tumor suppressor in many forms of cancer. As in human NHL, the promoter CpG island of DLC1 in canine NHL samples is abnormally hypermethylated, relative to normal lymphoid tissue. This study confirms that hypermethylation occurs in canine cancers, further supporting the use of companion dogs as comparative models of disease for evaluation of carcinogenesis, biomarker diagnosis, and therapy.