Faculty Bibliography

Rearrangements involving the MLL gene on chromosome band 11q23 are a hallmark of therapy-related acute myeloid leukemias following treatment with topoisomerase II poisons including etoposide. Therapy-related and de novo genomic translocation breakpoints cluster within a well-characterized 8.3-kb fragment of MLL. Repair of etoposide-stabilized DNA topoisomerase II covalent complexes may initiate MLL rearrangements observed in patients. We used a culture system of primary human hematopoietic CD34+ cells and inverse polymerase chain reaction to characterize the spectrum of stable genomic rearrangements promoted by etoposide exposure originating within an MLL translocation hotspot in therapy-related leukemia. Alterations to the region were observed at a readily detectable frequency in etoposide-treated cells. Illegitimate repair events after minimal repair included MLL tandem duplications and translocations, with minor populations of deletions or insertions. In stably repaired cells that proliferated for 10 to 14 days, the significant majority of illegitimate events were MLL tandem duplications, and several deletions, inversions, insertions, and translocations. Thus, etoposide promotes specific rearrangements of MLL consistent with the full spectrum of oncogenic events identified in leukemic samples. Although etoposide-initiated rearrangements are frequent, only a small subset of translocations occurs in cells that proliferate significantly.

We studied 6,141 consecutive, asymptomatic, nondiabetic patients who underwent electron beam tomography and explored the interaction between metabolic risk factors (RFs) and premature family history (FH) of coronary heart disease (CHD) in predicting the presence and severity of coronary arterial calcium (CAC). In the presence of >2 metabolic RFs, patients with a positive FH of premature CHD had a significantly higher prevalence of any CAC, CAC >/=100, and CAC >/=75th age-gender percentile than those without a FH of CHD. Our study demonstrated that a familial propensity to subclinical atherosclerosis interacts with the presence of >/=2 metabolic RFs, magnifying the risks for those exposed to both.

Background. Dialysis patients are hospitalized for an average of 15 days per patient-year. Understanding the reasons for hospital admissions and the factors affecting outcomes may suggest strategies to reduce hospital utilization. Methods. The records of all inpatients receiving hemodialysis (HD) at our center between May I and October 31, 2003, were reviewed for patient characteristics, admitting diagnosis, length of stay (LOS), and outcome. Admissions were classified as acute (new HD) or chronic HD admissions. Results. There were 194 inpatient HD admissions, consisting of 147 (76%) chronic and 47 (24%) acute admissions. Cardiovascular disease accounted for 49% of chronic and 40% of acute admissions. The most common admitting diagnoses for chronic admissions were pulmonary edema (20%) and acute coronary syndrome (16%). For acute admissions, the most common diagnoses were renal failure (30%) and acute coronary syndrome (15%). The median LOS for acute admissions was significantly longer than for chronic admissions (17 vs. 8 days, p < 0.001). Eighty-six percent of the patients requiring acute HD had chronic kidney disease (CKD). Conclusions. Cardiovascular disease is a major cause of hospital admission for HD patients. Most patients requiring acute HD have CKD. Strategies to reduce hospital utilization by HD patients include treatment of heart failure, maintenance of dry weight, coronary artery disease risk factor reduction, increased use of arteriouenous fistulas, interventions to reduce vascular access thromboses, and timely initiation of dialysis for patients with CKD. Studies of disease management strategies are warranted to reduce hospital utilization and improve patient outcomes

Drug safety is not as absolute as it has been made to appear in the media. Few drugs on the market are villains, and few are heroes.

Methicillin-resistant Staphylococcus aureus (MRSA) infection was identified in 2 horses treated at a veterinary hospital in 2000, prompting a study of colonization rates of horses and associated persons. Seventy-nine horses and 27 persons colonized or infected with MRSA were identified from October 2000 to November 2002; most isolations occurred in a 3-month period in 2002. Twenty-seven (34%) of the equine isolates were from the veterinary hospital, while 41 (51%) were from 1 thoroughbred farm in Ontario. Seventeen (63%) of 27 human isolates were from the veterinary hospital, and 8 (30%) were from the thoroughbred farm. Thirteen (16%) horses and 1 (4%) person were clinically infected. Ninety-six percent of equine and 93% of human isolates were subtypes of Canadian epidemic MRSA-5, spa type 7 and possessed SCCmecIV. All tested isolates from clinical infections were negative for the Panton-Valentine leukocidin genes. Equine MRSA infection may be an important emerging zoonotic and veterinary disease

OBJECTIVE: The burden of medical comorbidities was compared between older (> or =60 years) and younger patients with serious mental illness. METHODS: Patients (N=8,083) diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder in 2001 were identified from VA facilities in the mid-Atlantic region. Medical comorbidities were identified by an ICD-9-based clinical classification algorithm. RESULTS: Older, versus younger, patients were more likely to be diagnosed with cardiovascular or pulmonary conditions, and less likely to be diagnosed with substance-use disorders or hepatic conditions. CONCLUSIONS: More aggressive detection and management of general-medical comorbidities in older patients with serious mental illness is paramount

The foot and ankle are critical components in our ability to ambulate.Injuries to either can significantly interfere with a patient's ability to carry out normal activities. In severe cases, they can be devastating to a patient's independence. Careful examination of the foot and ankle using established mechanical tests, along with understanding of the anatomy of the complex,is needed to confirm the history and to assist in the diagnosis and treatment of foot and ankle injuries.The following points are key to clinical examination of the foot and ankle: .The examination of the foot and ankle needs to be done with the patient in both weight-bearing and non-weight bearing positions. .The examination of the foot and ankle should include an evaluation of the patient's gait. .Reproduction of a patient's symptoms is the key to making a correct diagnosis. .Although anatomic variants may predispose some individuals to injury,in general, if asymptomatic, no treatment should be done