Publications

BACKGROUND

Nonpolypoid (flat and depressed) colorectal lesions are increasingly recognized. Their endoscopic removal requires specialized EMR techniques, which are more complex to perform. Outcomes data on EMR of nonpolypoid neoplasms in the United States is needed.

OBJECTIVE

To determine the safety and efficacy of EMR in the resection of nonpolypoid colorectal neoplasms > or = 1 cm.

DESIGN

Retrospective analysis.

SETTING

Veterans Affairs Palo Alto Health Care System.

PATIENTS

Over a 5-year period, patients who underwent EMR for nonpolypoid colorectal lesions > or = 1 cm.

INTERVENTION

A standardized approach that included lesion assessment, classification, inject-and-cut EMR technique, reassessment, and treatment of residual tissue.

MAIN OUTCOME MEASUREMENTS

Complete resection, bleeding, perforation, development of advanced cancer, and death.

RESULTS

A total of 100 patients (125 lesions: 117 flat and 8 depressed) met inclusion criteria. Mean size was 16.7 +/- 7 mm (range, 10-50 mm). Histology included 5 submucosal invasive cancers, 5 carcinomas in situ, and 91 adenomas. Thirty-eight patients (48 lesions) did not receive surveillance colonoscopy: 8 had surgery, 16 had hyperplastic pathology, and 14 did not undergo repeat examination. Surveillance colonoscopy was performed on 62 patients (77 lesions). Complete resection was achieved in 100% of these patients after 1 to 3 surveillance colonoscopies. All patients received follow-up (mean [standard deviation] = 4.5 +/- 1.4 years); none developed colorectal cancer or metastasis.

LIMITATIONS

Single endoscopist, retrospective study.

CONCLUSIONS

A standardized EMR (inject-and-cut) technique is a safe and curative treatment option in nonpolypoid colorectal neoplasms (> or = 1 cm) in the United States.

BACKGROUND

Enhanced external counterpulsation (EECP) currently is used as an outpatient therapy for patients with refractory chronic angina.

HYPOTHESIS

We sought to determine the safety and feasibility of a portable EECP unit to treat patients with acute coronary syndrome and/or cardiogenic shock in the coronary care unit (CCU).

METHODS

Ten patients with acute coronary syndrome and/or cardiogenic shock who were not considered candidates for invasive intra-aortic balloon counterpulsation (IABP) by the treating cardiologist were prospectively enrolled in this single-center study. Each patient received 2-4 one-hour EECP treatments performed at the bedside in the CCU. Anticoagulation or recent femoral access was not an exclusion criterion.

RESULTS

The mean age was 58 +/- 19 years (range 28-81), and half were women. Patients had either acute coronary syndrome alone (n = 4), cardiogenic shock alone (n = 3), or both (n = 3). The cardiac indications for study enrollment included: acute inferior wall ST-segment elevation myocardial infarction with cardiogenic shock (n = 2), non-ST-segment elevation myocardial infarction with postinfarction angina (n = 2) or heart failure (n = 1), unstable angina with refractory rest angina (n = 2), cardiogenic shock from ischemic cardiomyopathy with severe mitral regurgitation (n = 1), and cardiogenic shock from nonischemic cardiomyopathy (n = 2). No adverse events were recorded during or as a consequence of EECP therapy, including no bleeding complications, no heart failure exacerbations, and no skin breakdown. The portable EECP unit did not interfere with ongoing critical care nursing.

CONCLUSIONS

EECP is safe and feasible for acute bedside therapy of critically ill patients with acute coronary syndrome and/or cardiogenic shock who are not candidates for IABP.

Homeless individuals experience high rates of morbidity and mortality, yet many homeless studies include small percentages of female participants. We therefore sought to determine correlates of homelessness separately for men and women in a sample of individuals visiting free food programs. Between August 2003 and April 2004, 324 individuals were recruited from San Francisco free food programs and interviewed regarding housing, sociodemographics, health, drug use, sex trade, and incarceration. Over one-half of women and almost three-fourths of men reported homelessness in the prior year. Among women, white race, younger age, not living with minor children, engaging in sex trade and recent incarceration were strongly associated with homelessness; however, only incarceration maintained the strong association in adjusted analysis (OR = 7.16, CI = 3.83-13.4). Among men, heavy alcohol use, drug use, years spent living in San Francisco and monthly income were strongly associated with homelessness; however, only years living in San Francisco (OR = 0.28, CI = 0.19-0.42) and monthly income maintained strong association in adjusted analysis (OR = 0.27, CI = 0.13-0.57). Housing patterns and the strongest correlates of homelessness among individuals visiting free food programs differ by sex. These results suggest the need to characterize homelessness and develop effective homeless interventions separately for men and women.

PblA and PblB are prophage-encoded proteins of Streptococcus mitis strain SF100 that mediate binding to human platelets. The mechanism for surface expression of these proteins has been unknown, as they do not contain signal sequences or cell wall sorting motifs. We therefore assessed whether expression of these proteins was linked the lytic cycle of the prophage. Deletion of either the holin or lysin gene resulted in retention of PblA and PblB in the cytoplasm, and loss of these proteins from the cell wall. Flow cytometric analysis revealed that induction of phage replication in SF100 produced a subpopulation of cells with increased permeability. This effect was abrogated by disruption of the holin and lysin genes. Treatment of these mutants with exogenous PblA and PblB restored surface expression, apparently via binding of the proteins to cell wall choline. Loss of PblA and PblB expression was associated with decreased platelet binding in vitro, and reduced virulence in an animal model of endocarditis. Thus, expression of PblA and PblB occurs via a novel mechanism, whereby phage induction increases bacterial permeability and release of the proteins, followed by their binding to surface of viable cells. This mechanism may be important for endovascular infection.

Early views on the relationship between adherence and resistance postulated a bell-shaped relationship that balanced selective drug pressure and improved viral suppression along a continuum of adherence. Although this conceptual relationship remains valid, recent data suggest that each regimen class may have different adherence-resistance relationships. These regimen-specific relationships are a function of the capacities of resistant virus to replicate at different levels of drug exposure, which are largely, but not entirely, determined by the impact of mutations on susceptibility of the virus and the impact of the mutations on the inherent ability of the virus to replicate efficiently. Specific patterns of adherence, such as treatment discontinuations, may influence adherence-resistance relationship to combination regimens comprised of medications with differing half-lives. Host genomics that alters antiretroviral drug distribution and metabolism may also impact adherence-resistance relationships. Optimal antiretroviral regimens should be constructed such that there is little overlap in the window of adherence that selects for antiretroviral drug resistance.

Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified. Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin. In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1. Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug.