Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
2011
Colonic perineuriomas are recently described benign mucosal polyps that are composed of a bland spindle cell proliferation surrounding crypts that often demonstrate hyperplastic/serrated epithelial changes. However, the origin of this unique stromal proliferation is still unclear, and the association with serrated polyps, including sessile serrated adenomas, has not been fully described. We evaluated the pathologic and molecular features of colonic polyps associated with perineurial-like proliferations in 2 retrospective cohorts: (1) a series of 198 consecutive sessile serrated adenomas and (2) 20 colonic polyps diagnosed as a perineurioma irrespective of the presence of serrated colonic crypts. Thirteen of 198 (6.5%) sessile serrated adenomas demonstrated a perineurial-like stromal proliferation, with most (12 of 13, 92%) involving the right (9 cases) and transverse colon (3 cases). In all 13 cases, the perineurial-like proliferation surrounded serrated colonic crypts and typically involved only a small area of the sessile serrated adenoma (average 9% of polyp size; range, 2% to 19%). All 11 polyps evaluated for epithelial membrane antigen (EMA) expression demonstrated stromal EMA staining limited to the perineurial-like proliferation. Twelve of 13 (92%) sessile serrated adenomas with perineurial-like proliferations demonstrated a pV600E BRAF mutation. Of the 20 colonic polyps diagnosed as a perineurioma, 18 (90%) demonstrated serrated crypts intimately associated with the perineurial-like proliferation. In 13 of 18 polyps with associated serrated crypts, all serrated crypts were invested with the perineurial proliferation. In 5 cases, serrated crypts were seen away from the perineurial proliferation. Of these 18 polyps, the majority (16 of 18, 89%) were microvesicular hyperplastic polyps involving the left colon. However, 2 (11%) polyps in the right colon demonstrated histologic features diagnostic of sessile serrated adenoma. All 18 polyps with serrated crypts demonstrated a pV600E BRAF mutation. In contrast, the 2 polyps not associated with serrated crypts were negative for a BRAF mutation. Our results show for the first time that perineurial-like stromal proliferations frequently occur in sessile serrated adenomas. The presence of focal perineurial-like stromal proliferations in sessile serrated adenomas and the common finding of serrated crypts in colonic perineuriomas are likely indicative of an epithelial-stromal interaction, possibly related to some factor elaborated by the serrated epithelium.
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UNLABELLED
Pain is common among people living with HIV/AIDS (PLWHA), but little is known about chronic pain in socioeconomically disadvantaged HIV-infected populations with high rates of substance abuse in the postantiretroviral era. This cross-sectional study describes the occurrence and characteristics of pain in a community-based cohort of 296 indigent PLWHA. Participants completed questionnaires about sociodemographics, substance use, depression, and pain. Cut-point analysis was used to generate categories of pain severity. Of the 270 participants who reported pain or the use of a pain medication in the past week, 8.2% had mild pain, 38.1% had moderate pain, and 53.7% had severe pain. Female sex and less education were associated with more severe pain. Depression was more common among participants with severe pain than among those with mild pain. Increasing pain severity was associated with daily pain and with chronic pain. Over half of the participants reported having a prescription for an opioid analgesic. Findings from this study suggest that chronic pain is a significant problem in this high risk, socioeconomically disadvantaged group of patients with HIV disease and high rates of previous or concurrent use of illicit drugs.
PERSPECTIVE
This article presents epidemiological data showing that unrelieved chronic pain is a significant problem for indigent people living with HIV. Participants reported pain severity similar to those with metastatic cancer. Despite high rates of substance use disorders, approximately half received prescriptions for opioid analgesics, although few for long-acting agents.
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2011
HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4(+) T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recognized as a major barrier to curing HIV-1 infection. The molecular mechanisms of latency are complex and include the absence in resting CD4(+) T cells of nuclear forms of key host transcription factors (e.g., NFκB and NFAT), the absence of Tat and associated host factors that promote efficient transcriptional elongation, epigenetic changes inhibiting HIV-1 gene expression, and transcriptional interference. The presence of a latent reservoir for HIV-1 helps explain the presence of very low levels of viremia in patients on antiretroviral therapy. These viruses are released from latently infected cells that have become activated and perhaps from other stable reservoirs but are blocked from additional rounds of replication by the drugs. Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir.
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PURPOSE
Because avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs) is recommended for most individuals with chronic kidney disease (CKD), we sought to characterize patterns of NSAID use among persons with CKD in the United States.
METHODS
A total of 12,065 adult (aged 20 years or older) participants in the cross-sectional National Health and Nutrition Examination Survey (1999-2004) responded to a questionnaire regarding their use of over-the-counter and prescription NSAIDs. NSAIDs (excluding aspirin and acetaminophen) were defined by self-report. CKD was categorized as no CKD, mild CKD (stages 1 and 2; urinary albumin-creatinine ratio of ≥ 30 mg/g) and moderate to severe CKD (stages 3 and 4; estimated glomerular filtration rate of 15-59 mL/min/1.73 m(2)). Adjusted prevalence was calculated using multivariable logistic regression with appropriate population-based weighting.
RESULTS
Current use (nearly every day for 30 days or longer) of any NSAID was reported by 2.5%, 2.5%, and 5.0% of the US population with no, mild, and moderate to severe CKD, respectively; nearly all of the NSAIDs used were available over-the-counter. Among those with moderate to severe CKD who were currently using NSAIDs, 10.2% had a current NSAID prescription and 66.1% had used NSAIDs for 1 year or longer. Among those with CKD, disease awareness was not associated with reduced current NSAID use: (3.8% vs 3.9%, aware vs unaware; P=.979).
CONCLUSIONS
Physicians and other health care clinicians should be aware of use of NSAIDs among those with CKD in the United States and evaluate NSAID use in their CKD patients.
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Approximately 1 in 4 individuals infected with the human immunodeficiency virus (HIV) in the United States is coinfected with the hepatitis C virus. Both conditions increase the risk for the development and progression of kidney disease. The effect, however, of coexisting HIV and hepatitis C infection on the spectrum and progression of kidney disease is not well known. To compare the clinical features, histopathologic kidney diagnoses, and proportion of individuals progressing to end-stage kidney disease (ESKD), we reviewed the clinical records of HIV-infected individuals with and without hepatitis C coinfection who underwent ultrasound-guided percutaneous kidney biopsies between February 7, 1995, and March 30, 2009.Of the 249 HIV-infected individuals included in this study, 58% were coinfected with hepatitis C. Coinfected individuals were older (mean age, 46 ± 7 vs. 44 ± 10 yr, respectively; p < 0.01) and more likely to have used illicit drugs (85% vs. 14%, respectively; p < 0.01) compared to HIV-infected individuals without hepatitis C. HIV-associated nephropathy was the most common histopathologic diagnosis in both groups. Immune-complex glomerulonephritides (ICGNs), including lupus-like nephritis, postinfectious glomerulonephritis, membranous glomerulopathy, membranoproliferative glomerulonephritis, IgA nephropathy, and nonspecific ICGNs, occurred more frequently in individuals coinfected with hepatitis C than in those not coinfected (22% vs. 11%, respectively; p = 0.02). Although the proportion of those who died was similar between the 2 groups, hepatitis C coinfection was independently associated with a greater risk of progression to ESKD (hazard ratio, 1.81; 95% confidence interval, 1.09-2.99; p = 0.02).The current study demonstrates that coinfection with hepatitis C in individuals infected with HIV predisposes these individuals to immune-complex glomerulonephritides and is associated with increased risk of ESKD in the biopsied population.
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Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve. These discoveries will change the way that breast cancer risk is understood in Mexico over the next few decades.
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STUDY OBJECTIVE
To evaluate the impact of a hospitalwide increase in the recommended vancomycin starting dose from 45 to 60 mg/kg/day on initial vancomycin trough concentrations in children suspected of having an invasive methicillin-resistant Staphylococcus aureus (MRSA) infection.
DESIGN
Retrospective medical record review.
SETTING
Dedicated children's hospital located in a tertiary care, academic medical center.
PATIENTS
A total of 182 children aged 1 month-12 years with normal renal function who had suspected MRSA infections treated with vancomycin during two different starting dose recommendation periods: 45 mg/kg/day divided every 8 hours during July 2006-June 2007 (low-dose group [88 children]) and 60 mg/kg/day divided every 6 hours during July 2008-June 2009 (high-dose group [94 children]).
MEASUREMENT AND MAIN RESULTS
Data on patient demographics, vancomycin doses, and initial vancomycin trough concentrations were collected. No significant demographic differences were noted between patients in the low-dose and high-dose groups. The mean ± SD initial vancomycin trough level increased from 7 ± 5 μg/ml in the low-dose group to 9 ± 5 μg/ml in the high-dose group (p<0.001). The percentage of patients with an initial trough level less than 5 μg/ml declined from 38% (33/88 children) in the low-dose group to 17% (16/94 children) in the high-dose group (p<0.001), whereas the percentage of patients with an initial trough concentration in the potentially adverse range (> 20 μg/ml) did not change between the two groups (2% vs 2%, p=0.9). Less than 14% (13/94 children) achieved a trough level in the range of 15-20 μg/ml in the high-dose group.
CONCLUSION
An increase in the recommended vancomycin starting dose to 60 mg/kg/day decreased the likelihood of an initial low vancomycin trough level (< 5 μg/ml), with no increase in the proportion of patients with trough levels in a potentially toxic range. The 60-mg/kg/day dose did not consistently achieve a vancomycin trough of 15-20 μg/ml, a goal suggested by some experts for adults. Comparative effectiveness studies are needed to directly evaluate vancomycin dosing regimens and clinical outcomes for children with invasive MRSA infections.
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Enterococcus faecalis is a gram-positive bacterium that is part of the indigenous microbiotica of humans and animals as well as an opportunistic pathogen. In this study, we have fractionated the membrane proteome of E. faecalis and identified many of its constituents by mass spectrometry. We present blue native-/SDS-PAGE reference maps that contain 102 proteins. These proteins are important for cellular homeostasis, virulence, and antibiotic intervention. Intriguingly, many proteins with no known function were also identified, indicating that there are substantial gaps in the knowledge of this organism's biology. On a more limited scale, we also provide insight into the composition of membrane protein complexes. This study is a first step toward elucidating the membrane proteome of E. faecalis, which is critical for a better understanding of how this bacterium interacts with a host and with the extracellular milieu.
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