Faculty Bibliography

The premise: Geralyn Lucas is just beginning a job when she's diagnosed with breast cancer at the age of 27. The non-invasive cancer has an extensive intraductal component involving three separate areas of her breast. After debating whether to have a lumpectomy or a mastectomy, she chooses the latter, with adjuvant chemotherapy. Despite frequent episodes of nausea and vomiting, Lucas (played by Sarah Chalke) continues to work, buoyed by her friends. She also bolsters her mood and self-image by dressing well, getting a tattoo -- and wearing lipstick. Although at first worried that her husband will leave her, especially when she spies him speaking privately with a nurse, he ultimately proves to be very supportive. Lucas goes on to become pregnant and deliver a healthy child

PURPOSE: To explore the relationship of HIV, hepatitis C (HCV), and alcohol abuse/dependence to risk for hepatocellular carcinoma and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Male veterans (n = 14,018) with a first HIV diagnosis in the Veterans Affairs Healthcare System from October 1997 to September 2004; and 28,036 age-, race-, sex-, and location-matched HIV-negative veterans were identified. We examined the incidence of hepatocellular carcinoma and NHL and presence of HCV and alcohol abuse/dependence using International Classification of Diseases, ninth revision (ICD-9-CM) codes. HIV-positive to HIV-negative incident rate ratios (IRRs) and 95% CIs for the occurrence of hepatocellular carcinoma and NHL were calculated using Poisson regression models. RESULTS: HIV-positive veterans were at greater risk for hepatocellular carcinoma than HIV-negative veterans (IRR = 1.68; 95% CI, 1.02 to 2.77). After adjusting for HCV infection and alcohol abuse/dependence, HIV status was not independently associated with hepatocellular cancer (IRR = 0.96; 95% CI, 0.56 to 1.63). HIV-positive veterans had 9.71 times (95% CI, 6.99 to 13.49) greater risk of NHL than HIV-negative veterans. After adjusting for HCV and alcohol abuse/dependence, the IRR for NHL comparing HIV-positive with HIV-negative veterans is similar (IRR = 10.03, 95% CI, 7.19 to 13.97). CONCLUSION: HIV-positive veterans have a higher relative incidence of hepatocellular carcinoma and NHL than HIV-negative veterans. For hepatocellular carcinoma, this association appears to be largely explained by the higher prevalence of HCV and alcohol abuse/dependence. Efforts to decrease hepatocellular carcinoma among persons with HIV should focus primarily on detecting and treating HCV and reducing heavy alcohol use

PURPOSE: To assess the safety and efficacy of a 4-drug, 3-tablet, once-daily (qd) regimen consisting of abacavir/lamivudine/zidovudine (ABC/3TC/ZDV; 2 tablets) and tenofovir (TDF) in antiretroviral-naive patients with plasma HIV-1 RNA 30,000 copies/mL at 48 weeks. METHOD: All participants received ABC/3TC/ZDV (300/150/300 mg) and TDF (300 mg) qd in this pilot, open-label, multicenter study. Intent-to-treat (ITT) analyses were conducted to evaluate virologic and immunologic efficacy. RESULTS: Of the 123 participants enrolled, 52 (42%) prematurely discontinued study for adverse events (14), were lost to follow-up (13), had virologic nonresponse (12), and withdrew for other reasons (13). At week 48, by ITT missing=failure analysis, 41% (51/123) and 51% (63/123) of participants had plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; by ITT-observed analysis, 75% (51/68) and 93% (63/68) had plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; 11% (14/123) met virologic nonresponse criteria. Median week 48 change in CD4+ cell count from baseline was +127 cells/mm3. Median week 48 changes from baseline for fasting lipids were as follows: cholesterol (-9 mg/dL), HDL (+1 mg/dL), LDL (-9 mg/dL), and triglycerides (-4 mg/dL). CONCLUSION: A high rate of premature discontinuations contributed to the overall suboptimal virologic response to ABC/3TC/ZDV+TDF qd; however, the regimen was not associated with high rates of virologic failure previously observed with TDF+ABC/3TC

OBJECTIVE:Clinically non-functioning pituitary adenomas (NFPAs) can express functional dopamine D2 receptors. Therapy with dopamine (DA) agonists may result in a NFPA size reduction. However, DA agonist-sensitive and -resistant NFPAs are clinically indistinguishable. We have studied the correlation between in vivo imaging of D2 receptors using (123)I-epidepride and the radiological response of NFPA to DA in 18 patients. METHODS:Patients were treated with either cabergoline (1-2 mg/week) or quinagolide (150-300 mug/day) for a mean period of 89.7 months (range, 34-187 months). RESULTS:Pituitary uptake of (123)I-epidepride varied from slight uptake classified as grade 0 to very high classified as grade 3. Grade 0 uptake was found in four patients; grade 1 in three; grade 2 in ten, and grade 3 in one. NFPA stabilization or shrinkage with DA agonist therapy showed no significant difference between grade 0, 1, and 2 tumors (mean tumor stabilization or shrinkage: 31, 30, and 36% respectively). However, when we considered a decrease in tumor size ranging from 0 to 20% as tumor stabilization and >20% decrease in tumor size as true shrinkage, one out of four NFPAs with grade 1 uptake, two out of three with grade 1 uptake, and eight out of ten with grade 2 uptake showed tumor shrinkage. CONCLUSION/CONCLUSIONS:In conclusion, there is limited clinical usefulness of dopamine D2 receptor imaging for predicting the clinical efficacy of DA agonist in selected patients with NFPAs. DA agonist therapy in NFPAs can result in tumor stabilization and shrinkage.

CONTEXT/BACKGROUND:Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Despite efforts to develop new therapeutic regimens for metastatic ACC, surgery remains the mainstay of treatment. Interferons are known to exert tumor-suppressive effects in several types of human cancer. DESIGN/METHODS:We evaluated the tumor-suppressive effects of type I interferons (IFN)-alpha2b and IFNbeta on the H295 and SW13 human ACC cell lines. RESULTS:As determined by quantitative RT-PCR analysis and immunocytochemistry, H295 and SW13 cells expressed the active type I IFN receptor (IFNAR) mRNA and protein (IFNAR-1 and IFNAR-2c subunits). Both IFNalpha2b and IFNbeta1a significantly inhibited ACC cell growth in a dose-dependent manner, but the effect of IFNbeta1a (IC50 5 IU/ml, maximal inhibition 96% in H295; IC50 18 IU/ml, maximal inhibition 85% in SW13) was significantly more potent, compared with that of IFNalpha2b (IC50 57 IU/ml, maximal inhibition 35% in H295; IC50 221 IU/ml, maximal inhibition 60% in SW13). Whereas in H295 cells both IFNs induced apoptosis and accumulation of the cells in S phase, the antitumor mechanism in SW13 cells involved cell cycle arrest only. Inhibitors of caspase-3, caspase-8, and caspase-9 counteracted the apoptosis-inducing effect by IFNbeta1a in H295 cells. In H295 cells, IFNbeta1a, but not IFNalpha2b, also strongly suppressed the IGF-II mRNA expression, an important growth factor and hallmark in ACC. CONCLUSIONS:IFNbeta1a is much more potent than IFNalpha2b to suppress ACC cell proliferation in vitro by induction of apoptosis and cell cycle arrest. Further studies are required to evaluate the potency of IFNbeta1a to inhibit tumor growth in vivo.

We present a novel approach for analysis of Mycobacterium tuberculosis complex (MTC) strain genotyping data. Our work presents a first step in an ongoing project dedicated to the development of decision support tools for tuberculosis (TB) epidemiologists exploiting both genotyping and epidemiological data. We focus on spacer oligonucleotide typing (spoligotyping), a genotyping method based on analysis of a direct repeat (DR) locus. We use mixture models to identify strain families of MTC based on their spoligotyping patterns. Our algorithm, SPOTCLUST, incorporates biological information on spoligotype evolution, without attempting to derive the full phylogeny of MTC. We applied our algorithm to 535 different spoligotype patterns identified among 7166 MTC strains isolated between 1996 and 2004 from New York State TB patients. Two models were employed and validated: a 36-component model based on global spoligotype database SpolDB3, and a randomly initialized model (RIM) containing 48 components. Our analysis both confirmed previously expert-defined families of MTC strains and suggested certain new families. SPOTCLUST, which is available online, can be further improved by incorporating data obtained using additional strain genetic markers and epidemiological information. We demonstrate on New York City (NYC) patient data how the resulting models can potentially form the basis of TB control tools using genotyping

BACKGROUND: Prior studies have found fluoroquinolone exposure to be a risk factor for infection with fluoroquinolone-resistant gram-negative rods in the acute care setting. However, risk factors may be different in the long-term care setting. METHODS: A case-control study design was used to determine whether fluoroquinolone exposure is a risk factor for fluoroquinolone-resistant Escherichia coli urinary tract infections in a long-term care center. Cases had fluoroquinolone-resistant E. coli urinary tract infections; 4 controls were selected for each case. RESULTS: Thirty-three case patients were eligible; 132 controls were then selected. In the multivariable analysis, fluoroquinolone-resistant E. coli urinary tract infection was more common with prior fluoroquinolone use (odds ratio 21.8, 95% confidence interval, 3.7-127.1). CONCLUSIONS: Prior fluoroquinolone use is a strong risk factor for fluoroquinolone-resistant E. coli urinary tract infection in the long-term care setting. Further studies are needed to examine the effect of interventions to decrease fluoroquinolone-resistant infections in the long-term care setting, including studying the effect of decreasing fluoroquinolone use.

The discovery of protease inhibitors was a revolutionary accomplishment in the world of virology that has changed the course of clinical disease for HIV patients. Here is how these drugs work: When the protease enzymes is blocked, HIV makes copies of itself that can no longer infect new cells. Studies have shown that these drugs reduce the amount of circulating virus in the blood and improve the body's immunological response to viruses. At a time when drug companies are routinely criticized for drug safety violations, it is good to recall the life-saving effects of the HIV drugs

BACKGROUND: One of the less well-defined complications of familial dysautonomia (FD) is chronic kidney disease (CKD). The goal of this report is to better define the prevalence and severity of kidney disease in this population and identify associated risk factors. METHODS: We conducted a retrospective analysis of the database of the Dysautonomia Treatment and Evaluation Center at New York University School of Medicine for patients with FD who were seen at ages 15, 20, 25, 30, 35, and 40 years. Estimated glomerular filtration rate (GFR) was compared with that of the general population. Changes in mean blood pressure from supine to erect at ages 15 and 20 years were analyzed for patients who eventually required dialysis therapy and compared with those of the other patients with FD. Percentage of patients requiring dialysis and duration of treatment also were analyzed. RESULTS: Mean estimated GFR of each predefined age group was considerably less than that of the general population starting at age 15 years (P < 0.001). Patients with FD were more likely to develop stage 3, 4, or 5 CKD than the general population. Of patients who remained alive at age 25 years, 19% eventually required dialysis. Those who required dialysis therapy were less likely to have had a feeding gastrostomy tube placed (P < 0.001) and had much more pronounced postural changes in blood pressure (P < 0.0001) by age 15 years. For those requiring dialysis therapy, average duration of treatment was 9 months. CONCLUSION: Patients with FD are far more likely than the general population to develop CKD. Patients with FD who eventually required dialysis showed a greater degree of orthostatic hypotension and were significantly less likely to have had a feeding gastrostomy tube placed for hydration before the age of 15 years. Dialysis therapy is not well tolerated in this population