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1.
Nucl Med Commun ; 44(9): 825-829, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37395540

ABSTRACT

OBJECTIVES: Determine if subspecialist second opinion review alters reporting of malignancy on 18 F-FDG PET/CT for patients with breast cancer. METHODS: This IRB-approved retrospective study compared 248 s opinion reads of 18 F-FDG PET/CT exams performed for patients with breast cancer against the original outside institution reports. Subspecialist reviews documented if malignant findings on the outside report were believed to be malignant and noted additional malignant findings not described on the outside report. Reference standard for malignancy or benignity was determined by pathology or follow-up imaging. RESULTS: Of 248 cases, 27 (11%) had discrepancies in the presence or absence of extra-axillary nodal or distant metastases. Of these 27, 14 (52%) had biopsy or imaging follow-up as a reference standard for malignancy/benignity. In cases with reference standard proof, the subspecialist second opinion review was correct in 13/14 (93%) of cases. This included eleven cases that the original report called malignant, but the subspecialist review called benign and subsequently proven to be benign; as well as two metastases called on subspecialist review, but not on the original report, and subsequently biopsy proven to be metastases. In one case, the second opinion read called a suspicious lesion that was biopsy proven to be benign. CONCLUSION: Subspecialist review improves the accuracy of diagnosis for the presence or absence of malignancy on FDG PET/CT examinations in patients with breast cancer. This demonstrates the value of performing second opinion reads of 18 F-FDG PET/CT studies in patients with breast cancer, particularly by subspecialist second opinion review reducing false positive reads.


Subject(s)
Breast Neoplasms , Positron Emission Tomography Computed Tomography , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Fluorodeoxyglucose F18 , Retrospective Studies , Positron-Emission Tomography/methods , Referral and Consultation , Radiopharmaceuticals
2.
J Am Coll Radiol ; 19(9): 1052-1068, 2022 09.
Article in English | MEDLINE | ID: mdl-35963282

ABSTRACT

OBJECTIVE: To quantitatively assess radiologists' preferences for Maintenance of Certification (MOC) and Continuing Certification (CC) using a survey of attitudes and perceptions. METHODS: A questionnaire that assessed attitudes and perceptions and included a discrete choice or trade-off task was developed by ACR staff in conjunction with an independent market research agency and the Survey Subcommittee of the ACR Task Force on Certification in Radiology. The trade-off exercise was integrated into this methodology to better understand the underlying utilities or preferences of the components of MOC-CC among respondents and to better enable specific recommendations on how to optimize the current program. The survey was administered via e-mail to 17,305 ACR members. The demographic and practice characteristics of the 1,994 (11.5%) respondents were similar to the ACR radiologist membership and correspond to a normal distribution. At a 95% confidence level, with a margin of error 2.1%, we believe that the respondent population fairly reflects the actual population. RESULTS: Similar proportions judged the existing program as excellent or very good (36%), or fair or poor (35%), with 27% neutral. MOC-CC was perceived more often as excellent or very good by those who were grandfathered yet still participating in MOC, were in academic practice, were in an urban setting, were older, or had a role with the ABR. In contrast, MOC-CC was more often judged as fair or poor by those who were not grandfathered, were in private practice, were in a rural setting, or were younger. The current MOC-CC program is not well regarded by diplomates, with few showing preference or acceptability. The program's reception is most sensitive to the following attributes: absence or presence of a practice quality improvement requirement, Online Longitudinal Assessment content including or excluding general radiology in addition to one's specialty and inclusion or exclusion of self-assessment as part of the CME. CONCLUSION: ACR members diverged in their attitudes toward MOC, with differences among specific demographic and practice characteristics. The current package of features of MOC-CC was widely viewed as unsatisfactory, and a more optimal feature set arose from a simulation exercise.


Subject(s)
Radiology , Specialty Boards , Certification , Clinical Competence , Education, Medical, Continuing , Humans , Radiologists , Radiology/education , United States
3.
Pediatr Radiol ; 52(3): 587-591, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34601621

ABSTRACT

Myositis ossificans is a benign, ossifying, soft-tissue pseudotumor that most commonly occurs in men ages 30-40 years after trauma. Myositis ossificans may also occur in children, but it is extremely rare in those younger than 10 years of age. While myositis ossificans can often mimic malignant soft-tissue tumors, it has many unique findings that can aid in diagnostic differentiation. This differentiation is critical to avoid unnecessary risk with potentially harmful procedures. We present a very unusual presentation of myositis ossificans in the immediate post-birth perinatal period, as well as a review of key imaging findings.


Subject(s)
Myositis Ossificans , Sarcoma , Soft Tissue Neoplasms , Adult , Child , Humans , Infant, Newborn , Magnetic Resonance Imaging , Male , Myositis Ossificans/diagnostic imaging , Myositis Ossificans/pathology , Soft Tissue Neoplasms/pathology
6.
Tomography ; 4(2): 43-45, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30206543

ABSTRACT

Prenatal ultrasonography in the early third trimester showed an unusual branching pattern of the right aortic arch. Echocardiography performed 4 h after birth showed the right aortic arch with mirror-image branching, patent ductus arteriosus, and patent foramen ovale. Because the location of the ductus arteriosus was unclear on echocardiography, cardiovascular magnetic resonance imaging was performed 3 days after birth. Advanced techniques including contrast-enhanced time-resolved magnetic resonance angiography and 3D time-of-flight magnetic resonance angiography allowed accurate diagnosis of a vascular ring comprising ascending and descending aorta, right aortic arch with mirror-image branching, and diverticulum of Kommerell giving rise to a left ligamentum arteriosum. The infant had hiccups, but no other symptoms. The esophagram was negative for obstruction. The infant was closely monitored; however, she developed esophageal obstruction at 7 months of age because of the vascular ring. She underwent lysis of the left ligamentum arteriosum followed by aortopexy for relief of esophageal obstruction. This report shows the utility of neonatal cardiovascular magnetic resonance imaging to evaluate complex congenital aortic arch anomalies.

7.
Pediatr Cardiol ; 39(5): 1063-1065, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29736793

ABSTRACT

A 16-year-old female, with a history of Williams syndrome, presented to our institution with a 2-week history of intermittent dizziness. Holter monitoring demonstrated occasional premature ventricular contractions with rare couplets and triplets as well as one short run of nonsustained ventricular tachycardia. Echocardiography revealed an abnormal and irregular left ventricular septum with multiple mobile, pedunculated muscular projections extending into the left ventricular cavity. Cardiac MR confirmed abnormally thickened trabeculations consisting of multiple parallel ridges of myocardium crossing the left ventricle. The appearance of these findings closely resembled bands of coral lining the ocean floor. As such, this finding can henceforth be known as the "coral sign." To our knowledge, no other reports of this finding in patients with Williams syndrome have been published.


Subject(s)
Myocardium/pathology , Williams Syndrome/diagnostic imaging , Adolescent , Adrenergic beta-Antagonists/therapeutic use , Echocardiography/methods , Electrocardiography, Ambulatory/methods , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Magnetic Resonance Imaging, Cine/methods , Tachycardia, Ventricular/etiology , Williams Syndrome/drug therapy
8.
Cureus ; 9(3): e1113, 2017 Mar 24.
Article in English | MEDLINE | ID: mdl-28446992

ABSTRACT

Secondary tumoral calcinosis (STC) refers to periarticular calcified masses associated with an identifiable condition. The most common of these identifiable conditions is a chronic renal failure. We present a unique case in which massive periarticular masses in a patient with calcinosis of chronic renal failure (CCRF) are demonstrated in the shoulder and hip on sonography, radiography and computed tomography (CT).

9.
J Clin Gastroenterol ; 51(5): 446-453, 2017.
Article in English | MEDLINE | ID: mdl-27779613

ABSTRACT

GOALS/BACKGROUND: Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality. STUDY: Prospective 15-center US cohort of patients with cirrhosis presenting with endoscopically proven AVH, all of whom received antibiotics, vapreotide (a somatostain analog) infusion and endoscopic band ligation. Patients were enrolled between August 2006 and April 2008. Primary outcome was 6-week mortality. Secondary outcome was 5-day treatment failure. The prognostic value of Child-Turcotte-Pugh (CTP) class, Model for End-stage Liver Disease (MELD) score and a recent recalibrated MELD were compared. RESULTS: Seventy eligible patient were enrolled; 18 (26%) patients died within 6-weeks of index bleed. Demographic, clinical, and laboratory data were compared between survivors and nonsurvivors. Multivariate models showed that admission CTP or the MELD score (separately) were independent predictors of survival. The discriminative values of CTP (area under receiver operating characteristic: 0.75) and MELD (area under receiver operating characteristic: 0.79) were good and not significantly different (P=0.27). However, calibration (correlation between observed and predicted mortality) test was significantly better for CTP than for MELD, with the recently described recalibrated MELD model having the worst agreement. Predicted mortality for CTP-A was <10%, CTP-B 10% to 30%; and CTP-C >33%. CONCLUSIONS: AVH mortality of 26% in the United States is in the upper range limit compared with recent series but may be due to inclusion of patients with more advanced cirrhosis. CTP score has the best overall performance in the prediction of 6-week mortality and is best at stratifying risk.


Subject(s)
Decision Support Techniques , Esophageal and Gastric Varices/diagnosis , Gastrointestinal Hemorrhage/diagnosis , Liver Cirrhosis/diagnosis , Disease Progression , Esophageal and Gastric Varices/mortality , Esophageal and Gastric Varices/therapy , Female , Gastrointestinal Hemorrhage/mortality , Gastrointestinal Hemorrhage/therapy , Humans , Liver Cirrhosis/mortality , Liver Cirrhosis/therapy , Male , Middle Aged , Predictive Value of Tests , Risk Assessment , Risk Factors , Time Factors , Treatment Failure , United States/epidemiology
10.
Gastroenterology ; 151(5): 902-909, 2016 11.
Article in English | MEDLINE | ID: mdl-27486033

ABSTRACT

BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. METHODS: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.


Subject(s)
Antiviral Agents/therapeutic use , Carbamates/therapeutic use , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Macrocyclic Compounds/therapeutic use , Sofosbuvir/therapeutic use , Sulfonamides/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Aminoisobutyric Acids , Cyclopropanes , Drug Administration Schedule , Drug Combinations , Drug Therapy, Combination , Female , Follow-Up Studies , Genotype , Humans , Lactams, Macrocyclic , Leucine/analogs & derivatives , Male , Middle Aged , Proline/analogs & derivatives , Quinoxalines , Serine Proteases , Treatment Outcome , Viral Nonstructural Proteins , Young Adult
11.
Case Rep Infect Dis ; 2016: 6151570, 2016.
Article in English | MEDLINE | ID: mdl-27313921

ABSTRACT

Eradication of chronic hepatitis C virus (HCV) infection is now possible with all oral antiviral medications, including the combination of ombitasvir, paritaprevir, dasabuvir, and ritonavir (PrOD) with or without ribavirin. While high rates of sustained virologic response (SVR) can be achieved, a small subset of patients experience on-treatment liver enzyme elevations, in particular women using concurrent estradiol-containing oral contraceptive medications (OCPs). Herein, we describe four cases of liver enzyme elevations within 2-3 weeks of PrOD initiation in African-American men infected with HCV genotype 1a or 1b. Three patients with varying degrees of hepatic fibrosis received a full treatment course without medication modification, achieved SVR, and experienced resolution of liver enzyme abnormalities. One patient with cirrhosis was switched mid-treatment to an alternate HCV regimen, experienced subsequent resolution of liver enzyme abnormalities, and achieved SVR. In summary, these cases suggest that all HCV patients treated with PrOD, independent of gender or concurrent medications, should have laboratory monitoring for liver enzyme elevations, with a particular emphasis on early monitoring in cirrhotic patients.

13.
Hepatology ; 61(1): 41-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25314116

ABSTRACT

UNLABELLED: Historically, clinical trials of regimens to treat chronic infection with hepatitis C virus (HCV) have used, as their primary efficacy endpoint, a sustained virological response (SVR)­defined as HCV RNA levels below a designated threshold of quantification­24 weeks after the end of treatment (SVR24). More recently, regulatory authorities have begun to accept SVR at 12 weeks post-treatment (SVR12) as a valid efficacy endpoint because of its high rate of concordance with SVR24. However, the concordance between SVR12 and SVR24 has not been systematically assessed with new regimens of recently approved direct-acting antiviral agents. The aim of this study was to assess the concordance between SVR at various post-treatment time points in phase III clinical trials of sofosbuvir (SOF)-containing regimens. We conducted a retrospective analysis of five trials enrolling 863 patients infected with HCV genotypes 1-6. The concordance between SVR at 4 weeks post-treatment (SVR4) and SVR12, and between SVR12 and SVR24, were determined, as well as positive predictive values (PPVs) and negative predictive values (NPVs). Overall, 779 of 796 patients (98.0%) with an SVR4 also achieved an SVR12, making the PPV of SVR4 for SVR12 98% and the NPV 100%. Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24, making the PPV of SVR12 for SVR24 >99% and the NPV 100%. Of patients who relapsed post-therapy, 77.6% did so within 4 weeks of completing therapy. CONCLUSION: Data from phase III studies demonstrate that with SOF-based regimens, with or without interferon, SVR12 and SVR24 correlate closely. Thus, SVR12 can be used effectively to determine "cure" rates in trials and in clinical practice.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Outcome Assessment, Health Care , RNA, Viral/blood , Uridine Monophosphate/analogs & derivatives , Adult , Female , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Recurrence , Sofosbuvir , Uridine Monophosphate/therapeutic use
14.
Hepatol Int ; 8(1): 83-93, 2014 Jan.
Article in English | MEDLINE | ID: mdl-26202409

ABSTRACT

PURPOSE: Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. METHODS: Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. RESULTS: CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10(-30)) was stronger than that between METAVIR (p = 3.86 × 10(-13)) or APRI (p = 5.48 × 10(-6)) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. CONCLUSION: The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40  KD)/ribavirin.

15.
Patient Prefer Adherence ; 5: 587-99, 2011.
Article in English | MEDLINE | ID: mdl-22163158

ABSTRACT

BACKGROUND: Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device. METHODS: In trial 1, 50 healthy adult subjects received one 180 µg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 µg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment. RESULTS: In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0-168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin. CONCLUSION: These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle.

16.
N Engl J Med ; 362(12): 1071-81, 2010 Mar 25.
Article in English | MEDLINE | ID: mdl-20335583

ABSTRACT

BACKGROUND: Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. RESULTS: Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. CONCLUSIONS: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)


Subject(s)
Anti-Infective Agents/therapeutic use , Gastrointestinal Agents/therapeutic use , Hepatic Encephalopathy/prevention & control , Lactulose/therapeutic use , Liver Cirrhosis/drug therapy , Rifamycins/therapeutic use , Aged , Anti-Infective Agents/adverse effects , Chronic Disease , Clostridioides difficile , Clostridium Infections/etiology , Double-Blind Method , Drug Therapy, Combination , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Liver Cirrhosis/mortality , Male , Middle Aged , Proportional Hazards Models , Rifamycins/adverse effects , Rifaximin , Secondary Prevention
17.
Am J Clin Nutr ; 87(4): 863-71, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18400708

ABSTRACT

BACKGROUND: We previously established furanocoumarins as mediators of the interaction between grapefruit juice (GFJ) and the model CYP3A4 substrate felodipine in healthy volunteers using a GFJ devoid of furanocoumarins. It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates. OBJECTIVE: The effects of furanocoumarin-free GFJ on drug disposition were further characterized by using the dual CYP3A4/P-glycoprotein substrate cyclosporine. DESIGN: By randomized crossover design, 18 healthy volunteers received cyclosporine (5 mg/kg) with 240 mL orange juice (control), GFJ, or furanocoumarin-free GFJ. Blood was collected over 24 h. Juice treatments were separated by > or = 1 wk. The effects of diluted extracts of each juice and of purified furanocoumarins on [3H]cyclosporine translocation in Caco-2 cells were then compared. RESULTS: The median (range) dose-corrected cyclosporine area under the curve and the maximum concentration with GFJ (P < or = 0.007), but not with furanocoumarin-free GFJ (P > or = 0.50), were significantly higher than those with orange juice [15.6 (6.7-33.5) compared with 11.3 (4.8-22.0) x 10(-3) h/L and 3.0 (1.6-5.8) compared with 2.4 (1.1-3.1) mL(-1), respectively]. The median time to reach maximum concentration and terminal elimination half-life were not significantly different between the juices (2-3 and 7-8 h, respectively; P > or = 0.08). Relative to vehicle, the GFJ extract, orange juice extract, and purified furanocoumarins partially increased apical-to-basolateral and decreased basolateral-to-apical [3H]cyclosporine translocation in Caco-2 cells, whereas the furanocoumarin-free GFJ extract had negligible effects. Reanalysis of the clinical juices identified polymethoxyflavones as candidate P-glycoprotein inhibitors in orange juice but not in GFJ. CONCLUSIONS: Furanocoumarins mediate, at least partially, the cyclosporine-GFJ interaction in vivo. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Citrus paradisi/chemistry , Cyclosporine/pharmacokinetics , Cytochrome P-450 CYP3A Inhibitors , Enzyme Inhibitors/pharmacokinetics , Furocoumarins/pharmacology , Adult , Area Under Curve , Beverages/analysis , Caco-2 Cells , Citrus/chemistry , Cross-Over Studies , Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Dose-Response Relationship, Drug , Female , Food-Drug Interactions , Fruit/chemistry , Humans , Male , Middle Aged
18.
Am J Clin Nutr ; 83(5): 1097-105, 2006 May.
Article in English | MEDLINE | ID: mdl-16685052

ABSTRACT

BACKGROUND: Grapefruit juice (GFJ) enhances the systemic exposure of numerous CYP3A4 drug substrates, including felodipine, by inhibiting intestinal (but not hepatic) first-pass metabolism. Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice, but their contribution to the GFJ effect in vivo remains unclear. OBJECTIVE: To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction, a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine. DESIGN: With the use of food-grade solvents and absorption resins, furanocoumarins were removed (approximately 99%) from whole GFJ, whereas other major ingredients (flavonoids) were retained. In an open, 3-way, randomized crossover design, 18 healthy volunteers ingested felodipine (10 mg) with 1 of the 3 juices (240 mL). Blood was collected over 24 h. At least 1 wk elapsed between juice treatments. RESULTS: The median and range of the area under the curve and the maximum concentration of felodipine were significantly (P < 0.001) greater with consumption of GFJ [110 (range: 58-270) nmol . h/L and 21 (7.6-50) nmol/L, respectively] than with that of orange juice [54 (29-150) nmol . h/L and 7.6 (3.4-13.9) nmol/L, respectively] or furanocoumarin-free GFJ [48 (23-120) nmol . h/L and 8.3 (3.0-16.6) nmol/L, respectively]. GFJ, orange juice, and furanocoumarin-free GFJ did not differ significantly (P > 0.09) in median time to reach maximum plasma concentration [2.5 (1.5-6), 2.8 (1.5-4), and 2.5 (2-6) h, respectively] or terminal half-life [6.6 (4.2-13.6), 7.8 (4.4-13.2), and 6.8 (2.6-14.4) h, respectively]. CONCLUSION: Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism.


Subject(s)
Beverages/analysis , Citrus paradisi/chemistry , Felodipine/pharmacokinetics , Fruit/chemistry , Furocoumarins/analysis , Furocoumarins/pharmacology , Adult , Caco-2 Cells , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme Inhibitors , Drug Interactions , Enzyme Inhibitors , Felodipine/blood , Female , Furocoumarins/chemistry , Humans , Intestines/ultrastructure , Male , Microsomes/enzymology
19.
J Clin Gastroenterol ; 40(3): 220-4, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16633123

ABSTRACT

GOAL: Our aim was to assess stigmatization by evaluating the impact of hepatitis C virus (HCV) on social interactions, feelings of rejection, internalized shame, and financial insecurity, and behavior. BACKGROUND: HCV patients suffer from slowly progressive disease. Although much research has improved the long-term prognosis of chronic HCV, quality of life may be affected by perceived social stigmatization. STUDY: In a cross-sectional study, HCV patients without cirrhosis or significant comorbidities were recruited from the University of North Carolina viral hepatitis clinic. Subjects completed a questionnaire administered by a trained interviewer that assessed changes in sexual behavior, personal hygiene habits, social function, and interactions. Additionally, subjects completed validated, standardized questionnaires, the Health Status Questionnaire, and the SCL-90-R. Frequencies were calculated for the prevalence of stigmatization and altered social interaction. Correlations between education and behavior changes were assessed. A series of multivariate analyses controlling for age, sex, and education were performed to assess the association between HCV acquisition risk and stigmatization. RESULTS: One hundred seventy-five of 217 potential subjects (81%) participated in the survey. The average age was 45.2+/-7.7 years. Fifty-five percent were men and 53% were single. Twenty-nine percent had some college education. Risk factors for HCV acquisition included transfusion (21%) and injection drug use (29%), whereas 32% had an unknown mode of infection. Among common activities, 47% were less likely to share drinking glasses, 14% were less likely to prepare food, and one-third of subjects were less likely to share a towel. Thirty-five percent of respondents reported changes in their sexual practices. Decreased frequency of kissing and sexual intercourse was reported in 20% and 27% of individuals, respectively. Almost half of the single subjects reported increased use of condoms compared with only 20% among married couples. The majority of subjects perceived financial insecurity, internalized shame, and social rejection. Only 39% reported health impairment. Education level did not influence behavior change. CONCLUSION: The majority of HCV subjects alter common behaviors and report financial insecurity, internalized shame, and social rejection, regardless of the method of HCV acquisition or socioeconomic status. These findings indicate that all HCV individuals be counseled and encouraged to participate in educational programs at the time of diagnosis to reduce unnecessary behavioral changes and stigmatization perceptions to improve quality of life.


Subject(s)
Hepatitis C, Chronic/psychology , Prejudice , Quality of Life/psychology , Cross-Sectional Studies , Female , Humans , Interpersonal Relations , Male , Middle Aged , Sickness Impact Profile , Surveys and Questionnaires
20.
Am J Transplant ; 4(7): 1133-8, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15196072

ABSTRACT

Studies suggest donor age and year of transplantation are associated with low graft survival in liver transplant recipients with hepatitis C. We sought to determine if advanced donor age and recent year of transplantation are associated with graft survival in hepatitis C recipients and to determine if the effect of donor age on graft survival is specific to hepatitis C. We analyzed the United Network for Organ Sharing liver transplant database from 1994 to 2002. Six thousand four hundred and four subjects transplanted for end-stage liver disease from chronic hepatitis C met our criteria. One-year graft survival in hepatitis C recipients with organs from donors <40 years old and >or=60 years old was 84% and 73%, p = 0.003, respectively. These rates in recipients with cholestatic liver disease and alcoholic liver disease were 85% and 82%, respectively, p = 0.11 and 82% and 78%, respectively, p = 0.14. Three-year graft survival in hepatitis C recipients transplanted from 1994 to 1995 and 1996 to 1999 was 67% and 69%, respectively, p = 0.10. Graft survival in hepatitis C recipients has not declined in recent years. Older donor age is associated with lower short-term graft survival in recipients with hepatitis C, but not in recipients with cholestatic or alcoholic liver disease.


Subject(s)
Graft Survival , Hepatitis C/complications , Liver Transplantation/methods , Adult , Age Factors , Aged , Databases as Topic , Female , Graft Rejection , Humans , Liver Diseases/therapy , Liver Diseases, Alcoholic/therapy , Male , Middle Aged , Multivariate Analysis , Time Factors , Treatment Outcome
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