Extraperitoneal ascending appendicitis: Usefulness of the split interfascial plane sign on MDCT.

PURPOSE: To retrospectively evaluate the multidetector computed tomography (MDCT) findings of extraperitoneal ascending appendicitis. MATERIALS AND METHODS: The MDCT examinations of 10 patients with extraperitoneal ascending appendicitis confirmed by laparoscopic surgery were retrospectively analyzed. Preoperative MDCT examinations were obtained after intravenous administration of iodinated contrast material in all patients. Transverse and coronal reformatted MDCT images were reviewed in consensus by two radiologists. The presence of the extraperitoneal triangle sign, the split interfascial plane sign, and the other classical findings of appendicitis were evaluated. RESULTS: Luminal dilatation, wall enhancement of the inflamed appendix, and fat infiltration were present in 10/10 patients (100%). The perforation of the inflamed appendix with abscess formation was present in 4/10 patients (40%). The split interfascial plane sign was present in 7/10 patients (70%), and parts of inflamed appendix or periappendiceal abscess were located behind the right extraperitoneal triangle in 8/10 patients (80%). CONCLUSION: The split interfascial plane sign and the presence of an appendiceal tip or periappendiceal abscess located in the right extraperitoneal triangle are highly suggestive of extraperitoneal ascending appendicitis on MDCT.

Multidetector-row computed tomography (MDCT) findings of adnexal torsion: An analysis of 116 patients.

PURPOSE: The purpose of this study was to identify differences in multidetector-row computed tomography (MDCT) findings of adnexal torsion (AT) according to the anatomical subtypes and identify MDCT findings that may predict conservative treatment. MATERIALS AND METHODS: A total of 295 consecutive women with pelvic pain who underwent preoperative MDCT and subsequent surgery less than 24 h after admission were included in this retrospective study. Among them, 116 women (mean age: 33.9 years; range: 3-80 years) with histopathologically confirmed AT after surgery were included in the final analysis. RESULTS: On histopathological examination, an underlying ovarian mass was found in 98 women (98/116, 84.5%). In the group without ovarian mass (n=18), massive edema (12/18, 66.7% vs. 16/98, 16.3%; P<0.001) was frequently found. However, in the group with ovarian mass (n=98), twisted tube or pedicle (5/18, 27.8% vs. 55/98, 56.1%; P=0.027) and concentric or eccentric wall thickening (5/18, 27.8% vs. 82/98, 83.7%; P<0.001) demonstrated a statistically significant higher incidence. Based on the surgical and pathological results, the 116 women were classified into three subtypes including ovary-tubal (89/116, 77%), ovary only (22/116, 19%) and tubal only subtype (5/116, 4%). In the ovary-tubal subtype, tubal thickening (88/89, 98.9% vs. 11/22, 50.0%; P<0.001), twisted tube or pedicle (57/89, 64.0% vs. 3/22, 13.6%; P<0.001) and remaining tubal enhancement (52/89, 58.4% vs. 7/22, 31.8%; P=0.025) were more frequently observed than in the ovary only subtype. There was no significant difference between the relative frequency of imaging findings in the cystectomy group and adnexectomy group of the ovary-tubal type. CONCLUSIONS: Knowledge of common and characteristic MDCT findings of AT according to the anatomical subtypes is important to make accurate diagnosis and avoid delayed treatment.

Multidetector-row computed tomography (MDCT) features of small bowel obstruction (SBO) caused by Meckel's diverticulum.

OBJECTIVES: To report the multidetector-row computed tomography (MDCT) findings of small bowel obstruction (SBO) caused by Meckel's diverticulum. MATERIALS AND METHODS: Ten patients (9 men and 1 woman; age range, 2-44 years; median age, 21years) with surgical proven Meckel's diverticulum who presented SBO on the preoperative MDCT were included in the study. RESULTS: On MDCT, all patients presented with SBO, either high-grade (n=6) or low-grade obstruction (n=4). Meckel's diverticulum was identified in five patients (n=5, 50%) on preoperative MDCT. In the five patients in whom a diverticulum was not seen on preoperative MDCT, MDCT showed a transition site on ileum with dilated proximal loops (n=3), pneumoperitoneum (n=1), jejuno-jejunal intussusception (n=1). Transition zone was located near midline in four patients (4/5, 80%). CONCLUSION: The diagnosis of Meckel's diverticulum complicated SBO can be made with certainty when the diverticulum is visualized on preoperative MDCT. However, the preoperative diagnosis is difficult if the Meckel's diverticulum is not noted on the MDCT. When the obstructive processes are visualized in the lower abdomen or pelvis, particularly near the midline, one should keep in mind that SBO may be caused by Meckel's diverticulum without prior surgical history.

Clinical efficacy of transcatheter embolization of visceral artery pseudoaneurysms using N-butyl cyanoacrylate (NBCA).

PURPOSE: Transcatheter endovascular embolization within a reasonable time before rupture or deterioration of a patient's general condition is an important procedure for managing visceral pseudoaneurysms. N-butyl 2-cyanoacrylate (NBCA, enbucrilate) is an embolic material used in the blockade of visceral pseudoaneurysms. This study evaluated the clinical efficacy of transcatheter embolization of visceral artery pseudoaneurysms using NBCA. PATIENTS AND METHODS: Between June 2004 and February 2014, 13 patients (9 males and 4 females; age range, 26-80years; mean, 57.9years) with 14 pseudoaneurysms were treated by transcatheter embolization using NBCA. NBCA was mixed with iodized oil at a 1:3 ratio to control its polymerization time and to render it radiopaque. Pseudoaneurysms were located on the gastroduodenal artery (n=1), pancreaticoduodenal artery (n=2), dorsal pancreatic artery (n=1), proximal jejunal artery (n=1), colic artery (n=1), splenic artery (n=3), renal artery (n=4; two in one patient), and hepatic artery (n=1). RESULTS: All patients recovered immediately following the embolization procedure, and two patients showed minor complications that required only medical observation. CONCLUSIONS: Transcatheter embolization using NBCA for the treatment of visceral pseudoaneurysms is a safe, effective, and low-cost treatment method with a high success rate.

Gender-dependent racial difference in disposition of cyclosporine among healthy African American and white volunteers.

Pharmacokinetic studies of intravenous and oral cyclosporine (cyclosporin) were performed in 22 healthy African American (n = 11) and white (n = 11) volunteers. Blood cyclosporine concentrations were measured by high performance liquid chromatography. Concentration versus time data were analyzed by noncompartmental models, and statistical analyses were performed by ANOVA. The clearance of intravenous and oral cyclosporine was 4.3 +/- 0.9 mL/min/kg and 13.5 +/- 4.5 mL/min/kg, respectively, in African Americans and 3.7 +/- 0.5 mL/min/kg and 9.6 mL/min/kg, respectively, in the white volunteers (P = .0001). There was a significant race and gender interaction (P = .038). Bioavailability was lower in African Americans (32.8 +/- 6.6%) compared with white volunteers (39.3 +/- 7.1%; P = .049), with a significant race and gender interaction (P = .048). The dose-adjusted area under the curve (AUC) of intravenous and oral cyclosporine was 54.3 +/- 10.6 ng x hr/mL per milligram and 18.1 +/- 4.1 ng x hr/mL per milligram, respectively, in African Americans and 61.9 +/- 6.8 ng x hr/mL per milligram and 24.2 +/- 4.6 ng x hr/mL per milligram, respectively, in white volunteers (P = .023). These findings suggest that disposition of cyclosporine is dependent both on race and on gender.

Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients.

This study investigated the effect of grapefruit juice on cyclosporine A (CsA) bioavailability in 10 renal transplant patients. Under CsA steady state conditions, patients were randomly administered their usual dose of CsA with either 8 ounces of grapefruit juice or 8 ounces of water. Using a crossover design, a 12-hr pharmacokinetic study was then conducted. Grapefruit juice increased the area under the concentration versus time curve (4218+/-1497 ng x hr/ml [grapefruit juice] vs. 3415+/-1288 ng x hr/ml [water], P=0.029) and 12-hr trough (244+/-214 ng x ml [grapefruit juice] vs. 132+/-56 ng x ml [water], P=0.09), but it did not change peak concentration (734+/-290 ng x ml [grapefruit juice] vs. 708+/-305 ng x ml [water], P=0.76). In addition, grapefruit juice delayed the time to peak concentration compared with water (5.4+/-3.0 hr [grapefruit juice] vs. 2.8+/-0.8 hr [water], P=0.025). These data suggest that concurrent administration of grapefruit juice with CsA will delay the absorption of CsA and increase the drug exposure of CsA without changing peak concentration.

Effect of grapefruit juice on the pharmacokinetics of microemulsion cyclosporine and its metabolite in healthy volunteers: does the formulation difference matter?

This study was conducted to determine the effect of grapefruit juice on the pharmacokinetics of microemulsion cyclosporine and its major metabolites, M1 and M17, in 12 healthy volunteers. Each subject received two oral doses of microemulsion cyclosporine with water or grapefruit juice. Each subject also received intravenous cyclosporine on a separate occasion. Blood samples were collected for assay of cyclosporine, M1, and M17 during a 24-hour period, and were analyzed by a high-performance liquid chromatography method. Compared with water, administration with grapefruit juice significantly increased peak concentration (Cmax) and area under the concentration-time (AUC) of cyclosporine. Administration with grapefruit juice increased the absolute bioavailability of microemulsion cyclosporine by 45%. For cyclosporine metabolites, administration with grapefruit juice decreased the Cmax and AUC of M1 by 21% and 15%, respectively. These findings suggest that concurrent administration with grapefruit juice increases the bioavailability of microemulsion cyclosporine significantly compared with water in healthy volunteers. The grapefruit juice affects each metabolite formation and its pharmacokinetics differently, which suggests that the major site of its formation is different.

Effect of grapefruit juice on pharmacokinetics of microemulsion cyclosporine in African American subjects compared with Caucasian subjects: does ethnic difference matter?

This study aims to determine the effect of grapefruit juice (GJ) on microemulsion cyclosporine (CsA) in 11 African American subjects, and it was compared to those in 11 Caucasian subjects. Each subject received two oral doses of CsA with water (W) or GI as well as i.v. CsA. Regardless of race, GJ significantly increased the peak concentration (Cmax) and area under the time-curve (AUC) of CsA; however, the magnitude of GJ effects was different between African American subjects and Caucasian subjects (p = 0.0003). GJ increased peak concentration of CsA by 39% in African American subjects, while the difference in Caucasian subjects was only 8% (p > 0.05). GJ also increased AUC of CsA in African American subjects by 60%, while GJ increased that in Caucasian subjects by 44% (p = 0.0001). The absolute bioavailability of CsA was 21% lower in African American subjects compared with Caucasian subjects when it was given with water (p = 0.048), but these differences disappeared when it was given with GJ (p = 0.6). These findings suggest that concurrent administration of GJ increases the bioavailability of CsA in African American subjects in greater magnitude compared with Caucasian subjects.

Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers.

A study was conducted to examine the effect of grapefruit juice on the disposition of quinidine sulfate and changes of QT intervals after oral administration to twelve healthy male volunteers. Participants received two oral doses of quinidine sulfate tablets (400 mg) with 240 mL of water or grapefruit juice, each separated by a 1-week washout period. Plasma samples for analysis of quinidine and its major metabolite, 3-hydroxyquinidine, were collected for a 24-hour period and analyzed by a high-performance liquid chromatography method. For pharmacodynamic data, the electrocardiograms (ECGs) were performed for 12 hours, and the recordings were marked for ECG interval at all blood collection time periods. There was no significant difference in pharmacokinetic parameters of quinidine when administered with grapefruit juice or water, except for time to maximum concentration (tmax), which was 1.6 hours after administration with water and 3.3 hours after administration with grapefruit juice. Administration with grapefruit juice also resulted in a 33% decrease in the area under the concentration-time curve (AUC) of 3-hydroxyquinidine compared with water, but did not increase the AUC of quinidine or change the ratio of AUC of 3-hydroxyquinidine to the AUC of quinidine. Pharmacodynamic parameters, including changes in the rate-corrected QT (QTc) interval, closely paralleled the pharmacokinetic data, in that administration with grapefruit juice led to delayed maximal effect on QTc and reduction in maximal effect. Administration with grapefruit juice therefore delays the absorption of quinidine and inhibits the metabolism of quinidine to 3-hydroxyquinidine.

A urine metabolic ratio of dextromethorphan and 3-methoxymorphinan as a probe for CYP3A activity and prediction of cyclosporine clearance in healthy volunteers.

Dextromethorphan (DM) is metabolized in the body to dextrophan (DT) and 3-methoxymorphinan (3-MM) by cytochrome P450 (CYP) 2D6 and 3A4, respectively, and cyclosporine (CsA) is a known substrate of CYP3A4. We attempted to determine if the urine metabolic ratio of DM:3-MM at various time intervals during 24 hours is predictive of CsA clearance in 11 healthy volunteers. Each subject took DM 30 mg orally, and serial urine samples were collected at 0-4, 4, and 4-24, and 0-24 hours. Subjects then were randomly assigned to receive either oral microemulsion CsA 5 mg/kg or intravenous CsA 1.5 mg/kg in a crossover fashion in a two-sequence pharmacokinetic study with a wash-out period of at least 7 days. A total of 17 blood samples were collected from each subject in the CsA pharmacokinetic study over 24 hours. Urinary DM, DT, and 3-MM were quantified by high-performance liquid chromatography (HPLC) with a fluorescence detector, and blood CsA concentrations were analyzed by HPLC with ultraviolet detection. All subjects were extensive metabolizers of CYP2D6 as determined by metabolic ratios of DM:DT (mean+/-SD 0.0255+/-0.048). There was no correlation between CYP2D6 and CYP3A4 (p=0.38). The metabolic ratios of DM:3-MM in any urine samples during the 24-hour collection period did not predict CsA pharmacokinetics, although the 0-24 hour sample had an unexpected positive correlation with CsA clearance (r2 = 0.38, p<0.0001). The correlation was similar for metabolic ratios of DM:3-MM with intravenous CsA clearance (r2 = 0.5, p<0.0001). Metabolic ratios of DM:3-MM based on 24-hour cumulative urine collection did not appear to have clinical utility in predicting CYP3A activity measured by CsA clearance.

Sudden hearing loss associated with tacrolimus in a kidney-pancreas allograft recipient.

A 38-year-old woman with type 1 diabetes underwent kidney-pancreas transplantation. Her postoperative course was complicated due to recurrent acute graft rejections and pancreatitis. After initial immunosuppression with microemulsion cyclosporine, mycophenolate mofetil, and prednisone with muromonab-CD3 induction, cyclosporine was switched to tacrolimus on day 44. The initial dosage was 5 mg twice/day, but it was gradually increased to 10 mg twice/day, aiming at 15-20 ng/ml. On day 17 of tacrolimus therapy the woman developed sudden hearing loss with tinnitus. The serum tacrolimus level was 28.3 ng/ml (therapeutic range 10-20 ng/ml) on day 20 of tacrolimus therapy, and peaked at 34.9 ng/ml on day 28. Two audiograms performed on days 28 and 29 confirmed bilateral hearing loss of 80% for speech perception, characterized as mild to moderate sensorineural hearing loss with speech reception threshold of 35 dB (normal < 20 dB) in both ears. The tacrolimus dosage was gradually reduced to 6 mg twice/day by day 36, with drug level 9.7 ng/ml, after which her hearing gradually recovered.

An abbreviated area-under-the-curve monitoring for tacrolimus in patients with liver transplants.

This study aims to assess the predictability of individual tacrolimus (FK) concentrations at different time points for the area under the curve (AUC) and to find the best sampling time for the abbreviated AUC to predict the total body exposure of FK. A total of 23 FK blood concentration versus time profiles (11 blood samples per 12 hours) was studied in 12 stable patients with liver transplants at steady state. Each AUC was calculated by the trapezoidal rule, and the relationship between individual concentrations or abbreviated AUC and total AUC was determined by linear regression. The trough concentrations from the morning dose predict AUC better than the trough concentration from the evening dose (r2 = 0.71 for morning dose and r2 = 0.35 for evening dose). In the case of single drug concentration, the 4-hour concentration could predict the total AUC reasonably well (r2 = 0.73). From stepwise multiple regression, the abbreviated AUC at 1, 2.5, 6, and 9 hours could predict the total AUC most accurately (r2 = 0.99). This study shows that the four levels at 1, 2.5, 6, and 9 hours or 1, 4, and 12 hours as an abbreviated AUC is as good as a full pharmacokinetic study. Alternatively, 4-hour concentration is a good predictor of the total body exposure of FK in the stable patients with liver transplants.