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This study evaluated an intervention to facilitate adaptive coping by persons living with HIV (PLWH), with the participation of their cohabiting partners as a dimension of the intervention. An experimental design with randomization was used, and 84 PLWH and their partners were recruited. The intervention was based on a psychosocial educational model that incorporated four 2-hour sessions focused on communication, stress appraisal, adaptive coping strategies, and building social support. Both members of the dyad were included in each session. The comparison control included four supportive phone calls to the PLWH alone. Data were collected from both the PLWH and their partner in each of the two groups at baseline, immediately following the intervention, and 3 months and 6 months posttreatment. Data were analyzed using repeated measures analysis of variance, with change scores from the partner data being covariates. Results indicated that the design was a feasible model, which demonstrated potential for the management of stress and possibly problems such as adherence in PLWH. A manual was developed as a part of this intervention and is currently available. [ABSTRACT FROM AUTHOR]

Objective: To determine, for individuals with type 2 diabetes and microalbuminuria, the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP) on renal function and secondarily on glycemia, lipid levels, and blood pressure.Research Design and Methods: In a randomized crossover trial, we compared 6 weeks of meals containing only PP with meals containing primarily AP (60% animal, 40% plant) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and/or oral antidiabetic agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6-week period, subjects were studied for 36 h on a metabolic unit.Results: There were no significant differences between diets for glomerular filtration rate, renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA(1c,) blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower (PP and AP: from 4.75 to 4.34 mmol/l, P < 0.01), HbA(1c) had significantly improved (PP: from 8.1 to 7.5%, P < 0.01; AP: from 7.9 to 7.4%, P < 0.01), and diastolic blood pressure was significantly lower (PP: from 83 to 80 mmHg, P < 0.02; AP: from 82 to 78, P < 0.02).Conclusions: There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, healthy diet, regardless of protein source. [ABSTRACT FROM AUTHOR]

Sixty-one parents of children with insulin-dependent diabetes mellitus completed modified versions of the Hypoglycemic Fear Survey (HFS) and the Diabetes Quality of Life (DQOL) scale. They also indicated their child's history of hypoglycemic-related seizures or loss of consciousness (SLC) events. Parental HFS scores were significantly greater if their child had ever experienced a SLC event or experienced a SLC event within the past year. Parental HFS scores were positively correlated with general parental worry about their child having diabetes. Adolescent children who experienced a SLC event during the past year reported greater HFS scores, greater general worry about diabetes, and a greater negative impact of having diabetes compared with adolescents with no such history. Despite the greater fear of hypoglycemia in parents and adolescents, there was no significant difference in HbA1 values between children with or without any history of SLC events or children with or without a SLC event within the past year. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the efficacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin dependent diabetes. Metabolic control, patients' psychosocial status, family functioning, perceived quality of life, patterns of parental/child responsibility for daily diabetes maintenance, and nursing time-on-task were evaluated. One hundred six pediatric patients (mean age = 13.3 years) were randomly assigned to an experimental or control outpatient clinic for 1 year Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks. Transmitted data were reviewed by nurse practitioners who telephoned subjects to discuss regimen adjustments. Control subjects received standard care with regimen adjustments made by physicians. There were no significant between-group differences for metabolic control, rates of hospitalization or emergency-room visits, psychological status, general family functioning, quality of life, or parent-child responsibility. A significant decrease was noted in nursing time-on-task for experimental subjects. [ABSTRACT FROM AUTHOR]

Parental worries, specific to having a child with diabetes, have been associated with poor diabetes control. This study addressed three questions relating to this issue: Does parental worry affect the metabolic control of the child with IDDM? What specific aspects of diabetes are the most worrisome to parents? Do these concerns change with the child's age and disease duration? Parents of 93 children with IDDM were given a modified version of the Diabetes Quality of Life measure to evaluate diabetes-specific worries. No correlation was found between parental worry and the child's metabolic control. Parents of younger children expressed the largest amount of worry, yet the kinds of things that parents were most concerned about were the same, regardless of age or duration of the child's disease. [ABSTRACT FROM AUTHOR]

Background: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. [ABSTRACT FROM PUBLISHER]

Background: Cholelithiasis is a frequent complication in pediatric sickle cell disease (SCD). Though it is standard practice to perform a cholecystectomy in pediatric SCD patients with symptoms of cholelithiasis, the use of elective cholecystectomy for asymptomatic patients remains controversial., Procedure: Records of 191 pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy were retrospectively reviewed. Patients classified as follows: (i) elective-no preoperative symptoms, cholelithiasis on screening ultrasound, comprehensive preoperative plan; (ii) symptomatic-preoperative symptoms of cholelithiasis on diagnostic ultrasound, comprehensive preoperative plan; or (iii) emergent-hospitalization for acute cholecystitis symptoms, cholelithiasis on diagnostic ultrasound, limited preoperative preparation. We compared the morbidity of cholecystectomy by examining pre- and post-cholecystectomy hospital admission days, length of stay for cholecystectomy, and surgical complications., Results: Patients with SCD underwent a total of 191 cholecystectomies over a 10-year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required emergent cholecystectomy had a longer postoperative hospitalization time than elective or symptomatic cholecystectomy (7.3 vs 4.3, P < 0.001). Baseline values for total bilirubin and aspartate aminotransferase (AST) were significantly elevated (P < 0.02 and P < 0.07, respectively) in patients requiring emergent cholecystectomy., Conclusions: This represents the largest reported retrospective review of pediatric cholelithiasis and cholecystectomy in SCD to date. These data strongly suggest that elective cholecystectomy decreases morbidity associated with emergent cholecystectomy. The overall outcomes for symptomatic and elective patients are favorable. However, our study indicates the need for prospective studies to identify clinical indicators for those emergent patients., (© 2016 Wiley Periodicals, Inc.)

Purpose: To evaluate common duct (CD) dilation by computed tomography (CT) in patients with intact gallbladders and diameter change over time in remote and interval cholecystectomy patients, frequency of visualization of the CD, and its relationship to age., Methods: This IRB-approved retrospective study evaluated baseline CD diameter, intrahepatic biliary dilation, and interval duct diameter change in patients with CTs ≥ 2 years apart (n = 324), in block-randomized order by two blinded board-certified radiologists. 272 patients were divided into three groups: (1) prior cholecystectomy before the first CT, (2) cholecystectomy between the first and last CTs, and (3) no cholecystectomy. A subset of 191 nonoperated patients was evaluated for age-related dilation., Results: Group 1 ducts were significantly larger than the other groups at both baseline and follow-up CTs (p < 0.001). Group 2 showed a greater increase in duct size than the other groups at follow-up (p < 0.001). The CD was measurable in 89% of the CT studies. In nonoperated patients, there was a statistically significant correlation between CD size and increasing age (p < 0.001), although the CD size remained within normal size limits., Conclusion: Remote cholecystectomy patients have larger CD diameters than the nonoperated and interval cholecystectomy groups. Greater increase in ductal diameter occurred between studies in the interval cholecystectomy patients, suggesting that dilation occurs after cholecystectomy. Also, the CD dilates slightly with age in nonoperated patients.

Objective: To determine whether curve magnitude of scoliosis at presentation correlates with BMI., Methods: Retrospective chart review of 180 patients presenting with scoliosis was performed. Curve pattern and magnitude, Risser status, occurrence of surgery, zip code, height and weight, race, and insurance status were recorded. Relationships were examined by Spearman rank and Pearson correlations, and logistic regression analysis was used to determine odds ratios., Results: For both thoracic and lumbar curve patterns, there was a correlation between BMI and curve magnitude. Spearman rank correlation was 0.19 for thoracic (P = .03) and 0.24 for lumbar curves (P = .02). Overweight or obese patients were not more likely, however, to present with curves at higher risk of progression or more likely to have surgical intervention. With respect to potential confounding socioeconomic variables, thoracic curve magnitude was negatively correlated with median family income (Spearman rank correlation -0.17, P = .04). Curve magnitude was not correlated with race, distance, or insurance payer., Conclusions: Patients with high BMI and scoliosis are more likely to present with larger curves, but not more likely to require surgery. This is concerning because of the national trend of increasing childhood obesity and because scoliosis treatment may be more complicated in larger curves. Socioeconomic factors may also be barriers to access., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Increased severity of illness in patient with acute hematogenous osteomyelitis (AHO) with methicillin-resistant Staphylococcus aureus (MRSA) necessitates prompt intervention, but overtreatment of methicillin-sensitive S. aureus (MSSA) may contribute to antibiotic resistance. Therefore, predicting methicillin sensitivity in suspected AHO is desirable. A previously published prediction algorithm has not performed well in settings with high prevalence of MRSA. We sought to develop a predictive equation using presenting factors to predict MRSA in our patient population with a predominance of MRSA., Methods: A retrospective chart review was performed. Consecutive cases of AHO with positive blood or bone cultures were identified at a single children's hospital. Presenting features were recorded including duration of symptoms, weight-bearing, prior antibiotic use, vital signs, complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Univariate comparison was made between the groups with MRSA and MSSA. Continuous variables were compared with t tests and discrete variables were compared using the Fischer exact test. Logistic regression was performed using a forward stepwise regression to develop a model to predict MRSA., Results: A total of 68 patients formed the study group, and 60% had MRSA (41 MRSA, 27 MSSA). Temperature, respiratory rate, heart rate, white blood cell count, absolute neutrophil count (ANC), ESR), and CRP were significantly higher in MRSA cases, whereas platelets were lower. Logistic regression resulted in a model utilizing temperature, ANC, and CRP. This model correctly predicted 87% of cases (92% of MRSA and 79% of MSSA) with an area under the curve of 0.919±0.035 with a 95% confidence interval of 0.851, 0.987., Conclusion: A logistic regression model incorporating temperature, ANC, and CRP correctly predicts methicillin resistance of S. aureus in 87% of cases. The model differs from one developed at an institution with a low rate of MRSA. Prediction of MRSA could help direct antibiotic management, whereas prediction of MSSA could help prevent overuse of antibiotics directed against MRSA., Level of Evidence: Diagnostic study level IV.

Prevention of tumors induced by environmental carcinogens has not been achieved. Skin tumors produced by polyaromatic hydrocarbons, such as 7,12-dimethylbenz(a)anthracene (DMBA), often harbor an H-ras point mutation, suggesting that it is a poor target for early immunosurveillance. The application of pyrosequencing and allele-specific PCR techniques established that mutations in the genome and expression of the Mut H-ras gene could be detected as early as 1 d after DMBA application. Further, DMBA sensitization raised Mut H-ras epitope-specific CTLs capable of eliminating Mut H-ras(+) preneoplastic skin cells, demonstrating that immunosurveillance is normally induced but may be ineffective owing to insufficient effector pool size and/or immunosuppression. To test whether selective pre-expansion of CD8 T cells with specificity for the single Mut H-ras epitope was sufficient for tumor prevention, MHC class I epitope-focused lentivector-infected dendritic cell- and DNA-based vaccines were designed to bias toward CTL rather than regulatory T cell induction. Mut H-ras, but not wild-type H-ras, epitope-focused vaccination generated specific CTLs and inhibited DMBA-induced tumor initiation, growth, and progression in preventative and therapeutic settings. Transferred Mut H-ras-specific effectors induced rapid tumor regression, overcoming established tumor suppression in tumor-bearing mice. These studies support further evaluation of oncogenic mutations for their potential to act as early tumor-specific, immunogenic epitopes in expanding relevant immunosurveillance effectors to block tumor formation, rather than treating established tumors., (Copyright © 2015 by The American Association of Immunologists, Inc.)

CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal-Wallis non-parametric ANOVA with Mann-Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA patients.

Purpose: This study aimed to determine if a single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) can differentiate high lipid content (HLC) from low lipid content (LLC) incidental adrenal lesions., Methods: A retrospective intrapatient study of 40 consecutive adults with known hepatic or pancreatic pathology who underwent multiphasic abdominal RSDE for nonadrenal-related clinical indications and had adrenal lesions was done. Arterial phase was acquired with RSDE, conventional unenhanced (CU) images with standard MDCT. RSDE measurements included lesion attenuation in Hounsfield units on simulated monochromatic 140-keV images and density (in milligrams per milliliter) on material decomposition images, using water-iodine and fat-iodine basis pairs. Each variable was correlated with CU Hounsfield units (Pearson coefficient). RSDE lesion values were compared with analysis of variance and Tukey HSD test. Receiver operating characteristic (ROC) analysis was performed to identify RSDE thresholds comparable to 10 HU on unenhanced MDCT., Results: Twenty-nine HLC and 18 LLC lesions were evaluated in 40 subjects (21 men; mean age, 66.5 years). RSDE variables correlated with CU Hounsfield units, r = 0.90-0.92, P < 0.001. Myelolipomas, HLC, and LLC lesions were different by analysis of variance, P < 0.001 for all dual-energy variables. Excluding myelolipomas from ROC curve analysis, ROC areas for Hounsfield unit 140-keV images, fat(-iodine), and water(-iodine) were 0.929 (0.039), 0.917 (0.046), and 0.912 (0.048), respectively (P < 0.001); using a specificity of 94.4%, 64% of adenomatous lesions had 140 keV values of less than 9.5 HU, 59% had fat(-iodine) values of less than 987 mg/mL, and 50% had water(-iodine) values of less than 994 mg/mL., Conclusions: There is a strong correlation between RSDE measures and accepted MDCT attenuation values for HLC and LLC adrenal lesions. In some patients undergoing postcontrast RSDE who are found to have incidental adrenal nodules, further unenhanced CT or adrenal-protocol CT or magnetic resonance imaging may not be necessary.

Previous gene microarray studies have shown that expression of 14-3-3θ is significantly decreased in an α-synuclein transgenic mouse model. In this study, we tested whether α-synuclein can regulate 14-3-3θ transcription. We demonstrate that the 14-3-3θ mRNA level is decreased in SH-SY5Y cells overexpressing α-synuclein. Luciferase activity under the control of the 14-3-3θ promoter is reduced both in stable SH-SY5Y cells constitutively overexpressing α-synuclein and in doxycycline-inducible SH-SY5Y cells upon α-synuclein induction, suggesting that the regulation of 14-3-3θ by α-synuclein occurs at the transcriptional level. Knockdown of α-synuclein by RNA interference does not increase the 14-3-3θ mRNA level. These findings suggest that α-synuclein represses 14-3-3θ transcription under pathologic conditions, but that regulation of 14-3-3θ expression is not a function of endogenous α-synuclein at baseline.

Purpose: The purpose of this study was to evaluate intravenous (IV) contrast-enhanced single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) material density assessment of hepatic steatosis compared to conventional unenhanced (CU) Multidetector computed tomography (MDCT)., Materials and Methods: This is an institutional review board-approved intrapatient study of 363 consecutive adults (189 men, 174 women; mean age, 59 years) evaluated with multiphasic IV abdominal RSDE. Material density virtual unenhanced water and fat hepatic parenchymal values were measured and correlated to Hounsfield units (HUs) on CU CT using linear regression. Study population was dichotomized into steatotic or nonsteatotic liver parenchyma on the basis of CU liver-spleen (L-S) difference. The RSDE fat(-iodine) values (in milligram per milliliter) were compared (t test), correlated to the L-S difference in HU, and a milligram-per-milliliter fat threshold for clinically significant steatosis was calculated using receiver operator curve (ROC) analysis., Results: Regression analysis revealed r value of 0.86 for mg/mL water (P < 0.001) and 0.87 for milligram-per-milliliter fat (P < 0.001). Twenty-seven participants were excluded from the L-S analysis (splenectomy). A total of 107 (32%) had steatosis (mean L-S, - 6.3; mean fat(-iodine) milligram per milliliter, 1018.4); 229 (68%) had no steatosis (mean L-S, 9.4; milligram per milliliter, 1028.4 [P < 0.001]). The RSDE fat material density measurement correlated to L-S less than 1 with r value of 0.74 (P < 0.001), with an area under receiver operator curve of 0.847. A threshold of 1023-mg/mL fat had 71% sensitivity and 80% specificity, and a threshold of 1027-mg/mL fat had 90% sensitivity and 61% specificity for steatosis., Conclusions: The RSDE milligram-per-milliliter fat values correlate well with hepatic steatosis defined by the L-S difference less than 1 on conventional MDCT. A threshold of 1027 mg/mL can identify 90% of steatotic livers when post-IV contrast RSDE is used, without obtaining additional CU scans. However, regression equations were not helpful to convert an individual participant's milligram-per-milliliter fat or milligram-per-milliliter water-derived from RSDE material density images to CU MDCT HU for the estimation of liver fat content.

Objectives: To evaluate changes in the common duct diameter on sonography over time in patients with and without cholecystectomy., Methods: We retrospectively evaluated the common duct diameter, central biliary dilatation, and interval change in 1079 patients who underwent sonography at least 2 years apart over a 6-year period. A board-certified radiologist, blinded to clinical and laboratory data, measured the duct diameter. A total of 893 patients (568 female and 325 male) were divided into 3 groups: group 1, remote cholecystectomy before sonography (mean, 9.7 years before sonography; n = 117); group 2, interval cholecystectomy between the first and second sonographic examinations (n = 56); and group 3, no cholecystectomy (n = 720). All groups were stratified by age, and group 3 was also stratified by the absence (n = 528) or presence (n=192) of gallstones., Results: Duct diameters at baseline and follow-up averaged 4.5 and 5.2, 3.6 and 4.9, and 3.5 and 3.9 mm in groups 1, 2, and 3, respectively. Group 1 ducts were larger at baseline than in the other groups (P < .001). At follow-up, group 2 ducts showed a greater interval diameter increase than the other groups (P < .001). In a subanalysis of each group based on age, there was a mild increase in duct size with increasing age, although not clinically significant and within normal limits. In group 3 patients who never had gallstones, there was a significant small increase in duct size over decades (P < .001). The baseline duct sizes for patients with gallstones were not significantly different from those who never had gallstones (P = .15)., Conclusions: Patients with remote cholecystectomy have larger common duct diameters than those with no or interval cholecystectomy. Most asymptomatic patients with or without cholecystectomy have a normal common duct diameter.

The goal of the study was to assess the efficacy of combined extracellular matrix metalloprotease inducer (EMMPRIN)- and death receptor 5 (DR5)-targeted therapy for pancreatic adenocarcinoma in orthotopic mouse models with multimodal imaging. Cytotoxicity of anti-EMMPRIN antibody and anti-DR5 antibody (TRA-8) in MIA PaCa-2 and PANC-1 cell lines was measured by ATPlite assay in vitro. The distributions of Cy5.5-labeled TRA-8 and Cy3-labeled anti-EMMPRIN antibody in the 2 cell lines were analyzed by fluorescence imaging in vitro. Groups 1 to 12 of severe combined immunodeficient mice bearing orthotopic MIA PaCa-2 (groups 1-8) or PANC-1 (groups 9-12) tumors were used for in vivo studies. Dynamic contrast-enhanced-MRI was applied in group 1 (untreated) or group 2 (anti-EMMPRIN antibody). The tumor uptake of Tc-99m-labeled TRA-8 was measured in group 3 (untreated) and group 4 (anti-EMMPRIN antibody). Positron emission tomography/computed tomography imaging with (18)F-FDG was applied in groups 5 to 12. Groups 5 to 8 (or groups 9 to 12) were untreated or treated with anti-EMMPRIN antibody, TRA-8, and combination, respectively. TRA-8 showed high killing efficacy for both MIA PaCa-2 and PANC-1 cells in vitro, but additional anti-EMMPRIN treatment did not improve the cytotoxicity. Cy5.5-TRA-8 formed cellular caps in both the cell lines, whereas the maximum signal intensity was correlated with TRA-8 cytotoxicity. Anti-EMMPRIN therapy significantly enhanced the tumor delivery of the MR contrast agent, but not Tc-99m-TRA-8. Tumor growth was significantly suppressed by the combination therapy, and the additive effect of the combination was shown in both MIA PaCa-2 and PANC-1 tumor models.

The objective of this study was to evaluate extracellular matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, whereas MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, whereas the other groups served as the control. In the residual tumor model, tumor growth of anti-EMMPRIN-treated group was successfully arrested for 21 days (15 ± 4 mm(3)), which was significantly lower than that of the EMMPRIN knockdown group (80 ± 15 mm(3); P=0.001) or the control group (240 ± 41 mm(3); P<0.001). In the established tumor model, anti-EMMPRIN therapy lowered tumor volume increase by approximately 40% compared with the control, regardless of the dose amount. Ki67-expressed cell density of group 5 was 939 ± 150 mm(-2), which was significantly lower than that of group 4 (1709 ± 145 mm(-2); P=0.006). Microvessel density of group 5 (30 ± 6 mm(-2)) was also significantly lower than that of group 4 (53 ± 5 mm(-2); P=0.014), whereas the microvessel size of group 5 (191 ± 22 μm(2)) was significantly larger than that of group 4 (113 ± 26 μm(2); P=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer and support its clinical translation.

Children with sickle cell anemia are at risk for brain injury. Physicians obtain brain magnetic resonance imaging (MRI) for clinical indications to determine if a patient has developed a brain injury. Controversy exists whether all children with sickle cell anemia should undergo MRI screening. This retrospective study evaluates the clinical and laboratory correlates for brain injury in 124 MRIs obtained for a variety of clinical indications. Seizure, sensory, or motor events were statistically associated with the highest risk for brain injury while less specific neurologic complaints of headache or poor school performance were not associated. Children with high systolic blood pressure, leukocytosis, and severe anemia demonstrate a higher probability for brain injury. These results indicate that brain MRI should be obtained on all children with seizure, sensory, or motor events. These data suggest that less specific neurologic symptoms should be screened if physical findings or abnormal lab or vital signs exist.

Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n  =  6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p < .001), bioluminescent signal (p  =  .050), microvessel densities (p  =  .002), and proliferating cell densities (p  =  .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.

Purpose: To measure reader agreement in determining whether lung nodules detected at baseline screening computed tomography (CT) had changed at subsequent screening examinations and to evaluate the variability in recommendations for further follow-up., Materials and Methods: All subjects were enrolled in the National Lung Screening Trial (NLST), and each participant consented to the use of their de-identified images for research purposes. The authors randomly selected 100 cases of nodules measuring at least 4.0 mm at 1-year screening CT that were considered by the original screening CT reader to be present on baseline CT scans; nodules considered by the original reader to have changed were oversampled. Selected images from each case showing the entire nodule at both examinations were preloaded on a picture archiving and communication system workstation. Nine radiologists served as readers, and they evaluated whether the nodule was present at baseline and recorded the bidimensional measurements and nodule characteristics at each examination, presence or absence of change, results of screening CT, and follow-up recommendations (high-level follow-up, low-level follow-up, no follow-up)., Results: On the basis of reviews during case selection, five nodules seen at follow-up were judged not to have been present at baseline; for 19 of the remaining 95 cases, at least one reader judged the nodule not to have been present at baseline. For the 76 nodules that were unanimously considered to have been present at baseline, 21%-47% (mean ± standard deviation, 30% ± 9) were judged to have grown. The κ values were similar for growth (κ = 0.55) and a positive screening result (κ = 0.51) and were lower for a change in margins and attenuation (κ = 0.27-0.31). The κ value in the recommendation of high- versus low-level follow-up was high (κ = 0.66)., Conclusion: Reader agreement on nodule growth and screening result was moderate to substantial. Agreement on follow-up recommendations was lower., (© RSNA, 2011.)

Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measured the early vascular changes after administration of TRA-8, bevacizumab, or TRA-8 combined with bevacizumab in breast tumor xenografts., Procedures: Groups 1-4 of nude mice bearing human breast carcinoma were injected with phosphate-buffered saline, TRA-8, bevacizumab, and TRA-8 + bevacizumab on day 0, respectively. DCE-MRI was performed on days 0, 1, 2, and 3, and thereafter tumors were collected for terminal deoxynucleotidyl transferase-mediated dUT nick end labeling and CD31 staining., Results: DCE-MRI measured a significant K (trans) change within 3 days after TRA-8 therapy that correlated with tumor growth arrest, which was not shown with statistical significance by histopathology at these early time points posttreatment. The K (trans) changes followed quadratic polynomial curves., Conclusion: DCE-MRI detected significantly lower K (trans) levels in breast tumor xenografts following TRA-8 monotherapy or combined therapy with bevacizumab.

Introduction: It is often not possible to determine whether small nodules detected on computed tomography (CT) in oncology patients are metastatic. We evaluated a group of oncology patients to determine the outcome of small pulmonary nodules and whether they can be ignored in the therapeutic decision process., Materials and Methods: Radiology reports of thoracic CTs from a 2-year period were searched for keywords indicating a small pulmonary nodule. All CT images were evaluated by two thoracic radiologists for nodules 4 mm or less. There were 102 cases that met criteria for inclusion., Results: Forty-seven had follow-up CT of less than 365 days, and 55 had follow-up CT for more than 365 days. For those with less than 365 days, the observed nodule was increased (17, 36%), increased and new nodules (9, 19%); stable (19, 40%); stable but new nodules developed (1); and decreased (1). For those with greater than 365 days follow-up, the observed nodule was increased (3, 5%); stable (51, 93%); and stable but new nodule developed (1). Combined, 28% of patient';s nodules increased (90% were within 365 days; 25% within 203 days; and 14% within 14 days)., Conclusion: In oncologic patients, 28% of small pulmonary nodules detected at initial CT will increase in size, suggesting metastasis. This increase in size tends to occur early, and follow-up CT in 3 months and 6 months would be appropriate in further evaluation. Small nodules that are stable in size for more than 365 days are unlikely to be pulmonary metastasis.

Objective: The purpose of the study was to determine whether a difference in patient preference exists between iohexol (Omnipaque) and diatrizoate sodium (Gastroview) as oral contrast medium for abdominal-pelvic CT. A secondary objective was to evaluate whether there are significant differences in bowel opacification and adverse effect profile for the two agents., Subjects and Methods: From August 2007 through March 2009, 300 patients were enrolled in this prospective study after informed consent was obtained. Eligible patients were identified from those scheduled for outpatient abdominal-pelvic CT. Subjects were randomly assigned to receive one of two oral contrast agents in a double-blinded fashion. Subjects graded the taste using a 5-point scale, and data regarding demographics, total volume, and adverse effects were collected. A direct comparison of 30 mL of each of the two diluted agents in randomized order was then performed. CT images were graded for bowel opacification by two blinded abdominal radiologists., Results: Of 287 subjects who expressed a preference, 233 patients (81%) preferred dilute iohexol compared with 54 patients (19%) who preferred dilute diatrizoate sodium (p < 0.001). Ten patients had no preference, and three patients did not complete the taste comparison study. No difference in bowel opacification was identified between the oral contrast agents (p = 0.27), nor was there a significant difference in adverse effects (p = 0.352)., Conclusion: Patents preferred dilute iohexol over dilute diatrizoate sodium for oral contrast for abdominal-pelvic CT. There was no significant difference in bowel opacification or adverse effect profile.

Objective: The purpose of this study was to determine whether preoperative neoadjuvant therapy in patients with locally advanced pancreatic cancer affects the ability of multiphasic MDCT to predict successful surgical resection., Materials and Methods: From 2000 to 2006, there were 12 patients with prior neoadjuvant therapy successfully downstaged by CT and 31 age-matched pancreatic cancer patients without preoperative therapy who underwent pancreatic MDCT followed by attempted pancreaticoduodenectomy. Three readers blinded to surgical findings independently analyzed immediate preoperative MDCT scans of 43 patients comprising the retrospective data set in random order for vascular involvement (degree of contact and narrowing) and distant metastases. Individual reader sensitivity and specificity for resectability prediction were compared for study and control groups using the Fisher's exact test. Interobserver agreement was assessed using the kappa statistic., Results: Seven (58%) of 12 neoadjuvant-treated adenocarcinomas and 10 (32%) of 31 control pancreatic carcinomas were resectable (p > 0.05). For resectable disease, sensitivities were 86%, 71%, and 14% for the neoadjuvant group and 90%, 90%, and 60% for the control group (p > 0.05). Specificities were 80%, 100%, and 100% for the neoadjuvant group and 57%, 43%, and 76% for the control group (reader 2 specificity difference, p = 0.04). The multi rater kappa value of resectability prediction for neoadjuvant patients was 0.28, and that for control subjects was 0.63 (p < 0.001). In the neoadjuvant group, the majority of individual reader errors were false-negative resectability interpretations resulting from overestimation of vascular involvement. Consideration of degrees of venous abutment did not improve estimation of resectability in patients with neoadjuvant therapy., Conclusion: Sensitivity for prediction of resectability tends to be lower for patients with locally advanced pancreatic cancer that has been downstaged by neoadjuvant therapy, but this trend is not statistically significant. Interobserver variability for determination of resectability is statistically higher than for controls who did not receive preoperative therapy.

Background & Aims: A goal of radiologists is to use computed tomography (CT) imaging less frequently in younger patients because of radiation exposure. We evaluated abdominal CT use among patients hospitalized for acute pancreatitis at a tertiary care hospital and compared estimated radiation doses with disease severity and patient age., Methods: We performed a retrospective analysis of numbers and types of CTs performed on patients with acute pancreatitis (1036 admissions, 869 patients; mean age, 50.8 y); 566 had 1081 abdominopelvic CTs performed from October 1, 2001, to September 30, 2006. Effective dose estimates for abdominopelvic CTs were used to estimate exposure. Disease severities were stratified using Balthazar CT grades and severity indexes., Results: The mean number of abdominopelvic CTs per patient, per hospitalization, was 1.9 (range, 1-12); the mean number was 3.0 over the 5-year period (range, 1-19). During hospitalization, each patient was exposed to a mean estimated radiation dose of 31.03 +/- 26.4 mSv (range, 14.7-176.9 mSv). Patients with pancreatitis grades D or E (n = 233) compared with grades A through C (n = 333) had longer periods of hospitalization (mean, 23.3 vs 10.8 d; P < .001), more days as an inpatient (mean, 2.54 vs 1.45 d; P < .001), more total CT scans (mean, 4.02 vs 2.37; P < .001), and higher total effective radiation doses (mean, 53.5 vs 35 mSv; P < .0001). Linear regression revealed a relationship between dose and disease grade, but not patient age., Conclusions: Regardless of age, patients with severe acute pancreatitis undergo more abdominopelvic CTs as inpatients and outpatients and are exposed to higher doses of radiation compared with patients with less severe disease. Awareness of CT ordering patterns for patients with acute pancreatitis may aid in the development of alternate imaging strategies to reduce radiation exposure in this population, especially for younger patients., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of our study was to examine the correlation between CT-based and radionuclide renography-based measures of split renal function in a healthy population of live potential kidney donors using 3D models generated from CT angiography., Materials and Methods: The records of 173 renal donor candidates who had undergone CT and radionuclide renography between March 1, 2005, and February 28, 2006, were retrospectively evaluated; of those 173 patients, 152 met study inclusion criteria. A blinded investigator using 3D models that were created semiautomatically from the unenhanced, arterial, and excretory phase data made measurements of CT renal volumes and attenuations. The mean renal attenuation and volume were used to calculate the net accumulation of contrast material and split renal function for comparison with radionuclide renography. Split function from CT was calculated in the arterial and excretory phases as well as based on split renal volume and the Patlak method., Results: All four CT-based methods for the calculation of split renal function showed correlation with no significant difference from radionuclide renography (p > 0.05, Student's t test). Pearson's correlation coefficients varied from 0.36 to 0.63 (p < 0.001 for each). Difference scores revealed that the excretory and renal volume splits had the narrowest range and showed a linear, nonzero relationship to the renography splits. Bland-Altman analysis confirmed that the majority of difference scores between each CT method and the radionuclide renography were within the 95% CI of the differences., Conclusion: Split renal function based on 3D CT models can provide a "one-stop" evaluation of both the anatomic and the functional characteristics of the kidneys of living potential kidney donors. The excretory phase data and the split renal volume data show the best correlation and the smallest difference scores compared with radionuclide renography data.

Objective: The purpose of our study was to evaluate the causes, waveform morphology, and clinical outcomes of high-resistance reversed diastolic flow in transplanted kidneys., Materials and Methods: To identify patients with reversed diastolic flow, we performed a review of 5,089 renal transplant Doppler sonograms obtained over a 10-year period. Waveform morphology was correlated with surgical-histologic findings and clinical outcomes., Results: Fifty-nine patients (33 male, 26 female; age range, 14-69 years) with reversed diastolic flow fell into three chronologic groups: acute group (six patients), transplant < 24 hours; perioperative group (34 patients), transplant < or = 30 days; and long-term group (19 patients), transplant > 30 days. Acute reversed diastolic flow was associated with higher likelihood of graft survival (p = 0.001, Fisher's exact test) compared with reversed diastolic flow discovered in the perioperative or long-term group. In the acute group, hematoma, acute tubular necrosis, renal vein thrombosis, and vascular kink produced reversed diastolic flow. The causes of reversed diastolic flow for the perioperative group were acute tubular necrosis, rejection, and renal vein thrombosis; for the long-term group, reasons for diastolic reversal were rejection, glomerulosclerosis, low cardiac output, and diabetic nephrosclerosis. The causes of reversed diastolic flow were not differentiated by waveform morphology., Conclusion: The causes of reversed diastolic flow cannot be distinguished by waveform morphology. Patients with reversed diastolic flow < 24 hours after transplantation warrant emergent exploration because correction of treatable causes may lead to recovered function. Long-standing renal transplants with reversed diastolic flow are not likely salvageable.

Background and Methods: Delivery of insulin to the deep lung presents unique challenges to the body's mucosal defense system. Pulmonary mucosal defense has the ability to discriminate between self and non-self antigens and has the potential for induction of immunologic tolerance. Published data concerning the immunogenicity of inhaled human insulin in drug trials will be reviewed, and data regarding the possible adverse effects of anti-insulin antibody development will be presented. Examination of the immunologic safety of inhaled human insulin will include discussion of comparator studies, factors affecting immunogenicity, the effects of insulin immunity on glycemic control and pulmonary function, and the relationship of insulin antibodies to dose requirements, pharmacodynamics, and hypoglycemia., Conclusions: Inhaled human insulin, whether formulated as a powder or liquid, has been shown to be more immunogenic than comparator insulins given by subcutaneous routes; however, adverse effects of antibody formation have not been demonstrated.

Objective: The purpose of this study was to evaluate the sensitivity and specificity of seven CT signs in the diagnosis of internal hernia after laparoscopic Roux-en-Y gastric bypass., Materials and Methods: With institutional review board approval, the CT scans of 18 patients (17 women, one man) with surgically proven internal hernia after laparoscopic Roux-en-Y gastric bypass were retrieved, as were CT studies of a control group of 18 women who had undergone gastric bypass but did not have internal hernia at reoperation. The scans were reviewed by three radiologists for the presence of seven CT signs of internal hernia: swirled appearance of mesenteric fat or vessels, mushroom shape of hernia, tubular distal mesenteric fat surrounded by bowel loops, small-bowel obstruction, clustered loops of small bowel, small bowel other than duodenum posterior to the superior mesenteric artery, and right-sided location of the distal jejunal anastomosis. Sensitivity and specificity were calculated for each sign. Stepwise logistic regression was performed to ascertain an independent set of variables predictive of the presence of internal hernia., Results: Mesenteric swirl was the best single predictor of hernia; sensitivity was 61%, 78%, and 83%, and specificity was 94%, 89%, and 67% for the three reviewers. The combination of swirled mesentery and mushroom shape of the mesentery was better than swirled mesentery alone, sensitivity being 78%, 83%, and 83%, and specificity being 83%, 89%, and 67%, but the difference was not statistically significant., Conclusion: Mesenteric swirl is the best indicator of internal hernia after laparoscopic Roux-en-Y gastric bypass, and even minor degrees of swirl should be considered suspicious.

Objective: To optimize forearm radiocephalic fistula success, many programs recommend a minimal cephalic vein diameter of 0.25 cm or greater on preoperative sonographic mapping. It is not established, however, whether a vein diameter before or after application of a tourniquet should be used in determining suitability for creation of a forearm fistula., Methods: Before forearm radiocephalic fistula placement, preoperative sonographic mapping measured the cephalic vein diameter before and after application of a tourniquet. The patients fell into 2 groups: those with a pretourniquet vein diameter of 0.25 cm or greater (group 1) and those with a pretourniquet vein diameter of less than 0.25 cm that increased to 0.25 cm or greater after application of the tourniquet (group 2). The adequacy of each fistula for dialysis was determined clinically., Results: Among 73 radiocephalic fistulas with known clinical outcomes, 28 were in group 1, and 45 were in group 2, on the basis of sonography. Fistula success rates were similar in group 1 patients (11 [39%] of 28) and group 2 patients (15 [33%] of 45) (P=.624, Fisher exact test). Inclusion of group 2 patients increased the number of patients recommended for placement of forearm fistulas and increased the total number of usable forearm fistulas from 11 to 26. The overall success rate of forearm fistulas was lower in women (19% versus 50%; P=.015, Fisher exact test)., Conclusions: The use of a venous tourniquet increases the number of patients eligible for forearm fistulas without decreasing the adequacy rate of these fistulas. Therefore, a tourniquet should routinely be used in patients with small cephalic veins on pretourniquet evaluation.

Progressive disease is the major cause of treatment failure after autologous hematopoietic stem cell transplantation for relapsed or refractory non-Hodgkin's lymphoma. An augmented high-dose regimen of cyclophosphamide 7,200 mg/m2, carmustine 300 - 400 mg/m2, and etoposide 2,400 mg/m2 (CBV) was developed in an attempt to improve disease control post-transplant. Sixty-seven adult patients received augmented CBV followed by infusion of unpurged autologous peripheral blood stem cells. Thirty seven patients had relapsed after standard chemotherapy, 28 patients had primary refractory disease, and 2 patients had transformed lymphoma in first partial response. Treatment-related mortality was 4%. Actuarial four year overall survival and progression-free survival were 46+/-8% and 36+/-6%, respectively. Risk factors for disease progression were histologic involvement of marrow by lymphoma and infusion of increased numbers of CD34 + cells per kg in the stem cell autograft. The outcome for patients with relatively chemorefractory disease (defined as 25 - 49% reduction in tumor volume after salvage chemotherapy) was no different than that for patients with chemosensitive disease. Compared to standard high-dose CBV regimens, augmented CBV does not appear to have substantially improved disease control. Prospective study of the association between inferior progression-free survival and infusion of higher CD34 + cell doses in stem cell autografts is warranted.

Background: Cisplatin-based chemotherapy followed by surgical extirpation of residual benign disease represents the usual sequence of curative therapy for metastatic nonseminomatous germ cell cancer of testicular origin. Occasionally, residual disease is malignant in the form of either a persistent nonseminomatous germ cell cancer tumor or degeneration into non-germ cell cancer. We reviewed our institution's experience with patients undergoing salvage operations to remove malignant intrathoracic metastases., Methods: From 1981 through 2001, 438 patients with nonseminomatous germ cell cancer had operations to remove residual intrathoracic disease after cisplatin-based chemotherapy at Indiana University Hospital. A subset of 134 patients who underwent 186 surgical procedures to remove malignant metastases is the basis of this review. Fifty-nine patients had removal of pulmonary metastases, 49 had removal of mediastinal metastases, and 26 had removal of both pulmonary and mediastinal metastases. Surgical pathology demonstrated 84 patients with persistent nonseminomatous germ cell cancer tumors, 38 with degeneration into non-germ cell cancer, and 12 with both malignant pathologic categories., Results: There were 4 (3.7%) operative deaths. The overall median survival was 5.6 years, with 55 (42.3%) patients alive and well after a mean follow-up of 5.1 years. Seventeen variables were analyzed by using Cox regression. Of these, older age, pulmonary metastases (vs mediastinal metastases), and 4 or more (vs 1) total intrathoracic metastases were significantly (P < or = .01) predictive of inferior long-term survival., Conclusions: Salvage thoracic surgery to remove malignant metastases from nonseminomatous germ cell cancer tumors of testicular origin can result in long-term survival in select patients. We identified variables that influence survival in this subset.

Background: We conducted an institutional review of patients with locally advanced esophageal cancer who had complete pretreatment and surgical staging to identify variables predictive of outcome., Methods: From 1993 through 2002, 286 patients presented for surgical therapy of esophageal cancer. Of these, 176 patients met criteria for review including pretreatment endoscopic ultrasound stages IIA through IVA and a transthoracic surgical approach with "two-field" lymph node dissection. This cohort was primarily male (84.7%, n = 149) with adenocarcinoma (88.6%, n = 156), and 101 patients (57.3%) demonstrated endoscopic ultrasound stage III or IVA., Results: Eighty-five (48.3%) patients presented to surgery after receiving neoadjuvant chemoradiation therapy, and 91 (51.7%) underwent surgery alone. Both groups were well matched with respect to comorbidities and pretreatment stage. Patients receiving neoadjuvant chemoradiation demonstrated a nonsignificant trend toward increased operative mortality and nonfatal morbidity. The overall median survival was 16.8 months, and there was no survival difference comparing patients treated with neoadjuvant chemoradiation followed by surgery or surgery alone (p = 0.82). The subset of 25 patients (29.4%) demonstrating a complete pathologic response after neoadjuvant chemoradiation therapy however had superior survival (median survival = 57.6 months, p < 0.01) as compared with neoadjuvant chemoradiation patients demonstrating partial downstaging (n = 36, 42.3%), no downstaging (n = 24, 28.2%), and surgery alone patients. Multivariate analysis identified a complete pathologic response, endoscopic ultrasound stage, and number of pathologically positive lymph nodes as independent predictors of survival., Conclusions: These data support the use of neoadjuvant chemoradiation for locally advanced esophageal cancer as the subset of patients who demonstrate a complete pathologic response experienced significantly better survival.

We tested the hypothesis that the presence of a CYP3A5*1 allele is associated with increases in blood pressure in 2 studies of subjects with a total of 683 participants. The first study involving 271 subjects was part of a longitudinal study conducted at Indiana University Medical Center that consisted of 2 phases. The first phase studied the relationship of salt sensitivity with blood pressure, whereas the second phase, conducted approximately 26 years later, studied the relationship between blood pressure, carbohydrate intolerance, and vascular compliance in the same subjects. The second study was a cross-sectional evaluation of 412 normotensive and hypertensive subjects conducted at the University of California San Diego. The second study (Mantel-Haenszel chi(2) test; P=0.05) showed that a greater proportion of black participants with poor blood pressure control had CYP3A5*1/*1 genotype. Evaluation of the untreated blood pressure from phase 1 of the first study showed that the blacks with CYP3A5*3/*3 (146+/-35 mm Hg) had a higher systolic blood pressure than those with the *1/*3 (119+/-14.1 mm Hg; P=0.0006) and *1/*1 (125+/-17.4 mm Hg; P=0.009) genotypes. For blacks in study 2, the CYP3A5*1 allele was more common in hypertensives (Fisher exact test; P=0.025) than normotensives. In whites there was no association between CYP3A5 genotype and blood pressure in either study. We conclude that although untreated blood pressure may be higher in blacks with the CYP3A5*3/*3 genotype, the CYP3A5*1 allele may be associated with hypertension that is more refractory to treatment in this ethnic group.

Background and Purpose: Shockwave lithotripsy (SWL) predictably damages renal tissue and transiently reduces function in both kidneys. This study characterized the effects on renal function of a supraclinical dose of shockwaves (SWs) (8000) in porcine kidneys and tested the hypothesis that such excessive treatment would intensify and prolong the resulting renal impairment., Materials and Methods: Pigs aged 6 to 7 weeks were anesthetized and assigned to one of three groups. Groups 1 (N=8) and 2 (N=6) each received 8000 SWs at 24 kV (Dornier HM3) to the lower-pole calix of one kidney. Group 3 (7 pigs) received sham treatment. Renal function was monitored for the first 4 hours after SW treatment in Group 1 and for 24 hours in Group 2. Plasma renin activity was measured in Groups 2 and 3., Results: The renal lesions produced by 8000 SWs comprised 13.8%+/-1.4% of the renal mass. In the 4-hour protocol, this injury was associated with marked reduction of the glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion in both kidneys, although fractional sodium excretion was reduced only in the shocked kidneys. In the 24-hour protocol, GFR and RPF remained below baseline in shocked kidneys at 24 hours. Evidence of progressive ischemic injury was noted in shocked tissue at 24 hours after SW treatment., Conclusions: These findings support the hypothesis that the severity of the renal injury caused by SWL is related to the number of SWs administered and demonstrate the connection in this relation between renal structure and function.

Pre-formed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong transplant waiting time. We hypothesized that rituximab (RIT) could reduce PRA via B-cell depletion. As part of a Phase I study of single RIT dose, we studied in vivo and ex vivo effects on T-cell immune responses. Nine subjects (n = 3) were treated at 50, 150, and 375 mg/m(2). Serum interleukin-1alpha (IL-1alpha), IL-6, IL-12, tumor necrosis factor beta (TNF-beta), and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay (ELISA). T-cell function was monitored with T-cell proliferation assays. IL-6 levels rose in eight patients (7.15 +/- 4.38 pg/mL to 86.22 +/- 77.08, p = 0.021). The high-dose group had detectable TNF-betapost rituximab infusion (874.7 +/- 1466.5 pg/mL). There was no decline in T-cell proliferation in response to phytohemagglutinin or allogeneic lymphocyte stimuli. Stimulation indices in the presence of both concentrations of tetanus toxoid rose significantly at 4 weeks.

Background: Preformed HLA antibodies (Ab), reported as panel-reactive antibody (PRA), prolong patient waiting time for kidney transplantation. We hypothesized that rituximab (RTX) could reduce PRA via B-cell depletion. This initial study reports the safety, pharmacokinetics, and pharmacodynamics of RTX in patients with end-stage renal failure., Methods: The study was an investigator-initiated single-dose, dose-escalation phase I trial of RTX in chronic dialysis patients (PRA >50%). It was approved by the Institutional Review Board and the Food and Drug Administration. Nine subjects were treated with a single dose of RTX (n=3 per group) at 50, 150, or 375 mg/m. Peripheral lymphocyte cell surface markers and HLA Ab levels (%PRA and titers) were tested using flow cytometry., Results: There were four significant adverse events: a suspected histoplasmosis infection; two Tenchkoff dialysis catheter infections; and fever (38.7 degrees C) during infusion. At 2 days after RTX therapy, there was depletion of CD19 cells (pre-RTX 181+/-137 vs. post-RTX 12+/-5.6, P =0.006). In 2 (22%) of 9 subjects, there was no appreciable change in PRA. Among the other seven patients, one had a decrease in PRA from 87% to 51% with a concurrent decrease in fluorescence intensity; five patients had changes in histogram architecture suggesting loss of antibody specificity; and one patient had a fourfold decrease in PRA titer from 1:64 to 1:16 at 6 months after treatment. In addition, one of the seven patients converted a donor-specific crossmatch to negative and underwent a successful living donor kidney transplantation., Conclusions: RTX can be safely administered and may be an effective agent to reduce high-titer anti-HLA Abs in subjects awaiting kidney transplantation.

The dyslipidemia of the metabolic syndrome is associated with alterations in triglyceride and high-density lipoprotein (HDL) metabolism. We examined the serum levels of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor HDL-associated protein, in a cohort with a wide range of insulin sensitivity. The mean serum GPI-PLD mass from 109 subjects was 58.9 +/- 18.4 microg/mL (mean +/- SD). GPI-PLD levels directly correlated with cholesterol, apolipoprotein AI, triglycerides, insulin, and homeostasis model assessment (HOMA) but not C-reactive protein. These results suggest that increased serum GPI-PLD is associated with the insulin resistance.

Objectives: The purpose of this study was to determine the pattern of mediastinal dissemination of nonseminomatous germ cell tumors of testicular origin and evaluate variables that may influence survival with mediastinal dissection in patients with metastatic nonseminomatous germ cell tumors., Methods: From 1981 to 2000, a total of 421 patients were seen at our institution for extirpation of residual lung or mediastinal disease after cisplatin-based chemotherapy for metastatic testicular nonseminomatous germ cell tumors. We reviewed 268 of these patients, with a mean age of 26.8 years, who required at least one surgical procedure to remove residual mediastinal disease. Pathologic types of resected residual mediastinal disease were necrosis (15%), teratoma (59%), persistent nonseminomatous germ cell cancer (15%), and non-germ cell carcinomatous degeneration (11%). Twelve variables were evaluated by univariate analyses, and four variables potentially statistically significant at P <.10 were subsequently entered into a Cox regression model., Results: All patients demonstrated metastases to the visceral mediastinum. Fewer patients also demonstrated metastases to the paravertebral sulcus or anterior compartments (16% and 7%, respectively). Overall 5- and 10-year survivals were 86% +/- 2% and 74% +/- 4%, respectively. According to multivariate analysis, disease-related survival was negatively influenced by an elevated preoperative beta-human chorionic gonadotropin level (P =.028) and adverse pathologic characteristics of residual mediastinal disease (P =.006)., Conclusions: Testicular nonseminomatous germ cell tumors follow a predictable pattern of mediastinal dissemination, primarily following the course of the thoracic duct and its major tributaries. Patients who require surgery to remove residual mediastinal disease after cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors have good to excellent long-term survivals. These results justify an aggressive surgical approach, including multiple surgical procedures if clinically indicated.

Renal blood flow falls in both kidneys following delivery of a clinical dose of shockwaves (SW) (2000 SW, 24 kV, Dornier HM3) to only one kidney. The role of renal nerves in this response was examined in a porcine model of renal denervation. Six-week-old pigs underwent unilateral renal denervation. Nerves along the renal artery of one kidney were identified, sectioned and painted with 10% phenol. Two weeks later the pigs were anesthetized and baseline renal function was determined using inulin and PAH clearances. Animals then had either sham-shockwave lithotripsy (SWL) (group 1), SWL to the innervated kidney (group 2) or SWL to the denervated kidney (group 3). Bilateral renal function was again measured 1 and 4 h after SWL. Both kidneys were then removed for analysis of norepinephrine content to validate the denervation. Renal plasma (RPF) flow was significantly reduced in shocked innervated kidneys (group 2) and shocked denervated kidneys (group 3). RPF was not reduced in the unshocked denervated kidneys of group 2. These observations suggest that renal nerves play a pivotal role in modulating the vascular response of the contralateral unshocked kidney to SWL, but only a partial role, if any, in modulating that response in the shocked kidney., (Copyright 2003 S. Karger AG, Basel)

Purpose: The current trend toward ungated shock wave lithotripsy means that more patients are being treated with shock waves delivered at a rapid rate (120 shock waves per minute or greater). However, no benefit of an increased shock wave rate has been shown and in vitro studies indicate that slowing the shock wave rate actually improves stone fragmentation. We tested the effect of the shock wave rate on stone comminution in a new animal model., Materials and Methods: Gypsum model stones were inserted via upper pole percutaneous access into the lower pole calix of the kidneys of female pigs weighing approximately 100 pounds. Shock wave lithotripsy was performed (400 shock waves uninterrupted at 20 kV. and 30 or 120 shock waves per minute) 2 hours later using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia). After en bloc excision of the urinary tract stone fragments were collected and sieved through 2 mm. mesh. The particles were weighed and surface area was determined., Results: Stones treated at 30 shock waves per minute broke more completely than stones treated at 120 shock waves per minute. The percent of fragments greater than 2 mm. was significantly higher for stones treated at the fast rate of 120 versus the slow rate of 30 shock waves per minute (mean +/- SEM 81% +/- 14% versus 45% +/- 12%, p <0.005). When stone fragmentation was expressed as the percent increase in fragment surface area, significantly greater fragmentation occurred at the slower than at the more rapid rate (327% +/- 63% versus 135% +/- 136%, p <0.02)., Conclusions: Slowing the rate of shock wave administration during shock wave lithotripsy significantly improves the efficiency of stone fragmentation in vivo.

Purpose: In studies to understand better the role of cavitation in kidney trauma associated with shock wave lithotripsy we assessed structural and functional markers of kidney injury when animals were exposed to modified shock waves (pressure release reflector shock pulses) that suppress cavitation. Experiments were also performed in isolated red blood cells, an in vitro test system that is a sensitive indicator of cavitation mediated shock wave damage., Materials and Methods: We treated 6-week-old anesthetized pigs with shock wave lithotripsy using an unmodified HM3 lithotriptor (Dornier Medical Systems, Marietta, Georgia) fitted with its standard brass ellipsoidal reflector (rigid reflector) or with a pressure release reflector insert. The pressure release reflector transposes the compressive and tensile phases of the lithotriptor shock pulse without otherwise altering the positive pressure or negative pressure components of the shock wave. Thus, with the pressure release reflector the amplitude of the incident shock wave is not changed but cavitation in the acoustic field is stifled. The lower pole of the right kidney was treated with 2,000 shocks at 24 kV. Glomerular filtration rate, renal plasma flow and tubular extraction of para-aminohippurate were measured in the 2 kidneys 1 hour before and 1 and 4 hours after shock wave lithotripsy, followed by the removal of each kidney for morphological analysis. In vitro studies assessed shock wave induced lysis to red blood cells in response to rigid or pressure release reflector shock pulses., Results: Sham shock wave lithotripsy had no significant effect on kidney morphology, renal hemodynamics or para-aminohippurate extraction. Shock waves administered with the standard rigid reflector induced a characteristic morphological lesion and functional changes that included bilateral reduction in renal plasma flow, and unilateral reduction in the glomerular filtration rate and para-aminohippurate extraction. When the pressure release reflector was used, the morphological lesion was limited to hemorrhage of vasa recta vessels near the tips of renal papillae and the only change in kidney function was a decrease in the glomerular filtration rate at the 1 and 4-hour periods in shock wave treated kidneys. Red blood cell lysis in vitro was significantly lower with the pressure release reflector than with the rigid reflector., Conclusions: These data demonstrate that shock wave lithotripsy damage to the kidney is reduced when cavitation is suppressed. This finding supports the idea that cavitation has a prominent role in shock wave lithotripsy trauma.

We conducted noninvasive measures of vascular compliance and glucose tolerance in 275 normotensive and hypertensive subjects. Of the total, 194 (70.5%) were hypertensive, 73 (26%) diabetic, 7 (2.5%) normotensive and diabetic and 66 (24%) both hypertensive and diabetic, and 74 (27%) normotensive and nondiabetic. In addition, 57 of the nondiabetic subjects had impaired glucose tolerance based on the results of blood glucose levels 2 h after a glucose challenge. For the entire population, large artery compliance was correlated with systolic (P < .001), diastolic (P = .041), and pulse (P < .001) pressures, whereas small artery compliance correlated significantly (P < .001) only with systolic and pulse pressures. Among hypertensives, a significant decrease in large and small vessel compliance was seen, which was reduced further in the case of small vessel compliance by the presence of diabetes. When the population was separated on the basis of glucose tolerance into normal, impaired, and diabetic groups, a progressive reduction (P < .001) in small artery compliance was seen that was independent of age. Similar significant (P < .001) progressive increases in body mass index and systolic pressure were seen with progression of carbohydrate intolerance. These findings confirm the close relationship between elevated blood pressure (BP) and carbohydrate intolerance and indicate that the vascular effects of both are separate, additive, and primarily on small blood vessel compliance. These findings have important implications for the preclinical detection and potential prevention of hypertension, diabetes, and associated vascular disease.