Pheochromocytomas: detection with 18F DOPA whole body PET--initial results.

PURPOSE: To evaluate fluorine 18 ((18)F) dihydroxyphenylalanine (DOPA) whole-body positron emission tomography (PET) as a biochemical imaging approach for detection of pheochromocytomas. MATERIALS AND METHODS: (18)F DOPA PET and magnetic resonance (MR) imaging were performed in 14 consecutive patients suspected of having pheochromocytomas (five sporadic, nine with von Hippel-Lindau disease); metaiodobenzylguanidine (MIBG) scintigraphy was performed in 12 of these patients. The individual imaging findings were assessed in consensus by specialists in nuclear medicine and radiologists blinded to the results of the other methods. The findings of the functional imaging methods were compared with those of MR imaging, the reference standard. Histologic verification could be obtained in eight patients with nine tumors. RESULTS: Seventeen pheochromocytomas (11 solitary, three bifocal; 14 adrenal, three extraadrenal) were detected with MR imaging. (18)F DOPA PET and MR imaging had concordant results in all 17 tumors. In contrast, MIBG scintigraphy had false-negative results in four patients with three adrenal tumors smaller than 2 cm and one extraadrenal tumor with a diameter of 3.6 cm. On the basis of these data, sensitivities of 100% for (18)F DOPA PET and of 71% for MIBG scintigraphy were calculated. Specificity was 100% for both procedures. CONCLUSION: (18)F DOPA PET is highly sensitive and specific for detection of pheochromocytomas and has potential as the functional imaging method of the future.     

Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

Test-retest reproducibility of quantitative CBF measurements using FAIR perfusion MRI and acetazolamide challenge.

The reproducibility of quantitative cerebral blood flow (CBF) measurements using MRI with arterial spin labeling and acetazolamide challenge was assessed in 12 normal subjects, each undergoing the identical experimental procedure on two separate days. CBF was measured on a 1.5T scanner using a flow-sensitive alternating inversion recovery (FAIR) pulse sequence, performed both at baseline and 12 min after intravenous administration of acetazolamide. T(1) was measured in conjunction with the FAIR scan in order to calculate quantitative CBF. The CBF maps were segmented to separate gray matter (GM) from white matter (WM) for region-of-interest (ROI) analyses. Post- acetazolamide CBF values (ml/100 g/min, mean +/- SD) of 87.5 +/- 12.5 (GM) and 46.1 +/- 10.8 (WM) represented percent increases of 37.7% +/- 24.4% (GM) and 40.1% +/- 24.4% (WM). Day-to-day differences in baseline CBF were -1.7 +/- 6.9 (GM) and -1.4 +/- 4.7 (WM) or, relative to the mean CBF over both days for each subject, -2.5% +/- 11.7% (GM) and -3.8% +/- 13.6% (WM) Day- to-day differences in absolute post-ACZ CBF increase were -2.5 +/- 6.8 (GM) and 2.7 +/- 9.4 (WM) or, relative to the mean CBF increase over both days for each subject, -4.7% +/- 13.3% (GM) and 9.1% +/- 26.2% (WM). Thus, FAIR- based CBF measurements show satisfactory reproducibility from day to day, but with sufficient variation to warrant caution in interpreting longitudinal data. The hemispheric asymmetry of baseline CBF and post-acetazolamide CBF increases varied within a narrower range and should be sensitive to small changes related to disease or treatment.     

Radial force and wall apposition of balloon-expandable vascular stents in eccentric stenoses: an in vitro evaluation in a curved vessel model

PURPOSE: Important criteria for optimized stent implantation are high radial force and complete apposition of the stent itself. The aim of this study was to develop a simple method to assess these parameters under controlled experimental conditions and to compare vascular stents of different designs with regard to these parameters. MATERIALS AND METHODS: Five balloon-expandable stents of different designs (Jostent Flex, MAC stent, ML-Tristar, ML-Ultra, and S670) were tested. Fourteen stents of each type were implanted in a curved plastic vessel model (curve radius, 10 mm; lumen diameter, 3.5 mm) with use of a balloon inflation pressure of 12 atm. Part of the model was a nonflexible eccentric stenosis which was 2 mm or 8 mm in length. After stent implantation, a stenosis of 10%-70% was induced and radial force of the stent struts was measured at the site of the stenosis. The apposition of the stent to the vessel wall was imaged by high-resolution radiography. RESULTS: Analysis of variance showed significant differences of radial force between the tested stents (P <.001). The ML-Tristar and ML-Ultra stents had the highest radial force with maximum mean values of 687 cN and 846 cN at a stenosis of 70% in the model with the long stenosis. The radial force of the S670 stent was the lowest whereas the MAC stents showed an intermediate radial force. Radial force of the ML-Ultra stent was as much as 3.8 times higher than the force of the S670 stent (P <.001). Fifty percent of the ML-Tristar and ML-Ultra stents did not expand sufficiently to touch the vessel surface at the outer curvature. With an inflation pressure of 17 atm, complete apposition of these stents was achieved. The highest number of apposition irregularities was found in the S670 group (13 of 14 stents), whereas the MAC stents revealed the lowest number of irregular appositions (three of 14 stents). A significant correlation was found between the number of interconnecting struts and the number of irregular apposition events (P <.01). CONCLUSIONS: This model allows an accurate in vitro evaluation of different stent parameters, such as apposition to the vessel wall and radial force. None of the investigated stents showed optimal results with respect to both parameters. The apposition behavior was significantly influenced by the architecture of the stents.     

The effect of ad libitum ingestion of a caffeinated carbohydrate-electrolyte solution on urinary caffeine concentration after 4 hours of endurance exercise

The purpose of the present study was to examine the effect of ad libitum ingestion of a carbohydrate-electrolyte solution (CES) with 150 mg x L (-1) caffeine (CAF) on urinary CAF concentration after 4 h of endurance exercise. Fifty-eight healthy and well-trained male subjects ingested ad libitum a 7 % CES with 150 mg x L (-1) CAF during 4 h cycling at 50 % of maximal work capacity. Total fluid consumption (mean +/- SE) was 2799 +/- 72 mL and CAF intake was 420 +/- 11 mg (5.7 +/- 0.2 mg x kg (-1) body weight). The post-exercise urinary CAF concentration (4.53 +/- 0.25 microg x mL (-1)) was below the doping level of the International Olympic Committee (12 microg x mL (-1)) in all subjects (range 1.20 - 10.84 microg x mL (-1)). A highly positive correlation was observed between CAF intake and post-exercise urinary CAF concentration (r = 0.68, p < 0.001). It is concluded that ad libitum ingestion of a CES with 150 mg x L (-1) CAF during 4 h cycling resulted in post-exercise urinary concentration below the doping level in all subjects.     

Prevalence,incidence, and natural course of anorexia and bulimia nervosa among adolescents and young adults

We aimed to assess the prevalence, incidence, age-of-onset and diagnostic stability of threshold and subthreshold anorexia nervosa (AN) and bulimia nervosa (BN) in the community. Data come from a prospective-longitudinal community study of 3021 subjects aged 14–24 at baseline, who were followed up at three assessment waves over 10 years. Eating disorder (ED) symptomatology was assessed with the DSM-IV/M-CIDI at each wave. Diagnostic stability was defined as the proportion of individuals still affected with at least symptomatic eating disorders (EDs) at follow-ups. Baseline lifetime prevalence for any threshold ED were 2.9 % among females and 0.1 % among males. For any subthreshold ED lifetime prevalence were 2.2 % for females and 0.7 % for males. Symptomatic expressions of EDs (including core symptoms of the respective disorder) were most common with a lifetime prevalence of 11.5 % among females and 1.8 % among males. Symptomatic AN showed the earliest onset with a considerable proportion of cases emerging in childhood. 47 % of initial threshold AN cases and 42 % of initial threshold BN cases showed at least symptomatic expressions of any ED at any follow-up assessment. Stability for subthreshold EDs and symptomatic expressions was 14–36 %. While threshold EDs are rare, ED symptomatology is common particularly in female adolescents and young women. Especially threshold EDs are associated with a substantial risk for stability. A considerable degree of symptom fluctuation is characteristic especially for subthreshold EDs.     

Probiotics partly reverse increased bacterial translocation after simultaneous liver resection and colonic anastomosis in rats

BACKGROUND: Bacterial translocation is one important cause of nosocomial infections following major abdominal surgery. Oral administration of probiotics has been proposed to diminish bacterial translocation. MATERIAL AND METHODS: In total 68 rats were divided into seven groups: five of the groups received standard rat chow and were subjected to either sham-operation, 70% liver resection, colonic anastomosis, or a combination of 30 or 70% liver resection with synchronous colonic anastomosis, respectively. In two additional groups with synchronous operation, a combination of four different lactic acid bacteria and four fibers was administered two times daily pre- and postoperatively. Bacterial concentrations in cecum, mesenteric lymph nodes, liver, and spleen were analyzed and blood cultures were taken 48 h after operation. Furthermore, the following parameters were assessed: histological changes in the intestine, intestinal paracellular permeability (Ussing chamber), bursting pressure of the colonic anastomosis, and mitosis rate of the remnant liver. RESULTS: Bacterial translocation was observed in all rats, except in the sham group. Following liver resection, the highest bacterial concentrations were seen in liver and spleen, following colon anastomosis in the mesenteric lymph nodes. Bacterial translocation was increased in the animals with combined operation, in parallel to the extent of liver resection. In rats with colon anastomosis, bacterial concentration in the cecum was also higher than in the sham group. Application of probiotics significantly decreased bacterial concentration in the lymph nodes. In addition, animals with a high cecal concentration of lactobacilli had less translocation than the others. No histological changes were observed in the intestine. Paracellular permeability for ions, but not for the larger molecule lactulose, was increased in the colon in all groups with colon anastomosis. The bursting pressure of the colon anastomosis was not significantly different between the groups. Seventy percent liver resection led to a high rate of hepatocyte mitosis, whereas combination with colon anastomosis impaired the regeneration process. CONCLUSION: Synchronous liver resection and colon anastomosis led to increased bacterial translocation compared to the single operations in the rat model. It is possible to diminish this process by oral administration of probiotics. Bacterial overgrowth in the cecum and impaired hepatic regeneration, but not histological changes or alterations of paracellular permeability, are potential pathogenic mechanisms for translocation in this setting.     

Postprostatectomy cancer-free survival of African Americans is similar to non-African Americans after adjustment for baseline cancer severity

African American men with localized prostate cancer are less likely than White men to receive a radical prostatectomy. This disparity may exist because African American men have prostate cancers that are more biologically aggressive. We investigated if similar stage cancers of African American men and White men show differences in cancer control after radical prostatectomy. Men with localized prostate cancer who underwent radical prostatectomy during a 6-yr period were stratified by race, and time to prostate-specific antigen recurrence was measured. We used Chi-square and t-tests to compare baseline clinical and pathological factors based on race. Cox proportional hazards model was used to determine effects of race on cancer control while controlling for baseline measures of cancer severity. There were 1,228 cases evaluated. At baseline, African American men were treated at a significantly younger age than White men (P = 0.0027) but showed no significant difference in prostate-specific antigen PSA, Gleason score, pathology stage, maximum tumor dimension, and surgical margin status. Multivariable Cox proportional hazards analysis controlling for cancer severity at prostatectomy revealed that cancer-free survival was not worse among African Americans compared to other subjects (P = 0.16). The responsiveness of prostate cancers among African American men to radical prostatectomy was similar to White men of similar stage and grade. Early detection in African American men may facilitate diagnosis of cancer amenable to prostatectomy. Studies are needed to evaluate the possible interaction of prostate cancer stage and grade shift in African American men and the disease free survival in this population.     

Chronic rejection: insights from a novel immunosuppressive-free model of kidney transplantation

The use of immunosuppressive drugs in models of chronic rejection may limit their usefulness for mechanistic studies. We have developed a new minor histocompatibility-mismatched rat kidney transplant model without the need for immunosuppression. Kidneys from LEW (RT1(l)) donors were transplanted to congenic WF.1L (RT1(l)) recipients and compared with the reversed strain combination and isogenic controls. Urinary protein excretion was measured serially in all recipients; kidneys were harvested 90, 120, and 180 d after transplantation for morphologic analysis and cytokine gene expression. In vitro lymphocytic reactivity and cytokine analysis of mixed lymphocyte reaction (MLR) culture supernatants by ELISA was also carried out. LEW into WF.1L kidney grafts developed proteinuria starting 120 d after transplantation and were associated with morphologic changes of focal segmental glomerulosclerosis together with interstitial cell infiltrates, upregulated gene expression of IL-1beta, IL-2, and TNF-alpha/-beta, as well as IL-2, IFN-gamma, and TNF-alpha production by lymphocytes in MLR culture supernatants. WF.1L kidneys transplanted into LEW recipients did not develop chronic rejection and had upregulation of Th2 cytokines, both within the allograft and in MLR supernatant of recipient lymphocytes cultured with WF.1L cells. Furthermore, these lymphocytes produced both Th1 and Th2 cytokines when cultured with WF cells, unlike lymphocytes from the LEW isografts, which produced Th1 cytokines when challenged with WF cells. These studies show that indirect allorecognition can cause strain-dependent chronic rejection associated with Th1-like cytokine production, whereas production of Th2 cytokines is associated with protection from the development of chronic rejection.     

Comparison of hydraulic and hemolytic properties of different impeller designs of an implantable rotary blood pump by computational fluid dynamics

A mixed-flow blood pump for long-term applications has been developed at the Helmholtz-Institute in Aachen, Germany. Central features of this implantable pump are a centrally integrated motor, a blood-immersed mechanical bearing, magnetic coupling of the impeller, and a shrouded impeller, which allows a relatively wide clearance. The aim of the study was a numerical analysis of hydraulic and hemolytic properties of different impeller design configurations. In vitro testing and numerical simulation techniques (computational fluid dynamics [CFD]) were applied to achieve a comprehensive overview. Pressure-flow charts were experimentally measured in a mock loop in order to validate the CFD data. In vitro hemolysis tests were performed at the main operating point of each impeller design. General flow patterns, pressure-flow charts, secondary flow rates, torque, and axial forces on the impeller were calculated by means of CFD. Furthermore, based on streak line techniques, shear stress (stress loading), exposure times, and volume percentage with critical stress loading have been determined. Comparison of CFD data with pressure head measurements showed excel-lent agreement. Also, impressive trend conformity was observed between in-vitro hemolysis results and numerical data. Comparison of design variations yielded clear trends and results. Design C revealed the best hydraulic and hemolytic properties and was chosen as the final design for the mixed-flow rotary blood pump.