Transport mechanisms of 3-[123I]iodo-alpha-methyl-L-tyrosine in a human glioma cell line: comparison with [3H]methyl]-L-methionine.

The amino acid analog 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) is under clinical evaluation as a SPECT tracer of amino acid transport in brain tumors. This study investigated the carrier systems involved in IMT transport in human glioma cells in comparison with [3H-methyl]-L-methionine (3H-MET). METHODS: Human glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C with IMT and 3H-MET in the lag phase (1.2 d after seeding), exponential growth phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments were performed in the presence and absence of Na+, during inhibition of system L amino acid transport by 2-aminobicyclo[2.2.1 ]heptane-2-carboxylic acid (BCH), and during inhibition of system A amino acid transport by 2-(methylamino)-isobutyric acid (MeAIB). RESULTS: IMT and 3H-MET uptake decreased by 55%-73% when the cells entered from the exponential growth phase into the plateau phase (P< 0.05; n = 3-11). Inhibition by BCH reduced uptake of IMT in the lag phase, exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and the uptake of 3H-MET by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium 3H-MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was not significantly different. MeAIB showed no significant effect on IMT or 3H-MET uptake in either phase. CONCLUSION: Transport of both IMT and 3H-MET depends on the proliferation rate of human glioma cells in vitro and is dominated by BCH-sensitive transport. These data indicate that system L is induced in rapidly proliferating glioma cells and is the main contributor to the uptake of both tracers. 3H-MET transport showed a minor Na+ dependency that was not attributable to system A. The similarity of transport mechanisms of both tracers emphasizes the clinical equivalence of IMT SPECT and (11)C-MET PET for the diagnostic evaluation of gliomas.     

Cortical hyperintensity on proton density-weighted images: An MR sign of cyclosporine-related encephalopathy.

PURPOSETo describe cortical hyperintensities in proton density-weighted images in six patients with presumed cyclosporine-induced neurotoxicity.METHODSIn six patients with clinical evidence of cyclosporine-related encephalopathy, MR imaging was performed after the onset of symptoms and signs (mean, 24 days after liver transplantation). Five of these patients had serial MR imaging for a period that varied from 2 to 20 months. Along with the imaging studies, the patients'' clinical status was evaluated and various laboratory parameters, including blood pressure and levels of cyclosporine, cholesterol, and magnesium, were monitored.RESULTSIn all six patients, initial MR studies showed hyperintensity of several cerebral gyri that was unequivocal only on proton density-weighted images. Although in five patients these signal abnormalities were limited to the cortex, one patient had increased signal in the subjacent white matter as well. In one patient, the images were also remarkable for areas of cortical hyperintensities on T1-weighted images. In another patient, cortical enhancement occurred after administration of gadopentetate dimeglumine, with a normal cortical signal on the precontrast images. The abnormal cortical signal began to fade after cyclosporine reduction, but in two patients it remained visible for at least 20 months. The neurologic symptomatology associated with cyclosporine-induced neurotoxicity included seizures (three patients), speech disorder (three patients), and disturbance of consciousness (three patients).CONCLUSIONCyclosporine-induced neurotoxicity occurring in patients after liver transplantation appears to affect the cerebral cortex preferentially. Because its MR equivalent resembles changes resulting from hypoxic injury or cortically centered vasculitis, we suspect the underlying mechanism may be a vascular injury that results in cortical hypoperfusion.     

Klatskin tumors of the bile ducts: sonographic appearance

The authors present 3 cases of surgically proved Klatskin tumor diagnosed by ultrasound alone. Sonographic features of these tumors include (a) dilatation of the intrahepatic biliary ducts but not the extrahepatic duct, (b) non-union of the right and left hepatic ducts, and (c) small, solid masses at the hepatic hilus. Local spread to the liver may also be seen. If the pancreas appears normal and no primary tumor can be found, Klatskin tumor can be diagnosed with a high degree of accuracy.     

Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

Background  

Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs.     

ASKyphoplan: a program for deformity planning in ankylosing spondylitis

A closing wedge osteotomy of the lumbar spine may be considered to correct posture and spinal balance in progressive thoracolumbar kyphotic deformity caused by ankylosing spondylitis (AS). Adequate deformity planning is essential for reliable prediction of the effect of surgical correction of the spine on the sagittal balance and horizontal gaze of the patient. The effect of a spinal osteotomy on the horizontal gaze is equal to the osteotomy angle. However, the effect of a spinal osteotomy on the sagittal balance depends on both the correction angle and the level of osteotomy simultaneously. The relation between the correction angle, the level of osteotomy and the sagittal balance of the spine can be expressed by a mathematical equation. However, this mathematical equation is not easily used in daily practice. We present the computer program ASKyphoplan that analyses and visualizes the planning procedure for sagittal plane corrective osteotomies of the spine in AS. The relationship between the planned correction angle, level of osteotomy and sagittal balance are coupled into the program. The steps taken during an ASKyphoplan run are outlined, and the clinical application is discussed. The application of the program is illustrated by the analysis of the data from a patient recently treated by a lumbar osteotomy in AS. The software can be used free of charge on the internet at under the heading “research” in the menu.     

Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

Background We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer. Methods T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m² twice daily (days 1–14, 25–38) added to RT with 50.4 Gy and surgery after 6–8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point. Results Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m² was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21. Conclusion Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.     

An evaluation of cardiac output by five arterial pulse contour techniques during cardiac surgery

The bias, precision and tracking ability of five different pulse contour methods were evaluated by simultaneous comparison of cardiac output values from the conventional thermodilution technique (COtd). The five different pulse contour methods included in this study were: Wesseling's method (cZ); the Modelflow method; the LiDCO system; the PiCCO system and a recently developed Hemac method. We studied 24 cardiac surgery patients undergoing uncomplicated coronary artery bypass grafting. In each patient, the first series of COtd was used to calibrate the five pulse contour methods. In all, 199 series of measurements were accepted by all methods and included in the study. COtd ranged from 2.14 to 7.55 l.min(-1), with a mean of 4.81 l.min(-1). Bland-Altman analysis showed the following bias and limits of agreement: cZ, 0.23 and - 0.80 to 1.26 l.min(-1); Modelflow, 0.00 and - 0.74 to 0.74 l.min(-1); LiDCO, - 0.17 and - 1.55 to 1.20 l.min(-1); PiCCO, 0.14 and - 1.60 to 1.89 l.min(-1); and Hemac, 0.06 and - 0.81 to 0.93 l.min(-1). Changes in cardiac output larger than 0.5 l.min(-1) (10%) were correctly followed by the Modelflow and the Hemac method in 96% of cases. In this group of subjects, without congestive heart failure, with normal heart rhythm and reasonable peripheral circulation, the best results in absolute values as well as in tracking changes in cardiac output were measured using the Modelflow and Hemac pulse contour methods, based on non-linear three-element Windkessel models.     

Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study

Background  

Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation.