Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved on PET/CT

OBJECTIVE: A potential source of false-positive FDG PET interpretations in oncologic imaging is FDG uptake in brown fat. The purpose of this study was to determine the prevalence, location, and appearance of hypermetabolic brown fat in the mediastinum. MATERIALS AND METHODS: All PET/CT scans obtained at our cancer institution from August to October 2003 were retrospectively reviewed for increased FDG uptake in the mediastinum localized to fat on CT. The following features were recorded: location, appearance, maximal standard uptake value (SUV(max)) of hypermetabolic mediastinal brown fat, and presence of extramediastinal brown fat. RESULTS: PET/CT scans were obtained in 845 oncologic patients. Fifteen patients (1.8%) with focal hypermetabolic mediastinal brown fat were identified: nine women and two men (age range, 27-79; mean, 55.1 years) and four children (age range, 5-16 years; mean, 10 years). Hypermetabolic mediastinal brown fat (mean SUV(max), 5.7) was more common in children (4/8) than in adults (11/837) and more common in women (9/372) than in men (2/465). Foci of hypermetabolic brown fat were localized to the paratracheal, paraesophageal, prevascular, and pericardial regions; interatrial septum; and azygoesophageal recess. Five patients had focal hypermetabolic brown fat isolated to the mediastinum. Ten patients also had extramediastinal hypermetabolic brown fat in the neck, thorax, and abdomen. There was no difference in the body weight (p = 0.876) or body mass index (p = 0.538) of patients with hypermetabolic brown fat compared with age- and sex-matched control subjects. CONCLUSION: Hypermetabolic brown fat can be localized to the mediastinum and manifests as focal increased FDG uptake. Knowledge of this potential pitfall and precise localization with fusion PET/CT are important in preventing misinterpretation as malignancy.     

A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors

KIT gain of function mutations play an important role in the pathogenesis of gastrointestinal stromal tumors (GISTs). Imatinib is a selective tyrosine kinase inhibitor of ABL, platelet-derived growth factor receptor (PDGFR), and KIT and represents a new paradigm of targeted therapy against GISTs. Here we report for the first time that, after imatinib treatment, an additional specific and novel KIT mutation occurs in GISTs as they develop resistance to the drug. We studied 12 GIST patients with initial near-complete response to imatinib. Seven harbored mutations in KIT exon 11, and 5 harbored mutations in exon 9. Within 31 months, six imatinib-resistant rapidly progressive peritoneal implants (metastatic foci) developed in five patients. Quiescent residual GISTs persisted in seven patients. All six rapidly progressive imatinib-resistant implants from five patients show an identical novel KIT missense mutation, 1982T-->C, that resulted in Val654Ala in KIT tyrosine kinase domain 1. This novel mutation has never been reported before, is not present in pre-imatinib or post-imatinib residual quiescent GISTs, and is strongly correlated with imatinib resistance. Allelic-specific sequencing data show that this new mutation occurs in the allele that harbors original activation mutation of KIT.     

The clinical development of new mitotic inhibitors that stabilize the microtubule

Microtubule-stabilizing agents are increasingly studied for cancer treatment based largely on the prior success of paclitaxel and docetaxel. In this review, we focus on the clinical development of epothilones and discodermolide, and we discuss salient preclinical and clinical highlights of these two novel natural products. These agents are distinguished by their biochemical features making them poor P-glycoprotein substrates and capable of inducing cytotoxicity in cell lines or in vivo tumor models harboring mutations in tubulin. There is now considerable data regarding the efficacy of the epothilones in human beings and discodermolide holds such promise, as well.     

吴茱萸的1H-NMR指纹图谱解析

目的对吴茱萸Evodia rutaecarpa(Juss.)Benth.的1H-NMR指纹图谱进行解析。方法应用硅胶柱色谱法分离吴茱萸的SCEA和SCEB化学成分,鉴定其结构,并对SCEA和SCEB进行1H-NMR研究,从而实现吴茱萸的1H-NMR指纹图谱的解析。结果吴茱萸SCEA的1H-NMR指纹图谱,主要显示evodiamine、rutaecarpine、dehydroevodiamine 3个化合物的特征共振信号,吴茱萸SCEB的1H-NMR指纹图谱,主要显示dehydroevodiamine的特征共振信号。不同来源的样品其1H-NMR指纹图谱有很好的重现性和特征性。结论吴茱萸的1H-NMR指纹图谱可用于其基源鉴定。     

中药抗疲I号对训练Wistar大鼠急进高原并运动力竭后心肌及其酶谱的影响

目的通过训练大鼠急进高原模型从心肌组织形态和酶谱改变,研究训练对心肌损伤的防护。方法于海拔1520m实地环境设实验组(EG)采用中药抗疲I号加入常规饲料中喂养,对照组(CG)常规饲料喂养,EG、CG各40只游泳训练4周后,各选35只3h急进海拔3850m实地静息1.5h,从中各选10只作为静息对照采集标本,EG、CG各20只游泳至力竭后1h、24h采集标本;测定比较各组心肌酶谱指标等,镜下观察比较各组心肌形态变化。结果EG血中心肌酶谱指标1h、24h指标均优于CG1h、24h结果;心肌组织学结构从纵断面看,EG心肌结构清晰,肌丝细密,横纹清楚,核周无空隙;横断面心肌纤维群间隙小,毛细血管平均为10～12个/HPF;CG心肌纤维界限不清晰,肌丝分散,横纹不清楚,横断面心肌纤维群间隙增宽,毛细血管平均为3～5个/HPF,毛细血管腔扩张,红细胞堆积,提示有水肿。结论急进高海拔地区运动后可使心肌纤维缺氧水肿,血中心肌酶谱增高,同时会使心肌营养不良而发生结构改变,对心肌的供氧能力好坏必然决定运动能力强弱,过度训练、改变运动集训环境或强体力劳动均可引起心肌供血能力下降,本研究是通过抗疲I号加入食品干预训练大鼠的,有利于改善心肌营养与供氧状况,并能降低心肌纤维水肿发生。     

Renal replacement therapies in pediatric intensive care patients: Experiences of one center in Turkey

BACKGROUND: Despite constant improvements in caring for critically ill neonates and infants with congenital cardiac disease, sepsis, bone marrow and solid organ transplantation, acute renal failure (ARF) is an important problem in these children. ARF, severe fluid overload and inborn errors of metabolism are some of the indications for acute dialysis in infants and children. METHODS: The authors had retrospectively evaluated the medical records of Pediatric Intensive Care Unit, Ankara University School of Medicine, Ankara, Turkey patients who had required acute renal replacement therapy between the dates of January 2002 to February 2005. RESULTS: Medical records of 332 patients were reviewed. Acute renal replacement therapy was performed in 21 patients (6.3%; mean age, 9.6 +/- 7.4 years). Dialysis modalities were peritoneal dialysis in 15 patients (71.4%; mean age, 3.9 +/- 5.6 years) and hemodialysis in six patients (28.6%; mean age, 12.1 +/- 3.2 years). A total of 90% of patients had severe systemic disease leading to ARF. A total of 95% of patients had multiple organ dysfunction syndrome. The most common cause of ARF was refractory shock. At the beginning of renal replacement therapy, 10 patients were anuric, nine patients had volume overload, seven patients had decompensated metabolic acidosis and nine patients had hypotension. The average dialysis period was 4.7 +/- 6.4 days. Mortality rate was 66.7%. Eight patients recovered from ARF and chronic renal failure had developed in one patient. CONCLUSION: In the Pediatric Intensive Care Unit, ARF is frequently seen together with multiple organ dysfunction syndrome and the mortality rate is high. Both peritoneal dialysis and hemodialysis are important renal replacement treatment modalities in patients with ARF. The age and hemodynamic status of the patients are important when choosing treatment modality; generally peritoneal dialysis is preferred in infants and toddler, while hemodialysis is preferred in older children.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

The use of 18F-fluorodeoxyglucose positron emission tomography for the diagnosis and management of invasive mould infections.

There is limited information on the utility of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for the diagnosis and management of invasive mould infections (IMIs). We retrospectively evaluated patients with IMIs who underwent FDG-PET in our institution (n = 13; December 1999 to April 2004), and reviewed the available literature (n = 9). In 16 non-neutropenic patients with available FDG-PET imaging studies (11 from our institution), FDG-PET revealed an occult IMI site (n = 3; 2 unidentified CNS involvement) and was helpful in guiding the duration of treatment (n = 8). Prospective evaluation of the role of FDG-PET in the work-up and management of IMIs is needed.