Pancreas divisum: thin-section CT

Twelve patients with known pancreas divisum underwent thin-section computed tomography (CT) to determine the capability of CT to depict this pancreatic anomaly. Focal pancreatic enlargement was present in five patients. Two distinct pancreatic moieties separated by a fat cleft were noted in three patients; a fourth patient had focal atrophy in the distribution of the dorsal pancreas. The two pancreatic moieties were identified at the same craniocaudal level in all four of these patients. The dorsal duct was depicted in all 12 patients, while the short ventral duct was seen in only five of the 12 patients. Failure of the ventral and dorsal pancreatic ducts to fuse was identified in all five patients in whom both ducts were seen. CT may not enable specific diagnosis of pancreas divisum in the majority of patients. If, however, distinct pancreatic moieties or unfused ductal systems are evident, the diagnosis may be confidently suggested.     

Sildenafil in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.KEY WORDS: Child, phosphodiesterase (PDE)-5 inhibitor, Pulmonary hypertension therapy     

四肢关节专用低场强MRI评估对膝关节损伤的诊断价值

目的：分析四肢关节专用低场强MRI诊断膝关节损伤的临床应用价值。 方法：于2004-12/2005-10解放军总医院全军骨科研究所收治经手术、关节镜检查或临床证实的膝关节损伤患者40例（43个膝关节）。应用Atorscan0.2T永磁型四肢关节专用低场强磁共振机,对膝关节损伤的MRI表现进行分析。 结果：四肢关节专用低场强MRI对半月板、前交叉韧带、骨挫伤等均可作出正确诊断。 结论：四肢关节专用低场强MRI对膝关节损伤的综合诊断具有重要意义,是膝关节损伤较理想的一种非创伤性检查方法。     

Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2

Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties

Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.