The role of Janus Kinase 2 V617F mutation in extramedullary hematopoiesis of the spleen in neoplastic myeloid disorders.

Extramedullary hematopoiesis (EMH) in the spleen is a characteristic feature of the chronic myeloproliferative disorders (CMPDs) and various other neoplastic or reactive myeloid conditions. However, the origin of these hematopoietic precursor cells and the molecular mechanisms underlying their development in the spleen is uncertain. The V617F mutation in the Janus Kinase 2 gene (JAK2(V617F)) was recently shown to be frequently and preferentially present in the peripheral blood and bone marrow cells of CMPD patients, and the resulting dysregulation of its downstream targets is important to CMPD pathogenesis. To determine the occurrence and potential role of JAK2(V617F) in splenic EMH cells, we studied splenectomy specimens from 47 patients with significant EMH. JAK2(V617F) was detected by real-time PCR melting curve analysis in 22 specimens, including 11/17 chronic idiopathic myelofibrosis, 7/7 polycythemia vera, 1/1 essential thrombocythemia, 1/3 CMPD unclassifiable, 1/5 chronic myelomonocytic leukemia, 0/5 chronic myelogenous leukemia, 1/3 myelodysplastic syndrome and 0/6 acute myeloblastic leukemia cases, whereas only the JAK2 wild-type allele was detected in the other 25. Nineteen of 20 cases with adequate bone marrow samples available for molecular examination demonstrated concordant JAK2 genotypes. Laser-capture microdissection was then used to enrich the EMH and non-EMH splenic cell fractions, confirming that the mutant alleles specifically originated from the EMH cells. Furthermore, megakaryocytes in the JAK2(V617F)-positive splenectomy specimens expressed higher levels of Bcl-xL, an antiapoptotic protein and downstream target of the JAK2/STAT5 pathway. Thus, JAK2(V617F) is frequently present in splenic EMH cells associated with CMPD, but it is rarely identified in splenic EMH cells associated with other myeloid disorders. Our results indicate that the precursor cells leading to extramedullary hematopoietic expansion in CMPD most likely originate from the transformed bone marrow clone. Also, dysregulation of downstream pathways such as Bcl-xL may be important to CMPD disease pathogenesis in the spleen.     

Phosphorylation profiles of protein kinases in alveolar and embryonal rhabdomyosarcoma.

Rhabdomyosarcoma is the most common pediatric soft-tissue sarcoma, which includes two major subtypes, alveolar and embryonal rhabdomyosarcoma. The mechanism of its oncogenesis is largely unknown. However, the oncogenic process of rhabdomyosarcoma involves multi-stages of signaling protein dysregulation characterized by prolonged activation of tyrosine and serine/threonine kinases. To better understand this protein dysregulation, we evaluated the phosphorylation profiles of multiple tyrosine and serine/threonine kinases to identify whether these protein kinases are activated in rhabdomyosarcoma. We applied immunohistochemistry with phospho-specific antibodies to examine phosphorylation levels of selected receptor and non-receptor tyrosine kinases, mammalian target of rapamycin (mTOR), p70S6K, and protein kinase C (PKC) isozymes on alveolar and embryonal rhabdomyosarcoma tissue microarray slides. Our results showed that the phosphorylation levels of these kinases are elevated in some rhabdomyosarcoma tissues compared to normal tissues. Phosphorylation levels of receptor and non-receptor tyrosine kinases are elevated between 26 and 68% in alveolar rhabdomyosarcoma and between 24 and 71% in embryonal rhabdomyosarcoma, respectively, compared to normal tissues. In addition, phosphorylation levels of mTOR and its downstream targets, p70S6K, S6, and 4EBP1, are increased between 50 and 72% in both subtypes of rhabdomyosarcoma. Further, phosphorylation levels of PKCalpha, PKCdelta, PKCtheta, and PKCzeta/lambda are upregulated between 57 and 69% in alveolar rhabdomyosarcoma and between 43 and 72% in embryonal rhabdomyosarcoma. This is the first report to create a phosphorylation profile of tyrosine and serine/threonine kinases involved in the mTOR and PKC pathways of alveolar and embryonal rhabdomyosarcoma. These protein kinases may play roles in the development or tumor progression of rhabdomyosarcomas and thus may serve as novel targets for therapeutic intervention.     

Rhenium-188 sulphur colloid as a radiation synovectomy agent

Radiation synovectomy has been shown to be an effective treatment for the rheumatoid arthritic knee. In this study, we evaluated the suitability of rhenium-188 as a radiation synovectomy agent. In addition, we were successful in labelling sulphur colloid with¹⁸⁸Re. In vitro stability tests revealed that more than 95% of the¹⁸⁸Re remained in colloid form over a 3-day period. Intra-articular injection of¹⁸⁸Re sulphur colloid into arthritic rabbit joints was followed by gamma camera imaging to quantify the leakage. The mean retention percentages of¹⁸⁸Re colloid in arthritic knees were 93.7% (±1.4%), 90.8% (±1.7%) and 87.2% (±0.6%) at 1 h, 1 day and 2 days, respectively. A biodistribution study of the arthritic rabbits revealed that the highest activity outside the knees was in the liver and the kidneys. Our preliminary results indicate that 188Re sulphur colloid may be an effective radiopharmaceutical for radiation synovectomy.     

Increasing expression of serine protease matriptase in ovarian tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters.

Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase in ovarian tumors and to assign clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 164 ovarian neoplasms including 84 serous adenocarcinomas, 23 mucinous adenocarcinomas, 10 endometrioid adenocarcinomas, six yolk sac tumors, 12 clear cell carcinomas, six dysgerminomas, eight granulosa cell tumors, four transitional cell carcinomas, five fibromas, and six Brenner tumors. All ovarian tumors except the fibromas and Brenner tumors showed significant expression of matriptase. The matriptase scores were significantly higher in the tumors than in their nontumor counterparts (304+/-26 for serous adenocarcinoma; 361+/-28 for mucinous adenocarcinoma; 254+/-17 for endometrioid adenocarcinoma; 205+/-19 for yolk sac tumor; 162+/-16 for clear cell carcinoma; 109+/-11 for dysgerminoma; 105+/-9 for granulosa cell tumor; and 226+/-18 for transitional cell carcinoma). Matriptase scores in serous adenocarcinoma were correlated with TNM stage and FIGO stage. Our findings demonstrate for the first time that matriptase is overexpressed in many malignant ovarian tumors. It may be a novel biomarker for diagnosis and treatment of malignant ovarian tumors.     

Instructor facilitation of the preceptorship relationship in nursing education

In recognition of the growing popularity of preceptorships as a means of teaching in nursing, a research study was conducted to examine the development of the preceptor relationship. Three questions were addressed: what are the specific elements essential to the development of the preceptorship relationship?; what is the role of the instructor in facilitating the developing preceptorship relationship?; and what are the variables affecting the developing preceptorship relationship? Based on naturalistic observations and direct feedback from 12 preceptor RNs, 12 students, and 2 instructors in acute care hospitals, seven commonly occurring themes were identified as important aspects of the developing relationship.     

Risk factors for urinary incontinence in Taiwanese women aged 60 or over

To determine risk factors of urinary incontinence (UI) in Taiwanese women aged 60 or over, face-to-face interviews with 1,517 women, selected by a multistage random method, were completed. The prevalence of UI in this age group was 29.8%. Factors and their prevalence associated with UI were age [odds ratio (OR)=1.04 per year], diabetes mellitus (39.8%, p = 0.002), hypertension (39.5%, p = 0.001), abdominal gynecological surgery (41.4%, p = 0.001), hysterectomy (42.4%, p = 0.003), history of drug allergy (41.3%, p = 0.001), smoking (45.5%, p = 0.010), hormone replacement therapy (41.5%, p = 0.026), and high body mass index (OR = 1.05 per unit). Alcohol consumption and marriage did not increase the risk of UI. UI is a common and costly problem in elderly women. It diminishes the quality of life of the affected women. Of the associated factors that are preventable, modifiable, or controllable, smoking, prior hysterectomy, and obesity may have the greatest impact on the prevalence of UI.     

Another option to treat Kümmell’s disease with cord compression

The efficiency of short-segment fixation with transpedicle body augmenter (a titanium spacer with bone-ingrowth porous surface, TpBA) to treat Kümmell's disease with cord compression (stage III) was retrospectively evaluated. No laminectomy or instrumentation reduction was done. Inclusion criteria included Frankel CDE, single-level within T10-L2. FU rate was 88%, i.e. 21 cases were included. Frankel function classification was 6E9D6C. Mean age was 72+/-8 years. F:M was 16:5. FU period was 48 M (range, 30-76 M). The hospitalization was 4.5+/-2.2 days; operation time, 70.4+/-17.2 min; blood loss, 150+/-72 cc. Final Frankel class was 20E1D. Complications included two superficial infection and one pneumonia. Body height and kyphosis were all corrected significantly and well preserved at the final visit. No TpBA dislodgement or implant failure was noted; however, three cases developed new compression fractures. The clinical outcome showed 81% with P1 or P2 by Denis pain scale. This method can decompress spinal canal, maintain kyphosis correction and vertebral restoration, prevent implant failure, and attain good clinical results.     

清除骨髓中癌细胞的磁性微球研究 II.聚苯乙烯磁性微球的研制

为制备能用于清除骨髓中癌细胞的磁性微球,首先合成了单分散、大粒径的多孔聚苯乙烯交联微球,借助微球多孔结构对其进行磁化。探讨了影响磁化效果的主要因素。为使其与单抗连接紧密,在微球表面聚合了一层聚丙烯醛膜,使其表面带上易与单抗反应的醛基。同时测定了所制微球的磁响应性。X-射线衍射证明磁性物质为γ-Fe₂O₃。     

PATIENT ACCIDENTS IN HOSPITAL: INCIDENCE,DOCUMENTATION AND SIGNIFICANCE

SUMMARY Many previous studies of reported patient accidents in hospital used the accident report forms as the only data source, without questioning their reliability and despite 80% of the accidents being unwitnessed. This paper reports on three studies using data from patient interviews, staff questionnaires, medical and nursing notes and the accident report forms. The studies confirm that falls amongst elderly patients are the most common type of patient accident. However, patients' and staff's versions of the event often differed widely. Accident reports are stated to be required for legal purposes, but they were often incomplete and unreliable. Patient accidents and safety are too important to remain marginalised to mere compliance with out-of-date regulations. A new, ‘slim-line‘, more accurate but less time-consuming patient accident reporting system should be developed, for which improvement in patient safety is the main aim and legal considerations the secondary aim.