按质付费的做法足够完美了吗？

Thomas L.Watkins是一位单独开业的全科医生．他的诊所在密歇根州Muskegon市。虽然没有购买电子健康记录系统，但他也有自己的法宝，而且从功能上看并不比电子健康记录逊色：基于网络的注册系统。这个系统有他的全部病人列表．在门诊时会提醒他哪些病人需要预防性用药，哪些病人需要进行长期护理。这个登记系统还会创建工作记录，里面包含了医生的工作时间、病人数量、药物资费等信息。[第一段]     

A SaTScan™ macro accessory for cartography (SMAC) package implemented with SAS<Superscript>®</Superscript>software

Background  

SaTScan is a software program written to implement the scan statistic; it can be used to find clusters in space and/or time. It must often be run multiple times per day when doing disease surveillance. Running SaTScan frequently via its graphical user interface can be cumbersome, and the output can be difficult to visualize.     

Practice and Physician Characteristics Associated with Influenza Vaccination Delivery Rates Following a Patient Reminder Letter Intervention

As part of the “Provider and Patient Reminders in Ontario: Multi-strategy Prevention Tools” demonstration project, the purpose of this study was to explore the practice and physician characteristics associated with influenza vaccination rates following a reminder letter intervention for patients 65 years of age and older. Using a sample of 179 physicians, we estimated a multiple linear regression model to examine variables predictive of vaccination delivery rates. Several provider characteristics, including certification with the College of Family Physicians of Canada and practicing in an urban area, were predictive of the success of the reminder letter campaign. Examining other physician and practice factors associated with vaccination delivery following a reminder letter campaign may help improve such prevention efforts.     

Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphoma

PURPOSE: The ubiquitin-proteasome pathway has been validated as a target in non-Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib. EXPERIMENTAL DESIGN: Another potentially attractive target is the human homologue of the murine double minute-2 protein, HDM-2, which serves as the major p53 E3 ubiquitin ligase; we therefore evaluated the activity of a novel agent, MI-63, which disrupts the HDM-2/p53 interaction. RESULTS: Treatment of wild-type p53 mantle cell lymphoma (MCL) cell lines with MI-63 resulted in a dose- and time-dependent inhibition of proliferation, with an IC(50) in the 0.5 to 5.0 micromol/L range. MI-63 induced p53 and HDM-2 accumulation, as well as other downstream p53 targets such as p53 up-regulated modulator of apoptosis and p21(Cip1). This was associated with cell cycle arrest at G(1)-S; activation of caspase-3, caspase-8, and caspase-9; cleavage of poly-(ADP-ribose) polymerase; and loss of E2F1. HDM-2 inhibition caused phosphorylation of p53 at multiple serine residues, including 15, 37, and 392, which coincided with low levels of DNA strand breaks. DNA damage occurred in a small percentage of cells and did not induce phosphorylation of the DNA damage marker H2A.X(Ser139). Combinations of MI-63 with the molecularly targeted agents bortezomib and rapamycin showed synergistic, sequence-dependent antiproliferative effects. Treatment of primary MCL patient samples resulted in apoptosis and induction of p53 and p21, which was not seen in normal controls. CONCLUSIONS: These findings support the hypothesis that inhibition of the HDM-2/p53 interaction may be a promising approach both by itself and in combination with currently used chemotherapeutics against lymphoid malignancies.     

ITCH is a putative target for a novel 20q11.22 amplification detected in anaplastic thyroid carcinoma cells by array‐based comparative genomic hybridization

Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than 1 year after diagnosis. To date, however, cytogenetic information on this disease has been very limited. During the course of a program to screen a panel of ATC cell lines for genomic copy‐number aberrations using array‐based comparative genomic hybridization, we identified a high‐level amplification of the ITCH gene, which is mapped to 20q11.22 and belongs to the homologous to the E6‐associated protein carboxylterminus ubiquitin ligase family. The expression of ITCH was increased in 4 of 14 ATC cell lines (28.6%), including 8305C in which there was a copy‐number amplification of this gene, and six of seven primary cases (85.7%). Among the primary thyroid tumors, a considerable number of ITCH high expressers was found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%). Furthermore, knockdown of ITCH by specific small interfering RNA significantly inhibited the growth of ITCH‐overexpressing cells, whereas ectopic overexpression of ITCH promoted growth of ATC cell lines with relatively weak expression. These observations indicate ITCH to be the most likely target for 20q11.22 amplification and to play a crucial role in the progression of thyroid carcinoma. (Cancer Sci 2008; 99: 1940–1949)     

Establishment of an ovarian metastasis model and possible involvement of E‐cadherin down‐regulation in the metastasis

Clinical observations of cases of ovarian metastasis suggest that there may be a unique mechanism underlying ovarian‐specific metastasis. This study was undertaken to establish an in vivo model of metastasis to the ovary, and to investigate the mechanism of ovarian‐specific metastasis. We examined the capacity for ovarian metastasis in eight different human carcinoma cell lines by implantation in female NOD/SCID mice transvenously and intraperitoneally. By transvenous inoculation, only RERF‐LC‐AI, a poorly differentiated carcinoma cell line, frequently demonstrated ovarian metastasis. By intraperitoneal inoculation, four of the eight cell lines (HGC27, MKN‐45, KATO‐III, and RERF‐LC‐AI) metastasized to the ovary. We compared E‐cadherin expression among ovarian metastatic cell lines and others. All of these four ovarian metastatic cell lines and HSKTC, a Krukenberg tumor cell line, showed E‐cadherin down‐regulation and others did not. E‐cadherin was then forcibly expressed in RERF‐LC‐AI, and inhibited ovarian metastasis completely. The capacity for metastasizing to the other organs was not affected by E‐cadherin expression. We also performed histological investigation of clinical ovarian‐metastatic tumor cases. About half of all ovarian‐metastatic tumor cases showed loss or reduction of E‐cadherin expression. These data suggest that E‐cadherin down‐regulation may be involved in ovarian‐specific metastasis. (Cancer Sci 2008; 99: 1933–1939)     

Combination chemotherapy with cisplatin and irinotecan in patients with adenocarcinoma of the small intestine

Background  Small-bowel adenocarcinoma (SBA) is a rare tumor that has a poor response to chemotherapy and a poor prognosis. Treatment strategies for SBA have not been clearly established. Methods  All patients with SBA treated using a combination of cisplatin and irinotecan (IP) as first-line chemotherapy at the National Cancer Center Hospital in Japan between January 1999 and February 2007 were studied retrospectively. Results  Eight patients received IP as first-line chemotherapy. The median follow-up was 9.5 months (range, 4.2–37.5 months). The median number of cycles of IP was three (range, 1–5). The overall response rate (complete or partial response) was 12.5% (complete response, n = 0; partial response, n = 1). The disease control rate (complete or partial response or stable disease) was 75%. The median time to treatment failure was 4.5 months (95% confidence interval, 0.9–5.8 months), and overall survival was 17.3 months (range, 1.9–21.3 months). The most common adverse events were neutropenia and anorexia. Conclusion  IP combination chemotherapy may be an acceptable option for patients with SBA. Further studies are warranted to determine the optimal chemotherapeutic regimen for SBA.     

Fatal lactic acidosis in infancy with a defect of complex III of the respiratory chain

We report our studies on the metabolic defects which caused a newborn infant to present with a severe lactic acidemia (25 mM) and to die on the 3rd d after birth despite intensive supportive measures. The mitochondrial fractions prepared from skeletal muscle and liver oxidised NAD+-linked substrates and succinate slowly. Spectrophotometric assays for complexes I, II, and III of the respiratory chain demonstrate a specific defect of complex III in the skeletal muscle and liver mitochondrial fractions. The concentrations of cytochrome b were 75% lower in the skeletal muscle and heart mitochondria than in control preparations. The amount of non-heme iron sulphur protein of complex III was low in skeletal muscle, liver, and heart. This case differs from previous reports of complex III deficiency in three respects: the patient presented in the neonatal period, the defect was expressed in several tissues, and it was fatal.     

Differentiation of a Ewing's Sarcoma Cell Line towards Neural and Mesenchymal Cell Lineages

Two different pathways of differentiation were investigated in Ewing's sarcoma (ES) cell line, designated CADO-ES1, which has been established in our laboratory. This cell line was induced to differentiate and display a neural phenotype when treated with dibutyryl cyclic adenosine mono-phosphate or when cultured in serum-free medium (HB101). In these in vitro differentiation studies, two different phenotypes were demonstrated by light and electron microscopy. One phenotype, present in a major portion of the cell population, had long neurites in which microtubules were ultrastructurally demonstrated. The other one, present in a minor portion of the cell population, consisted of flat cells with many short processes. After differentiation in serum-free medium, tumorigenicity in nude mice or colony-forming efficiency in soft agar was strongly depressed. In the cells, N- myc , c- fos and c- src genes were not amplified, and although c- myc was amplified by up to 2-fold, depending on the culture conditions, this appeared to be unrelated to the changes of phenotype. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue.     

Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine,etoposide and adriamycin in human glioma cells

The multidrug-resistance phenotype in human tumors is partly associated with over-expression of the 170 kDa-P-glycoprotein encoded by the multidrug-resistance-1 (MDRI) gene. Another related, but non-P-glycoprotein, multidrug-resistance-associated protein (MRP) gene encodes a 190 kDa membrane ATP-binding protein. Glioblastoma multiforme is a highly malignant primary neoplasm of the central nervous system which is refractory to anti-cancer chemotherapy, but the mechanism underlying this drug resistance is unknown. Out of glioma cell lines, 2, namely IN500 and T98G, which had elevated MRP mRNA levels, showed the highest resistance to multiple anti-cancer agents such as etoposide, vincristine and adriamycin, and decreased intracellular accumulation of etoposide. In the remaining 5 cell lines, various degrees of sensitivity to adriamycin and etoposide appeared to correlate with their respective MRP mRNA levels. Our study proposes that MRP may be involved in spontaneous multidrug resistance in human gliomas.