Molecular analysis of primary gastric cancer, corresponding xenografts, and 2 novel gastric carcinoma cell lines reveals novel alterations in gastric carcinogenesis

We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using methylation-specific multiplex ligation-dependent probe amplification, and TP53 and CDH1 mutation analysis where relevant. The primary tumors and xenografts were histologically comparable and shared expression of 11 of 14 immunohistochemical markers (E-cadherin, beta-catenin, COX-2, p53, p16, TFF1, cyclin E, MLH1, SMAD4, p27, KLK3, CASR, CHFR, and DAPK1). Gains of CASR, DAPK1, and KLK3--not yet described in gastric cancer--were present in the primary tumors, xenografts, and cell lines. The most prominent losses occurred at CDKN2A (p16), CDKN2B (p15), CDKN1B (p27/KIP1), and ATM. Except for ATM, these losses were found only in the cell line or xenograft, suggesting an association with tumor progression. However, examination of p16 and p27 in 174 gastric cancers using tissue microarrays revealed no significant correlation with tumor stage or lymph node status. Further losses and hypermethylation were detected for MLH1, CHFR, RASSF1, and ESR, and were also seen in primary tumors. Loss of CHFR expression correlated significantly with the diffuse phenotype. Interestingly, we found the highest rate of methylation in primary tumors which gave rise to cell lines. In addition, both cell lines harbored mutations in CDH1, encoding E-cadherin. Xenografts and gastric cancer cell lines remain an invaluable research tool in the uncovering of the multistep progression of cancer. The frequent gains, losses, and hypermethylation reported in this study indicate that the involved genes or chromosomal regions may be relevant to gastric carcinogenesis.     

A mechanism for effective cell-seeding in rigid,microporous substrates

Seeding cells into porous ceramic substrates has been shown to improve outcomes in surgical repair of large bone defects, but the physics underlying cellular ingress into such scaffolds remains elusive. This paper demonstrates capillary forces as a novel, yet simple, self-loading or self-seeding mechanism for rigid, microporous substrates. Capillary forces were found to draw cells through a microporous network with interconnections smaller than the diameter of the cells in suspension. Work here emphasizes CaP-based bone scaffolds containing both macroporosity (>100 μm) and microporosity (5–50 μm); these have been shown to improve bone formation in vivo as compared to their macroporous counterparts and also performed better than microporous scaffolds containing BMP-2 by some measures of bone regeneration. We hypothesize that capillary force driven self-seeding in both macro- and micropores may underlie this improvement, and present a mathematical model and experiments that support this hypothesis. The cell localization and penetration depth within these two-dimensional substrates in vitro depends upon both the cell type (size and stiffness) and the capillary forces generated by the microstructure. Additional experiments showing that cell penetration depth in vitro depends on cell size and stiffness suggest that microporosity could be tailored to optimize cell infiltration in a cell-specific way. Endogenous cells are also drawn into the microporous network in vivo. Results have important implications for design of scaffolds for the healing of large bone defects, and for controlled release of drugs in vivo.     

Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Myelinated and nonmyelinated nerves: comparison of proton MR properties

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Esophageal strictures in children: treatment by serial balloon catheter dilatation

Grüntzig balloon catheters were used to dilate ten esophageal strictures in eight infants and children. Five infants who had anastomotic strictures following esophageal atresia repair gained complete resolution of their strictures, usually after one or two dilatations. Three older children who had strictures following esophageal re-operation or reconstruction required longer courses of dilatations to achieve consistent esophageal patency. The technique failed in two chronic strictures of two and one-half and nine years' duration. Balloon catheter dilatation, begun in the early postoperative period, is a safe, effective method for dilating esophageal strictures.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

Iotrol versus metrizamide in lumbar myelography: a double-blind study

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.     

Surface shield: device to reduce personnel radiation exposure

A simple device is described that can reduce personnel exposure from scatter radiation by up to 75%. The device consists of an oblong piece of shielding (0.75-mm lead equivalent) that is taped to the side of the patient during percutaneous renal stone removal and other interventional procedures. Contrary to other shields and barriers, this does not interfere with access to the patient. Scatter exposure data from phantom studies are presented and the rationale for surface shielding discussed.