Radical effects on mutation spectra in lambda phage.

Mutations in the lambda repressor gene cI (710 bp) were induced by 60Co-gamma radiation in dissolved lambda phage DNA. After in vitro DNA packaging to lambda phage particles (pack phage) and phenotypic expression of the mutants, DNA was sequenced directly. Two-thirds of mutations were located in the amino terminus region of the gene without any signs of hotspots. Changes consisted of (+1) insertions (25%) and base substitutions (75%). Transitions were exclusively G/C to A/T. Transversions were mostly G/C to C/G and few G/C to T/A. We did not find A/T to T/A transversions, A/T to G/C transitions, deletions and gross rearrangements. In most of the base substitutions a pre-existing base pair had been replaced by an A/T pair; this might come from 'non-instructional sites' like abasic sites. Several mechanisms for base substitutions are considered.     

Ki-1 Large Cell Lymphoma with Regressing Lesions in a Child

An 8-year-old boy was seen with a cutaneous Ki-1 anaplastic, large cell lymphoma with multiple lesions. Some of the lesions showed spontaneous regression. During more than seven years of disease no systemic involvement was observed, but recurrent, self-healing lesions did appear. Histopathologic examination of five lesions revealed a variety of findings, from an inflammatory infiltrate to a highly anaplastic pattern. The neoplastic cells expressed Ki-1 and leukocyte common antigens. Ultrastructurally, those cells showed ruffled indentations. The differential diagnosis includes microvillous malignant lymphoma. The patient has had a four-year follow-up without relapses.     

The orthopan tomoscintigram — a new application of emission computed tomography for facial bone scanning

The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, which was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging.     

Entwicklung eines Tibiamarknagels auf der Basis anatomischer Untersuchungen der intraossären Gefäße

The design of the tibial medullary nail can be improved in order to preserve intraosseus vessels by osteosynthesis of the tibia. The nutrient artery of the human tibia enters the compacta in an average height of 33% dorsally and is leaving it in a height of 50% of the tibial length. In the medullary cavity the vessel splits up. The main branch continues the distal course on the dorsal/dorsolateral side of the medullary cavity (endosteal). In the distal diaphysis this endosteal vessel is of great importance, since the periosteal blood supply in this region with high incidence of pseudarthrosis is guaranteed only by branches of the anterior tibial artery. Using a new unreamed tibial nail, which is flattened dorsally, it is possible to preserve the endostal main artery of the tibia.     

Measurement of bone by dual-photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DEXA)

Bone densitometry is essential for (a) confirming a diagnosis of osteoporosis, (b) determining the degree of osteopenia and risk of fracture, and (c) monitoring the response of bone to therapeutic agents. Fracture risk at specific axial fracture sites (spine, proximal femur), is associated directly with bone mineral density (BMD) at these sites. ROC analysis demonstrates that the diagnostic sensitivity of spine and femur BMD for spine and/or femur fracture is substantially superior to BMD of appendicular sites in the immediate postmenopausal period. Femoral neck BMD affords high diagnostic sensitivity for proximal femur fracture even in the elderly. Recent prospective studies have shown that bone densitometry can predict future fractures in postmenopausal women. Conventional DPA with 153Gd provides high accuracy for total body, spine, and femur BMD with adequate clinical precision of 1%, 2% and 3%, respectively. Dual-energy x-ray absorptiometry (DEXA), using either switched kVp or by k-edge filtering, offers better precision; typically the precision error is halved. The higher flux available from x-ray sources provides other advantages over DPA, including: improved spatial resolution (2 vs 4 mm), reduced radiation exposure (1 vs 2 mrem), and decreased scan times (3 to 10X). Improved DPA systems, with automatic gain stabilization to minimize drift, could offer clinical precision comparable to DEXA but the scan time and spatial resolution remain as before. Both DPA and DEXA allow detection of therapeutic efficacy in individual patients over the first year or two of therapy.     

Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.     

Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats

Background The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat. Materials and methods Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection. Results Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8–25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not. Conclusions In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.     

Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood–spinal cord barrier

Angiogenesis precedes recovery following spinal cord injury and its extent correlates with neural regeneration, suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to the formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two-component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant + ECs or implant + NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a fourfold increase in functional vessels compared with the lesion control, implant alone or implant + NPCs groups and a twofold increase in functional vessels over the implant + ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for the formation of the blood–spinal cord barrier. No other groups have shown positive staining for the blood–spinal cord barrier in the injury epicenter. This work provides a novel method to induce angiogenesis following spinal cord injury and a foundation for studying its role in repair.     

聚乙烯颗粒对人单核细胞分泌促炎因子与抗炎因子的影响

[目的]探讨聚乙烯颗粒对人单核细胞分泌促炎因子与抗炎因子的影响.[方法]用Ceridust 3615 颗粒(聚乙烯颗粒)(平均直径14.27,6.39,1.74,1.01,0.54和0.28 μm)分别刺激人单核细胞,颗粒体积与细胞数的比例为100:1和10:1.在颗粒刺激细胞24 h后,运用ELISA检测培养上清液中的促炎因子(白介素-1β,白介素-6和细胞坏死因子α)及抗炎因子(白介素-10)的表达.[结果]Ceridust 3615 颗粒可刺激单核细胞分泌白介素-1β(IL-1β)、白介素-6(IL-6)和细胞坏死因子α(TNFα),但未能引起白介素-10(IL-10)的表达.颗粒比例增高可促使单核细胞分泌更多的IL-6和TNFα,却减少IL-1β分泌,对IL-10的分泌则无影响.个体差异使巨噬细胞对同种颗粒的刺激产生不同的反应,其差异可达到30倍.[结论]个体差异是影响人工关节寿命的重要因素,聚乙烯颗粒可刺激单核细胞产生炎因子但对产生抗炎因子(IL-10)的作用不明显,提示促炎因子与抗炎因子的不平衡或许是人工关节松动不断进展的另一重要因素.