Correlation between dynamic MRI and outcome in patients with malignant gliomas

We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.     

Induction of mixed allogeneic chimerism for leukemia

Hybrid (C56BL/6 x DBA) (BDF1; H-2b/H-2d) mice bearing the P815 leukemia (H-2d) were grafted with a (CBA x C57BL/6)F1 (CBF1; H-2k/H-2b) cell suspension, comprising bone marrow cells (BMC; 25 x 10(6)/mouse) and spleen cells (SC; 55 x 10(6)/mouse) on day-4, then treated with cyclophosphamide (200 mg/kg) on day-2 and finally grafted once more with CBF1 cells (25 x 10(6) BMC + 7 x 10(6) SC) on day 0. Allogeneic cell graftings performed in this way induced durable mixed hematopoietic chimerism and significantly prolonged the survival of recipients, compared with that of leukemia-bearers grafted with syngeneic cells. The results obtained raise the possibility of using allogeneic hematopoietic tissue transplantation in combination with non-lethal cytoreductive therapy to induce a long-lasting graft-vs-leukemia effect.     

Purification, potency, and efficacy of the botulinum neurotoxin type A binding domain from Pichia pastoris as a recombinant vaccine candidate

Recombinant botulinum neurotoxin serotype A binding domain [BoNT/A(Hc)], expressed in Pichia pastoris, was developed as a vaccine candidate for preventing botulinum neurotoxin type A (BoNT/A) intoxication. After fermentation and cell disruption, BoNT/A(Hc) was purified by using a three-step chromatographic process consisting of expanded-bed chromatography, Mono S cation-exchange chromatography, and hydrophobic interaction chromatography. Two pools of immunogenic product were separated on the Mono S column and processed individually. Both products were more than 95% pure and indistinguishable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Each protein was assayed for potency in mice at immunogen doses ranging from 2.4 ng to 10 microg, followed by challenge with 1,000 mouse intraperitoneal 50% lethal doses (i.p. LD50) of BoNT/A. The calculated 50% effective dose for both peaks was approximately 0.1 microg/mouse. Peak 1 was evaluated further in a mouse efficacy assay. Mice were injected either once, twice, or three times at five different doses and subsequently challenged with 100,000 mouse i.p. LD50 of BoNT/A. In general, multiple injections protected better than one, with complete or nearly complete protection realized at doses of >/=0.5 microg/mouse. Serum neutralization and ELISA titers were also determined. Tellingly, 82 of 83 mice with antibody titers of >/=1, 600, as measured by ELISA, survived, but only 6 of 42 mice with titers of 相似文献   

Peptide nucleic acids and their phosphonate analogues: synthesis and hybridization characteristics

The synthesis of a series of DNA mimics--peptide nucleic acids, phosphonate analogues of peptide nucleic acids, and their hybrids--is described. The preparative synthesis of the corresponding monomers and the solid phase automated synthesis of oligomers-mimics are developed. Modified phosphonate analogues of peptide nucleic acids, in particular chiral derivatives and those with additional hydroxyl groups in the side chains of the backbone as well as pyrene derivatives of peptide nucleic acids and their phosphonate analogues, are prepared. The ability of the resulting oligomers specifically to hybridize to DNA and RNA complementary chains is studied. It is shown that phosphonate analogues of peptide nucleic acids and their hybrids with peptide nucleic acids can form complexes with the DNA and RNA complementary strands, the stability of the complexes increasing in parallel with the increase in the number of peptide nucleic acid residues in the chain of the mimic. This property, along with good water solubility, provides the precondition for further evaluation of these compounds as antisense and antigene agents.     

The fate of pelvic osteolysis after reoperation. No recurrence with lesional treatment

Twenty-three hips (21 patients) with 30 pelvic osteolytic lesions underwent reoperation and were observed prospectively for 25 to 74 months (average, 40 months) to assess the fate of pelvic osteolysis after reoperation. The average radiographic dimensions of the lytic lesions were 2.4 x 1.9 cm with the largest lesion measuring 7 x 5 cm. The porous ingrowth acetabular component shell had been left in situ in 15 hips and had been revised in eight. There was no difference in the average lesional size for hips with revised shells compared with those with unrevised shells. In cases where the shell was left in situ, the osteolytic lesions were curetted by working around the component perimeter or through holes in the shell. In 18 hips the bone defect(s) were grafted with autograft or allograft. Regardless of the management of the acetabular shell or the absence or presence of bone graft, none of the osteolytic lesions have progressed. Twenty-six of the 30 lesions have increased radiographic density. All acetabular components remain radiographically well fixed. There were no new osteolytic lesions. All hips were functioning well, and none have required subsequent reoperation for any reason. There was a statistically significant reduction in the operative time and the amount of blood loss when the acetabular component was not revised. It does not appear necessary to remove a well fixed and well positioned cementless acetabular component for the treatment of pelvic osteolysis. Debridement of periarticular inflammatory tissue and lesional curettage, either with or without bone graft, is effective in managing this type of bone loss. Revision of the acetabular component shell was associated with a significant increase in operative time and blood loss. These results support routine radiographic evaluation after total hip arthroplasty to monitor the development of osteolysis. On the basis of this experience, the authors recommend lesional treatment of progressive pelvic osteolysis to avoid more difficult surgery and minimize patient morbidity.     

Systematic, computer-assisted optimisation of the isolation of Thermus thermophilus 50S ribosomal proteins by reversed-phase high-performance liquid chromatography

Isolation of the 50S ribosomal proteins from Thermus thermophilus has been achieved for the first time using reversed-phase high-performance liquid chromatography based on the use of the non-end-capped LiChrospher RP-18 sorbent and computer-assisted method development for optimisation of the resolution. The separation approach for these basic ribosomal proteins utilised mobile phases of high ionic strength, to suppress silanophilic interactions with this type of reversed-phase sorbent. These conditions were found to be a key requirement for achieving good resolution with minimal peak-tailing. The retention times of the 50S ribosomal proteins of Thermus thermophilus were observed to be in very close agreement with the values predicted by computer simulation procedures based on linear solvent strength concepts, with an average error of only 0.5%, whilst base-line resolution was achieved for most of the adjacent peak zones. Following N-terminal sequencing, the proteins TthL5, TthL9, TthL18, TthL24, TthL29, TthL32, TthL34, TthL35 and TthL36 of Thermus thermophilus were readily identified. This approach thus provided a readily optimised strategy for the isolation of the 50S ribosomal proteins from Thermus thermophilus and should be generally applicable to the corresponding ribosomal proteins from various other species, as well as other classes of basic proteins present in crude extracts derived from other biological sources.     

Effects of curvature and stenosis-like narrowing on wall shear stress in a coronary artery model with phasic flow

To gain insight into the details of intracoronary flow we have used computational fluid dynamic techniques to determine the velocity and wall shear stress distributions in both steady- and phasic-flow models of a curved coronary artery with several degrees of stenosis. The steady-flow Reynolds number was 500 and the peak phasic flow Reynolds number was 700. Without stenosis and at 25% (area) stenosis wall shear stress and velocities are higher at the outer wall than the inner wall but retain the same direction as the superimposed flow. At higher stenoses laminar flow separation occurs and the inner wall is exposed to shear stresses that vary widely, both temporally and spatially.     

Differential diagnosis of posterior cranial fossa: potentialities and unsolved problems

This study describes nurse practitioners' (NPs) practice and employment trends, primary care/direct patient care involvement, scope of practice issues, productivity, and demographic characteristics. Data were collected by mailed survey from 2,499 NPs in New York State. NPs were predominantly certified as Adult, Pediatric or Family NPs. The vast majority of NPs were working (64.1% full-time; 22.7% part-time). Fifty percent said they spend over 80% of their time providing primary care. Over 50% of the NPs employed in non-hospital settings said that their organizations had contracts with four or more managed care organizations.