The Impact of Gabapentin Administration on Brain GABA and Glutamate Concentrations: A 7T 1H-MRS Study

Gamma-aminobutyric acid (GABA) and glutamate are implicated in numerous neuropsychiatric and substance abuse conditions, but their spectral overlap with other resonances makes them a challenge to quantify in humans. Gabapentin, marketed for the treatment of seizures and neuropathic pain, has been shown to increase in vivo GABA concentration in the brain of both rodents and humans. Gabapentin effects on glutamate are not known. We conducted a gabapentin (900 mg) challenge in healthy human subjects to confirm and explore its effects on GABA and glutamate concentrations, respectively, and to test the ability of single voxel localized proton magnetic resonance spectroscopy (¹H-MRS) to reliably measure GABA and glutamate in the visual cortex at the ultra-high magnetic field of 7 Tesla. Reproducibility of GABA and glutamate measurements was determined in a comparison group without drug twice within day and 2 weeks apart. Although GABA concentration changes were small both within day (average 5.6%) and between day (average 4.8%), gabapentin administration was associated with an average increase in GABA concentration of 55.7% (6.9–91.0%). Importantly, drug-induced change in GABA levels was inversely correlated to the individual''s baseline GABA level (R²=0.72). Mean glutamate concentrations did not change significantly with or without drug administration. In conclusion, localized ¹H-MRS at 7 Tesla can be successfully applied to the measurement of GABA concentration and is sensitive to acute drug-induced changes in cortical GABA. Whether baseline GABA concentrations predict clinical efficacy of gabapentin is an area worthy of exploration.     

Mathematical modeling of stem cell proliferation

The mathematical models prevalently used to represent stem cell proliferation do not have the level of accuracy that might be desired. The hyperbolastic growth models promise a greater degree of precision in representing data of stem cell proliferation. The hyperbolastic growth model H3 is applied to experimental data in both embryonic stem cells and adult mesenchymal stem cells. In the embryonic stem cells the results are compared with other popular models, including the Deasy model, which is used prevalently for stem cell growth. In the case of modelling adult mesenchymal stem cells, H3 is also successfully applied to describe the proliferative index. We demonstrated that H3 can accurately represent the dynamics of stem cell proliferation for both embryonic and adult mesenchymal stem cells. We also recognize the importance of additional factors, such as cytokines, in determining the rate of growth. We propose the question of how to extend H3 to a multivariable model that can include the influence of growth factors.     

Variability of ferritin measurements in chronic kidney disease; implications for iron management

Serum ferritin levels are a proxy measure of iron stores; and existing guidelines for managing anemia in hemodialysis patients suggest that serum ferritin concentrations should be maintained at >200 ng/ml. The KDOQI recommendations further state there is insufficient evidence advocating routine intravenous iron when ferritin levels exceed 500 ng/ml. Here we determined the interassay differences and short-term intraindividual variability of serum ferritin measurements in patients on chronic hemodialysis to illustrate how these variances may affect treatment decisions. Intermethod variations of up to 150 ng/ml were found comparing six commonly used ferritin assays that evaluated thirteen pools of serum from hemodialysis and nonhemodialysis patients. The intraindividual variability for ferritin in 60 stable hemodialysis patients ranged between 2-62% measured over an initial two-week period and from 3-52% when factored over a six-week period. Our results suggests that single serum ferritin values should not be used to guide clinical decisions regarding treatment of chronic hemodialysis patients with intravenous iron due to significant analytical and intraindividual variability.     

Transportation and aging: a research agenda for advancing safe mobility

PURPOSE: We review what we currently know about older driver safety and mobility, and we highlight important research needs in a number of key areas that hold promise for achieving the safety and mobility goals for the aging baby boomers and future generations of older drivers. DESIGN AND METHODS: Through the use of a framework for transportation and safe mobility, we describe key areas of screening and assessment, remediation and rehabilitation, vehicle design and modification, technological advancements, roadway design, transitioning to nondriving, and alternative transportation to meet the goals of crash prevention and mobility maintenance for older adults. RESULTS: Four cross-cutting themes emerged from this review: safe transportation for older adults is important; older adults have a variety of needs, abilities, and resources; research to help meet the transportation needs of older adults may be of benefit to persons with disabilities; and transportation issues concerning older adults are multifaceted. IMPLICATIONS: Safe mobility is essential to continued engagement in civic, social, and community life, and to the human interactions necessary for health, well-being, and quality of life. When safe driving is no longer possible for older adults, safe and practicable alternative transportation must be available. Furthermore, older adults are individuals; they have specific needs, abilities, and resources. Not all older adults will have difficulty meeting their transportation needs and no single transportation solution will work for all people. Research and countermeasures intended to help meet the transportation needs of older adults will likely also benefit younger users of the transportation system, particularly those with disabilities. The issues surrounding the maintenance of safe transportation for older adults will require an interdisciplinary research approach if we are to make significant progress in the next decade as the baby boomers begin to reach age 70.     

Genetic-based dosing in orthopedic patients beginning warfarin therapy

High variability in drug response and a narrow therapeutic index complicate warfarin therapy initiation. No existing algorithm provides recommendations on refining the initial warfarin dose based on genetic variables, clinical data, and international normalized ratio (INR) values. Our goal was to develop such an algorithm. We studied 92 patients undergoing primary or revision total hip or knee replacement. From each patient we collected a blood sample, clinical variables, current medications, and preoperative and postoperative laboratory values. We genotyped for polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase (VKORC1) genes. Using stepwise regression, we developed a model for refining the warfarin dose after the third warfarin dose. The algorithm explained four fifths of the variability in therapeutic dose (R(2)(adj) of 79%). Significant (P > .05) predictors were INR value after 3 doses (47% reduction per 0.25-unit rise), first warfarin dose (+7% per 1 mg), CYP2C9*3 and CYP2C9*2 genotype (-38% and -17% per allele), estimated blood loss (interacting with INR(3)), smoking status (+20% in current smokers), and VKORC1 (-11% per copy of haplotype A). If validated, this model should provide a safer, more effective process for initiating warfarin therapy.     

A study on motility of sphincter of Oddi in postcholecystectomy syndrome

Endoscop c manometry of sphincter of Oddi(SO)and serumlevels of gastrin,glucagon,and somatostatin were measured in patients withpostcholecystectomy syndrome(n=12),asymptomatic cholecystectomised pa-tients(n=6),and controlled subjects(n=14).Pentagastrin-stimulated gastricacid secretion test was also performed in part of patients who had symptoms orno symptoms after gallbladder resection.The results showed that the patientsof symptomatic group had hypertonic dyskinesia of SO as shown by deep andwide waves superimposed on high basal pressure plateau of SO.The symptoma-tic group also had a higher serum level of gastrin and a greater BAO than tho-se of other two groups.No difference of serum levels of glucagon and soma-tostatin was found among these three groups.The hypertonic dyskinesia of SOand hypergastrinemia are considered as possibly important factors in the patho-genesis of postcholecystectomy syndrome.     

Rat myometrial smooth muscle cells express endothelial nitric oxide synthase

We examined if rat myometrial cells in culture generate nitric oxide (NO) and express various isoforms of NO synthase (NOS). Myometrial cells isolated from rats on day 18 of gestation were incubated with various stimulators and inhibitors of NOS for 24 and 48 h, and NO production was evaluated by measuring nitrites in the media and NOS proteins in the cell lysates. NO was produced by myometrial cells and its production inhibited by N(G)-methyl-L-arginine (L-NMMA). This inhibition was reversed by L-arginine (3 mM). Interleukin-1beta (IL- 1beta) significantly stimulated NO production, in a dose-dependent manner. The IL-1beta-stimulated NO production was inhibited by the NOS inhibitor, L-NMMA, whose effects were reversed by L-arginine. Abundant NOS III protein was detectable in freshly isolated myometrial cells, and this was maintained in culture in the presence of fetal bovine serum (FBS; 10%). In the absence of FBS, NOS III levels decreased significantly (by 90%) within 24 h. In contrast, NOS I and NOS II proteins were undetectable in freshly isolated muscle cells and in cells cultured without IL-1beta. However, NOS II protein in these cells was induced by IL-1beta. Thus, NO is produced by myometrial cells through the NOS III isoform, and the myometrial NO may be important in maintaining uterine quiescence during pregnancy.      

Fully endoscopic endonasal vs. transseptal transsphenoidal pituitary surgery.

A long-term retrospective study of 300 patients who underwent fully endoscopic endonasal pituitary adenoma resection between November 1998 and October 2004. The patients' records as well as the data obtained from postoperative follow-up visits was used to determine outcomes. Additionally, the data were then compared to mean values calculated from several transseptal-transsphenoidal reports. From a total of 300 pituitary adenomas, 139 (46 %) were hormonally active, while 161 (54 %) were non-functioning. Mean follow-up period was 38.2 months. The average length of hospital stay (LOS) was 1.4 days. All patients had postoperative magnetic resonance imaging (MRI) studies to assess residual or recurrent disease; all patients with hormonally active tumors had additional postoperative hormonal studies. Remission, being defined as no hormonal or radiological evidence of recurrence within the time-frame of the follow-up, was demonstrated in 127/134 (95 %) of enclosed and 144/166 (87 %) of invasive adenomas. A comparison of fully endoscopic endonasal vs. transseptal-transsphenoidal remission results revealed an improved outcome using the fully endoscopic endonasal technique: ACTH (86 % vs. 81 %), PRL (89 % vs. 66 %) and GH (85 % vs. 77 %). The remission rate for non-functioning adenomas was 149/161 (93 %). Additionally, we noted a marked reduction in complications related to the endoscopic procedure. Our results conclude that the fully endoscopic endonasal technique is a safe and effective method for removal of pituitary adenomas providing more complete tumor removal and reducing complications.     

医学生心理健康状况与人格特征的相关分析

目的 :了解在校医学生的心理健康状况 ,为今后开展心理健教育提供有益的依据。方法 :采用 SCL-90和 EPQ量表对在校 5 88名医学生调查并作相关分析。结果 :医学生出现各类心理问题的比例为 6.80 %～ 3 2 .11% ,以强迫、人际敏感、抑郁和偏执为主。临医和护理专业学生心理问题的侧重点不同。女生在人际敏感、抑郁和恐怖等方面均高于男性。情绪稳定性 N和精神质 P与各因子及总均分呈正相关关系 (P<0 .0 1) ,掩饰度 L 与各因子呈显著负相关 (P<0 .0 1)。多因素回归分析表明 ,情绪稳定性 N和掩饰度 L对心理健康的影响起着重要作用。结论 :搞好学生的心理健康 ,加强健全人格教育是关键 ,同时要根据不同性别和专业区别地对待