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21.
Christine E. Marx William T. Trost Lawrence J. Shampine Robert D. Stevens Christine M. Hulette David C. Steffens John F. Ervin Marian I. Butterfield Daniel G. Blazer Mark W. Massing Jeffrey A. Lieberman 《Neuropsychopharmacology》2006,60(12):1287-1294
BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD. 相似文献
22.
Tony R Cucuzzella Elva G Delport Nancy Kim Julie Marley Christine Pruitt Anton G Delport 《The spine journal》2006,6(4):364-369
BACKGROUND CONTEXT: Substantial variation exists regarding the use of sedation before interventional spine techniques. Patient preference should play an important role in decision making regarding the need for sedation. However, little is known about patients' anxiety levels before spinal injections and their perceptions about the necessity of sedation. PURPOSE: To determine patient perception for need for sedation before epidural steroid injections and zygapophyseal joint injections. STUDY DESIGN/SETTING: Survey of consecutive spinal injection patients in an outpatient spine center. PATIENT SAMPLE: 500 consecutive lumbar, thoracic, and cervical patients receiving spinal injections. OUTCOME MEASURES: A 12-item questionnaire assessing patients' perceived anxiety before to a spinal injection. METHODS: Subjects were given the questionnaire after their spinal injection. Percentages requesting sedation for a first and potential second procedure were assessed. Additionally, anxiety level and pain rating, location of injection, age, sex, and other medication use were analyzed to determine the effect on the request for sedation. RESULTS: 17% of patients questioned requested sedation before an injection, and 28% would request sedation if they were to have a second injection. CONCLUSIONS: Routine sedation before diagnostic and therapeutic injections is not necessary as the majority of patients would not request sedation before the procedure when given the option. However, in some patients sedation is indicated, and all patients would benefit from educational material on sedation before the injection. 相似文献
23.
Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation 总被引:2,自引:0,他引:2
Rolf N. Barth Christina A. Janus Christine A. Lillesand Nancy A. Radke John D. Pirsch Bryan N. Becker Luis A. Fernandez L. Thomas Chin Yolanda T. Becker Jon S. Odorico Anthony M. D''Alessandro Hans W. Sollinger Stuart J. Knechtle 《Transplant international》2006,19(11):885-892
Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor. 相似文献
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26.
Christine M Sapienza Michael P Cannito Thomas Murry Ryan Branski Gayle Woodson 《J. Speech Lang. Hear. Res.》2002,45(5):830-843
Acoustic analysis of a reading passage was used to identify the abnormal phonatory events associated with adductor spasmodic dysphonia (ADSD) pre- and postinjection of Botulinum Toxin A (Botox). Thirty-one patients (age 22 to 74 years) diagnosed with ADSD were included for study. All patients were new recipients of Botox, and the examination of their voice occurred before and after their initial injection of Botox. Acoustic events were identified from reading samples of the Rainbow Passage produced by each of the patients. These events were examined from sentences containing primarily voiced sound segments. Dependent variables included the number of phonatory breaks, frequency shifts, and aperiodic segments--all variables previously defined by the investigators. Additionally, calculated variables were made of the percentage of time these events occurred relative to the duration of the cumulative voiced segments. A sex- and age-matched control group (+/-2 years) was included for statistical comparison. Results indicated that those with ADSD produced more aberrant acoustic events than the controls. Aperiodicity was the predominant acoustic event produced during the reading, followed by frequency shifts and phonatory breaks. Within the ADSD group, the number of atypical acoustic events decreased following Botox injection. It is important that the occurrence of specific abnormal acoustic events was sufficient to differentiate the disordered speakers from the controls following as well as preceding initial Botox injection, as indicated by discriminant function analysis. This paper complements our previous work using this acoustic analysis method for defining the abnormal events present in the voice of those with ADSD and further suggests that these measures can be used in conjunction with perceptual impressions to differentiate speakers on the basis of initial severity. 相似文献
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28.
Katherine Berry Richard Drake Catherine Stewart Lisa Marie Aitkin Jane Byrne Christine Barrowclough Nitin Purandare 《The American journal of geriatric psychiatry》2007,15(9):800-806
OBJECTIVE: To investigate whether orofacial tardive dyskinesia (OTD) is associated with frontal lobe dysfunction and whether either are related to the coping abilities independent of psychiatric symptoms in older people with psychotic disorders. METHODS: A total of 52 patients, aged over 65 years or over, who satisfied International Classification of Diseases, Tenth Revision criteria for psychotic disorders (F20-F29) were recruited into the study. OTD was measured using the Abnormal Involuntary Movements Scale and Waddington et al.'s (1993) criteria. Neuropsychological measures were specifically selected to assess different aspects of frontal function and coping was measured using a semistructured interview. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients with OTD showed more severe global cognitive impairment compared to patients without OTD. Group differences on measures of frontal lobe dysfunction were not maintained following adjustment for global cognitive impairment. Patients with OTD did not differ from patients without OTD on coping measures. Scores on the general psychopathology subscale of the PANSS, which includes symptoms associated with depression and anxiety, consistently predicted patients' negative perceptions of stressors and appraisals of coping, but cognitive impairment did not predict coping independent of symptoms. CONCLUSION: The association between coping and general psychopathology in older patients with psychosis warrants further investigation as both variables may be amenable to psychological interventions. 相似文献
29.
A new micelle system formed from methoxy (polyethylene glycol)-b-poly (5-benzyloxy-trimethylene carbonate; MePEG-b-PBTMC 5000-b-4800) was investigated as a delivery system for the hydrophobic anti-cancer agent, ellipticine. The ellipticine was loaded into the MePEG-b-PBTMC micelles with a loading efficiency of 95% using a high-pressure extrusion technique. The ellipticine-loaded micelles have a spherical morphology and an average diameter of 96 nm. The anti-cancer activity of ellipticine was confirmed to be retained following formulation in the MePEG-b-PBTMC micelles. The extent of protein adsorption to the MePEG-b-PBTMC micelles was investigated by transmission electron microscopy, dynamic light scattering and gel filtration chromatography. Overall, the amount of protein both loosely and tightly associated with the micelles was found to be minimal and insignificant. The partitioning properties of ellipticine between an aqueous medium containing protein and the MePEG-b-PBTMC micelles were examined over a range of protein concentrations. Under physiologically relevant conditions, it was found that 61% of the drug remained within the micelle fraction while 39% was in the protein-containing aqueous phase. In addition, the in vitro drug release profile of ellipticine from the micelles was fit using a modified Higuchi model and found to be accelerated in the presence of protein. These studies demonstrate that although there are no significant interactions between micelle and protein, the properties of the micelle as a delivery vehicle may be strongly influenced by protein-drug interactions. 相似文献
30.
Andreas G Schatzlein Bernd H Zinselmeyer Adurrahim Elouzi Christine Dufes Ya Tsz A Chim Clive J Roberts Martyn C Davies Avril Munro Alexander I Gray Ijeoma F Uchegbu 《Journal of controlled release》2005,101(1-3):247-258
Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration. 相似文献