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Anjali Shah Eric Eggenberger Robert Zivadinov Olaf Stüve Elliot M. Frohman 《Neurotherapeutics》2007,4(4):627-632
Physicians who treat multiple sclerosis (MS) face the challenge of patients exhibiting ongoing disease activity, including
exacerbations, loss of functional capabilities, intellectual decline, and radiologic progression, despite being on a disease-modifying
agent (DMA). After searching for factors that might at least in part explain these changes—such as nonadherent drug-taking
behavior, or the presence of interfer-on-neutralizing antibodies—some providers may ultimately decide to switch the patient
to another DMA. In most circumstances, patients likely derive only partial effects from these agents, even in the absence
of compromising factors. Thus, a number of factors must be considered in order to intensify the treatment regimen in response
to disease progression. In the context of an inadequate treatment response to a DMA, some clinicians will convert the patient
to an alternative therapy, and others will instead use a second agent in combination with the first (the so-called platform
agent). In the first of this two-part series, we explored the use of anti-inflammatory CS and ACTH to treat MS exacerbations.
Although we underscored the limited availability of evidence-based studies to support specific regimens for this purpose,
there is an even greater paucity of data to support the routine use of these agents in order to achieve chronic disease-modifying
effects in those who continue to deteriorate clinically, radiographically, or both. Without doubt, a number of factors influence
the formulation of combination treatment plan for MS. Nevertheless, we will focus on the rationale and practical schemes that
can be considered for using corticosteroids (CS) (and perhaps even ACTH) in an attempt to modify various domains of ongoing
disease activity. 相似文献
4.
Markus Kohlhaas Olaf Stahlhut Joachim Tholuck Gisbert Richard 《Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft》1997,94(7):515-518
Ziel der vorliegenden Untersuchung war es, das Ausma? der Hornhautsch?digung durch eine Kataraktextraktion im Hinblick auf
das Hornhautendothel und die Hornhautdicke zu untersuchen.
Patienten und Methode: In einer prospektiven Untersuchung wurde die Entwicklung der Hornhautdicke und der Endothelzelldichte
an 48 Patienten untersucht. Die Patienten wurden mittels Phakoemulsifikation operiert. Die Hornhautdicke wurde dabei mit einem
Ultraschallpachymeter bei 12 Uhr und im Hornhautzentrum und die Endothelzelldichte mit einer Endothelzellkamera an den gleichen
Me?punkten pr?operativ sowie 4 Wochen, 4 Monate und 1 Jahr postoperativ bestimmt.
Ergebnisse: Ein Jahr postoperativ nahm die Hornhautdicke nach Phakoemulsifikation an der 12-Uhr-Position um ca. 9% und im
Hornhautzentrum um ca. 12% im Vergleich zum pr?operativen Wert zu. Die Endothelzelldichte war 1 Jahr postoperativ an der 12-Uhr-Position
um ca. 27% und im Zentrum um ca. 18% reduziert. Das Patientenalter korrelierte signifikant mit dem Zellverlust an beiden Me?punkten.
Bezüglich der Dickenzunahme ist keine signifikante Korrelation festzustellen.
Schlu?folgerung: Nach einer Kataraktextraktion ist der Hornhautstoffwechsel reduziert. Als Indikator k?nnen der Verlauf der
Endothelzelldichte und der Dicke herangezogen werden.
相似文献
5.
Kari T Kivist? Olaf Grisk Ute Hofmann Konrad Meissner Klaus-Uwe M?ritz Christoph Ritter Katja A Arnold Dieter Lutj?ohann Klaus von Bergmann Ingrid Kl?ting Michel Eichelbaum Heyo K Kroemer 《Drug metabolism and disposition》2005,33(11):1593-1596
The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats. 相似文献
6.
Marc Schmitter Olaf Gabbert Brigitte Ohlmann Alexander Hassel Diana Wolff Peter Rammelsberg Bodo Kress 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2006,102(2):220-224
OBJECTIVES: The purpose of this study was to evaluate both reliability and validity of the assessment of the shape of the mandibular condyle in panoramic images of the TMJ. STUDY DESIGN: Forty subjects were included and were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders. Panoramic radiographs (PRs) and magnetic resonance images (MRIs) were completed for all subjects. Both MRIs and PRs were rated by raters blinded to the clinical diagnosis. Kappa statistics were used to compare the results of the raters of the PRs. Additionally, the specificity and the sensitivity of the PRs were calculated for 2 scenarios: one with MRI and the other with clinical findings as the gold standard. RESULTS: The sensitivity was 0.94 (specificity = 0.45) for the assumption that MRI is the gold standard and 0.86 (specificity = 0.49) for the assumption that the clinical examination is the gold standard. For reliability, the results for kappa ranged from 0.06 to 0.327. CONCLUSION: It can be concluded that PRs are not a reliable method of accurately judging the shape of the mandibular condyle. 相似文献
7.
Olaf M Hoffmann Doreen Becker Joerg R Weber 《Journal of cerebral blood flow and metabolism》2007,27(11):1792-1797
Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci -- in particular, Streptococcus pneumoniae, the most frequent pathogen in bacterial meningitis -- release hydrogen peroxide (H(2)O(2)) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H(2)O(2) production on regional cerebral blood flow (rCBF) and intracranial pressure (ICP). Compared to wild-type D39 pneumococci, the increase of rCBF was diminished in meningitis induced by the H(2)O(2) defective SpxB(-) mutant (maximum increase, 135% +/- 17% versus 217% +/- 23% of the individual baseline; P<0.01) or after treatment of D39-induced meningitis with H(2)O(2)-degrading catalase or with tetraethylammonium (TEA), a blocker of calcium-sensitive potassium channels, which mediate H(2)O(2)-induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB(-), supporting the predominant role of bacterial H(2)O(2). We conclude that in addition to host-sided mediators, bacterial-derived H(2)O(2) acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis. 相似文献
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Olivier Chataigner Elie Fadel Bedrettin Yildizeli Abdallah Achir Sacha Mussot Dominique Fabre Olaf Mercier Philippe G. Dartevelle 《European journal of cardio-thoracic surgery》2008,33(5):837-843
Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival. 相似文献
10.
Michael Madeja Ulrich Mußhoff Christoph Lorra Olaf Pongs Erwin-Josef Speckmann 《Brain research》1996,722(1-2)
The action of the epileptogenic agent pentylenetetrazol (PTZ) on a cloned potassium channel of the rat brain was studied. The Kv1.1 channel was expressed in oocytes ofXenopus laevis and potassium currents were investigated in outside-out and inside-out membrane patches. The results show that PTZ increased the multi-channel potassium currents at strongly negative potentials and decreased them at potentials positive to −35 mV both in outside-out and inside-out membrane patches. The extent and manner of PTZ action, the concentration dependence as well as the onset and time course of the PTZ effect were the same both in outside-out and inside-out membrane patches. The single-channel potassium currents showed an increase in open probability and frequency of opening and a decrease in close time at −50 mV and vice versa at 0 mV with application of PTZ. The amplitude of single-channel current, the open time and the latency to the first channel opening remained almost unchanged under PTZ. The results indicate that PTZ acts via the cell membrane and influences the membrane-associated part of the potassium channel. Thereby, PTZ accelerates the transition from the inactivated to the open state of the channel at strongly negative potentials and reduces it at slightly negative and positive potentials. This mechanism may be the basis for a gate function which is in favour of the development of epileptic discharges. 相似文献