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Measurable Response (measurable + response)
Selected AbstractsEvaluation of the Photosensitizer Tookad® for Photodynamic Therapy on the Syrian Golden Hamster Cheek Pouch Model: Light Dose, Drug Dose and Drug,light Interval Effects,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2003François Borle ABSTRACT We have evaluated the efficacy of the new photosensitizer (PS) Tookad® in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection,light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad® could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels. [source] An evaluation of laparoscopic tissue harvesting for human adult urological smooth muscle physiological experimentationBJU INTERNATIONAL, Issue 3 2005John F. Bolton OBJECTIVE To evaluate the properties of laparoscopically harvested bladder neck and ureteric smooth muscle, compared with tissue obtained at open surgery. MATERIALS AND METHODS Bladder neck was harvested from patients undergoing open (eight) or laparoscopic radical prostatectomy (11). Ureter was obtained from patients undergoing nephrectomy (laparoscopic or open) and cystectomy (open only); obtained openly from 16 and laparoscopically from seven. Muscle strips dissected from these samples were perfused in a Brading-Sibley organ bath, and stimulated using standard agonists (100 µmol/L carbachol for bladder neck, 100 mmol/L KCl-enriched Krebs' solution for ureteric muscle). Tensions produced were recorded using strain gauges and analysed using data-acquisition software. Results were compared by a two-tailed Fisher's exact test to determine significance. RESULTS Openly harvested bladder neck muscle strips from six patients showed a measurable response to the standard agonist. Laparoscopically harvested bladder neck strips from only two patients showed any measurable response. Openly harvested ureteric muscle strips from 12 patients responded to K-enriched solution, while one patient's laparoscopically harvested strips responded to stimulation. This difference was significant in both tissue groups separately (P < 0.025). Histological evaluation identified no specific differences between openly and laparoscopically harvested tissue. CONCLUSION The yield of smooth muscle available for research is significantly less when the resection is laparoscopic; this might be a result of diathermy damage at a subcellular level. With the increasing use of the laparoscopic approach in urological surgery, the effect on tissue availability for human smooth muscle physiological study is important to researchers in this field. [source] Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkeyCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009A. Tomkinson Summary Background Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics. Objective Studies were performed to characterize the allergen-induced cutaneous early- and late-phase response (EPR and LPR) in the cynomolgus monkey. Methods Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post-injection, and skin biopsies were collected at 8,24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes. Results The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02). Conclusion Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis. [source] Group-level variations in motor representation areas of thenar and anterior tibial muscles: Navigated Transcranial Magnetic Stimulation StudyHUMAN BRAIN MAPPING, Issue 8 2010Eini Niskanen Abstract Navigated transcranial magnetic stimulation (TMS) can be used to stimulate functional cortical areas at precise anatomical location to induce measurable responses. The stimulation has commonly been focused on anatomically predefined motor areas: TMS of that area elicits a measurable muscle response, the motor evoked potential. In clinical pathologies, however, the well-known homunculus somatotopy theory may not be straightforward, and the representation area of the muscle is not fixed. Traditionally, the anatomical locations of TMS stimulations have not been reported at the group level in standard space. This study describes a methodology for group-level analysis by investigating the normal representation areas of thenar and anterior tibial muscle in the primary motor cortex. The optimal representation area for these muscles was mapped in 59 healthy right-handed subjects using navigated TMS. The coordinates of the optimal stimulation sites were then normalized into standard space to determine the representation areas of these muscles at the group-level in healthy subjects. Furthermore, 95% confidence interval ellipsoids were fitted into the optimal stimulation site clusters to define the variation between subjects in optimal stimulation sites. The variation was found to be highest in the anteroposterior direction along the superior margin of the precentral gyrus. These results provide important normative information for clinical studies assessing changes in the functional cortical areas because of plasticity of the brain. Furthermore, it is proposed that the presented methodology to study TMS locations at the group level on standard space will be a suitable tool for research purposes in population studies. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [source] Ifosfamide/carboplatin/etoposide (ICE) as front-line, topotecan/ cyclophosphamide as second-line and oral temozolomide as third-line treatment for advanced neuroblastoma over one year of ageACTA PAEDIATRICA, Issue 2004A Donfrancesco Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front-line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second-line treatment for children with relapsed neuroblastoma, particularly after high-dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty-one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty-one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow-up is needed to confirm a survival advantage. Second-line treatment was effective in obtaining remissions, some of them long lasting. Third-line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients. [source] | |||||||||||||