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Medical Expulsive Therapy For Ureteral Calculi With Alphal Adrenoreceptor Antagonists

Posted on:2008-12-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:W XiongFull Text:PDF
GTID:1104360218960371Subject:Surgery
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Objectives Although enthusiasm is growing for theα1adrenoreceptor antagonist tamsulosin treatment for ureteral calculi, there areconflicting data regarding their effectiveness and no agreement on theregimen of the tamsulosin based medical expulsive therapy. We assessed theefficacy of medical expulsive therapy for ureteral calculi with tamsulosin bymeta-analysis method, and explored the distribution and mRNA expressionof alphal adrenoreeeptor subtypes in different segments of human ureter.Methods The PubMed, MEDLINE, EMBASE, BIOSIS,International Pharmaceutical Abstracts(IPA) databases, Cochrane Libraryand Chinese Journal Full-text Database from 1995 to September of 2006and the urological scientific conferences from 2000 to 2006 were retrieved. The randomized controlled clinical trials which compared the effectivenessbetween tamsulosin and other therapies for ureteral calculi among adultswere included. Data was extracted by two reviewers independently andsynthesized by STATA9.0 version.Harvesting the healthy ureteral segments including proximal/media/distaland ureterovesical segments from the surgical samples following operation.And measure the thickness of longitudinal coursing muscle of ureteralsegments in HE dying and the alphal adrenoreceptor subtypes expressionwas examined in different ureteral segments by immunocytochemistry. Thealphal adrenoreceptor subtypes mRNA expression in different ureteralsegments was examined using different gene specific primers as primers forsemi-quantitative reverse transcription-polymerase chain reaction.Results 16 studies involving 1521 patients with distal orjuxtavesical ureteral calculi were identified. Compared to conservativetherapy receiving oral hydration(2 liters daily)and analgesics giving ondemand, tamsulosin and combination therapy of tamsulosin plus deflazacortshowed higher expulsion rate with pooled relative ratio of 1.50(95%CI, 1.20to 1.87, P<0.0001) and 1.59 (95%CI, 1.31 to 1.93, P<0.00001), respectively,with reduction of expulsion time with standardized mean difference of-1.29(95%CI, -2.27 to -0.31, P<0.00001) and -0.8(95%CI, -1.18 to -0.42,P<0.00001), and later ESWL or ureteroscopy with pooled relative ratio of0.40(95%CI, 0.27 to 0.59, P<0.0001) and 0.13 (95%CI, 0.06 to 0.31,P<0.00001), Compared to nifedipine plus deflazacort, the tamsulosin plus deflazacort therapy had a higher expulsion rate with pooled relative ratio of1.20 (95%CI, 1.07 to 1.35, P=0.002). There was no statistical difference inexpulsion rate between tamsulosin plus deflazacort therapy and tamsulosinmonotherapy, but the combination therapy had a lower rate of later ESWLor ureteroscopy with pooled relative ratio 0.09 (95%CI, 0.02 to 0.47,P=-0.004). But the included studies had variable quality and there was a mildrisk of publication bias.The mierostructure of human ureter from proximal segment to juxtavesicalsegments shows the muscle bundles are so arranged that morphologicallydistinct longitudinal and circular layers cannot be clearly distinguished. Andour immunocytochemistry shows that theα1 adrenoreceptor subtypesα1A-AR,α1B-AR,α1D-AR mainly locate at the longitudinal musclebundles and the relative expression density ofα1 adrenoreceptors arejuxtavesical segment>distal segment>media segment>proximal segmentby usingα1 adrenoreceptor subtypes specific monoclonal antibodies.Theα1 adrenoreceptor mRNA ofα1A-AR andα1D-AR subtypes dominatein every segments and the density ofα1 adrenoreceptors mRNA arejuxtavesical segment>distal segment>media segment>proximal segment.The mRNA of muscarinicacetylcholine receptor 1 and 2, neuropeptide Yreceptors was measured by RT-PCR but not detected.Conclusions The meta-analysis results demonstrates: tamsulosinhas a beneficial effect on expulsion of ureteral calculi, especially for distal and juxtavesical ureteral calculi. The tamsulosin based medical expulsivetherapy with 0.4mg daily is an effective and safe dose for patients withdistal ureteral calculi. The validity of different regimen, such as combinationof tamsulosin plus deflazacort requires larger studies.Our data suggests that the longitudinal muscle bundles dominate in humanureter. And theα1 adrenoreceptor subtypesα1A-AR,α1B-AR,α1D-ARmainly locate at the longitudinal muscle bundles of the ureter and therelative expression density ofα1 adrenoreceptors are juxtavesical segment>distal segment>media segment>proximal segment.Theα1 adrenoreceptor mRNA ofα1A-AR andα1D-AR subtypes dominatein every segments and the density ofα1 adrenoreceptor mRNA arejuxtavesical segment>distal segment>media segment>proximal segment.The mRNA of muscarinicacetyicholine receptor 1 and 2, neuropeptide Y receptorswas measured by RT-PCR but not detected and suggests theα1-ARs play acritical role in regulating the tension of the ureter.
Keywords/Search Tags:α1-adrenoreceptor antagonist, Tamsulosin, Ureteral calculi, Medical expulsive therapy, Meta-analysis, α1-adrenoreceptor, Reverse transcription-Polymerase chain reaction (RT-PCR)
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