肾移植术后肾功能延迟恢复原因及术后血液净化的干预作用

目的：分析肾移植术后常见并发症肾功能延迟恢复的诱因，并观察术后血液净化干预所发挥的临床效应。方法：选择1996—12/2006—12在解放军第三军医大学大坪医院野战外科研究所泌尿外科明确诊断为肾移植术后肾功能延迟恢复的患者193例，其中接受尸肾移植192例，活体肾移植1例，均知情同意。根据患者的临床资料，分析术后肾功能延迟恢复的主要原因。除5例因术前安置腹膜透析管继续采用腹膜透析外，其余均选择血液透析治疗，其中35例穿插接受过连续性肾脏替代治疗或血液透析滤过，8例血浆置换2-5次。终止透析的标准为每日尿量〉1500mL，血肌酐〈300μmol／L。分析术后肾功能延迟恢复的原因，观察接受透析治疗后肾功能延迟恢复患者的临床疗效。结果：193例患者全部进入结果分析。①术后肾功能延迟恢复的病因：急性肾小管坏死89例（46．1％），术后早期低血压42例（21．8％），排斥反应37例（19．2％），动静脉吻合口狭窄9例（4-7％），尿路梗阻8例（4．1％），动脉过长扭曲5例（2．6％），环孢素A肾毒性2例（1．0％），髂内动脉粥样硬化斑块阻塞1例（0．5％）。（④术后肾功能转归：移植肾功能恢复正常者145例（75．1％）；术后3个月血肌酐135-300μmol／L29例（15．3％）；〉300μmol/L15例（7．8％）；因超急性排斥反应切除移植肾2例（1％），肺部重症感染死亡2例（1％）。③术后接受血液透析次数：术后接受血液透析189例，透析1—5次移植肾功能恢复正常20例（13．8％）；6-10次41例（28．3％）；11-20次82例（56．6％）；21-25次2例（1．4％）；〉25次44例，仅1例恢复正常（0．7％），其余43例患者带肾存活。结论：急性肾小管坏死、术后早期低血压和排斥反应是引起肾移植术后肾功能延迟恢复的主要原因。在肾功能延迟恢复患者确定以血液净化为主的方案后，绝大多数移植肾功能可以恢复。     

Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord: potential antinociceptive targets

Activation of histamine H3 receptors (H3Rs) reduces inflammation and nociception, but the existence of H3Rs on peripheral innervation has never been demonstrated. Here we use antibodies to locate H3Rs in whisker pads, hairy and glabrous hind paw skin, dorsal root ganglia (DRGs), and spinal cords of rats, wild type mice, and H3R knockout (H3KO) mice. Although H3Rs have been hypothesized to be on C and sympathetic fibers, H3R-like immunoreactivity (H3R-LI) was only detected on presumptive periarterial A delta fibers and on A beta fibers that terminated in Meissner's corpuscles and as lanceolate endings around hair follicles. The H3R-positive periarterial fibers were thin-caliber and coexpressed immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, acid sensing ion channel 3, and 200 kDa neurofilament protein (NF). H3R-LI was also detected on epidermal keratinocytes and Merkel cells, but not on Merkel endings, C fibers, any other A delta fibers, or sympathetic fibers. In DRGs, H3R-LI was preponderantly on medium to large neurons coexpressing NF-LI and mostly CGRP-LI. In dorsal horn, CGRP-positive fibers with and without H3R-LI ramified extensively in lamina II; many of the former formed a plexus in lamina V. Low levels of H3R-LI were also present on A beta fibers penetrating superficial and into deeper laminae. The distribution of H3R-LI was similar in rats and wild type mice, but was eliminated or strongly reduced in A delta fibers and A beta fibers, respectively, in H3KO mice. Taken with recently published behavioral results, the present findings suggest that periarterial, peptidergic, H3R-containing A delta fibers may be sources of high threshold mechanical nociception.     

Long-term sequelae of critical illness: memories and health-related quality of life

Impaired health-related quality of life after critical illness has been demonstrated in a number of studies. It is not clear exactly how or why critical illness and intensive care lead to impaired health status, but understanding this association is an important step to improving long-term outcomes of the critically ill. There is growing evidence that neuro-psychological symptoms play a significant role in this impairment and that management of patients in the intensive care unit (ICU) may influence these symptoms. This commentary examines a recent study and places this study in the context of previous studies suggesting that both amnesia and persisting nightmares of the ICU experience are associated with impaired quality of life. Further research is needed if we are effectively to understand, prevent and treat the negative sequelae of critical illness.     

Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes

The idiotypic determinants of surface immunoglobulins on B-cell lymphomas and lymphocytic leukemias represent tumor-specific antigens, individually unique for each tumor. As such they have both diagnostic and therapeutic potential, particularly for those neoplasms with no serum monoclonal immunoglobulin arising from synthesis of the protein for export. We describe the raising in animals of anti-idiotype sera directed against two examples of a nonexporting neoplasm, human chronic lymphocytic leukemia. The procedure involves exposing the cells to papain so as to remove the Fab fragments (containing the idiotypic determinants) from the surface immunoglobulin, recovering the Fab on cellulose immunosorbent particles, and immunizing animals with the immunosorbent-Fab complex.     

慢性移植肾失功356例危险因素分析

目的:慢性移植肾失功是导致后期移植肾丧失的重要原因之一,文章拟探讨慢性移植肾失功的相关因素及防治措施。方法:①选择1993-12/2006-12于解放军第三军医大学大坪医院行肾移植术后发生慢性移植肾失功患者356例,回顾性分析其临床资料。②调整免疫抑制剂方案,停服硫唑嘌呤、环孢素A或减少环孢素A30%￣50%剂量,改用他克莫司0.5￣1mg/(kg·d)、霉酚酸酯1￣2g/d、西罗莫司1￣2mL/d等药;控制血糖、血脂、血压,抗凝及补充鱼肝油丸;服用雷公藤、百令胶囊或尿毒清等中药,给予低蛋白、低磷及高维生素、氨基酸饮食;必要时手术切除移植肾。③分析肾移植术后发生慢性移植肾失功的危险因素并观察其治疗结果。结果:①慢性移植肾失功的危险因素:急性排斥反应254例(71.35%),巨细胞病毒感染65例(18.26%),移植肾肾小球肾炎21例(5.9%),药物中毒(环孢素A/他克莫司)9例(2.53%),高血压/高血脂/高血糖5例(1.41%),肾单位减少(高龄供肾/性别差异)2例(0.56%)。②治疗结果:切除移植肾194例(54.49%),带肾存活、恢复血液透析87例(24.44%),经治疗血肌酐维持在200￣300μmol/L63例(17.70%),死亡12例(3.37%)。结论:急性排斥反应是引起肾移植术后慢性移植肾失功的主要因素。提高供肾质量,严格组织配型,减少移植肾功能延迟恢复的发生,制定个体化免疫方案,定期监测药物浓度及肝肾功能,预防巨细胞病毒感染,可减少慢性移植肾失功的发生。     

Significance of cannabinoid CB1 receptors in improgan antinociception.

Improgan is a congener of the H(2) antagonist cimetidine, which produces potent antinociception. Because a) the mechanism of action of improgan remains unknown and b) this drug may indirectly activate cannabinoid CB(1) receptors, the effects of the CB(1) antagonist/inverse agonist rimonabant (SR141716A) and 3 congeners with varying CB(1) potencies were studied on improgan antinociception after intracerebroventricular (icv) dosing in rats. Consistent with blockade of brain CB(1) receptors, rimonabant (K(d) = 0.23 nM), and O-1691 (K(d) = 0.22 nM) inhibited improgan antinociception by 48% and 70% after icv doses of 43 nmol and 25 nmol, respectively. However, 2 other derivatives with much lower CB(1) affinity (O-1876, K(d) = 139 nM and O-848, K(d) = 352 nM) unexpectedly blocked improgan antinociception by 65% and 50% after icv doses of 300 nmol and 30 nmol, respectively. These derivatives have 600-fold to 1500-fold lower CB(1) potencies than that of rimonabant, yet they retained improgan antagonist activity in vivo. In vitro dose-response curves with (35)S-GTPgammaS on CB(1) receptor-containing membranes confirmed the approximate relative potency of the derivatives at the CB(1) receptor. Although antagonism of improgan antinociception by rimonabant has previously implicated a mechanistic role for the CB(1) receptor, current findings with rimonabant congeners suggest that receptors other than, or in addition to CB(1) may participate in the pain-relieving mechanisms activated by this drug. The use of congeners such as O-848, which lack relevant CB(1)-blocking properties, will help to identify these cannabinoid-like, non-CB(1) mechanisms. PERSPECTIVE: This article describes new pharmacological characteristics of improgan, a pain-relieving drug that acts by an unknown mechanism. Improgan may use a marijuana-like (cannabinoid) pain-relieving mechanism, but it is shown presently that the principal cannabinoid receptor in the brain (CB(1)) is not solely responsible for improgan analgesia.     

Reduced longitudinal excursion of the median nerve in carpal tunnel syndrome

OBJECTIVE: To determine if longitudinal excursion of the median nerve is reduced in patients with carpal tunnel syndrome (CTS). DESIGN: Case-control study. SETTING: University human movement laboratory. PARTICIPANTS: Nineteen patients with CTS (8 men, 11 women; mean age, 57+/-15 y), and 37 healthy controls (8 men, 29 women; mean age, 48+/-10 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Longitudinal excursion of the median nerve, and the ratio of nerve to flexor digitorum superficialis tendon excursion at the carpal tunnel evoked by finger extension. Measurements were taken using a validated Doppler ultrasound technique, and tests were conducted with the elbow positioned in extension and flexion. RESULTS: Mean longitudinal excursion of the median nerve was significantly greater in controls (11.2+/-2.8 mm) than patients (8.3+/-2.6 mm) with the elbow extended (P=.013), but not with the elbow flexed (controls, 12.5+/-2.5 mm; patients, 10.2+/-3.1 mm; P=.089). Mean nerve/tendon excursion ratios were significantly greater in controls (.32+/-.07) than patients (.23+/-.06), with the elbow extended (P<.001), and flexed (controls, .36+/-.06; patients, .28+/-.10; P=.019). Discriminant analysis identified that 11 (58%) of the 19 patients and 3 (8%) of the 37 controls showed a nerve/tendon excursion ratio of .25 or less when tested with the elbow in extension. CONCLUSIONS: Reduced longitudinal excursion of the median nerve at the carpal tunnel was identified in a substantial proportion of patients with CTS. Further studies are merited to determine if reduced median nerve excursion at the carpal tunnel is clinically relevant in CTS, and can be influenced by movement-based interventions.     

Evaluation of the effect of paliperidone extended release and quetiapine on corrected QT intervals: a randomized, double-blind, placebo-controlled study

The effect of two atypical antipsychotics on QTc intervals (heart rate-corrected QT interval) was evaluated. Patients (N=109) with schizophrenia (79%) or schizoaffective disorder (21%) were randomly assigned in 2 : 2 : 1 ratio to paliperidone extended release (ER), quetiapine, or placebo. Doses of 12 and 18 mg/day of paliperidone ER were compared with quetiapine 800 mg/day. Least-squares mean change from baseline in population-specific linear-derived correction method from baseline to days 6-7 at individual tmax was 5.1 ms less [90% confidence interval: -9.2 to -0.9] with paliperidone ER 12 mg/day than with quetiapine 800 mg/day. On the basis of a prespecified 10-ms noninferiority margin, paliperidone ER was thus declared noninferior to quetiapine (primary analysis). Mean change in population-specific linear-derived correction method from baseline to days 11-12 at individual tmax was 2.3 ms less (90% confidence interval: -6.8 to 2.3) with paliperidone ER 18 mg/day than with quetiapine 800 mg/day. Treatment-emergent adverse events occurred in 36 (82%) patients treated with paliperidone ER, 41 (95%) patients treated with quetiapine, and 14 (64%) patients treated with placebo. No adverse events of a proarrhythmic nature were noted. The effect on the QTc interval in patients with schizophrenia or schizoaffective disorder was comparable between paliperidone ER 12 mg/day (maximum recommended dose), paliperidone ER 18 mg/day (supratherapeutic dose), and quetiapine 800 mg/day.     

Plasma renin activity-guided strategy for the management of hypertension

Despite the wide array of antihypertensive agents and the availability of national guidelines regarding treatment for hypertension, the disease remains uncontrolled in nearly 50% of affected patients. Furthermore, the number of patients with resistant hypertension continues to increase. For patients with resistant hypertension, the American Heart Association has advocated for clinical studies to determine appropriate pharmacologic treatment strategies. One proposed strategy involves ambulatory measurement of plasma renin activity (PRA) to guide the selection of antihypertensive therapy. Patients with low PRA would be prescribed natriuretic volume-mediated therapies (e.g., diuretics and calcium channel blockers), whereas those with high PRA would receive antirenin system therapies (e.g., β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). This review focuses on the principles of PRA-guided therapy, its historical development, alternative approaches to classifying patients into categories of response to antihypertensive agents, and recent data supporting the use of plasma renin activity-guided hypertension management.