Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p<0.004). Patients carrying the DR2 alleles, DRB1*1501,*1502 or*1601 were at a lower risk of producing anti-donor HLA antibodies.     

Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells

Autosomal-dominant polycystic kidney disease is a multiorgan disease and its vascular manifestations are common and life-threatening. Despite this, little is known about their pathogenesis. Somatic mutations to the normal PKD allele in cystic epithelia and cyst development associated with the unstable Pkd2(WS25) allele suggest a two-hit model of cystogenesis. However, it is unclear if this model can account for the cardiovascular pathology or if haploinsufficiency alone is disease-associated. In the present study, we found a decreased polycystin-2 (PC2, protein encoded by Pkd2 gene) expression in Pkd2( +/-) vessels, roughly half the wild-type level, and an enhanced level of intracranial vascular abnormalities in Pkd2 (+/-) mice when induced to develop hypertension. Consistent with these observations, freshly dissociated Pkd2 (+/-) vascular smooth muscle cells have significantly altered intracellular Ca(2+) homeostasis. The resting [Ca(2+)](i) is 17.1% lower in Pkd2 (+/-) compared with wild-type cells (P=0.0003) and the total sarcoplasmic reticulum Ca(2+) store (emptied by caffeine plus thapsigargin) is decreased (P<0.0001). The store operated Ca(2+) (SOC) channel activity is also decreased in Pkd2 (+/-) cells (P=0.008). These results indicate that inactivation of just one Pkd2 allele is sufficient to significantly alter intracellular Ca(2+) homeostasis, and that PC2 is necessary to maintain normal SOC activity and the SR Ca(2+) store in VSMCs. Based on these findings, and the fact that [Ca(2+)](i) signaling is essential to the regulation of contraction, production and secretion of extracellular matrix, cellular proliferation and apoptosis, we propose that the abnormal intracellular Ca(2+) regulation associated with Pkd2 haploinsufficiency is directly related to the vascular phenotype.     

Fiber type composition of muscle units in the cat diaphragm

The fiber type composition of muscle units in the cat diaphragm was examined. As expected, slow-twitch units were composed of type I fibers and fast units were composed of type II fibers. Fast fatigable units were composed of type IIB fibers and fast fatigue resistant units were composed of type IIA fibers. Surprisingly, fast fatigue intermediate units were comprised of both type IIA and IIB fibers.     

Residual ethanol content of donor sclera after storage in 95% ethanol and saline rinse of various durations

PURPOSE: Some surgeons are wary of using alcohol-preserved sclera for allografts because they fear a toxic effect on surrounding tissue after placement. We set out to determine the amount of ethanol remaining in scleral allograft material after storage in 95% ethanol. METHODS: Sixty half scleras from 30 donors were preserved in 95% ethanol for an average of 31+/-14 days (range, 11 to 50 days). Rehydration was performed by soaking each half sclera in 4 ounces of balanced salt solution. Half scleras were randomly assigned to six groups of 10 each. Assays for ethanol were performed on the following groups: no balanced salt solution soak and balanced salt solution soak for 10 minutes, 20 minutes, 30 minutes, 40 minutes, and 50 minutes. Ethanol assay was performed by Headspace Gas Space Chromatography at ChemaTox Laboratory, Inc, Boulder, Colorado. RESULTS: The 10 half scleras without balanced salt solution soak had a mean ( SD) ethanol level of 175+/-14.1 mg per g of sclera. After 10 minutes of balanced salt solution s oak, the level decreased to 7.57+/-1.56 mg per g, then 3.77+/-3.02 mg per g at 20 minutes, 1.59+/-0.61 mg per g at 30 minutes, 1.07+/-0.30 mg per g at 40 minutes, and 0.96+/-0.26 mg per g at 50 minutes. Approximately 96% of the ethanol is leeched out of the half sclera by 10 minutes and 98% by 20 minutes. CONCLUSIONS: For sclera preserved in 95% ethanol, soaking in balanced salt solution for 20 minutes or longer leeches approximately 98% of the ethanol from the preserved donor sclera.     

Rectal thiopental for sedation of children for computed tomography.

Rectally administered thiopental was evaluated for sedation in pediatric computed tomography and compared with "cardiac cocktail" sedation. The drug produced sedation as effective as the "cocktail" with easier administration, more rapid onset, and shorter duration of sedation. Although no complications were observed, careful observation for respiratory depression is suggested.     

脊髓损伤(SCI)后呼吸运动功能的恢复

 高颈段脊髓损伤(spinal cord injury,SCI)往往导致膈肌麻痹,了解如何恢复SCI患者膈神经的节律活动至关重要。控制膈运动神经元(phrenic motor neuron,PhMn)的兴奋性前运动神经元主要起源于同侧延髓,因此,当C2脊髓半离断(spinal cord hemisection,SH)后,损伤侧的下行冲动中断,同侧膈神经的节律消失。随后,潜在的对侧下行冲动逐渐增强(神经可塑性),使PhMn的节律性活动恢复。众多证据表明神经营养因子(如脑源性神经营养因子,brain derived neurotrophic factor, BDNF)通过原肌球蛋白相关激酶受体(如TrkB)在神经可塑性中发挥重要作用。我们的实验结果表明,在鞘膜内注射BDNF能促进PhMn节律性的恢复,而注射TrkB-Fc(一种可抑制细胞外BDNF的融合蛋白)则延迟恢复。应用腺病毒载体(adeno-associated viral vector,AVV)靶向诱导PhMn中TrkB的表达也可促进PhMn节律性的恢复,而Si-RNA诱导的PhMn中TrkB表达抑制则延缓恢复。总之,增强PhMn的BDNF-TrkB信号通路可能是促进SCI后功能恢复的有效治疗手段。     

Allergic and nonallergic reactions to nitroglycerin.

Allergic and nonallergic reactions to nitroglycerin occur. The aims of this study were to review the different manifestations of nitroglycerin allergy, to explain how to evaluate for it, and to discuss its treatment. We reviewed relevant literature in peer-reviewed journals, computerized databases, and references identified from relevant bibliographics. Nitroglycerin's most common side effects are headache, facial flushing, head throbbing, fainting, hypotension, tachycardia, and syncope. The majority of reported skin reactions to topical and transdermal nitroglycerin products are irritant contact dermatitis, allergic contact dermatitis, and urticaria. Five cases of presumed allergic reactions to oral, sublingual, intravenous, or perianal nitroglycerin products have been described. Patch testing may be helpful in subjects with skin reactions to topical or transdermal nitroglycerin. In subjects with positive patch tests to nitroglycerin (allergic contact dermatitis), transdermal nitroglycerin patches and other topical nitroglycerin products should be avoided. Most patients with contact dermatitis to nitroglycerin have tolerated oral nitroglycerin, sublingual nitroglycerin, or oral isosorbide challenges.     

Calcium apatite crystals in synovial fluid rice bodies

BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice bodies containing apatite clumps and examine their clinical pictures. Methods: All synovial fluid analysis reports for 10 years were reviewed for rice bodies and eight patients were reported on. A series of patients with a variety of diseases with synovial fluid rice bodies found to contain calcific material is described. All were examined by compensated polarised light and alizarin red stain, and four were examined by electron microscopy. RESULTS: The eight patients all had alizarin red S chunks embedded throughout the rice body. Transmission electron microscopy disclosed the presence of a matrix of collagen, fibrin, and amorphous materials containing typical apatite crystals. Clinical diagnoses, radiographic findings, and leucocyte counts varied, but six of the eight patients had had previous repeated corticosteroid injections into the joints. CONCLUSION: Aggregates of apatites may be more common than previously recognised in rice bodies as they are not routinely sought. Whether they are a result of joint damage or depot steroid injections and whether that might contribute to further joint injury now needs to be investigated.