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目的:探讨沙利度胺(thalidomide)对子宫内膜异位症(endometriosis,EMs)病灶生长和血管生成的影响,为从抗血管途径治疗EMs提供依据.方法:将EMs患者在位子宫内膜种植于重度复合性免疫缺陷病(severe combined immunodeficiency disease, SCID)小鼠皮下,建立EMs鼠模型.接种后第3周给予治疗,治疗组(n=10)腹腔注射沙利度胺50mg/kg/d,对照组(n=10)腹腔注射等体积PBS,连用14d;每隔3d测量异位病灶体积一次;病灶组织采用免疫组化法测定病灶微血管密度(microvessel density,MVD)及血管内皮生长因子(VEGF)的表达.结果:SCID小鼠皮下种植内异症模型内膜存活率高且观察方便;治疗组病灶体积增长有缩小趋势,但与对照组相比差异无统计学意义(P>0.05);治疗组MVD显著低于对照组(P<0.05);治疗组和对照组VEGF的表达差异无统计学意义(P>0.05).结论:沙利度胺对EMs异位病灶的血管生成有明显抑制作用;抑制VEGF的表达可能不是沙利度胺抑制EMs血管生成的主要原因. 相似文献
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C. C. Harland G. B. Steventon J. R. Marsden 《European journal of clinical pharmacology》1995,49(1-2):1-6
A pharmacogenetic predisposition to thalidomide-induced neuropathy has been investigated. Differences of drug metabolism were examined in 16 patients with severe orogenital ulceration, who were treated with thalidomide (200 mg/day) for 0.3–5.0 years. Eight had evidence of early peripheral neuropathy according to nerve conduction studies. Rates of C-hydroxylation, N-acetylation, and conjugation reactions with sulphate, glucuronide and glycine, were tested with the probe compounds debrisoquine, sulphadimidine, paracetamol and aspirin, respectively. Urinary drug metabolites were analysed by high pressure liquid chromatography. Results were compared with 16 healthy age- and sex-matched volunteers.Of the patients 6.25% and 13.3% of the controls had a poor Debrisoquine Hydroxylator Ratio (DMR); none of the patients with neuropathy had a poor DMR as compared to 12.5% without neuropathy. Of the patients 40.0% and 35.7% of the controls were slow acetylators; 28.6% with neuropathy were slow acetylators as opposed to 50% without neuropathy. Similarly, there were no significant differences in rates of conjugation between groups. All unaffected patients were active smokers, whereas only two of those with neuropathy smoked. Cumulative dose or duration of therapy were unrelated to risk of neuropathy.In conclusion, changes of nerve conductivity are a frequent and unpredictable adverse effect of thalidomide (200 mg/day), although smoking may have a protective action against their development. Nerve conduction studies are required before and during treatment, irrespective of the prescribed dose. 相似文献
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Metronomic therapy can increase quality of life during paediatric palliative cancer care,but careful patient selection is essential 下载免费PDF全文
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Background: Thalidomide is used in cutaneous lupus erythematosus (CLE) refractory to conventional therapies. Peripheral neuropathy (PN) is the most severe side effect, but the incidence of PN and its relation to thalidomide dose are still unclear.Objective: To prospectively evaluate the efficacy as well as the occurrence of PN in CLE patients treated with thalidomide, and to assess whether PN, when occurs, correlates with thalidomide dose and/or length of treatment.Methods: Fourteen female patients with CLE in low-dose thalidomide therapy were followed for up to 24 months. Prior to, and regularly during treatment patients underwent rheumatological, dermatological, neurological and electrophysiological evaluations. A decline in sural SNAP of 50% or more from baseline value was considered as criterion of sensory axonal PN.Results: All patients showed a dramatic improvement of skin manifestations. Ten patients (71.4%) developed a sensory axonal PN. The median time free from this complication was 14 months. No correlations were found between age of the patients nor thalidomide cumulative dose and occurrence of PN (Mann-Whitney U Test; p>0.16). Other adverse effects were: tremor, paresthesias, somnolence, amenhorrea, constipation and thoracic pain.Conclusions: Low does thalidomide is efficacious in treating CLE, but PN is a common complication whose occurrence does not seem to correlate with total thalidomide dose, whereas with the duration of therapy. A closer electrophysiological follow-up is therefore recommended in the long-term treatment. 相似文献
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Studies in pregnant rabbits were conducted to evaluate if there are any differences in the uptake of thalidomide into the intrauterine compartment and developmental toxicity risk following oral and intravaginal administration. Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and embryo following intravaginal administration were 2- to 7-fold lower than their respective levels after oral administration. Ratios of thalidomide concentration in YSC fluid to maternal plasma were similar between these two routes, indicating no difference in uptake into the intrauterine compartment. A rabbit embryo–fetal development study using oral and intravaginal thalidomide administration at 2 mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in human semen) did not result in any developmental abnormalities. These data demonstrated no preferential transfer mechanism of thalidomide from vagina to conceptus, and no additional embryo–fetal developmental toxicity risks with thalidomide exposure via the vaginal route. 相似文献
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《Transfusion and apheresis science》2022,61(4):103422
Blood grouping discrepancy in patients with hematological disorders can occur due to red cell sensitization following transfusion, transplantation, and pregnancy or pre-analytical errors. Prompt initiation of root cause analysis is vital to avoid complications of wrong blood transfusion. We present an unusual case of Rh mismatched grouping report of 24 year old female thalassemia patient being managed in our hospital since 2015. Her current type and screen were observed as O Rh D negative with negative antibody screen while the historical blood group was O Rh D positive. The pre-analytical errors were ruled out and blood grouping performed from fresh sample also demonstrated as O Rh D negative despite antigen enhancement techniques and had no recent transfusion history. We sought to reason out the possibilities for discordant Rh grouping report, historical and present group through “Funnel based problem solving 5 WHY analysis” approach. The review of the past clinical history revealed that the patient had undergone Rh mismatch bone marrow transplant (Rh D positive donor and Rh D negative recipient) at 5 years of age which soon resulted in graft failure. Yet, she continued to receive Rh D positive blood thereafter with no development of anti-D which explains the historical blood group. Recently the patient was started on thalidomide, the Hb F inducer drug, which helped in maintaining her hemoglobin level between 9 and 10 g/dl without transfusion support for two months. This allowed unmasking of native Rh D negative blood and the review of clinical history played a significant role in resolution of grouping discrepancy. 相似文献