甲磺酸伊马替尼治疗晚期慢性粒细胞白血病致多浆膜腔积液2例

目的:通过2例晚期慢性粒细胞白血病(CML)患者接受甲磺酸伊马替尼治疗后出现多浆膜腔积液的病例分析和文献复习,探讨甲磺酸伊马替尼在治疗晚期慢性粒细胞白血病中的安全性。方法:对2例甲磺酸伊马替尼治疗晚期慢性粒细胞白血病的临床资料进行分析并结合文献复习使其在今后治疗中可能出现的不良反应引起重视。结果:2例分别确诊为晚期慢性粒细胞白血病的患者接受甲磺酸伊马替尼治疗后,出现多浆膜腔积液。结论:甲磺酸伊马替尼治疗晚期慢性粒细胞白血病时可能会出现严重的不良反应。     

甲磺酸伊马替尼治疗晚期慢性粒细胞白血病致多浆膜腔积液2例

目的通过2例晚期慢性粒细胞白血病(CML)患者接受甲磺酸伊马替尼治疗后出现多浆膜腔积液的病例分析和文献复习,探讨甲磺酸伊马替尼在治疗晚期慢性粒细胞白血病中的安全性.方法对2例甲磺酸伊马替尼治疗晚期慢性粒细胞白血病的临床资料进行分析并结合文献复习使其在今后治疗中可能出现的不良反应引起重视.结果2例分别确诊为晚期慢性粒细胞白血病的患者接受甲磺酸伊马替尼治疗后,出现多浆膜腔积液.结论甲磺酸伊马替尼治疗晚期慢性粒细胞白血病时可能会出现严重的不良反应.     

老年白血病bcr/abl融合基因的表达及其临床意义

目的　观察bcr/abl融合基因在老年白血病的表达及其临床意义。　 方法 　应用逆转录聚合酶链反应 (RT PCR)一步法检测 62例老年白血病患者bcr/abl融合基因的表达。　 结果 　 62例患者中bcr/abl融合基因阳性 5 3例 ,阳性率 85 5 % ,其中急性淋巴细胞白血病 (ALL) 17例 ,阳性 9例 (5 2 9% ) ;慢性粒细胞白血病 (CML)45例 ,阳性 44例 (97 88% )。DOCP方案治疗 7例bcr/abl ALL患者完全缓解 (CR)率 2 8 6% ,6例bcr/abl-ALL患者CR率 66 7% (P <0 0 1)。　 结论　bcr/abl融合基因检测有助于CML和ALL的临床诊断、治疗选择、微小残留病变 (MRD)监测以及预后判断 ;老年ALLbcr/abl融合基因阳性率较高 ,可能是其治疗效果较差的原因之一 ;bcr/abl ALL患者CR率明显低于bcr/abl-ALL患者 ;RT PCR一步法特异性好、敏感性高、简便快速 ,尤其适用于MRD的临床监测。     

尼洛替尼治疗伊马替尼耐药的慢性髓系白血病的临床观察

目的:探讨尼洛替尼在伊马替尼耐药的慢性髓系白血病( CML)患者中的疗效及不良反应.方法:9例伊马替尼耐药的CML患者,其中慢性期6例,进展期3例,持续口服尼洛替尼400 mg 2次/d,观察其疗效及不良反应.结果:6例CML慢性期患者,5例获得完全血液学反应,2例获得主要细胞遗传学反应；3例CML进展期患者均获得血液...     

达沙替尼治疗伊马替尼耐药的慢性髓细胞白血病急变期临床分析

目的:评价达沙替尼治疗伊马替尼耐药的BCR-ABL阳性慢性髓细胞白血病急变期(CML-BC)的疗效和安全性。方法:对7例伊马替尼耐药的CML-BC患者,给予达沙替尼100 mg/d口服治疗,观察达沙替尼对CML患者的血液学、遗传学及分子生物学反应,并监测不良反应,评估疗效和耐受情况。结果:7例伊马替尼耐药的BCR-ABL阳性CML-BC患者服用达沙替尼治疗后均获得完全血液学缓解,4例达到完全细胞遗传学缓解,1例达到完全分子学反应。4例达沙替尼治疗后检测到突变,4例死亡。2例出现3~4级中性粒细胞减少和3~4级血小板减少。结论:达沙替尼治疗伊马替尼耐药的BCR-ABL阳性CML-BC患者起效迅速,可获得完全血液学及细胞遗传学缓解,甚至获得完全分子生物学缓解,但维持时间短,容易再次出现疾病进展。达沙替尼治疗后可出现新的ABL激酶区突变,导致患者对达沙替尼耐药。     

格列卫治疗进展期慢粒白血病的临床观察

目的评价甲磺酸伊马替尼(格列卫)治疗Ph阳性慢性髓细胞白血病(CML)进展期(即加速期、急变期)的临床疗效。方法18例对α干扰素(IFN-α)耐药或不能耐受的CML进展期患者设为实验组,予以格列卫口服,持续314个月。同期在我院行传统化疗的患者为对照组。结果实验组血液学总有效率为44.4%,主要遗传学缓解率为16.7%;而对照组总有效率为16.7%。血液学不良反应是主要的不良反应,并与疗效相关。非血液学不良反应较轻且易耐受。结论与传统化疗相比,格列卫对慢性粒细胞白血病进展期患者有较好的疗效,副作用亦较轻。     

甲磺酸伊马替尼治疗慢性粒细胞白血病54例近期疗效观察

目的 观察甲磺酸伊马替尼(imatinib)治疗慢性粒细胞白血病(CML)的近期疗效。方法 54例CML患者接受imatinib治疗,其中慢性期(CP)17例,加速期(AP)13例,急变期(BC)24例。imatinib用法：CP患者400mg／d,AP和BC患者600mg／d,均为餐后一次顿服。治疗前全面查体,查血象、骨髓象、Ph染色体和(或)bcr／abl融合基因。治疗期间第1个月每周查血象2次,1个月后每周或2周1次。每2～4周查一次肝、肾功能。待血液学取得完全缓解(CR)后择期复查骨髓、Ph染色体和(或)bcr／abl基因。根据血象和患者对药物耐受情况及时调整药物剂量。结果 经中位时间5个月(1～10个月)随访,17例CML CP期患者16例(94．1％)取得血液学CR,其中6例(35．2％)Ph染色体转阴;13例AP患者8例(61．5％)回到CP;24例BC患者9例(37．5％)回到CP。药物不良反应有造血功能抑制、眶周和下肢轻度水肿、全身肌肉关节酸痛和恶心、呕吐、低热(37．5～38℃)、皮疹、胆红素升高等。结论 imatinib对CML有较好近期疗效,其疗效以CP最好,AP其次,BC较差。远期疗效有待进一步观察。药物不良反应可以耐受。     

血管内皮生长因子检测对伊马替尼治疗慢性粒细胞白血病的疗效判定价值

目的检测伊马替尼治疗前后的慢性粒细胞白血病(CML)患者VEGF质量浓度,研究血管内皮生长因子(VEGF)在CML中的表达及临床意义,探讨VEGF对伊马替尼治疗CML疗效判定的价值。方法2003-08～2005-02中国医科大学第一临床学院选择CML患者32例。伊马替尼治疗达血液学完全缓解12例。应用ELISA法检测血浆VEGF的表达质量浓度。结果32例患者血浆VEGF表达质量浓度为(296.16±18.19)ng/L,明显高于对照组(P<0.01)。伊马替尼治疗达血液学完全缓解的CML患者的VEGF质量浓度为(198.23±16.51)ng/L,明显低于治疗前(P<0.05)。结论CML患者血浆VEGF表达明显增高。血浆VEGF可能成为判定伊马替尼疗效的一个指标。     

流式细胞术分析慢性髓性白血病细胞酪氨酸磷酸化水平

目的：探讨慢性髓性白血病（CML）患者骨髓细胞酪氨酸磷酸化水平（p-Tyr），探讨甲磺酸伊马替尼（商品名：格列卫）治疗对p-Tyr水平的作用和影响。方法：对38例CML患者（其中16例接受格列卫治疗）及5例健康对照者的骨髓细胞进行细胞膜CD45和细胞质内PTyr（PY99）荧光标记，应用流式细胞术（FCM）分析不同病期CML各群细胞p-Tyr水平。结果：①未经甲磺酸伊马替尼治疗的慢性期（CP）、加速期（AP）患者骨髓各群细胞p-Tyr水平高于健康对照者，而CP与AP之间p-Tyr水平差异无统计学意义；②CP患者应用甲磺酸伊马替尼治疗〉12个月者的骨髓细胞p-Tyr水平低于用药〈12个月者；AP期用药≥40个月者的幼稚细胞群p-Tyr水平亦低于用药〈12个月者；③随CML病程延长，幼稚细胞群p-Tyr水平增高，但无明显影响；年龄对p-Tyr水平无明显影响。结论：①应用FCM测定细胞p-Tyr水平可作为快速、敏感的方法检测BCR-ABL（＋）细胞；②CML各期细胞的p-Tyr水平均高于正常对照；③甲磺酸伊马替尼对慢性期白血病细胞p-Tyr水平的降低程度随用药时间延长而增强。     

甲磺酸伊马替尼治疗43例慢性粒细胞白血病进展期患者的疗效观察

目的:探讨甲磺酸伊马替尼(STI571,格列卫)治疗慢性粒细胞白血病(CML)进展期(即加速期、急变期)患者的临床疗效。方法:43例疾病进展期CML患者口服格列卫治疗,评价其血液学、细胞遗传学及分子遗传学疗效。结果:43例患者的完全血液学反应(CHR)率、完全细胞遗传学反应(CCyR)率和完全分子遗传学反应(CMR)率分别为44.2%、30.0%和21.9%,观察期内总病死率为25.6%,均于12个月内死亡,不同年龄(≤25岁,>25岁)患者之间病死率有统计学意义(P<0.05)。结论:格列卫对慢性粒细胞白血病进展期患者有一定的疗效,但耐药现象较普遍,年轻患者的预后可能较差。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.