Are <Emphasis Type="Italic">Thymidylate synthase</Emphasis> and <Emphasis Type="Italic">Methylene tetrahydrofolate reductase</Emphasis> genes linked with methotrexate response (efficacy,toxicity) in Indian (Asian) rheumatoid arthritis patients?

Methotrexate (MTX) is among the best-tolerated disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA); major drawbacks of MTX therapy are the large interpatient variability in clinical response and the unpredictable appearance of a large spectrum of side effects. Several studies have demonstrated gene polymorphism that may regulate intracellular methotrexate metabolic pathway enzymes linked to drug efficacy and safety, but the evidence available is not yet conclusive. We decided to run a pilot study to determine the incidence of Methylene tetrahydrofolate (MTHFR; C677T, A1298C) and Thymidylate synthase (TS; 5′ UTR repeat, 3′ UTR deletion) gene polymorphism in rheumatoid arthritis patients in our community (Indian Asian) and further explore its association with MTX response (efficacy, toxicity). Thirty-four naïve RA patients on supervised MTX therapy and 139 healthy controls were genotyped for A1298C and C677T polymorphism of the MTHFR gene and 5′ UTR repeat and 3′ UTR deletion polymorphism of the TYMS gene by polymerase chain reaction-restriction fragment length polymorphism. Association, if any, between gene polymorphism and MTX response in RA patients was analyzed. The MTHFR A1298C ‘C’ allele incidence among RA patients (46%) was significantly higher (χ ²?=?4.24, P?相似文献   

术前罗哌卡因联合右美托咪定和地塞米松髂筋膜间隙阻滞在高龄患者半髋关节置换术中的应用及对患者应激反应的影响

目的 探讨术前罗哌卡因联合右美托咪定和地塞米松行髂筋膜间隙阻滞对高龄患者半髋关节置换术后镇痛效果和应激反应的影响。方法 选取2020年01月至2021年10月入住中国人民解放军总医院第六医学中心拟行半髋关节置换术的高龄患者90例并随机分成两组,每组患者均于术前24 h及手术当日麻醉前30 min行骨折侧超声引导下腹股沟韧带上髂筋膜间隙阻滞,对照组患者使用0.375%罗哌卡因30 mL,观察组患者使用0.375%罗哌卡因联合0.5 μg/kg右美托咪定和0.1mg/kg地塞米松共30 mL,术后两组患者均连接静脉自控镇痛泵。比较两组患者入院后即刻（T0）、术前实施神经阻滞后12 h（T1）、入室时（T2）、术后12 h（T3）、24 h（T4）和48 h（T5）的静息视觉模拟评分（visual analogue scores, VAS）及T3~T5时刻的运动VAS评分;并记录两组患者术后镇痛泵的首次按压时间,镇痛药的使用剂量和不良反应的发生率;同时比较两组患者术前和术后1 d血清白细胞介素-6（interleukin-6, IL-6）、C反应蛋白（c reactive protein, CRP）、皮质醇（cortisol, Cor）、去甲肾上腺素（norepinephrine, NE）和肾上腺素（epinephrine, E）水平。结果 与对照组比较,观察组患者T2和T4时刻的静息VAS评分以及T3~T5时刻的运动VAS评分均降低（P<0.05）,且术后镇痛泵的首次使用时间推迟,镇痛药的使用剂量减少（P<0.05）。术后1 d,观察组血清IL-6、CRP、Cor、NE和E的水平明显低于对照组（P<0.05）,但两组患者术后并发症和不良反应的发生率比较,差异无统计学意义（P>0.05）。结论 术前罗哌卡因联合右美托咪定和地塞米松行髂筋膜间隙阻滞可有效减轻高龄患者半髋关节置换术后的疼痛程度、延长镇痛时间、减轻术后炎症和应激反应,且安全可靠。     

静脉注射免疫球蛋白无应答不完全性川崎病1例临床经验交流北大核心CSCD

该文报道1例静脉注射免疫球蛋白(intravenous immunogloblin,IVIG)无应答不完全性川崎病患儿。1岁女性患儿,表现为发热、皮疹、指端脱皮、冠状动脉扩张,给予第一剂IVIG治疗结束36 h后仍发热,再次给予第二剂IVIG治疗后体温恢复正常,出院1个月后随访冠状动脉内径恢复正常。该文总结了IVIG无应答不完全性川崎病的诊治经验,以期减少冠状动脉损害的发生。     

Effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen: a prospective randomized controlled study北大核心CSCD

目的 探讨生长抑素对急腹症患儿术后胃肠功能及应激水平的影响。 方法 选取2019年8月至2021年6月徐州市儿童医院收治的行手术治疗的102例急腹症患儿为研究对象。将患儿随机分为观察组和对照组,每组各51例。对照组患儿术后给予止血、抗感染等常规治疗,观察组在常规治疗的基础上加用生长抑素。术前、术后第1天及术后第5天采集两组患儿外周血,比较两组患儿血清血管内皮素-1（endothelin-1,ET-1）、促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）、皮质醇（cortisol,Cor）及胃泌素、胃动素水平,以及两组患儿术后恢复情况及并发症发生率。 结果 术前两组患儿血清ET-1、ACTH、Cor、胃动素及胃泌素水平差异无统计学意义（P>0.05）。术后第1天、第5天,观察组患儿血清ET-1、ACTH、Cor水平均显著低于对照组（P<0.05）;术后第5天,观察组患儿胃动素与胃泌素水平均高于对照组（P<0.05）。术后观察组患儿首次肛门排气时间、肠鸣音恢复时间、首次排便时间、住院时间均较对照组缩短（P<0.05）。观察组并发症发生率（6%）显著低于对照组（24%,P<0.05）。 结论 生长抑素可显著降低急腹症患儿术后应激反应,改善胃肠功能,降低并发症发生率,有益于疾病预后。     

急性心肌梗死患者经皮冠脉介入术后无/慢复流发生与炎症

目的探讨急性心肌梗死患者行冠脉介入术(PCI)后无/慢复流现象发生与炎症的关系。方法前瞻性研究656例急性心肌梗死行PCI的患者,其中632例患者随访至一年,60例发生PCI术后无/慢复流现象为复流不良组;从其余的572例患者中,用Excel随机函数表随机抽取120例患者设为对照组,为避免统计学偏差。结果复流不良组炎症指标,如白细胞总数、中性粒细胞总数、高敏C反应蛋白,以及死亡率、心脏不良事件、糖尿病及胰岛素水平均高于对照组(P<0.05或P<0.01);复流不良患者左室射血分数减低、左室舒张末期内径增大(P<0.01)。结论炎症反应与急性心肌梗死患者PCI术后无/慢复流现象的发生有关,并严重影响患者的预后。     

Melatonin reduces UV-induced reactive oxygen species in a dose-dependent manner in IL-3-stimulated leukocytes

Reactive oxygen species (ROS) are presumed to be involved in inflammatory UV reactions of the skin. This in vitro study was performed to investigate the suppressive effect of melatonin in interleukin-3 (IL-3) stimulated leukocytes. Neutrophilic granulocytes were isolated from EDTA-treated whole blood and placed in a phosphate-buffered saline (PBS) containing IL-3. Cell suspensions were either treated with PBS (control) or with increasing doses of melatonin (0.1, 0.5, 1, 2, 3, 5, 7.5, 10 mmol). One PBS solution was left unirradiated and the other nine solutions (PBS and melatonin) were irradiated with 750 mJ/cm2 UVB light (280-360 nm, max: 310 nm). Radical formation was measured by the chemiluminescence technique. UV-irradiated leukocytes showed a 5-fold higher radical formation than unirradiated leukocytes. Melatonin, in increasing doses in powers of ten, led to a maximum suppression of free radicals at 10 nmol (P= 0.01) and 1 mmol melatonin (P= 0.001), showing a biphasic, non-linear, dose response relationship. Melatonin, given in amounts of 0.1-10 mmol, led to a direct dose-dependent suppression of ROS. Radical formation was suppressed significantly in a range from 0.5 to 10 mmol (P= 0.001). Melatonin is known to function as a radical scavenger and antioxidant; some of these melatonin effects may be receptor independent, while others may be receptor dependent.     

TREATMENT OF HAIRY CELL LEUKEMIA WITH INCREASING DOSES OF RECOMBINANT ALPHA A INTERFERON

:Since July 1984, eight patients with advanced hairy cell leukemia have received treatment with recombinant alpha A interferon. At commencement of interferon, seven patients had progressive cytopenia, and one was in leukemic phase (>20times10⁹/L circulating hairy cells). All patients had had previous splenectomy. Interferon was administered subcutaneously. The initial dose was 3times10⁶ U/day, continued until peripheral counts stabilised. Subsequently, patients received 6times10⁶ U/day, 9times10⁶ U/day, and finally 12 times 10⁶ U/day. The dose increases proceeded every 8–12 weeks, as tolerated. Seven patients had an objective response. There were four complete remissions, two partial remissions, and one minor response. Complete remission was documented only in patients on at least 6 times 10⁶ U/day for 12 weeks. The median time to complete remission was 40 weeks (range 35–53). Normalisation of peripheral blood counts preceded histologic marrow improvement. The median times for response (platelets ≤ 100 times 10⁹L, hemaglobin > 12 gm/dL, neutrophils < 1.5 times 10⁹/L), were six to eight and 17 weeks, respectively. Toxicity included myelosuppression during the first four weeks of therapy. With increasing doses of interferon, myelosuppression did not recur. A transient, mild, flu-like syndrome affected all patients. Two patients developed asymptomatic transaminitis at doses >6 times 10⁶ U/day. This resolved with dose reduction. In one case impotence was reported during the first four weeks of each interferon level. One patient discontinued after two weeks due to an exacerbation of systemic vasculitis. The median duration of treatment for the seven responding patients is 78 weeks (range 30–156). All remain on interferon without disease progression. This report confirms a high remission rate, which may reflect a dose-response phenomenon for long-term treatment with alpha interferon in hairy cell leukemia. (Aust NZ J Med 1988; 18: 557–562).     

Differential effect of corticosterone deficiency on the expression of LH, prolactin and insulin receptors on rat Leydig cells

The adverse effects of glucocorticoid deficiency on the expression of genes encoding Leydig cell surface receptors and the response to LH/prolactin/insulin to produce testosterone production are yet to be recognized. Following metyrapone-induced corticosterone deficiency, serum corticosterone, testosterone and insulin levels decrease, whereas serum prolactin exhibits a significant increase and serum LH remains unaltered. LH binding and LH receptor mRNA expression were not altered, but a significant decrease in PRL and insulin binding and in the mRNA expressions of their receptors were observed in corticosterone-deficient rats in vivo. Corticosterone deficiency significantly decreases the Leydig cellular basal as well as hormone-stimulated testosterone production in vitro. Simultaneous administration of corticosterone prevented its deficiency-induced changes in Leydig cells both in vivo and in vitro. Our results show that metyrapone-induced corticosterone deficiency impairs Leydig cell insulin and prolactin receptors, and their mRNA expression and the response of Leydig cells to LH/PRL/insulin on testosterone production.     

Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients

Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I–III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-γ and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9–5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19⁺ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.