A Case of Severe Hypomagnesaemia

Hypomagnesaemia is a common finding that occurs in hospitalised patients and can be caused by renal or extrarenal wasting. Because it is not routinely tested, even severe hypomagnesaemia can be missed. In cases of extrarenal wasting, the kidney can decrease its magnesium excretion to very low levels. A systematic diagnostic approach allows the proper diagnosis and treatment of hypomagnesaemia. We report on a 72-year-old Caucasian male patient with repeated drops and amyosthenia caused by severe hypomagnesaemia. In this report, we discuss the pathophysiology, clinical signs, diagnostic investigation and treatment of magnesium depletion.

Hypomagnesaemia associated with long-term use of proton pump inhibitors

Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare longterm side-effects of proton pump inhibitors(PPIs).The PPIs may inhibit active magnesium(Mg)absorption by interfering with transcellular transient receptor potential melastatin-6 and-7(TRPM 6 and 7)channels.More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole.After being treated with a range of PPIs,the four patients in our case series developed hypomagnesaemia,which responded to withdrawal of therapy and initiation of Mg replacement.Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long-term use of PPIs.

氨基酸螯合钙口服液对产后奶牛健康状况及乳品质的影响

本研究旨在探讨氨基酸螯合钙口服液及复方氨基酸螯合钙口服液对产后奶牛健康状况和乳品质的影响。选取某大型牧场产后奶牛,按照分娩顺序交替指定为对照组、试验Ⅰ组和试验Ⅱ组,对照组饲喂常规日粮,试验Ⅰ组灌服氨基酸螯合钙口服液,试验Ⅱ组灌服复方氨基酸螯合钙口服液,定时采集血样和乳样,用于分析血浆生化指标及乳品质,同时观察产后奶牛的健康状况。结果表明:与对照组相比,试验Ⅰ组产后奶牛血浆钙含量及乳汁中乳蛋白含量升高,血浆甲状旁腺素含量、亚临床型低钙血症、胎衣不下的发病率显著降低;试验Ⅱ组产后奶牛血浆钙、镁含量和乳汁中乳蛋白含量升高,亚临床型低钙血症、胎衣不下的发病率及乳汁中体细胞数显著降低,在产后第7天极显著提高血浆中降钙素含量,极显著降低低镁血症的发病率。结果提示,氨基酸螯合钙口服液及其复方口服液,对控制奶牛产后疾病、提高乳品质量具有较好的效果,且复方口服液的效果更理想。

体外循环预充液中补充镁剂对预防儿童先天性心脏病术后心律失常的作用

目的:探讨体外循环(CPB)预充液中补充镁剂对儿童先天性心脏病(先心病)修补术后早期心律失常发生的预防性作用。方法:99例CPB下实施先心病心内直视修补手术的患儿被随机双盲地分成两组,实验组(即预充液补镁,n=49)和对照组(预充液补充生理盐水,n=50)。在7个检测点即术前1天、停CPB时、术后0h〔入重症监护室(ICU)即刻〕和ICU内术后6h、术后12h、术后24h、术后48h,测量血清镁浓度。术后48h内实施持续动态心电图监测。结果:在5个检测点(从停CPB时到术后24h)对照组血清镁浓度明显低于实验组。差异有统计学意义(P<0.01～0.05)。术后24h内对照组心律失常发生率明显高于实验组(P=0.003)。在ICU最初的24h内对照组有6例(12.0%)发生异位性交界区心动过速(JET),实验组没有观察到异位性交界区心动过速发生,差异有统计学意义(P=0.012)。结论:低镁血症与术后早期心律失常的发生有关,并提高异位性交界区心动过速的发生率。CPB预充液中补充镁剂可以预防儿童先心病CPB术后心律失常的发生。

Gitelman综合征14例临床特征分析

目的:分析Gitelman综合征(GS)的临床特征,以提高该病的诊治水平。方法:回顾性分析南京医科大学第一附属医院内分泌科近5年住院诊治的14例GS病例资料。结果:患者发病年龄13～54(32.9±12.0)岁,男5例,女9例。病程最短为1个月,最长为15年。体质指数(BMI):(21.0±2.9)kg/m2,收缩压:(109.6±10.8)mmHg,舒张压(69.6±6.7)mmHg。临床上以双下肢无力、发作性四肢软瘫、多饮、多尿、夜尿增加、手足抽搐等为主要表现。实验室检查均表现为低血钾、低血镁、低尿钙、高尿钾、代谢性碱中毒。卧立位试验结果显示:卧位及立位血浆肾素活性(PRA)、血管紧张素Ⅱ和醛固酮有不同程度升高。肾脏穿刺病理提示球旁器增生(3/4)。补钾补镁、联合安体舒通等药物治疗后症状缓解,但血钾(11/14)、血镁(10/14)未升至正常水平。结论:GS的临床特征包括:低血钾、低血镁、低尿钙、正常偏低血压以及高PRA、高血管紧张素Ⅱ、高醛固酮和高血气pH值,可以总结为"四低四高"。本病治疗以补钾补镁为主,可以联合应用醛固酮拮抗剂,一般预后良好。

高钙尿症和低镁血症在Bartter综合征和Gitelman综合征分型中的临床价值

目的评价血镁和尿钙水平在Bartter综合征(Bartter syndrome,BS)和Gitelman综合征(Gitelman syn-drome,GS)中鉴别诊断的价值。方法选取北京儿童医院临床诊断为BS和GS患儿72例,以尿钙/肌酐>0.2作为高钙尿症的标准,以血镁<0.8 mmol/L作为低镁血症的标准,对72例患儿进行分组,比较高钙尿症组与尿钙正常组、低镁血症组与血镁正常组发病年龄、生长发育指标和电解质水平的差异。结果 72例患儿中,男52例,女20例;年龄2个月至15.5岁,平均(5.55±4.59)岁。患儿就诊时常无典型的症状,以发热咳嗽(25.0%)、生长发育迟缓/矮小(22.2%)、呕吐(18.1%)、四肢无力(13.9%)为主。高钙尿症组患儿年龄低于尿钙正常组[(2.64±2.95)岁vs.(7.76±4.49)岁,P=0.00];体重的标准差积分值(standard deviation score,SDS)低于尿钙正常组,分别为(-2.57±1.11)SDS和(-1.59±1.26)SDS(P=0.005),但身高和BMI的SDS值2组间差异无统计学意义。血镁正常组患儿体重和BMI的SDS值低于低镁血症组,分别为(-2.42±1.60)SDS vs.(-1.42±1.13)SDS(P=0.005),(-1.82±1.77)SDS vs.(-0.82±1.37)SDS(P=0.018);且血镁正常组患儿年龄也低于低镁血症组,分别为(3.78±4.14)岁和(7.66±4.47)岁(P=0.00)。结论年龄是BS患者的危险因素。小年龄患儿出现高钙尿症,常伴有BMI降低和发育落后,但血镁水平正常;低镁血症易出现在大年龄患儿,且预后相对较好。通过检测尿钙和血镁水平,可有助于BS和GS患者亚型的分析并提供个体化诊疗。

抗表皮生长因子受体单克隆抗体——西妥昔单抗在结直肠癌治疗中的临床进展

最近,一些临床试验的结果肯定了西妥昔单抗(cetuximab)作为一种表皮生长因子受体(EGFR)单克隆抗体在结直肠肿瘤的治疗作用。本文从转移性结直肠癌治疗的角度综述西妥昔单抗这一EGFR抗体的临床观察结果,回顾分析了多篇近年发表的关于西妥昔单抗在结直肠癌和其它恶性肿瘤临床应用的文献。西妥昔单抗在转移性结直肠肿瘤的无进展生存期的延长上获得了肯定的疗效(3.9月vs2.56月,P<0.01)。然而,在作为第二线治疗时,西妥昔单抗与依立替康的联合治疗对比依立替康单药治疗并没有使平均生存期得到延长。在副作用方面,痤疮样皮疹的严重程度可以预示肿瘤对西妥昔单抗的应答强弱,外用糖皮质激素和润肤剂可以治疗这一副作用。低镁血症是该药引起的一个比较特殊的副作用,使用静脉补镁是治疗低镁血症的有效方法。

Association of Low Serum Magnesium Levels in Type 2 Diabetes Mellitus with &without Hypertension

Background: Diabetes Mellitus is a widespread metabolic abnormality that constitutes a most important physical dilemma in the world. Hypomagnesaemia accelerates the rate of diabetic complications. Objective: To analyze the association of magnesium levels in DM (Type 2 Diabetes Mellitus) with and without complication of Hypertension. Design: It was a comparative analytical study. Setting: This research was carried out in medicine department, Peoples Medical College Hospital, Nawabshah from March 2016 to February 2017. Samples: 245 patients with Type 2 DM after fulfilling the selection criteria were included, out of them 123 with hypertension and 122 without hypertension. Methods: After a short-lived consultation, all the subjects were categorized for variable analyses like age, gender, Type 2 DM with and without hypertension, duration of diabetes and presence of hypomagnesaemia. Joint National Committee (JNC 8) classification of Hypertension was applied to collect data. Blood samples were drawn for research purpose in fasting state for serum magnesium level analyses on the basis of hypertension and without hypertension. Results: In 245 diagnosed Type 2 diabetic patients, 160 were males and 85 were females. Out of them, 123 were hypertensive while 122 were non hypertensive. Normal magnesium was present in 120 (48.97%) and low magnesium was present in 125 (51.02%) patients overall. A decreased serum level of magnesium was observed in 52.04% hypertensive subjects with diabetes and 50% non-hypertensive subjects with diabetes. Conclusion: Frequency of decreased serum magnesium is widespread in T2DM with and without hypertension.

抗表皮生长因子受体单克隆抗体引起离子紊乱的研究进展

抗表皮生长因子受体(EGFR)单克隆抗体对多种实体肿瘤的治疗具有重要意义,但这类药物可引起离子紊乱如低镁血症、低钙血症和低钾血症,早期症状因不够典型而容易被忽视。EGFR较多的表达于肾远曲小管和集合管,而抗EGFR单克隆抗体抑制了离子在肾髓袢升支粗段的重吸收,从而使镁离子在尿中的排泄增多,低镁血症继而引起低钙血症和低钾血症。不同的靶向药物以及不同肿瘤发生部位所出现的离子紊乱情形各有不同。低镁血症发生的风险与治疗时间、患者年龄及基础血清镁值相关。低镁血症倾向于可作为预后较佳的预测因素。3级或4级低镁血症需要延长靶向治疗间隔时间,同时静脉补充离子治疗,通常低镁血症是可逆的。该文参考既往的临床试验和研究,讨论离子紊乱的发生率、机制、危险因素、治疗以及疗效预测。

Assessment of Serum Magnesium Level in Type 2 Diabetes Mellitus with Diabetic Foot Ulcers (Grade I and II) at Nawabshah, Pakistan

Diabetes Mellitus is a metabolic disorder increasing morbidity and mortality worldwide, which needs exact identification and proper management. Aim of this study was to analyze the serum Mg (magnesium) level in patients with Type 2 Diabetes Mellitus with grade I & II diabetic foot ulcers. This descriptive cross sectional study was conducted at Medicine Department, PMCH Nawabshah from June 2015 to December 2016. A total of 110 Type 2 Diabetes Mellitus with foot ulcer patients, 51 with grade I and 59 with grade II out of total were included by purposive sampling. After consultation, subjects were categorized as gender, age, Type 2 DM and foot ulcer duration, foot ulcer grading and grouping for analyses. Wagner’s classification of diabetic foot ulcers used to analyze the data and blood samples were collected for research purpose in fasting state for serum Magnesium level analyses. Out of 110, 67 (65.5%) males and 43 (34.5%) females were reported with Type 2 diabetic patients. Hypomagnesaemia was reported in 59% patients out of total, 24 found with grade I and 38 found with grade II from the studied subjects. P value &le;0.000 was in the studied population in relation to hypomagnesaemia. In conclusion, Hypomagnesaemia is common in Type 2 Diabetes Mellitus patients with grade I & II foot ulcers. As the duration of Diabetes along with duration of diabetic foot ulcer in Grade I and II increases, the level of serum magnesium decreases. As the duration of Diabetes Mellitus increases, the severity of complications might also increase.

Association of Hypomagnesemia in Type 2 Diabetic Patients with and without Peripheral Neuropathy

Background: Diabetes Mellitus is a wide-ranging metabolic disorder, which constitutes a most important physical condition dilemma in the world. Hypomagnesaemia accelerates the rate of diabetic complications. Objective: To analyze the association of serum magnesium (Mg) in Type 2 Diabetes Mellitus with and without complication of peripheral neuropathy. Design: A cross sectional study. Setting: This research was carried out in medicine department, Peoples Medical College Hospital Nawabshah from May 2016-April 2017. Sample Size: Total 271 patients of both genders with Type 2 DM with and without peripheral neuropathy, each group after fulfilling the selection criteria were included. Material and Methods: After a short-lived consultation, the subjects were categorized for variable analyses like sex, age, Type 2 Diabetes Mellitus with and without peripheral neuropathy, duration of diabetes mellitus and presence of hypomagnesaemia. Clinical examination with monofilament was applied for diagnosis of peripheral neuropathy. Blood samples for magnesium analysis were collected in fasting condition. Results: In 271 diagnosed patients of Type 2 diabetes mellitus, 180 male and 91 were females. Peripheral neuropathy was observed in 136 subjects out of them 94 males and 42 were females. While 135 were without peripheral neuropathy out of them 86 males and 49 were females. Normal magnesium was seen in 119 (43.91%) and low magnesium was present in 152 (56.09%) patients overall. A decreased serum level of magnesium was observed in 56.09% diabetic subjects with peripheral neuropathy and 50% subjects with diabetes without peripheral neuropathy. Conclusion: Frequency of hypomagnesaemia is common in subjects with in Type 2 DM with and without peripheral neuropathy.

CLDN16基因复合杂合突变致家族性低镁血症高钙尿症与肾钙质沉着症一例报告并文献复习

目的探讨家族性低镁血症高钙尿症与肾钙质沉着症（familial hypomagnesaemia with hypercalciuria and nephrocalcinosis，FHHNC）患者的临床特点和致病基因特征。方法2016年2月收治1例女性患者，年龄24岁。入院前1个月外院腹部X线片（KUB）检查示左肾结石，双肾钙质沉着。患者于外院行经皮肾镜取石术清除大部分左肾结石。本次入院后实验室检查：血镁0.65 mmol/L，24 h尿钙364.0 mg，血甲状旁腺激素187.4 pg/ml，血肌酐101.5μmol/L。行输尿管软镜碎石术清除左肾残余结石。考虑患者为FHHNC，对患者及其父母行外周血CLDN16和CLDN19基因测序分析。结果基因测序结果显示患者CLDN16基因的第2外显子第123密码子一个碱基缺失（c.368delA），第2外显子第139密码子发生错义突变[c.416C→T（p.A139V）]。患者母亲的第139密码子第2个碱基胞嘧啶变为胸腺嘧啶（c.416C→T）；患者父亲的第123密码子第2个碱基腺嘌呤缺失（c.368delA）。该患者确诊为FHHNC，口服氢氯噻嗪、枸橼酸钾、钙镁片治疗。随访6个月，复查血镁1.0 mmol/L，24 h尿钙156.0 mg，血甲状旁腺激素139.6 pg/ml，泌尿系结石无复发，双肾钙质沉着症及肾功能损伤无明显加重。结论CLDN16基因复合杂合突变致FHHNC的临床三联症为低镁血症、高钙尿症和肾钙质沉着症，确诊依靠CLDN16和CLDN19基因测序。肾功能严重受损前以对症治疗为主，给予氢氯噻嗪、枸橼酸钾、钙镁片治疗有可能明显改善低镁血症和高钙尿症。

遗传性低镁血症继发低钙血症2例及4个TRPM6基因新突变

目的探讨遗传性低镁血症继发低钙血症的临床、生化、影像及TRPM6基因突变特点。方法 2例于2014年至2016年就诊于北京大学第一医院来自不同家系的男童,分别于9岁、1岁2个月时因"癫痫、发育落后"入院,通过临床调查、生化代谢分析、影像进行病因研究,采用全外显子分析明确基因诊断,对TRPM6基因突变进行验证。结果例1出生后3个月起反复抽搐发作,发育落后,9岁起视力下降,智力运动倒退,伴高血压。血镁(0.13~0.15 mmol/L)和血总钙(1.43~2.00 mmol/L)显著降低,伴血钾(1.85~3.25 mmol/L)及甲状旁腺素降低。TRPM6基因检出2个新的无义突变c.2771G>A(p.Trp924Ter)和c.115C>T(p.Gln39Ter)。例2出生后2周出现抽搐发作,发育落后。血镁(0.17~0.35 mmol/L)和血总钙(1.32~1.34 mmol/L)显著降低,甲状旁腺素降低。TRPM6基因检测发现2个新突变c.1239G>A(p.W413X)和c.146G>A(p.C49Y)。2例患儿血清镁、钙显著降低,甲状旁腺素降低,符合遗传性低镁血症继发低钙血症。经大剂量硫酸镁补充治疗后,2例患儿临床症状显著改善,血镁提高,血钙达到正常水平。例1由于脑损伤严重,仍有发育落后。例2已经康复。结论遗传性低镁血症继发低钙血症是一种严重的遗传代谢病,早期诊断、大剂量镁剂治疗预后良好。本研究报道了2例中国患儿,以癫痫、发育落后形式起病,经血液生化及基因分析确诊,并发现了TRPM6 4个新突变。

镁对预防1岁以内先天性心脏病患儿术后异位性交界区心动过速的作用

目的：探讨1岁以内先天性心脏病患儿实施体外循环心内直视矫治术后早期补充硫酸镁对异位性交界区心动过速（junctional ectopic tachycardia,JET）发生的预防性作用。方法325例体外循环下实施先天性心脏病心内直视矫治手术的1岁以内的患儿被随机分成两组,即试验组（162例,50 mg /kg 25% MgSO4）和对照组（163例,生理盐水）。在5个时间点检测血清镁浓度,术后24 h 内实施持续动态心电图监测。结果在 T3时间点（静脉补充50 mg /kg 的25% MgSO4和等量的生理盐水后1 h）,试验组平均血清镁浓度明显高于对照组[（1.79±0.33）mmol /L vs.（0.92±0.18）mmol /L, P ＝0.001]；在 T4和 T5时间点（补镁和生理盐水后12 h 和24 h）,试验组平均血清镁浓度始终高于对照组[T4：（1.24±0.24）mmol /L vs.（0.83±0.17）mmol /L；T5：（1.20±0.16）mmol /L vs.（0.80±0.19）mmol /L,P ＝0.024,P ＝0.035]。JET 总发生率为5.2%（17/325）,对照组 JET 发生率（9.2%,15/163）明显高于试验组（1.2%,2/162）,差异有统计学意义（P ＝0.013）；对照组 JET 发生时间明显早于试验组（P ＝0.019）。JET 病例中,14例（82.4%）存在低镁血症,JET 病例术后呼吸机应用和 CICU 滞留时间明显延长。结论1岁以内先天性心脏病患儿体外循环心内直视矫治术后早期积极补充镁剂可以降低 JET 的发生率,低镁血症与 JET 的发生有相关性。

4例家族性低镁血症继发低钙血症药物治疗分析

目的探讨家族性低镁血症继发低钙血症(familial hypomagnesaemia with secondary hypocalcaemia,HSH)的药物治疗。方法回顾性分析2015年1月至2018年12月在首都医科大学附属北京儿童医院神经内科诊治的HSH患儿的临床特征及药物治疗,并对其进行8个月至3年8个月的随访观察。结果4例患儿中男、女各2例,临床表现主要有惊厥、易惊、易激惹及发育落后。初始治疗给予MgSO4注射液0.17~0.44mmol·kg^-1·d^-1肌内注射,症状缓解后镁剂口服的维持剂量为0.09~0.19 mmol·kg^-1·d^-1。4例患儿均未达到血镁正常水平,但随访显示均无惊厥发作,其中3例预后良好,发育正常,1例因未及时明确诊断及补镁治疗,遗留极重度发育落后。结论推荐HSH长期口服补镁的治疗目标为维持患者达到无低镁临床症状并使钙代谢正常化的镁剂量。持续口服补镁治疗后患儿虽长期处于低镁状态,但未对患儿神经发育造成不良影响。