Early prediction of the outcome of a paracetamol overdose based on an analysis of 163 patients.

Clinical and biochemical data obtained from 163 patients who had taken an overdose of paracetamol were examined to determine which factors or measurements were of value in predicting the severity of ensuing liver damage early after ingestion of tablets. Although the overall severity of hepatic necrosis was found to increase with the dose of paracetamol ingested, correlation was not sufficiently close to provide an accurate prognostic index in individuals. Severe hepatic damage was less likely if the patient had vomited or had a stomach wash-out within 6 hr of overdose. The plasma concentrations of paracetamol, measured at known times after overdose, distinguished those who developed hepatic dysfunction from those who did not, but there was a poor correlation, particularly in the first 6 hr after ingestion of tablets, between these values and the severity of ensuing liver damage. Estimates of early plasma paracetamol half-lives from three or more samples taken within 4 hr of admission showed that all patients developing moderate or severe liver damage had half-lives greater than 4 hr, but this was also the case in nearly one-third of those with minimal liver lesions only. It is concluded that there is no completely reliable early prognostic test for individual patients with paracetamol overdose. If each patient is selected for treatment with cysteamine (mercaptamine) or other agents on the basis of plasma paracetamol levels, up to 30% may receive this agent who are at risk from trivial hepatic damage only.     

Hemodialysis in methyprylon overdose. Some pharmacokinetic considerations.

Serial measurements of serum methyprylon concentration were made in the case of a 14-year-old girl who ingested an overdose of the drug. Our data indicate that, in the presence of high plasma levels of the drug, much longer half-lives than the usually reported four hours may be observed. It is postulated that saturation kinetics may be a possible mechanism for this observation. The striking clinical improvement after six hours of hemodialysis demonstrated the efficacy of this mode of treatment in our patient.     

Liver toxicity after acetaminophen ingestion. Inadequacy of the dose estimate as an index of risk

With increasing frequency, the physician is confronted with the problem of determining the risk of liver toxicity in a person who may have ingested an overdose of acetaminophen. To be effective, antidotal therapy must be given early after acetaminophen ingestion when the patient, despite the toxic injury occurring in his liver, may appear quite well. We have reviewed the cases of the first five persons who came to our institution with a history of having ingested a large overdose of acetaminophen. In each case plasma or serum acetaminophen levels were low and substantial liver injury did not occur. Measurement of acetaminophen levels, indicating the amount of drug absorbed, were a more reliable index of the risk of toxic liver injury and the need for antidotal therapy than the estimate of the dose ingested.     

Antidepressant blood levels in acute overdose.

Plasma antidepressant levels and clinical condition were measured sequentially for at least 24 hr in eight patients who presented with acute antidepressant overdosage. There was no evidence to suggest that a knowledge of the drug plasma levels had anything to offer in the management of a patient whose overdose included a tricyclic antidepressant.     

104例药物过量病人血苯二氮(艹卓)类药物浓度测定

目的:对疑苯二氮(艹卓)类药物(BZDs)过量患者测定其血BZDs浓度,确定药物过量与BZDs浓度的关系.方法:对急诊疑BZDs药物过量病人104例,采用荧光偏振免疫法测定血BZDs浓度.结果:104例药物过量病人血BZDs药物呈阳性,浓度高低不一.浓度低于1000ng/ml的病人其预后明显好于浓度超过1000ng/ml的病人.结论:采用该法测定BZDs药物血药浓度对临床及时诊断和治疗有一定参考价值,但要注意测定结果并不能代表临床病情的轻重.     

Plasma carcinoembryonic antigen and erythrocyte sedimentation rate in patients with colorectal carcinoma.

Preoperative and postoperative plasma carcinoembryonic antigen (CEA) levels in patients with colorectal carcinoma have been reported to correlate with tumour mass and prognosis. The erythrocyte sedimentation rate (ESR) has previously been reported to be elevated in most patients with metastatic carcinoma. In this study of 17 patients with advanced colorectal carcinoma and of nine patients who were disease-free more than three years after resection of their tumour, the plasma CEA and ESR levels demonstrated a close correlation, both in frequency and in degree of elevation, with the disease status. Of nine patients who were disease-free more than three years after resection of their colorectal carcinoma, all except one had plasma CEA levels of less than 20 ng/ml and an ESR less than 20 mm in one hour respectively. The incidence of plasma CEA more than 20 ng/ml and ESR more than 20 mm in one hour in the locally advanced and distant metastases groups, as compared with those patients in the more than three years group, was increased at a level of statistical significance (P less than 0.05). This study showed that the ESR, an inexpensive and simple estimation, may be as effective as the estimation of plasma level of CEA in monitoring the disease status of patients with colorectal carcinoma.     

Torsades de pointes occurring in association with terfenadine use

Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although found in many clinical settings, torsades de pointes is most often drug induced. This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone. Measured serum concentrations of terfenadine and its main metabolite showed excessive levels of parent terfenadine and proportionately reduced concentrations of metabolite, suggesting inhibition of terfenadine metabolism. We believe that a drug interaction between terfenadine and ketoconazole resulted in the elevated terfenadine levels in plasma and in the cardiotoxicity previously seen only in cases of terfenadine overdose.     

Acetaminophen: a practical pharmacologic overview

Acetaminophen is an effective analgesic and antipyretic agent with few adverse effects when used in recommended dosages. The drug is metabolized mainly in the liver, and the several end products have no harmful effects. An intermediate compound in a minor metabolic pathway, however, is toxic; it is normally inactivated by glutathione. In the case of an acetaminophen overdose the hepatic stores of glutathione seem to become depleted, leaving the toxic intermediate free to damage liver tissue. Such damage is unlikely to occur unless the plasma concentration of acetaminophen peaks above 150 micrograms/mL--a level far in excess of the 5 to 20 micrograms/mL achieved with therapeutic doses of the drug. Long-term therapeutic use of acetaminophen does not appear to be associated with liver damage, although some case reports suggest the possibility. Acetaminophen poisoning follows an acute overdose and, if untreated, is manifested clinically by an initial phase of nonspecific signs and symptoms, a latent period in which the liver transaminase levels rise and then, 3 to 5 days after the ingestion, signs of more serious hepatic dysfunction. Most patients do not progress beyond the first or second phase. They and those who survive the third phase recover with no residual injury to the liver. Appropriate antidotal therapy markedly reduces the severity of the initial damage.     

Vitamin supplementation of patients receiving haemodialysis

In order to assess the necessity of vitamin supplementation for patients who are receiving haemodialysis, measurements of vitamin status were made, and both dietary and supplementary intakes were assessed, in 26 patients who were undergoing haemodialysis. Blood samples were collected from these patients before they underwent haemodialysis, after an overnight fast, for the measurement of plasma retinol, alpha-tocopherol and ascorbate levels. Serum and erythrocyte folate levels were measured also. Thiamin status was assessed by the effect of added thiamin pyrophosphate on erythrocyte transketolase activity and pyridoxine status was assessed by the effect of added pyridoxal-5'-phosphate on erythrocyte aminotransferase activity. All patients had elevated plasma retinol levels; 48% of patients had elevated plasma alpha-tocopherol levels; the plasma ascorbate level was low in 50% of patients but was elevated in 25% of patients; and plasma and erythrocyte folate levels were elevated in 76% and 91% of patients, respectively. Thiamin status was normal in all but one patient and the pyridoxine level appeared to be low in two other patients. Many patients had low dietary intakes of vitamin C, folate and vitamin B6. We conclude that supplements of vitamins A and E are not required and, when dietary intakes of water-soluble vitamins are marginal, these should be supplemented at a dose as near as possible to the recommended dietary intake.     

Severe meprobamate poisoning: successful treatment with haemoperfusion

Charcoal haemoperfusion used to treat a 56-year-old woman who had taken a very large overdose of meprobamate was followed by fully recovery. The plasma clearance of meprobamate was 153 ml/min and this compares favourably with values obtained for haemodialysis. The indications for haemoperfusion are reviewed.     

Children's multiple vitamins: overuse leads to overdose

A suburban Ontario community hospital encountered 21 +/- 1 overdoses of children's multiple vitamins yearly between 1978 and 1981. Of these, 35% involved one particular cartoon character preparation. Parents were surveyed to determine whether this particular preparation resulted in a disproportionate number of accidental overdoses. However, the use of vitamins with a cartoon character format did not lead to a greater risk of overdose than did conventional preparations. Of the 1051 families who had given multiple vitamins to their children 34 (3%) had experienced an overdose. The number of vitamin preparations used by each family was the most powerful determinant of overdose (p less than 0.001). The risk of accidental overdose increased from 1.5% with one multiple-vitamin preparation to 8% with four or more preparations. Among all the variables examined, exposure was the most important element in the risk of multiple-vitamin overdose.     

Clinical contact preceding suicide.

Of the 400 consecutive completed suicides investigated over a 5-year period, 114 (28.5%) who had consulted a doctor in the week preceding death were specifically reviewed and compared with those who did not. The study comprised an analysis of the medical history, the scene of death and a complete autopsy with histological and toxicological examination and the identification of features which occurred more frequently in this group when compared with other suicides not contacting their doctors. Suicide-associated factors include psychiatric illness (58.8%), deteriorating health (16.7%), and a loss of spouse (7.0%); all these features were manifested by this group of suicides more frequently than by those who made no clinical contact (P < 0.001). A pre-indication of suicidal intention was made by 45% of these patients. This feature, as with previous attempts, occurred more commonly in patients who consulted a doctor (P < 0.001). Drug overdose was the most common suicidal method chosen (50.9%) and anti-depressants predominated (35%); 78% of those who overdosed ingested prescribed drugs. Poisoning was more common in this group (P < 0.001). Half of the victims committed suicide within 24 hours following consultation; of these, 51% overdosed on drugs with 61% of them ingesting their prescribed drugs. Of these 114 cases, the final consultation in 43% was to collect more drugs. All suicidal threats should be taken seriously, and particular care should be taken in prescribing and dispensing medication which may be fatal in overdose.     

盐酸地芬尼多急性中毒的临床特征研究

背景　盐酸地芬尼多是用于治疗各种原因所致眩晕的非处方药物。近年来因过量服用盐酸地芬尼多急性中毒的个案时有报道,但至今尚无基于急性中毒患者血药浓度的临床特征报道。目的　通过总结9例因过量服用盐酸地芬尼多中毒患者的临床特征及诊疗结果,分析血药浓度检测在因过量服用盐酸地芬尼多急性中毒患者诊治过程中的价值。方法　本文回顾性分析了2019年6月-2020年5月因过量服用盐酸地芬尼多急性中毒就诊于北京大学第三医院急诊科的9例患者的临床表现、血药浓度、治疗经过及预后。结果　9例盐酸地芬尼多急性中毒患者中女7例,男2例;平均年龄（20.7±1.9）岁;平均服药剂量（2 700±1 478）mg;中位服药至就诊间隔时间为3.5（6.5）h;血药浓度为3.15（26.27）mg/L。2例盐酸地芬尼多最高血药浓度≥35 mg/L的患者出现昏迷〔格拉斯哥昏迷量表（GCS）评分为3分〕、抽搐、呼吸衰竭、持续性低血压及心脏骤停的严重中毒表现,其中1例死亡。4例最高血药浓度≤2.5 mg/L的患者中毒表现相对较轻,主要为头晕、恶心呕吐、肢体乏力、肢体震颤等症状。首次血液灌流治疗前后动态监测盐酸地芬尼多血药浓度下降（47.51±22.16）%。出院时8例存活,存活率为88.9%,平均住院天数为（4.7±3.3）d。结论　在盐酸地芬尼多中毒患者的诊治中,服药剂量与最高血药浓度的关系不明确,监测血药浓度可能有利于对疾病严重程度及预后的评估。当患者出现昏迷、持续性低血压和呼吸衰竭时要警惕心脏骤停的风险,血液灌流可有效降低盐酸地芬尼多血药浓度。     

严重烧伤后高迁移率族蛋白B1的变化及其与脓毒症的关系

目的动态观察严重烧伤患者血浆中高迁移率族蛋白B1(HMGB1)水平的变化并探讨其与脓毒症及内毒素血症的关系。方法25例烧伤总体表面积大于30%患者,根据是否并发脓毒症分组(脓毒症组14例、非脓毒症组11例),采用酶联免疫吸附实验及改良基质显色法鲎实验分别检测患者伤后1、3、5、7、14、21、28d血浆HMGB1及内毒素含量的变化。结果严重烧伤患者伤后第1天血浆中HMGB1含量显著升高,其中伤后第7、21、28天脓毒症组HMGB1含量显著高于非脓毒症组(P<0.05)。脓毒症患者存活组伤后第3、21天HMGB1含量显著低于非存活组(P<0.05,P<0.01),血浆中HMGB1含量与是否易并发脓毒症有关,但与烧伤总体表面积无相关性(P>0.05)。伤后第3、5、7、21天血浆HMGB1与内毒素含量呈显著正相关(P<0.05,P<0.01)。结论HMGB1作为重要的晚期炎症介质参与严重烧伤后脓毒症的病理生理过程,其诱生与内毒素刺激密切相关,动态观察其水平有助于烧伤后病程监测及患者预后判断。     

Adrenal insufficiency after operative removal of apparently nonfunctioning adrenal adenomas

We describe a woman who developed adrenal insufficiency after removal of an apparently nonfunctional adrenal adenoma. She displayed no stigmata of Cushing's syndrome and had normal plasma and urinary cortisol levels. A second patient without clinical findings of Cushing's syndrome also had normal basal steroid levels. This patient displayed partial suppressibility with dexamethasone, had low-normal levels of serum corticotropin, and excreted a low concentration of urinary 17-ketosteroids. She also developed mild adrenal insufficiency after the operation. We believe the adrenal adenomas in these patients secreted enough cortisol to suppress the contralateral adrenal gland but not enough hormone to elevate basal steroid levels. Therefore, we suggest that all patients with adrenal masses be studied with the overnight dexamethasone suppression test rather than basal steroid hormone measurements to detect low levels of autonomous cortisol secretion. In addition, patients with adrenal masses that are not removed surgically should have serial adrenal function tests performed.     

Plasma warfarin concentrations after a massive overdose

The plasma pharmacokinetics of warfarin were studied in a patient who took an overdose of warfarin (2000 mg by mouth), together with 25 X 10(4) units of heparin administered subcutaneously. The plasma warfarin level fell rapidly (half-life, 21.7 h), and there was no convincing evidence for dose-dependency in its disposition.     

乳腺癌患者血清CA15-3的检测及临床意义

目的：探讨肿瘤相关抗原ＣＡ１５－３水平和阳性率与肿瘤复发、转移等预后因素的关系。方法：选择６０例不同病理类型乳腺癌患者作前瞻性研究,并采用免疫放射分析法（ＩＲＭＡ）进行检测ＣＡ１５－３水平。结果：发现不同淋巴结及远处癌转移状况、不同的乳腺癌患者血清ＣＡ１５－３水平及其阳性率差异显著（Ｐ＜０．０５）。对患者术后随访期间ＣＡ１５－３动态观察发现,术后较术前有所下降,局部或对侧复发者较无瘤生存者明显升高,对手术治疗的彻底性也有一定指导意义。结论：对乳腺癌患者尤其是在术后定期检测血清ＣＡ１５－３水平变化,可作为监测复发和转移等的一项有价值的指标。     

并发重症抑郁障碍的卵巢癌患者血IL-6水平与HPA活化的研究

目的比较是否并发抑郁症的卵巢癌患者血IL-6水平和DST的差异，并探讨抑郁程度与IL-6和DST阳性率的相关性。方法平均分为四组：对照组、患有抑郁症的患者、未患抑郁症的卵巢癌患者、患有抑郁症的卵巢癌患者。选择符合CCMD-2-R中抑郁发作的诊断标准的患者。抑郁症的严重程度由汉密尔顿抑郁量表测定。进行血IL-6测定及地塞米松抑制试验。结果并发抑郁症的卵巢癌患者血浆IL-6水平均比其他组明显高。患者对小剂量地塞米松抑制试验呈现超敏感现象，为该类患者存在持久亢进的垂体-肾上腺轴功能的假说提供了证据。结论通过了解并发重症抑郁障碍的卵巢癌患者血浆地塞米松和IL-6水平的变化，对探讨卵巢癌并发重症抑郁障碍的神经内分泌和神经免疫学发病机制将有深远的意义。     

系统性红斑狼疮患者血浆D-二聚体水平测定及其临床意义

目的 了解系统性红斑狼疮(SLE)患者D-二聚体的水平及其临床价值.方法 用单克隆抗体乳胶凝集试验法测定62例SLE患者血浆D-二聚体水平,研究其与SLE的疾病活动、临床表现的关系及治疗前后的变化.结果 (1)SLE患者血浆D-二聚体水平较正常组显著增高(P＜0.001);治疗后血浆D-二聚体水平较治疗前明显降低(P＜0.05);(2)血浆D-二聚体水平与SLE DAI得分呈显著正相关(r=0.451,P＜0.01);(3)血浆D-二聚体水平在初发患者中明显高于复发者(P＜0.01),合并浆膜炎、白细胞降低及栓塞的患者分别显著高于无浆膜炎、白细胞正常及无栓塞的患者(均P＜0.01);(4)抗心磷脂抗体阳性、抗dsDNA抗体阳性患者的血浆D-二聚体水平高于抗心磷脂抗体阴性、抗dsDNA抗体阴性者(分别为P＜0.01,P＜0.05);(5)SLE患者血浆D-二聚体水平与血沉呈正相关(r=0.428,P＜0.001),与补体C3水平呈负相关(r=-0.275,P＜0.05).结论 SLE患者血浆D-二聚体检测有助于SLE疾病活动性和临床疗效的评估.