Acute endosulfan poisoning with cerebral edema and cardiac failure

BACKGROUND: Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide with several deaths. Despite their widespread use in agriculture during the 1940s to 1960s and the well-known signs and symptoms of intoxication, the clinical picture in case of poisoning varies. We report two cases of acute intentional endosulfan intoxication with cerebral edema and cardiac failure. CASE REPORTS: Both cases developed life-threatening signs like epileptic state, respiratory insufficiency and hemodynamic instability soon after ingestion. The survivor developed severe myocardial insufficiency and pulmonary edema documented by echocardiography and x-ray of the chest. The deceased patient developed severe cerebral edema and multiorgan failure ten days after ingestion of Thiodan 35. The peak serum concentration of endosulfan in the survivor was 0.12 mg/L approximately 23 hours after ingestion, whereas the peak blood concentration in the fatal case was 0.86 mg/L approximately 25 hours post-ingestion. Post-mortem endosulfan levels in different organs were determined. CONCLUSION: Endosulfan is a highly toxic organochlorine insecticide that produces well-known neurological symptoms of tonic-clonic convulsions, headache, dizziness and ataxia but also can cause gastrointestinal symptoms and metabolic disturbances. Life-threatening cerebral edema and hemodynamic instability may occur. Treatment is symptomatic and supportive.     

Acute zolpidem overdose--report of two cases.

This report describes two cases of acute zolpidem overdose. The decedent in the first case was a 36-year-old female found dead in bed in her secured home. She had a history of psychiatric illness, including paranoid disorder, depression with panic episodes, and post-traumatic stress disorder. She was treated with risperidone and sertraline. Nine months prior to her death, the decedent was also prescribed zolpidem (Ambien). The postmortem examination revealed white foam within the larynx and upper trachea, which is indicative of pulmonary edema. Toxicological analyses of the urine showed the presence of caffeine, risperidone, and zolpidem. Subsequent quantitation of postmortem iliac serum revealed 5.6 microg/L of 9-hydroxyrisperidone and the following zolpidem concentrations: blood (subclavian), 4.5 mg/L; blood (iliac), 7.7 mg/L; vitreous humor, 1.6 mg/L; bile, 8.9 mg/L; urine, 1.2 mg/L; liver, 22.6 mg/kg; and gastric contents, 42 mg. The second case involved a 58-year old female, also found dead in bed, with white foam around her mouth. The decedent had a 25-year history of hypertension and mental illness--manic depression and schizophrenia. She was medicated with carbamazepine, naproxen, risperidone, and zolpidem. The postmortem examination revealed cardiomegaly, pulmonary edema, hepatomegaly, mild coronary atherosclerosis, and no signs of trauma. Toxicological analyses of the urine showed the presence of zolpidem and carbamazepine and metabolite. Zolpidem concentrations were as follows: blood (iliac), 1.6 mg/L; vitreous humor, 0.52 mg/L; bile, 2.6 mg/L; liver, 12 mg/kg; and gastric contents, 0.9 mg. The zolpidem blood concentrations of these cases are consistent with those of the previously published fatalities. The blood/vitreous humor ratios of zolpidem were 2.81 (subclavian) and 4.81 (iliac) in the first case and 3.08 (iliac) in the second case. These ratios, along with the sampling times of blood and vitreous humor for both cases, are not conclusive to indicate a definitive presence or absence of postmortem drug redistribution of zolpidem. The cause of death for both cases was determined to be acute zolpidem overdose, and manner of death was suicide.     

胺碘酮相关肺间质纤维化

1例73岁男性患者,因心房颤动给予胺碘酮治疗。800mg/d静脉滴注1周后,改为口服600mg/d1个月、400mg/d2个月、200mg/d3个月。用药6个月后患者出现干咳、气促。肺CT示双肺呈间质性改变。实验室检查示：WBC22.68×10^9/L,N0.76,BUN11.20mmol/L,SCr182μmol/L。pH值7.36,PO235mmHg,PCO249mmHg,SaO264%。考虑为胺碘酮所致肺间质纤维化合并感染。给予面罩吸氧,左氧氟沙星0.5g静脉滴注,1次/d,头孢哌酮-舒巴坦3.0g静脉滴注,2次/d;甲泼尼龙40mg静脉滴注,2次/d及乙酰半胱氨酸0.6g,口服2次/d。治疗第14天患者肺弥散功能严重下降,重度低氧血症（SaO2曾降至50%以下）;BUN18.90mmol/L,SCr286μmol/L,尿量200mL/d以下。入院第21天检查示BUN24.10mmol/L,SCr357μmol/L。患者血压明显下降伴频发心房颤动,终因多脏器衰竭和肺部感染死亡。     

Dietary Pyridoxine Protects against Stress and Maintains Immunohaematological Status in Chanos chanos Exposed to Endosulfan

The amelioration effect of water‐soluble vitamin pyridoxine against stress was evaluated in milkfish, Chanos chanos exposed to endosulfan. Two hundred and twenty‐five fish were distributed randomly into five treatments, each with three replicates. Four isocaloric and isonitrogenous diets with graded levels of pyridoxine feed were as follows: normal water and fed with control diet (En0/PY0); endosulfan‐treated water and fed with control diet (En/PY0); and endosulfan‐treated water and fed with 50 (En/PY 50 mg/kg), 75 (En/PY 75 mg/kg) and 100 mg/kg (En/PY 100 mg/kg) pyridoxine‐supplemented feed. The endosulfan in treated water was maintained at a level of 1/40th of LC₅₀ (0.52 ppb). The effect of dietary pyridoxine supplementation was studied in terms of antioxidative enzymes (catalase, superoxide dismutase, glutathione‐S‐transferase), stress markers [heat‐shock protein 70, caspase‐3, cortisol, acetylcholine esterase (AChE), blood glucose], immunohaematological parameters (total protein, albumin, globulin and A/G ratio, nitroblue tetrazolium, RBC, WBC, Hb), gill histopathology and a subsequent challenge study with Vibrio parahaemolyticus. The antioxidative enzymes, stress markers, albumin and A/G ratio were significantly (p < 0.01) elevated, brain AChE and immunohaematological parameters were significantly (p < 0.01) decreased, and chromosome aberration and gill histopathology were also altered due to endosulfan exposure. The relative survival % was reduced due to the combined effect of endosulfan stress and bacterial challenge. Fish fed the diet supplemented with pyridoxine at 75 and 100 mg/kg was found to restore the studied parameter towards normal compared with control and indicated protection against endosulfan‐induced stress significantly (p < 0.01). Results obtained in the present study indicate that the supplementation of 75 and 100 mg/kg of pyridoxine in the diet has a definitive role in the mitigation of the endosulfan‐induced stress in milkfish, C. chanos fingerlings.     

Protective effects of allozyme genotype during chemical exposure in the grass shrimp, Palaemonetes pugio

The primary objective of this research was to determine if the genotype of the enzymes glucose phosphate isomerase (Gpi), phosphoglucomutase (Pgm), or mannose phosphate isomerase (Mpi) are factors affecting survival during acute endosulfan, fluoranthene, and chromium(VI) exposures. Palaemonetes pugio were exposed in the laboratory to 6.3 microg/L endosulfan, 100 mg/L chromium(VI), or 0.6 mg/L fluoranthene. Dead shrimp were removed at approximately 15-30 min intervals and the individual's genotypes for the Gpi, Mpi, and Pgm enzymes were determined. These data were used to establish whether allozyme genotype was related to tolerance as analyzed with non-parametric methods (i.e. development of survival curves using the Kaplan-Meier method of estimation) and parametric methods (i.e. proportional hazards models). Since the sex and/or size of the organism was expected to affect tolerance, these variables were accounted for in the proportional hazards models. Results indicated individuals that were heterozygous (MF) for the Gpi allozyme survived longer and had less overall mortality than the homozygous MM genotype when exposed to chromium(VI) and to fluoranthene. No allozyme genotypes were related to tolerance during the endosulfan exposure when sex was included as a covariate in the analysis. These results support the hypothesis that there is a genetic basis for tolerance in P. pugio during acute exposures to chromium(VI) and to fluoranthene. Although a relationship between Gpi genotype and contaminant tolerance has been identified in previous studies, no such relationship has been documented in P. pugio or with chromium(VI) as the contaminant.     

Environmentally relevant concentrations of endosulfan impair development, metamorphosis and behaviour in Bufo bufo tadpoles

Endosulfan is a widely used organochlorine pesticide with well-documented neurotoxic effects in both humans and laboratory animals (mammals and fish). Neurotoxicity has been implied also in amphibians after short-term exposure to endosulfan. Little is known about effects of chronic exposure of endosulfan in amphibians. Previously, we examined the short-term toxicity of endosulfan in common toad (Bufo bufo) tadpoles and determined the LC50 value to 0.43 mg/L. In the present study, we investigated the effects of endosulfan on B. bufo tadpoles after chronic exposure to ecologically relevant concentrations. Tadpoles were exposed in a static renewal test, from shortly after hatching (Gosner stage 25) to completed metamorphosis, to 0.01, 0.05 and 0.1mg endosulfan/L (nominal). The exposure period lasted 43-52 days. Mortality, larval growth (mass), development (reached Gosner stage at various times and deformities presence), metamorphosis and behaviour (swimming activity) were monitored regularly over the entire course of larval development. Our results show that 0.05 and 0.1mg endosulfan/L caused impaired behaviour, prolonged time to metamorphosis, increased incidences of mouth and skeletal malformations as well as mortality, and reduced body weight (observed also at 0.01 mg/L) in B. bufo tadpoles. Behavioural effects occurred at exposure day 4, before any other effects occurred, indicating a neurotoxic effect. Endosulfan levels found in groundwater and surface water range from 0.1 to 100 microg/L and after extraordinary runoff events, concentrations exceed 0.5 mg/L in surface water. Our results indicate that endosulfan may negatively affect wild frog populations in agricultural areas.     

Effects of combinations of endosulfan, dimethoate and carbaryl on immune and hematological parameters of rats.

IgG and IgM levels and hematological parameters (red and white blood cell counts, thrombocyte, monocyte, lymphocyte and granulocyte counts and hemoglobin concentrations) were determined in albino rats exposed to combinations of endosulfan, dimethoate and carbaryl. Two and 3 combinations of 100- and 1000-fold acceptable daily intake (ADI) of endosulfan (ADI = 0.00612 mg/kg), dimethoate (ADI = 0.0204 mg/kg) and carbaryl (ADI = 0.0101 mg/kg) were administered po to male albino rats for 3.5 mo. Animals were immunized s.c. with tetanus toxoid in Freund's complete adjuvant 20 d before terminating exposures. At 100-fold ADI dosing, administration of each of the pesticides alone did not cause any difference in the parameters, but numbers of white blood cells and monocytes increased in rats given endosulfan + dimethoate while numbers of red blood cells increased with dimethoate + carbaryl. Rats given 1000-fold ADI endosulfan + dimethoate + carbaryl had significant differences in almost every parameter, while IgG, IgM white blood cells and lymphocytes decreased, and monocytes and % granulocytes increased from single endosulfan dosing. Lymphocyte counts were reduced by single dimethoate or carbaryl dosing. Endosulfan + dimethoate + carbaryl produced the most effective changes in comparison to single dosing or other pesticide combinations.     

Metaxalone (Skelaxin)-related death

The case history and toxicological findings of a fatal multi-drug overdose involving metaxalone (Skelaxin) are presented. Gas-liquid chromatography with flame-ionization detection and gas chromatography-mass spectrometry were used to determine the following drug concentrations (mg/L) in aortic blood: 19 mg/L metaxalone; 190 mg/L acetaminophen; 0.28 mg/L hydrocodone; and < 0.1 mg/L diazepam, nordiazepam, amitriptyline, and nortriptyline. The following concentrations of metaxalone were reported in alternate specimens: 17 mg/L in femoral blood; 44 mg/L in bile; 70 mg/kg in liver; 7 mg/L in urine; 202 mg/kg in gastric contents; and 14 mg/L in vitreous humor. These concentrations were determined using both direct extraction and the method of standard addition. The quantitative results obtained by both procedures were in good agreement. Because of the limited information published on metaxalone toxicity, the pathologist assigned the manner and cause of death as accidental acute hydrocodone intoxication. Four additional cases in which metaxalone was present were analyzed for comparison. Two cases were probable drug-related deaths and had metaxalone aorta blood concentrations of 18 and 11 mg/L. The other two cases had therapeutic metaxalone concentrations in the aortic blood of < 0.75 and 2.1 mg/L.     

痰热清注射液治疗慢性阻塞性肺疾病急性加重期患者的临床疗效与机制分析

目的 探讨痰热清注射液治疗慢性阻塞性肺疾病急性加重期患者临床疗效与机制.方法 180例慢性阻塞性肺疾病急性加重期患者,以信封法随机分为研究组与对照组,每组90例.对照组患者按照2011年中华医学会呼吸病学分会制定的《慢性阻塞性肺疾病诊疗指南》给予规范处理,研究组患者在对照组治疗基础上给予痰热清注射液治疗.比较两组患者治...     

老年慢阻肺急性加重期应用C反应蛋白与降钙素原作为预后评价标志物的意义

目的探讨老年慢性阻塞性肺疾病（慢阻肺）急性加重期应用C反应蛋白与降钙素原作为预后评价标志物的意义。方法选取100例老年慢阻肺急性加重期患者和100例稳定期患者,测定患者血清中C反应蛋白（CRP）与降钙素原（PCT）的含量,并通过对应的FEV1/FVC值与FEV1%值分析患者肺功能和对应的死亡率变化。结果急性加重期组和感染组患者CRP浓度（分别为57.6±12.2和77.6±15.9 mg/L）与PCT浓度（分别为1.06±0.32和1.57±0.36μg/L）明显高于稳定期组和非感染组CRP（24.5±6.2和30.4±6.6 mg/L）和PCT（0.15±0.06和0.25±0.08μg/L）,相比较差异具有统计学意义（P〈0.001）;急性加重期组和感染组患者死亡率也显著高于稳定期组和非感染组,肺功能明显差于稳定期组和非感染组。结论 C反应蛋白与降钙素原随着老年慢性肺阻塞肺疾病病情（肺功能和患者死亡率）的变化而发生变化,是一种老年慢性肺阻塞性肺疾病良好的预后评价标志物。     

Protective Role of Ascorbic Acid on Subacute Sperm Toxicity in Male New Zealand White Rabbits Treated with Endosulfan

The ameliorating effect of oral ascorbic acid (AA) was evaluated against changes in sperm parameters in New Zealand White (NZW) rabbits treated with endosulfan. Rabbits (6 to 8 months old) were divided into four groups of six animals each. Rabbits in TRT-I served as control and received corn oil by oral gavage for 6 weeks. Rabbits in TRT-II received endosulfan (1 mg/kg bw per day) in corn oil. TRT-III group received oral corn oil daily and ascorbic acid (AA; 20 mg/kg bw) every other day for 6 weeks. TRT-IV group received the same amounts of endosulfan and AA. Endosulfan alone significantly reduced the sperm count and motility and increased the presence of sperm with morphologic problems. AA treatment showed significant amelioration when coupled with endosulfan. Ameliorations were up to control levels in all cases except for sperm motility. The data suggested that AA has beneficial influences in neutralizing the toxic effects of endosulfan in the spermatologic parameters of NZW males.     

慢性阻塞性肺疾病患者继发肺动脉栓塞的Cox风险分析

目的　采用Cox风险比例模型探讨慢性阻塞性肺疾病（COPD）患者继发肺动脉栓塞（PE）的主要危险因素,为提高临床早期识别高危患者和早期干预提供参考依据。方法　选择2019年1月至2021年1月郴州市第一人民医院诊断COPD患者共245例,其中男143例,女102例,年龄（58.6±10.3）岁,随访时间11.0～22.5个月。采用CT肺动脉造影确诊继发PE共29例（11.84%）,记录确诊PE的时间;比较PE组和非PE组患者的一般临床资料、凝血指标、炎症指标和CT肺动脉定量参数,采用Cox分析影响继发PE的主要危险因素。计数资料采用χ²检验,计量资料采用独立样本t检验。结果　一般临床资料比较发现,PE组重症肺炎和心力衰竭比例升高、预防性抗凝治疗比例较低、COPD严重分级较高,差异均有统计学意义（均P<0.05）;凝血指标比较发现,PE组活化部分凝血活酶时间（APTT）缩短［（34.3±4.5）s比（41.6±4.8）s］、D-二聚体［（0.5±0.1）mg/L比（0.2±0.1）mg/L］和纤维蛋白原（FIB）［（4.2±0.4）g/L比（3.3±0.2）g/L］水平均升高（均P<0.05）;炎症指标比较发现,PE组血清高敏C反应蛋白（hs-CRP）［（9.8±1.3）mg/L比（6.5±1.1）mg/L］、白介素-6（IL-6）［（56.5±12.3）mg/L比（42.2±9.6）mg/L］和肿瘤坏死因子-α（TNF-α）［（35.6±8.7）mg/L比（22.4±6.5）mg/L］水平均升高（均P<0.05）;CT肺动脉定量参数比较,PE组肺动脉压力升高［（45.6±6.3）mmHg比（38.9±5.4）mmHg（1 mmHg=0.133 kPa）］、血流灌注速度降低［（21.8±4.7）cm/s比（32.4±5.2）cm/s］、肺气肿评分增加［（8.6±2.4）分比（4.5±1.3）分］（均P<0.05）。经Cox分析发现,未进行预防性抗凝治疗、COPD严重分级较高、D-二聚体水平升高、hs-CRP水平升高、血流灌注速度降低均是继发PE的主要危险因素（均P<0.05）。结论　临床中针对未进行预防性抗凝治疗、COPD严重分级较高、D-二聚体水平升高、hs-CRP水平升高、血流灌注速度降低的COPD患者应高度警惕继发PE的风险。     

Endosulfan acute toxicity in Bufo bufo gills: ultrastructural changes and nitric oxide synthase localization

Endosulfan is an organochlorine pesticide used in agriculture for a wide range of crops. Endosulfan concentrations of up to 0.7 mg/L can be found in ponds and streams near sprayed agricultural fields. We investigated the short-term toxicity of endosulfan in common toad (Bufo bufo) tadpoles after 24, 48, and 96 h of exposure. Acute toxicity was evaluated at nominal concentrations ranging from 0.01 to 0.6 mg/L: concentrations that could be found after the application of pesticide. Our results show that 0.43 mg/L of endosulfan caused 50% mortality (LC(50)). The effects of a sublethal endosulfan concentration (0.2mg/L) on gill apparatus morphology were evaluated by scanning and transmission electron microscopy. Immunohistochemical methods were also applied to detect the expression pattern of the inducible isoform of nitric oxide synthase (iNOS) in the gills using the confocal laser scanner microscope. Exposure to 0.2mg/L of endosulfan caused an apparent increase in mucus production, the occurrence of secretory vesicles and lamellar bodies, a widening of intercellular spaces and additionally there was evidence of an inflammatory response in the gill apparatus. The morphological alterations occurred after 24h and were more pronounced after 48 and 96 h of exposure. Altered morphology and increased mucus secretion indicate impaired gas exchange and osmoregulation in the gills. In addition, there was an increase of iNOS expression after 24 and 48 h which may reflect hypoxia and inflammation in the gill epithelium. Our results clearly indicate that short-term exposure to a sublethal concentration of endosulfan, near the high end of the environmental range, disrupts gill morphology and function in B. bufo tadpoles.     

Protective role of ascorbic acid on subacute sperm toxicity in male New Zealand white rabbits treated with endosulfan

The ameliorating effect of oral ascorbic acid (AA) was evaluated against changes in sperm parameters in New Zealand White (NZW) rabbits treated with endosulfan. Rabbits (6 to 8 months old) were divided into four groups of six animals each. Rabbits in TRT-I served as control and received corn oil by oral gavage for 6 weeks. Rabbits in TRT-II received endosulfan (1 mg/kg bw per day) in corn oil. TRT-III group received oral corn oil daily and ascorbic acid (AA; 20 mg/kg bw) every other day for 6 weeks. TRT-IV group received the same amounts of endosulfan and AA. Endosulfan alone significantly reduced the sperm count and motility and increased the presence of sperm with morphologic problems. AA treatment showed significant amelioration when coupled with endosulfan. Ameliorations were up to control levels in all cases except for sperm motility. The data suggested that AA has beneficial influences in neutralizing the toxic effects of endosulfan in the spermatologic parameters of NZW males.     

红细胞分布宽度、C-反应蛋白及肺泡表面活性蛋白-D水平对慢性阻塞性肺疾病病情变化的意义

目的 探讨红细胞分布宽度、C-反应蛋白(CRP)及肺泡表面活性蛋白-D水平在慢性阻塞性肺疾病(COPD)的变化及其意义.方法 选取COPD急性期病人60例,纳入COPD急性期组;选取同期COPD稳定期病人60例,纳入COPD稳定期组;另选健康人员60例,纳入健康对照组.比较三组红细胞分布宽度、CRP、白细胞计数、肺泡表面活性蛋白-D水平及COPD病人肺功能情况.结果 与健康对照组相比,COPD急性期组与COPD稳定期组病人红细胞分布宽度、白细胞计数、肺泡表面活性蛋白-D水平较高(P<0.05);与COPD稳定期组相比,COPD急性期组病人血清CRP、肺泡表面活性蛋白-D水平较高(P<0.05).与COPD稳定期组相比,COPD急性期组病人第1秒用力呼气容积与用力肺活量比值较低(P<0.001).结论 红细胞分布宽度、CRP及肺泡表面活性蛋白-D水平可用于评价慢性阻塞性肺疾病病人的病情变化,值得临床推广.     

胸腺肽α1在慢性阻塞性肺疾病稳定期的应用价值

目的 观察胸腺肽α1对慢性阻塞性肺疾病（COPD）稳定期患者的治疗效果.方法 60例慢性阻塞性肺疾病稳定期患者随机分为两组,两组均给予常规基础治疗,治疗组同时给予胸腺肽α1 1.6 mg皮下注射,隔日1次,连续4周,此后2次/周,持续5个月.两组患者均进行6个月随访观察,每2周门诊随访1次,进行临床病情评价,并于治疗前、治疗6个月后检查患者CD3、CD4和CD8水平.结果 治疗6个月后,治疗组患者发生急性加重次数和急性加重天数均明显低于对照组（均P＜0.01）,血清CD4及CD4/CD8比值均明显升高（均P＜0.01）.结论 胸腺肽α1通过增强患者细胞免疫功能,可有效预防慢性阻塞性肺疾病的急性加重.     

老年人不同类型脑梗死与血浆氧化型低密度脂蛋白、血糖、C-反应蛋白及白细胞介素6的关系

目的 探讨老年人急性脑梗死患者血浆氧化型低密度脂蛋白(OX-LDL)、血糖、C-反应蛋白(CRP)和白细胞介素6(IL-6)水平变化及与不同类型急性脑梗死的关系.方法 100例急性脑梗死患者(A组)及30例同期住院的非脑梗死健康患者(B组)行血浆OX-LDL、血糖、CRP、IL-6和颈动脉超声检查.并按低分子肝素试验TOAST病因分型标准分型,对不同类型脑梗死相关危险因素进行分析.结果 A组OXLDL、血糖、CRP和IL-6分别为(627.2±174.7) μg/L、(8.8±1.7) mmol/L、(107.5±19.4) mg/L、(79.5±12.1)ng/L,均高于B组的(506.1±152.4) μg/L、(6.9±1.5) mmol/L、(87.2±13.6)mg/L、(58.5±10.3) ng/L(t=2.74,3.18,2.61,2.91,均P＜0.05).结论 老年人急性脑梗死与血浆OX-LDL、血糖、CRP和IL-6含量升高有关,且血浆OX-LDL增高易发大动脉粥样硬化型脑梗死,血糖增高发生小动脉闭塞型脑梗死的可能性大.     

急性加重期慢性阻塞性肺疾病患者血清C 反应蛋白及降钙素原水平变化及意义

目的：探讨急性加重期慢性阻塞性肺疾病（COPD）患者血清C反应蛋白（CRP）及降钙素原（PCT）的变化及临床意义。方法纳入急性加重期COPD患者120例,同时按随机数字表法抽取COPD稳定期患者120例,所有受试者均给予相应的对症支持治疗,观察治疗前、治疗后1 d、7 d、14 d患者血清CRP与PCT水平变化。结果与治疗前相比,治疗后1 d、7 d、14 d急性加重期COPD患者血清 CRP[（12．32±6．59）mg／L、（9．05±3．31）mg／L、（7．31±2．31）mg／L、（4．45±1．54）mg／L]与PCT[（0．34±0．05）μg／L、（0．26±0．04）μg／L、（0．18±0．04）μg／L、（0．10±0．03）μg／L]水平呈下降趋势,不同时间点差异有统计学意义（均P＜0．05）;与稳定期患者相比,治疗前、治疗后1 d、7 d血清CRP与PCT水平均明显高,差异有统计学意义（均P＜0．05）;但治疗后14 d血清CRP与PCT水平差异无统计学意义（P＞0．05）。结论急性加重期COPD患者早期血清CRP及PCT水平明显增高,治疗后其水平明显下降,联合观察血清CRP及PCT水平可以更好地反映COPD急性加重期的炎性反应。     

Phase I Study of Irofulven (MGI 114), an Acylfulvene Illudin Analog, in Patients with Acute Leukemia

Irofulven (MGI 114, 6-hydroxymethylacylfulvene, HMAF)is a semisynthetic illudin analog with broad in vitroanti-neoplastic activity. In this leukemia phase I study, weinvestigated the toxicity profile and activity of Irofulven inpatients with primary refractory or relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), ormyelodysplastic syndromes (MDS). Irofulven was given as anintravenous infusion over five minutes daily for five days.The starting dose was 10 mg/m²/day (50mg/m²/course). Courses were scheduled to be givenevery 3-4 weeks according to toxicity and antileukemicefficacy. Twenty patients {AML: 17 patients; MDS: onepatient; ALL: one patient; mixed lineage acute leukemia: onepatient} were treated. Nausea, vomiting, hepatic dysfunction,weakness, renal dysfunction, and pulmonary edema were doselimiting toxicities, occurring in two of five patientstreated at 20 mg/m²/day and two of three patientstreated at 12.5 mg/m²/day. The MTD was defined as10 mg/m²/day for five days. One patient withprimary resistant AML achieved complete remission. Proposedphase II studies will further define the activity of Irofulvenin patients with better prognosis AML and in otherhematological malignancies, both as a single agent and incombination regimens, particularly with topoisomerase 1inhibitors.     

Cyclosporine-sparing effects of daclizumab in renal allograft recipients.

PURPOSE: The safety and efficacy of reduced-dose cyclosporine in renal transplantation were studied. METHODS: Patients receiving their first renal transplant received daclizumab 1 mg/kg every 14 days for a total of five doses, mycophenolate mofetil 1 g twice daily, corticosteroids per the institution's routine protocol, and half of the institution's usual cyclosporine dosage. Trough cyclosporine concentrations targeted were half the customary goals, or 150-200 ng/mL for the first six months and 125-175 ng/mL for months 7-12. A retrospective control group included 15 matched patients who had received full-dose cyclosporine, mycophenolate mofetil, and corticosteroids without daclizumab induction therapy. RESULTS: Thirty patients were studied (15 in each group). At baseline, the control group had a significantly lower panel reactive antibody level (0.13%) than the treatment group (5.2%) (p = 0.01). Mean cyclosporine concentrations at 1, 6, and 12 months were significantly lower in the treatment group (p < 0.0001). No patient in either group had an acute rejection episode. All control patients had cyclosporine-associated adverse effects, compared with seven treatment-group patients (p = 0.0022). The treatment group had 19 infections, versus 29 in the control group (p = 0.39). Three study-group patients and eight control patients required a fine-needle aspiration or biopsy (p = 0.13). CONCLUSION: Among kidney transplant patients at low risk of acute rejection, those treated with daclizumab and low-dose cyclosporine had an identical rate of acute rejection (none) and fewer cyclosporine-associated adverse effects compared with patients in a retrospective control group who received full-dose cyclosporine without daclizumab.