治疗性单克隆抗体药动学相互作用的风险评估策略

生物制剂可用于治疗各种疾病,包括肿瘤、风湿、胃肠道疾病、皮肤科疾病、呼吸道疾病、激素缺乏症和感染。尽管近来批准了很多生物制品,但有关其药物间相互作用临床研究还不多。单克隆抗体是最主要的一类治疗性生物制品,本文介绍评价其药物间相互作用的风险评估策略,指出了评估中的关键因素,并建议将相互作用风险评估作为治疗性生物制品综合药物开发的一部分。     

Factors associated with delivery complications in rural Bangladesh

Objectives There are only a few studies on maternal morbidity, delivery complications and maternal mortality in Bangladesh. This study analyzes data from a follow-up study conducted by the Bangladesh Institute of Research for Health and Technologies (BIRPERHT) on maternal morbidity in rural Bangladesh in 1993. Methods A total of 1020 pregnant women were interviewed in the follow-up component of the study. The survey collected information on socioeconomic and demographic characteristics, pregnancy-related care and practice, morbidity during the period of follow-up as well as in the past, information concerning complications at the time of delivery and during the postpartum period. For the purpose of this study, we selected 993 pregnant women with at least one antenatal follow-up. Both bivariate and multivariate analyses were conducted to identify the potential risk factors for complication during delivery and duration of labor. Results and conclusions It appears that complications during the antenatal period can result in various complications at the time of delivery. Some of the important findings are: hemorrhage during the antenatal period increases the risk of excessive hemorrhage during delivery, the risk of obstructed labor increases significantly if abdominal pain is observed during the antenatal period, prolonged labor appears to be significantly higher for the first pregnancy, and pregnancies suffering from abdominal pain during pregnancy tend to have a higher risk of prolonged labor during delivery. The duration of labor appears to be negatively associated with the number of previous pregnancies, being longest for the first pregnancies. The duration of labor pain is significantly higher for the respondents who reported the index pregnancy as undesired, and, similarly, the respondents who were reported to be involved with gainful employment would have a shorter duration of labor pain than those having no involvement with gainful employment.     

雷公藤红素对IL-1和IL-2活性及PGE2释放的抑制作用

雷公藤红素0.1～1.0μg/ml在试管内能降低LPS诱导的小鼠腹腔巨噬细胞外和细胞内白细胞介素-1(IL-1)的活性,也能抑制ConA诱导的小鼠脾细胞产生白细胞介素-2(IL-2).动态观察表明,雷公藤红素经预处理8h和3h后已能分别抑制IL-1和IL-2的产生。此外,雷公藤红素能降低A23187刺激家兔滑膜细胞释放前列腺素E₂(PGE₂)。     

Randomized phase II trial of gemcitabine and either day 1 or day 8 carboplatin for advanced non‐small‐cell lung cancer: Is thrombocytopenia predictable?

Aim:   Two 21-day gemcitabine–carboplatin schedules were evaluated in patients with advanced non-small cell lung cancer in order to assess the effect of timing of the carboplatin dose on toxicity and efficacy.
Methods:   Patients were randomized to gemcitabine (1000 mg/m² on days 1 and 8 of a 21-day cycle) and carboplatin (AUC 5, on day 1) (Carbo d1 arm) or the same gemcitabine schedule with carboplatin given on day 8 (Carbo d8 arm). Twenty patients with Stage IIIB or IV non-small-cell lung cancer were enrolled in each arm.
Results:   The achieved dose intensities of both gemcitabine and carboplatin were significantly higher in the Carbo d1 arm. The total rates of grade 3 or 4 hematological and non-hematological toxicities (any toxicity, any cycle) were 80% and 65%, respectively, with no significant differences between the two arms. Nine patients in the Carbo d1 arm, but only one patient in the Carbo d8 arm, required a platelet transfusion. There were 10 partial responses (four Carbo d1 arm, six Carbo d8 arm), giving an overall response rate of 25% (95% CI 13–41%).
Conclusion:   Administration of carboplatin on day 8 of this regimen confers no clear advantage compared with day 1 carboplatin, with similar toxicity but lower dose intensity. A formula for the prediction of thrombocytopenia is proposed.     

Infectious disease complications of simultaneous pancreas kidney transplantation

BACKGROUND: Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. METHODS: We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. RESULTS: Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). CONCLUSIONS: Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.      

A field trial of wheat-based oral rehydration solution among Afghan refugee children

A total of 326 Afghan children aged between 6 months and 5 years with uncomplicated nondysenteric diarrhea for the previous 24 h to 5 days were treated at home by their mothers with either wheat-salt solution (WSS) or World Health Organization recommended glucose-oral rehydration salts (G-ORS). For 7 consecutive days the children were examined in the household and the mothers interviewed to assess the progress, feeding practices, and perception of treatment efficacy. Children treated with WSS recovered significantly earlier; the mean duration on treatment was 4.0 days (SD 1.7 days) on WSS compared to 6.4 days (SD 1.7 days) on G-ORS. By the second day of treatment, significantly more mothers using WSS (56%) reported that their children had formed stools versus 11 % of their G-ORS counterparts; the mean stool frequency after 2 days was also significantly reduced; 3 stools day⁻¹ (SD 2.1) on WSS versus 5 (SD 2.9) on G-ORS. The cereal-based solution was not confused with normal food and led to better feeding patterns. By day 2, 74% of the mothers using WSS had resumed their normal feeding frequencies as opposed to 33% of G-ORS mothers. On recovery the WSS group had gained significantly more weight; the WSS group gained 169 g (SD 142 g) while the G-ORS group lost 150g (SD 174 g). This study suggests by subjective and objective measures that WSS could be considered as an effective home fluid for the first-line treatment of diarrhea.     

强痛宁中延胡索乙素的质量标准研究

用薄层扫描色谱法测定了复方中药制剂中延胡索乙素的含量,方法回收率为102.2％±1.85％,在0.51～4.6μg范围内呈良好的线性关系,并用薄层色谱法对本品中的冰片进行了鉴别。     

Granulocytic sarcoma (chloroma): CT manifestations

Nests of granulocytic tumor cells in patients who have myelogenous leukemia are termed chloromas. Eight cases of chloroma seen on CT were reviewed. Lymph nodes, subcutaneous tissues, peritoneum, pleural space, pelvis, and portal hepatis were involved. Two patients exhibited chloroma as the sole manifestation of their disease during bone marrow remission. The extracranial appearance of chloroma on CT is that of small, nonenhancing, nodular densities that resemble lymphoma. Cranial involvement is characteristically in the orbit. The central nervous system appearance is variable, however, and high attenuation masses may occur that mimic lymphoma, hematoma, and metastatic neuroblastoma. The recognition of these lesions is important, since radiation, not chemotherapy, is often the preferred treatment for localized chloroma.     

The beta-globin gene on the Chinese delta beta-thalassemia chromosome carries a promoter mutation

A new type of delta beta-thalassemia characterized by decreased expression of the beta-globin gene and increased expression of both G gamma and A gamma globin gene in the absence of a detectable deletion has recently been described in the Chinese population. In this study we characterize the mutant beta-globin gene from this delta beta- thalassemia chromosome. An A to G transversion is identified in the "ATA" sequence of the promoter region that leads to decreased expression of the beta-globin gene in vivo and in vitro. We also demonstrate the presence of this mutation in every individual with a high fetal hemoglobin phenotype in this family and its absence in every individual with a normal hemoglobin phenotype. This same promoter mutation has recently been detected in Chinese beta-thalassemia genes where it is present on chromosomes of the same haplotype as that of the delta beta-thalassemia chromosome we are studying. These data support the hypothesis that an as yet unidentified mutation occurred on the ancestral chromosome carrying the promoter mutation and subsequently gave rise to the delta beta-thalassemia phenotype.