头孢克肟胶囊人体药动学研究及生物等效性评价

目的：研究头孢克肟胶囊在健康人体内的药动学及生物等效性。方法：以18名健康志愿者为试验对象，采用同体交叉试验方法，分别单剂量口服受试制剂或参比制剂各400mg，采用HPLC法测定血浆中药物浓度。结果：参比制剂和受试制剂的tmax分别为（3．39±0．50）和（3．39±0．50）h，cmax分别为（2．33±0．33）和（2．27±0．25）μg／mL，t1／2分别为（3．92±0．85）和（4．41±0．68）h，AUC0～16分别为（14．61±2．67）和（14．82±2．02）μg·h·mL^-1，AUC0～∞分别为（16．00±3．13）和（16．81±2．62）μg·h·mL^-1。结论：受试制剂与参比制剂生物等效，受试制剂的相对生物利用度为（98．69±13．13）％。     

Atlanto-axial rotatory fixation: Improved demonstration using spiral CT

Atlanto-axial rotatory fixation (AARF) is an uncommon condition which is often missed at presentation because of its rarity and the relative subtlety of plain film X-ray findings, but early detection and appropriate management are vital for a cure. We describe three cases in which the use of spiral computed tomography scanning with 3D and sagittal reconstructions greatly aided diagnosis and management. The 3D images gave a more graphic picture of the overall alignment of the upper cervical spine and the skull base, while the sagittal reconstructions demonstrated the presence or absence of compensatory atlanto-occipital subluxation. The literature is briefly reviewed.     

Phenotypic variation and detection of carrier status in the partial androgen insensitivity syndrome

The partial androgen insensitivity syndrome occurs in 46,XY subjects with phenotypes ranging from perineoscrotal hypospadias with cryptorchidism and micropenis (mild undervirilisation) to clitoromegaly and partial labial fusion (marked undervirilisation). Within an affected family, wide variation in the degree of genital ambiguity between individuals can be seen. Two cousins of a previously reported subject who had severe genital ambiguity and partial androgen insensitivity were investigated. Neither of the cousins had genital abnormalities as marked as the index case, who also had qualitatively abnormal androgen binding and two mutations of the androgen receptor gene. Despite marked phenotypic differences between the index case and his cousins, similar androgen binding and the same androgen receptor mutations were shown in the cousins. Furthermore, one of the androgen receptor gene mutations has been shown in the mother and sister of one of the boys indicating that they are carriers. Thus phenotypic variation in families affected by partial androgen insensitivity is dependent on factors other than abnormalities of the androgen receptor gene alone. Although carrier status in partial androgen insensitivity can be determined, the severity of genital abnormalities in an affected offspring cannot be reliably predicted.     

大鼠实验性急性胰腺炎时血浆和组织脂质过氧化物的变化

本文观察了大鼠实验性急性胰腺炎时血浆和组织脂质过氧化物(LPO)的动态变化。发病后10h动物血浆LPO即见升高,而血浆淀粉酶水平则开始下降。发病10、20h心、肝、肾、肺组织LPO也有不同程度的升高。这证实了氧自由基在急性胰腺炎病理过程中起一定作用。与用血清淀粉酶水平判断急性胰腺炎的发生、发展这一传统方法相比,血浆LPO更能反映急性胰腺炎后期病变的程度及此时全身器官组织受损的情况。     

Infradiaphragmatic versus supradiaphragmatic Hodgkin lymphoma: a retrospective review of 1,114 patients

Infradiaphragmatic Hodgkin lymphoma (IDH) accounts for 4-13% of cases of stage I-II Hodgkin lymphoma (HD). It has been associated with distinct pre-treatment characteristics and outcomes when compared with supradiaphragmatic HD (SDH). The comparison of IDH vs SDH can only be made in early and intermediate stages (I-II), such a comparison is not possible for advanced stages (III-IV). This study retrospectively compared two groups of 1013 patients with stage I-II SDH and 101 patients with IDH (10%). These two sub-groups of patients were treated in 1988-1993 in 2 prospective randomized clinical trials in Germany for early and intermediate stages of Hodgkin lymphoma. IDH-patients were older (median 39 vs 31 years; p < 0.001), predominantly male (73% vs 52%; p < 0.001) and more often had involvement of 3 lymph node areas (LNA) (80% vs 55%; p < 0.001). Histology in IDH was more likely to be mixed cellularity (46.5% vs 23.6%, p < 0.001) or lymphocyte predominant (20 vs 10%, p = 0.003) and less likely nodular sclerosis (25% vs 63%, p < 0.001). In early-stage unfavorable disease, IDH was associated with a higher treatment failure rate (unadjusted hazard ratio 2, 95% CI, 1.3-3.4; p = 0.003). After controlling for age, sex, stage, histology, B-symptoms and involvement of 3 LNA, the adjusted hazard ratio was 1.25 (95% CI, 0.65-2.4; p = 0.51) so that IDH was no longer associated with a statistically significant treatment failure rate. Poorer outcomes with IDH as compared to SDH are attributable to its association with known adverse prognostic risk factors, but IDH, in itself, is not an independent adverse prognostic factor for treatment failure or survival.     

Intragenic suppression of trafficking-defective KCNH2 channels associated with long QT syndrome

Mutations in the KCNH2 or human ether-a-go-go-related gene-encoded K(+) channel reduce functional KCNH2 current (I(KCNH2)) to cause long QT syndrome (LQT2) by multiple mechanisms, including defects in intracellular transport (trafficking). Trafficking-deficient, or class 2, LQT2 mutations reduce the Golgi processing and surface membrane expression of KCNH2 channel proteins. Drugs that associate with pore-S6 intracellular drug binding domain of KCNH2 channel proteins to cause high-affinity block of I(KCNH2) also can increase the processing of class 2 LQT2 channel proteins through the secretory pathway. We used a strategy of intragenic suppression to test the hypothesis that amino acid substitutions in the putative drug binding domain at residue Y652 could compensate for protein folding abnormalities caused by class 2 LQT2 mutations. We found that the Y652C substitution, and to lesser extent the Y652S substitution, resulted in intragenic suppression of the class 2 LQT2 G601S phenotype; these substitutions increased Golgi processing of G601S channel proteins. The Y652C substitution also caused intragenic suppression of the class 2 LQT2 V612L and F640V phenotypes but not the LQT2 N470D or F805C phenotypes. These are the first findings to demonstrate that a single amino acid substitution in the putative KCNH2 drug binding domain can cause intragenic suppression of several LQT2 mutations.