5-氟尿嘧啶缓释剂瘤内注射治疗胰腺癌的实验研究

目的:观察5FU缓释剂瘤内注射对裸鼠胰腺癌肿瘤细胞的影响,探讨其作用机制。方法:体外培养胰腺癌细胞株PC3,以2×106个细胞分别接种于70只裸鼠。4周后挑选肿瘤大小一致的裸鼠60只,随机分成5组,即静脉NS对照组、5FU静注组(10mg/kg)、基质植入组、5FU缓释剂(4mg/kg)植入组及5FU缓释剂(1mg/kg)植入组。于治疗前及治疗后14d内测量肿瘤大小,计算肿瘤生长速度;观察组织学变化和细胞分裂指数;免疫组化法测定bcl2和Bax的蛋白表达水平;采用脱氧核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测凋亡指数(AI)。结果:5FU缓释剂瘤内注射组裸鼠移植瘤生长速度减慢(P<0.05),最终瘤重小于其他各组(P<0.05);细胞分裂指数亦均低于其他各组(P<0.05)。5FU缓释剂瘤内注射组肿瘤组织中炎症反应和血管内膜增厚程度明显高于其他各组(P<0.05)。5FU缓释剂瘤内注射组荷瘤裸鼠的bcl2基因蛋白表达明显低于其他各组,而Bax基因的蛋白表达明显高于其他各组,其肿瘤细胞的AI明显高于其他各组(P<0.05)。结论:5FU缓释剂瘤内注射可明显抑制裸鼠胰腺癌瘤体的生长,其作用机制与药物在肿瘤组织中引起的炎症反应和血管内膜增厚等因素有关,并可能与诱导肿瘤细胞的凋亡有关。     

The -141C Ins/Del and Taq1A polymorphism in the dopamine D2 receptor gene may confer susceptibility to schizophrenia in Asian populations

It has been reported that two single nucleotide polymorphisms (SNP) Taq1A and -141C Ins/Del in the DRD2 gene may be associated with susceptibility to schizophrenia. Due to inconclusive and mixed results, a meta-analysis was conducted to further clarify the relationship between the two SNP and schizophrenia susceptibility. A systematic literature search for the association of these two SNP with schizophrenia susceptibility was conducted using PubMed, ScienceDirect, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the associations reported. A total of 5558 schizophrenic patients and 6792 healthy controls from 31 articles were included in this study. Evidence regarding the association between -141C Ins/Del polymorphism and schizophrenia was found in the allele frequency comparison (Ins versus Del: OR 1.29, 95% CI 1.06–1.57; p = 0.01, P_raw = 0.1, P_{False Discovery Rate} = 0.023). In ethnic subgroup analysis, the result revealed that the 141C Ins/Del polymorphism was associated with schizophrenia in all genetic models in Asians, but not in Caucasians. For Taq1A polymorphism, a significant association was found in the allele frequency (A1 versus A2: OR 0.71, 95% CI 0.52–0.98, p = 0.03). Stratification by ethnicity indicated an association between the Taq1A polymorphism and schizophrenia in Asians, but not Caucasians. The present study suggests that the -141C Ins/Del polymorphism carries a significantly increased risk of schizophrenia, while the Taq1A polymorphism carries a significantly decreased risk of schizophrenia susceptibility in Asians.     

SH-SY5Y神经细胞中α7神经型尼古丁受体基因过表达对CaMK Ⅱ和CREB的影响

目的研究SH-SY5Y神经细胞中α7 nAChR基因过表达对CaMKⅡ和CREB的影响。方法复苏稳定转染α7 nAChR-pc DNA3.1质粒及空载质粒的SH-SY5Y神经细胞后,用含G418的培养液进行筛选培养;应用实时荧光定量PCR法和蛋白印迹法(Western blot)检测α7 nAChR基因过表达组、空载质粒组和正常对照组细胞中CaMKⅡ、CREB mRNA及蛋白表达水平的变化。结果与对照组相比,α7 nAChR基因过表达细胞组的CaMKⅡ、CREB mRNA表达水平分别增加了116.8%和114.7%(P0.01);及CaMKⅡ、CREB蛋白表达水平分别增加了8.7%(P0.05)和41.4%(P0.05)。结论α7 nAChR的神经保护作用可能与上调细胞CaMKⅡ、CREB水平有关。     

Multidimensional anatomy of ‘modern type depression’ in Japan: A proposal for a different diagnostic approach to depression beyond the DSM‐5

Japan's prototype of depression was traditionally a melancholic depression based on the premorbid personality known as shūchaku‐kishitsu proposed by Mitsuzo Shimoda in the 1930s. However, since around 2000, a novel form of depression has emerged among Japanese youth. Called ‘modern type depression (MTD)’ by the mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives that begin to suggest that MTD is a phenomenon that may exist not only in Japan but also in many other countries with different sociocultural and historical backgrounds. It is therefore of interest to establish whether MTD is a culture‐specific phenomenon in Japan or a syndrome that can be classified using international diagnostic criteria as contained in the ICD or the DSM. We propose a novel diagnostic approach for depression that addresses MTD in order to combat the current confusion about depression under the present diagnostic systems.     

Survival following resection for colorectal cancer

The crude overall five-year survival rate for New Zealand patients with colorectal cancer treated surgically was 42 percent. Less than 50 percent of patients with Stage I and Stage II tumors survived ten years. Women survived longer after surgery than men. It was not possible to determine a biologic cure rate because postmortem data were not available. Read at the joint meeting of the American Society of Colon and Rectal Surgeons with the Section of Colo-Proctology, Royal Society of Medicine, and the Section of Colonic and Rectal Surgery, Royal Australasian College of Surgeons, New Orleans, Louisiana, May 6 to 11, 1984.     

Palliative dilation of esophageal carcinoma

The authors' experience with palliative dilation of 46 consecutive patients evaluated for squamous cell carcinoma of the esophagus was retrospectively reviewed. Thirty-nine of 46 patients (85%) underwent dilation in order to palliate symptoms, enable endoscopy and biopsy, or prepare for placement of an esophageal prosthesis. Thirty-two of the 46 patients (70%) were treated with radiation therapy and seven (15%) underwent placement of an esophageal prosthesis. Thirty-five of the 39 patients dilated (90%) noted improvement in swallowing, allowing resumption of a soft or regular diet. Complications were noted in three of the 39 patients dilated (8%). The authors conclude that peroral dilation is a safe, effective, and probably underutilized method of palliation in patients with squamous cell esophageal carcinoma.     

Dissociation of uterine eosinophilia and water imbibition from other estrogen-induced responses by nafoxidine pretreatment

We investigated the effect of pretreatment of immature rats with 5 or 50 micrograms nafoxidine (UA), or with 0.05 micrograms 17 beta-estradiol (E2) on several uterine responses elicited by treatment with a test injection of 15 micrograms E2, administered 48 h after pretreatment. Early (6 h) and late (24 h) responses were measured, including wet weight, RNA, protein and glycogen content and number of blood eosinophils per uterus. The results showed that, like a 24 h pretreatment with 5 micrograms UA, a 48 h pretreatment with either of the UA doses dissociated the early wet weight response from the late responses to E2 treatment, only the former being restored. In the case of E2 pretreatment, both types of response to E2 treatment were reinstalled. By contrast, uterine eosinophilia, induced 6 and 24 h after E2 treatment, was not only restored but even markedly amplified following any of the 3 pretreatments. This was obtained without amplification of the early wet weight response and with various levels of the other parameters at the time of administration of the test E2 injection (i.e. due to the pretreatment alone). From this it may be concluded that if the previously documented correlation between estrogen-induced eosinophilia and edema actually reflects the existence of a causal link between the 2 responses, as postulated by Tchernitchin in 1972, this would be with eosinophils controlling edema, rather than the reverse. Testable working hypotheses for the mechanism of amplification of the eosinophil response are proposed.     

Evaluation of dopaminergic tone in hyperprolactinemia. III. Thyroid-stimulating hormone response to metoclopramide in differential diagnosis and postoperative follow-up of prolactinoma patients

Recently, it has been shown that patients with a PRL-secreting pituitary adenoma have a greater thyroid stimulating hormone (TSH) release after dopamine (DA)-receptor blockade than normal subjects. We have compared the TSH and PRL responses to metoclopramide (MCP) in normal and postpartum lactating women with those in 28 patients with hyperprolactinemia of different origin. Patients with a PRL-secreting pituitary adenoma were also tested after transsphenoidal removal of the tumor in order to establish the prognostic value of this test in such patients. Following MCP administration, percent increases in plasma PRL levels were greater in normal female subjects than postpartum lactating women. Plasma TSH levels did not increase in postpartum women and had a modest increment in normal subjects. In patients with hypothalamic tumors and empty sella syndrome plasma PRL and TSH levels showed modest or no increases after MCP administration. In ten patients harboring a microprolactinoma, plasma TSH levels showed an exaggerated increment after DA-receptor blockade. Postoperatively, despite normal or borderline PRL levels in the immediate postoperative period, a TSH response to MCP was present (in five patients one to two weeks after the operation, and in five patients one to three years after the operation), suggesting an increased DA activity even in the absence of hyperprolactinemia. In conclusion, the TSH test can easily detect increased DA-activity in patients with a microprolactinoma both preoperatively and postoperatively. It is possible that some patients with increased DA-activity in presence of normal PRL levels and normal PRL responsiveness to stimulation will experience a recurrence of hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis and classification of atrial septal aneurysm by two-dimensional echocardiography: report of 80 consecutive cases

Atrial septal aneurysms have been related (either by association or as potential causes) to systolic clicks, atrial arrhythmias, systemic and pulmonary embolism, atrioventricular valve prolapse and atrial septal defect. To study these associations and the incidence of atrial septal aneurysm, we reviewed 80 consecutive patients (female to male ratio 1.9:1, mean age 47 years, range 1 day to 89 years) who had been identified prospectively as having an atrial septal aneurysm. These were found in 36,200 two-dimensional echocardiographic studies (incidence: 0.22% overall; 0.29% in the last year of the study done between 1978 and 1984). Three types of fossa ovalis aneurysm and one type of aneurysm involving the entire atrial septum were observed; a fossa ovalis aneurysm with leftward projection and excursion of less than 5 mm or an aneurysm involving the entire atrial septum with rightward projection was not observed. Atrial septal aneurysm occurred more often as an isolated abnormality than in association with other cardiac malformations, although all patients with an aneurysm involving the entire atrial septum had complex congenital cardiac anomalies of the hypoplastic right heart type. The reported associations between atrial septal aneurysms and atrial septal defect, atrioventricular valve prolapse, midsystolic clicks, atrial arrhythmias and cerebral ischemic events were examined. A hypothesis based on interatrial pressure gradients is proposed to explain the different motions and configurational characteristics of fossa ovalis aneurysms observed in these patients. All patients in whom atrial septal aneurysm is demonstrated should undergo examination for atrial septal defect. Atrial septal aneurysm should be specifically looked for in patients who have these associations and who undergo two-dimensional echocardiography, especially if these abnormalities are unexplained.     

Failure of the urinalysis and quantitative urine culture in diagnosing symptomatic urinary tract infections in patients with long-term urinary catheters

Since urine culture and urinalysis are both of uncertain reliability in diagnosing symptomatic urinary tract infections in patients with chronic urinary catheters, we performed sequential quantitative cultures and urinalyses on 177 urine specimens from 14 patients with long-term urinary catheters during a 12-month period. We found high concentrations of greater than or equal to 2 species of aerobic bacteria or fungi in most specimens examined. Pyuria was common even during asymptomatic periods; hematuria was less common. During symptomatic urinary tract infections, neither urinalyses nor quantitative urine cultures exhibited changes specific for such infections. Thus neither urinalysis nor urine culture appears to be a reliable test for symptomatic urinary tract infections in patients with chronic urinary catheters.