临床药理学讲座(3) 掌握药物相互作用的机理 实行合理的联合用药(续二)

2.3.3 相互作用影响药物的代谢 肝脏是药物代谢的重要器官,肝微粒体酶是代谢药物的酶系,亦称药物代谢酶,简称“药酶”。此种酶系的活动直接影响许多药物的代谢,而许多药物对药酶也会发生作用,其有两种作用方式。

Gastric malignancies in Northern Jordan with special emphasis on descriptive epidemiology

AIM:To study the epidemiology of gastric malignancies in Jordan as a model for Middle East countries where such data is scarce. METHODS:Pertinent epidemiological and clinicopathological data for 201 patients with gastric malignancy in north of Jordan between 1991 and 2001 were analyzed. RESULTS:Male:female ratio was 1.8:1.The mean age was 61.2 years,and 8.5% of the patients were younger than 40 years of age.The overall age-adjusted incidence was 5.82/100 000 population/year.The age specific incidence for males raised from 1.48 in those aged 30-39 years to 72.4 in those aged 70-79 years.Adenocarcinomas, gastric lymphomas,malignant stromal tumors,and carcinoids were found in 87.5%,8%,2.5%,and 2% respectively.There was an average of 10.1-month delay between the initial symptoms and the diagnosis.Only 82 patients underwent“curative”gastrectomy.Among adenocarcinoma groups,Lauren intestinal type was the commonest(72.2%)and the distal third was the most common localization(48.9%).The mean follow up for patients with gastric adenocarcinoma was 25.1 mo(range 1-132mo).The 5-year survival rates for stages Ⅰ(n=15), Ⅱ(n=41),Ⅲ(n=59),and Ⅳ(n=53) were 67.3%,41.3%, 5.7%,and 0% respectively(P=0.0001).The overall 5 year survival was 21.1%. CONCLUSION:Despite low inddence,some epidemiological features of gastric cancer in Jordan mimic those of high- risk areas.Patients are detected and treated after a relatively long delay.No justification in favor of a possible gastric cancer screening effort in Jordan is supported by our study;rather,the need of an earlier diagnosis and subsequent better care.

Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1,2 and 4 in colorectal adenocarcinoma:Immunohistochemical analysis and correlation with clinicopathological factors

AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class.Angiopoietin (Ang)-1 is known as a ligand ofTie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4expression profile in human colorectal adenocarcinomas.METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors.RESULTS: Among the 96 cases of adenocarcinoma, 87(90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells.CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.

Extremely well-differentiated adenocarcinoma of the stomach: Clinicopathological and immunohistochemical features

AIM： Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma （EWDA）, is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS： Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT： Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions （mean follow-up period, 56 too）. All 9 cases of EWDA could be classified into gastric phenotype （5 lesions） and intestinal phenotype （4 lesions）. The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cellsand their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION： Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.

Expressions of claudin-4 and claudin-1 in endometrial cancer and their significance

Objective:To observe the expressions of claudin-4 and claudin-1 in endometrial cancer and explore their correlations with clinicopathological parameters of endometrial cancer.Methods:Immunohistochemical methods(SP) were used to detect the expressions of claudin-4 and claudin-1 in 52 tissue samples of endometrial cancer,24 of atypical hyperplasia,20 of pericancerous endometrium,and 19 of endometrium at proliferative phase.And then the expressions were analyzed statistically to find out the correlations with clinicopathological parameters of endometrial cancer.Results:Positive rate of claudin-4 was 36.8%,70.8% and 90.4% in endometrium at proliferative phase,atypical hyperplasia and endometrial cancer,respectively,with significantly differences between them(P<0.05),and it was statistically different between pericancer endometrium and endometrial cancer(P<0.05).Positive rate of claudin-1 was 89.5%,66.7% and 63.5%,respectively showing a descending tendency and significantly differences between endometrium at proliferative phase and endometrial caner(P<0.05),and it was also statistically significantly different between pericancer endometrium and endometrial cancer(P<0.05).The high expression rate of claudin-4 was related to invasion depth,but not to histological grading,pathological staging or lymph node metastasis of endometrial cancer,and the low expression of claudin-1 in endometrial cancer was not associated with histological grading,pathological staging,invasion depth or lymph node metastasis.Conclusion:The expression levels of claudin-4 and claudin-1 are correlated with onset and development of endometrial cancer.

Expression of pituitary homeobox 1 gene in human gastric carcinogenesis and its clinicopathological significance

AIM： To investigate the effect of pituitary homeobox 1 （PITX1） expression in cases of human gastric cancer on cancer differentiation and progression, and carcinogenesis. METHODS： Using polyclonal PITX1 antibodies, we studied the expression of PITX1 in normal gastric mucosa, atypical hyperplasia, intestinal metaplasia, and cancer tissue samples from 83 gastric cancer patients by immunohistochemistry. Moreover, semi-reverse transcription polymerase chain reaction （semi-RT-PCR） was performed to detect the mRNA level of PITX1 in three gastric cancer cell lines and a normal gastric epithelial cell line. Subsequently, somatic mutations of the PITX1 gene in 71 gastric cancer patients were analyzed by a combination of denaturing high performance liquid chromatography （DHPLC） and DNA sequencing. RESULTS： Immunohistochemistry showed that PITXl was strongly or moderately expressed in the parietal cells of normal gastric mucosa （100%）, while 55 （66.3%） out of 83 samples of gastric cancers showed decreased PITXl expression. Moreover, PITXl expression was reduced in 20 out of 28 cases （71.5%） of intestinal metaplasia, but in only 1 out of 9 cases （11%） of atypical hyperplasia. More importantly, PITXl expression was significantly associated with the differentiation, position and invasion depth of gastric cancers （r = -0.316, P 〈 0.01; r = 0.213, P 〈 0.05; r = -0.259, P 〈 0.05, respectively）. Similarly, levels of PITXl mRNA were significantly decreased in 2 gastric cancer cell lines, BGC-823 and SGC-7901, compared with the normal gastric epithelial cell line GES-1 （0.306 ± 0.060 vs 0.722 ± 0.102, P 〈 0.05; 0.356 ± 0.081 vs 0.722 ± 0.102, P 〈 0.05, respectively）. Nevertheless, no somatic mutation of PITX1 gene was found in 71 samples of gastric cancer by DHPLC analysis followed by sequencing. CONCLUSION： Down-regulation of PITX1 may be a frequent molecular event in gastric carcinogenesis. Aberrant levels of PITXl expression may be closely correlated with the progression and differentiation of gastric cancer,

Clinicopathological and immunohistochemical analysis of gastrointestinal stromal tumor

AIM： To investigate the clinicopathological features of gastrointestinal stromal tumor （GIST） and to study the reference indexes for malignancy. METHODS： Fifty-two cases of primary GIST were distinguished from a group of gastrointestinal mesenchymal tumors using a panel of antibodies such as CD117 and CD34 by immunohistochemical SP method. Their biological behaviors were analyzed using the expression of p21WAF1 and Bax in 52 cases of GIST. RESULTS： Grossly, the tumor size was between 1.5 cm and 13 cm （mean： 5.5 cm）. Focal areas of hemorrhage, necrosis, or small cyst formation could be seen. Microscopically, the tumor was composed of spindle cells （20 cases）, epithelioid cells （20 cases） and mixed cells （12 cases）. Immunohistochemically, CDl17 and CD34 showed diffuse strong positive expressions, the positive rates were 98.1% and 92.3%. SMA, S-100, NSE, NF and MBP showed focal positive expressions, the positive rates were 48.1%, 28.8%, 25%, 21.2% and 42.3% respectively. Vimentins were all positive desmin and CgA were all negative. In normal adult stomach and intestine, the immunoreactive staining for CD117 and CD34 showed immunoreactive interstitial cells of Cajal in myenteric neuroplexus. Among the 52 cases of GIST, 27 were positive for p21WAF1 （51.9%）, 29 for Bax （55.8%）. The expression of p21WAF1 and Bax had no significent difference with the localization, size, histological subtype of GIST, but had a significent difference with the histological grade （P = 0.000, respectively）, p21WAF1 expression had a positive correlation to Bax expression （r = 0.461, P = 0.001, k = 0.459）. CONCLUSION： GIST has complicated arrangements and various cell types. Positivity of CD117 and CD34 is the most valuable factor in diagnosing GIST. Expression of p21WAF1 and Bax plays an important role in potential malignancy and malignancy rather than in benign GIST. p21WAF1 and Bax may be used as the markers in the assessment of GIST malignant potential.

Clinicopathological Significance of E-cadherin and PCNA Expression in Hunman Non-small Cell Lung Cancer

OBJECTIVE This study was designed to assess E-cadherin (E-cad)and proliferating cell nuclear antigen(PCNA)expression as well as their clinicopathological significance in hunman non- small cell lung cancers(NSCLCs).Possible molecular mechanisms of differentiation and metastasis of NSCLCs are discussed. METHODS Immunohistochemical and immunofluorescence double staining were performed to examine the expression of E-cad and PCNA in 68 primary NSCLCs cases. RESULTS The E-cad expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.E-cad expression had a positive correlation with the histological- differentiated grade.A significant difference of E-cad expression was found between metastatic and non-metastatic groups.PCNA expression in squamous cell carcinomas and adenocarcinomas showed no significant difference.The PCNA expression had a reverse correlation with the histological-differentiated grade.A significant difference of PCNA expression was found between metastatic and non-metastatic groups.The E-cad and PCNA expression presented a reverse correlation. CONCLUSION E-cad expression is not associated with the histological type of NSCLC,but is associated with differentiation and metastasis of the cancer.Down-regulation of E-cad expression affects the proliferation of cancer cells.Conjoint analysis of E-cad and PCNA expression is a good way to evaluate tumor biological behavior.

Exploring factors that motivate nursing students to engage in skills practice in a laboratory setting:A descriptive qualitative design

Objectives:The aim of this study was to explore factors that motivate students to engage in skills practice in a laboratory setting,and to identify their motivation types and the regulatory styles.Methods:Semi-structured interviews were conducted with 23 nursing students from three universities between November 2017 and January 2018.A thematic analysis was used to identify factors associated with students’motivation to engage in skills practice in a laboratory.The types and the regulatory styles of student motivation were identified based on the self-determination theory.Results:Seven motivating factors were identified.These factors included the students’desire“to acquire the skills necessary to work as a nurse”,the“desire to improve skills in preparation for clinical practicum”,and their felt“obligations to patients as a nurse”.Moreover,“the impetus to study arising from the objective evaluation of oneself and others”and“wanting to pass the skills examination”motivated the students to engage in skills practice.A“learning environment that facilitates students’learning”and the“supportive involvement of educators”facilitated their learning.Based on the self-determination theory,the students were found to embrace extrinsic motivation with four regulatory styles of motivation,namely integrated,identified,introjected,and external regulation.Conclusions:Nurse educators should understand the motivating factors of students,and help students embrace a more internally controlled motivation by helping them envision their future careers as nurses,and by fostering their ethical duty to care for patients.

Abnormalities of masseter inhibitory reflex in patients with episodic tension-type headache

Objective： To investigate the masseter inhibitory tension-type headache （TTH）. Methods： MIR was studied in 21 sex matched to the study cohort. Median age of patients was reflex （MIR） and its eventual changes in patients with episodic patients with episodic TTH and 30 healthy subjects, with age and 17.0 years （ranged 16-49 years）, median duration of disease 12 months （1-5 years）, and median frequency of headache 7.5 d per month. Results： The second period of suppression （$2） of MIR was reduced in intensity and duration in 10% of controls and 66.7% （confidence interval （CI） 45.3%-85%; P〈0.05） of patients with episodic TTH （X2=74.9; P〈0.001）. In 3 （14.3%） of patients with episodic TTH, S2 was completely absent. No significant correlation between the duration of disease and headache frequency was found. Conclusion： Our results confirm the link between episodic TTH and reduction or absence of S2. Teenage patients with episodic TTH may exhibit marked pathological changes in S2 in contrast to older individuals.