Heterogeneous epithelial expression of class II (HLA-DR) determinants and secretory component related to dysplasia in ulcerative colitis

The intensity and degree of heterogeneous epithelial marker expression were evaluated immunohistochemically in 29 mucosal biopsy specimens from 7 ulcerative colitis (UC) patients with dysplasia. Biopsy specimens from UC patients with mild (n = 7) or severe (n = 6) inflammation and from histologically normal samples (n = 7) served as controls. HLA-DR showed heterogeneous epithelial expression in all lesions with high grade dysplasia and in 6 of 8 with low grade dysplasia. SC was heterogeneous stained in 17 of 21 lesions with high grade dysplasia and in all but two lesions with low grade dysplasia. In histologically normal mucosa, SC was homogeneously expressed and epithelial DR was virtually absent. In mildly inflamed UC lesions, SC exhibited patchy distribution in only one sample and DR in two, whereas both SC and DR showed a slight degree of heterogeneous expression in all lesions with severe inflammation. Moreover, the overall intensity of SC staining tended to decrease with increasing degree of inflammation, whereas the opposite was seen for DR. Decreased SC and increased DR expression thus seemed to be related to intensified inflammatory activity, whereas heterogeneous expression of these markers was significantly more related to dysplasia.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Flow cytometric DNA ploidy pattern in dysplastic mucosa, and in primary and metastatic carcinomas in patients with longstanding ulcerative colitis

Eighty-nine fresh tissue samples from flat colonic mucosa, polypoid lesions, macroscopically evident carcinomas, and metastatic carcinomas from ten patients with longstanding ulcerative colitis (greater than or equal to 8 years duration) were analysed by DNA flow cytometry and light microscopy. Of a total of ten carcinomas found in six patients, six showed DNA aneuploidy. Three patients developed metastatic carcinomas, all with aneuploid cell populations with similar DNA indices as in the primary carcinoma. Furthermore, aneuploid cell populations with similar DNA indices often occurred, both in separate mucosa samples, as well as in mucosa and carcinoma samples, from the same patient. DNA aneuploidy was found in flat mucosa in five of the six patients with carcinoma, and in one of the four patients without carcinoma (P greater than 0.1). High grade dysplasia was found in only four of the six cases with carcinoma, indicating that high grade dysplasia is insufficient as marker for malignant development. DNA aneuploidy was found in 24% of the dysplastic mucosa samples, and in 18% of the non-dysplastic mucosa samples (n.s., both with regard to high and low grade dysplasia). Since abnormal DNA ploidy pattern was not confined to dysplastic epithelium only, DNA aneuploidy in flat mucosa may constitute an additional marker in the identification of patients at increased cancer risk who could benefit from a closer surveillance.     

Ontogenesis of the secretory immune system and innate defence factors in human parotid glands

Immunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands. (1) Fetal specimens. Occasional IgM- and IgA- but no IgD-, IgG- or IgE- producing cells were seen (ratios, IgM:IgA:IgD:IgG:IgE approximately 4:1:0:0:0). The IgAl subclass dominated (median 90%, range 50-95%) and these cells were mostly J-chain-positive (median 97%, range 94-98%). Only few IgA2-producing cells were seen (median 10%, range 5-50%) and they were also mostly J-chain-positive (median 99%, range 98-100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (IgA:IgM:IgD:IgG:IgE approximately 4:2:1:1:0). The IgAl subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10-50%). Most IgAl (median 97%, range 67-100%) and IgA2 (median 94%, range 75-100%) cells were J-chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity.     

Large-bowel carcinomas with different ploidy, related to secretory component, IgA, and CEA in epithelium and plasma.

Immunofluorescence staining for carcinoembryonic antigen (CEA), secretory component (SC), and epithelial IgA was evaluated semiquantitatively in 85 large-bowel carcinomas in relation to degree of tumour differentiation, Dukes'' stage, and plasma CEA level. The tumours were divided into a near-diploid (ND, 28) and an aneuploid group (AN, 57) by means of flow-cytometric DNA measurements. Expression of SC and IgA in neoplastic epithelium was positively related to differentiation in both groups. The AN tumours scored significantly higher for CEA than the ND ones, but the staining was apparently unrelated to differentiation or Dukes'' stage. CEA expression in the transitional mucosa adjacent to ND tumours was negatively correlated with tumour differentiation, whereas epithelial IgA and SC in this zone showed a substantially higher positive correlation with tumour differentiation, and a somewhat stronger negative correlation with Dukes'' stage in the ND than in the AN group. Plasma CEA levels were significantly related to Dukes'' stage, only in patients with AN tumours, and only in this group were positively correlated with estimates of total tumour CEA for Dukes'' stages A and B. For Dukes'' stages C and D (disseminated tumours), moreover, the plasma CEA levels were found to be significantly higher in the AN group. These findings indicate that the DNA profile of large-bowel carcinomas is related both to the way neoplastic cells influence the activity of the transitional mucosa and their capacity for expression and release of epithelial products. AN tumours thus seem to be more active as "secretors" of CEA than ND ones.     

Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years.

BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. RESULTS: Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.     

The brain‐derived neutrophic factor val66met polymorphism and sudden unexpected infant death

Aim: Findings of hypoxia prior to death and involvement of a dysregulation of the serotonergic network in sudden infant death syndrome (SIDS) may indicate that brain‐derived neutrophic factor (BDNF) also is of importance with regard to sudden unexpected infant death. Based on this, the purpose of this study was to investigate the BDNF val66met polymorphism in SIDS cases, cases of infectious death and controls. Methods: The polymorphism was investigated in 163 SIDS cases, 34 cases of infectious death and 121 controls, using real‐time PCR and fluorescence melting curve analysis. Results: There were no differences in val66met genotype distribution between neither the SIDS cases nor the cases of infectious death and controls (p = 0.95 and p = 0.52, respectively). Conclusion: The study indicates that the val66met polymorphism is not important for sudden unexpected infant death. However, several other SNPs in the BDNF gene, as well as in other genes involved in this pathway, including G‐protein, have to be investigated to fully exclude any involvement of BDNF in SIDS.     

国产利培酮（索乐）治疗精神分裂症多中心开放性临床研究

目的：评价国产利培酮（索乐）治疗精神分裂症的疗效和安全性。方法：通过对全国45家精神病医院的962例精神分裂症患者进行多中心,大样本,开放性的为期8周的治疗观察。采用PANSS、CGI、SAS和TESS评定疗效和不良反应。结果：国产利培酮（索乐）对精神分裂症总有效率84.3%,临床总体疗效肯定,不良反应轻,主要是轻度的锥体外系反应,体重增加,因其程度轻,病人基本能耐受。结论：国产利培酮（索乐）对精神分裂症阳性症状及阴性症状均有效,起效快,安全性高,患者对该药依从性好,可作为精神分裂症的首选药物之一。     

发挥科研优势 促进学科发展

<正> 暨南大学医学院第一附属医院,又名广州华侨医院,经过20年的发展已成为一所集医、教、研为一体的大型三级甲等医院。医院的科研发展始终坚持"以学科建设为基础,人才培养是关键"的科研办院思路,从建院初期以调入人才为主到目前的以人才引进为辅、培养人才为主,20年来培养了一批中青年学术带头人,形成了一批技术力量强大的学科群。从建院初期仅有眼科学、内科学(血液病专业)2个硕士学位授与点发展到现在拥有眼科学、内科学、妇产科学3个博士学位、14个硕士学位授权点,1998年还被国家教委批准为临床医学专业学位授与点的试点单位。在各类学术期刊上发表文章3089篇,主编及参与编写171部专著,承担各级科研课题695项,获国家科技进步奖1项,省部级成果奖25项,厅局级科技进步奖69项,获专利9项。医院在培育科研优势的同时更注意发挥学科优势促进学科的发展。