1998年 · 第111卷第05期

OBJECTIVE To induce experimental immune tolerance in rabbits and observe its effects on heterotopic cardiac transplantation. METHODS Donor's splenic lymphocytes pretreated with platinum metal chelator were injected into the recipient's mesenteric-portal vein. Cyclosporin A was perfused through the donor's heart. RESULTS The injection of donor's splenic lymphocytes before transplantation could significantly prolong the survival time of the heterotopically transplanted heart. The effect of two injections was better than that of one. Radioactive tracer studies showed that the 99mTc-HMPAO tagged lymphocytes injected into the recipient rabbit were later concentrated in the liver, though initially they were distributed in multiple organs. The induced immune tolerance was antigen-specific, and it neither affect the other immune functions of the lymphatic system prominently nor exert any harmful effect on the recipient's liver and renal functions. The perfusion of cyclosporin A through the donor heart could block the glycosyl groups, such as D-glucose, D-mannose or N-acetyl-galactosamine on the surface of the myocardial cells, thus might change the antigenic expression, effectively preventing rejection of the graft by the host, and might be considered as a new method to block graft rejection in cardiac transplantation. The combined use of the above-mentioned two methods acted on both the host and the donor, thus reducing the exposed antigens on the donor organ as well as the immune reaction against the donor antigens, and resulting in synergistic effect in inducing immune tolerance in adult rabbits, and resulting in relatively long-term survival of transplanted hearts. CONCLUSIONS This report may provide the experimental basis for inducing immune tolerance in clinical transplantation.

OBJECTIVE To make clear the incidence, clinical characteristics and possible regional difference of gallbladder cancer in China. METHODS A total of 430 cases of gallbladder cancer from 28 hospitals between 1986-1996 were reviewed, according to a standard protocol called "the clinical epidemiological list of gallbladder cancer". RESULTS The incidence of gallbladder cancer was higher in the females than in the males. There was significant difference in the incidence between the north and south of China, and between the mountain area and flatlands. Gallbladder cancer accounted for 1.6% of bile tract disease in the same period. Gallstones were found in about 50% of the cases of gallbladder cancer. The clinical symptoms included abdominal pain, ictus, etc. The major pathohistologic type was adenocarcinoma, and 58% of tumors were localized in the whole gallbladder. Metastasis occurred mainly along the biliary tract or directly to the bed of gallbladder and liver. Ultrasonography and CT were useful to diagnosis. The positive imaging diagnostic rate was higher in 1991-1996 than in 1986-1990 P<0.05) [corrected]. The rate of operative resection was 100% for stage I and II disease, 75% for stage III and IV, and significantly lower for stage V (P<0.05). The 3-year survival rate in patients with stage I or II disease was significantly higher than that in those with terminal cancer (P<0.05). CONCLUSIONS There is specific populational, time and regional difference in the distribution of gallbladder cancer. Ultrasonography and CT are the most important diagnostic methods. Early diagnosis and early radical resection are the key to increasing the 5-year survival rate.

OBJECTIVE To protect the transplanted islets from the host's immune system by means of immunoexclusion membranes. METHODS Rat islets were isolated from Wistar rat pancreas by ductal collagenase distention, stationary digestion, and finally with the aid of dextran gradient separation. Then the islets were encapsulated in alginate-polylysine-alginate (APA) semipermeable membranes. RESULTS In vitro studies demonstrated that encapsulated islets secreted insulin in response to glucose challenge for at least 8 weeks, which was similar to free islets. In vivo studies showed that 15 streptozotocin (STZ)-induced diabetic mice were transplanted intraperitoneally with 1000 encapsulated islets without immunosuppression. Diabetes was reversed within 3 days, and the mice remained normoglycemic for up to 160 days, with a mean xenograft survival time of 126 days. The encapsulated islets had a significantly greater effect than unencapsulated islets, which functioned for less than 8 days. CONCLUSIONS Encapsulation of pancreatic islets in semipermeable membranes can effectively prolong xenograft survival without immunosuppression in an animal model.

OBJECTIVE To explore the possibility of reducing reperfusion injuries of internal organ with acidic and basic fibroblast growth factors (aFGF and bFGF). METHODS Two kinds of ischemia and reperfusion animal models were used in this study. In rat model of superior mesenteric artery (SMA) occlusion, microvascular clamp was placed on the root of SMA to cut off the blood flow for 45 minutes, and then the clamp was removed. In rat model of bilateral renal ischemia and reperfusion, both renal arteries were clipped to get complete cessation of blood flow for 60 minutes, then the blood flow was allowed to return. At the onset of reperfusion, the doses of 4.0 μg/rat of bFGF in SMA occluded rats or 2.6 μg/rat of aFGF in rats with acute renal injury were administered through the jugular vein. The liver and renal function examination, tissue bacterial study and histopathological evaluation were done to evaluate the treatment results. RESULTS The functional impairment of ischemic liver, gut and kidney were reduced with venous administration of aFGF or bFGF at the onset of reperfusion. The results of pathological and tissue bacterial examination supported the assertion of significant protective effects of FGFs. CONCLUSIONS The protective effects of FGFs may come from the non-mitogenic effects of FGFs at the early and the mitogenic effects at the late stage of tissue repair. These results indicate a potential for clinical use of FGFs as a therapeutic modality in ischemic visceral organ injuries in the future.

OBJECTIVE To explore the application of monoclonal antibody (McAb) to targeted treatment of bladder carcinoma through a series of in vitro and in vivo studies carried out in animal model and patients with bladder carcinoma. METHODS Monoclonal antibody BDI-1 against bladder carcinoma was prepared by the lymphocyte hybridoma technique. McAb was conjugated with 99mTc by direct reduction method. Momodin (MD) was covalently linked to McAb by SPDP method. Radioimmunoimaging of nude mice xenografts and patients with bladder carcinoma were performed with BDI-1-99mTc conjugates. An immunotoxin (BDI-1-MD) was inducted via a catheter into the bladder. Targeted treatment with BDI-1-MD was carried out in 18 patients. RESULTS This study showed the specificity of McAb, and clear imaging of nude mice bearing xenografts. Distribution analysis of 99mTc-BDI-1 in nude mice showed the highest value of T/NT in bladder tumor. Targeted diagnosis and treatment for patients by intravesical administration are very safe and effective. CONCLUSIONS The bladder cancer seems an ideal model for diagnostic and therapeutic approaches using regional administration of McAb conjugates via a catheter direct into the bladder.

OBJECTIVE To investigate the expression of Fas/APO-1 in urogenital tumor cell lines. METHODS With direct immunofluorescence, the expression of Fas/APO-1 in six urogenital malignant cell lines and one primary in vitro cultured normal renal fibroblast was detected by flow cytometry. RESULTS Expression of Fas/APO-1 was detected in all six urogenital tumor cell lines, but with limited positive cell percentage and relatively lower fluorescence intensity, compared with expression of Fas/APO-1 in normal control of primary in vitro cultured renal fibroblast. CONCLUSIONS Lower expression of Fas/APO-1 in urogenital malignant cell lines than that in normal cells might be the reason for occurrence and progression of urogenital malignant tumors.

OBJECTIVE Hyperthyroidism and a diffuse goiter are the main symptoms of Graves' disease (GD) associated with autoantibodies to thyroid-stimulating hormone (TSH) receptor (TRAb). The present study was conducted to evaluate effects of autoantibodies in patients with GD (TRAb-IgG) on induction of the proliferation and c-fos mRNA expression in FRTL-5 cells (Fisher rat thyroid cell line). METHODS Highly purified IgG fractions were isolated from 11 patients with GD, TRAb-IgG and 15 normal individuals (normal controls) with Protein A Sepharose CL-4B affinity column chromatograph. FRTL-5 cells, which had been grown to subconfluency and deprived of TSH for a few days. Then, these cells were used for measuring cAMP content,3H-thymidine incorporation in cells and the expression of c-fos mRNA respectively. RESULTS After stimulation of TRAb-IgG, the cAMP production and 3H-thymidine incorporation in FRTL-5 cells were much higher than those from normal controls (P<0.05 respectively). Using32P labelled v-fos probe by the Northern Blot method, the expression of c-fos mRNA could be induced by IgGs from patients with GD. CONCLUSIONS These data suggest that the stimulation of TRAb-IgG followed by cAMP production and 3H-thymidine incorporation is related to the induction of c-fos mRNA and, thus, to the growth of FRTL-5 cells.

OBJECTIVE Familial hypertrophic cardiomyopathy (FHCM) is a primary myocardial disease characterized by unexplained ventricular hypertrophy. The application of the techniques of reverse genetics has identified at least five chromosomal loci as the major causes for FHCM in diverse ethnic populations, suggesting substantial genetic heterogeneity for FHCM. Recently, the defective gene loci of two Chinese families with FHCM have been mapped to chromosome 11 and 14q1, respectively. For further understanding of the molecular basis of FHCM in Chinese, we analyzed the linkage between four other Chinese kindreds and DNA markers from chromosome 14q1. METHODS Six unrelated Chinese families with FHCM, including two previously reported, were studied. Totally 90 family members were included for analysis. DNA from 80 individuals was extracted and polymerase chain reactions were performed using the primers designed according to the sequences derived from the α and β myosin heavy chain gene. Totally four polymorphisms were studied, including three polymorphic microsatellite sequences and one single strand conformation polymorphism. Genetic linkage analysis were performed using the Linkage program. RESULTS In the six studied families, 39 of the 90 family members were found to be affected diagnosed either by echocardiography or by clinical evaluation. The pattern of inheritance in all six studied families was most consistent with an autosomal dominant trait with a high degree of penetrance. Genetic linkage analysis using polymorphisms on the α and β MHC genes showed a combined maximal lod score of 6.2 for trinucleotide repeat polymorphism AMHC-I 15 at θ=0.00 for three studied families without recombination. Exclusion of linkage to the chromosome 14q1 location was noted in two of three other families with the maximal lod score of -2 or less. CONCLUSIONS These results provide further evidence that FHCM in Chinese is genetically heterogeneous. Chromosome 14q1 locus, probably the β myosin heavy chain gene, is important as the molecular basis for FHCM in Chinese.

OBJECTIVE To summarize the experience of utilization of video-assisted endoscopy in 91 patients operated on at Chang Gung Memorial Hospital, Taipei, China. METHODS From October 1995, through August 1996, 91 patients (44 male and 47 female) received video-assisted cardiac surgery (VACS). Their ages ranged from 1 year to 79.5 years (25.7±21.7). Indications for surgery were atrial septal defect (59 patients), ventricular septal defect (15), coronary artery disease (4), severe mitral regurgitation (4), severe tricuspid regurgitation (3), thrombosis of mitral mechanical prosthesis (3), left atrial tumor (2), and left ventricular thrombus with dilated cardiomyopathy (1). The VACS was performed through right or left anterior minithoracotomy and guided by video-assisted endoscopic techniques by means of projected images on the video monitor under extracorporeal circulation. The aorta was not cross-clamped and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest (rectal temperature 22.6±4.0 ℃). Conventional instruments were used. RESULTS All lesions were corrected successfully. The bypass time was 27 to 335 minutes (72.8±52.7). The operative time was 1.3 to 8.5 hours (3.0±1.7). There were no operative deaths and 3 late deaths. Follow-up was complete in all survivors (6 to 16 months, mean 8.7). Most of them were found to be in NYHA functional Ⅰ or Ⅱ. CONCLUSIONS Our preliminary experiences demonstrate that VACS is simple and effective in surgical correction of selected cardiac lesions. Short-term results show good outcomes.

OBJECTIVE To observe apoptotic process in various cardiovascular disorders with a particular attention to the ultrastructural morphology of apoptosis in cardiomyocytes, fibroblasts, vascular endothelial cells and smooth muscle cells. METHODS Transmission electron microscopic observations of the tissue specimens obtained from endomyocardial biopsies or surgical excisions of left ventricular myocardium or calcified aortic valves were carried out in 50 patients with various cardiovascular diseases. RESULTS The ultrastructural features of apoptosis was consistently observed in cardiomyocytes, fibroblasts, vascular endothelial cells and smooth muscle cells in all diseased tissues. In cardiomyopathies and rheumatic heart diseases apoptosis was commonly observed in the cardiomyocytes. It was often found that fibroblasts underwent apoptosis in calcific aortic valve tissues. Apoptosis of arterial smooth muscle cells was a frequent finding in renal arterial stenosis due to Takayasu's arteritis and fibromuscular dysplasia. Regardless of the cell types, the nuclear hallmarks of apoptosis were identical with minor modifications of the fragmentation of the condensed cells into apoptotic bodies. CONCLUSIONS Based on electron microscopic findings, it is suggested that the underlying disease processes determine which type of cells predominantly undergoes apoptotic changes in various cardiovascular disorders. In addition, different cells with similar structural morphology may have common ultrastructural features of apoptosis.

OBJECTIVE To develop a diagnostic framework that would help defining clinical problems by the expanded understanding with traditional Chinese medicine (C Med) and western medicine (W Med). METHODS The basic attributes of diagnosis and the use of diagnostic techniques of W Med and C Med are reviewed. Some of the various diagnostic labels and their meanings are also preliminarily reviewed. A consolidatory approach is made to synergize the usefulness of the two disciplines based on the principles of the two schools. RESULTS A synergized basic diagnostic framework is developed. The disease (the disease diagnosis, 病症), the state of the inner core (the core diagnosis, 本候) should be defined. The term "systemic clues" is used to describe the symptom complex and conglomerate evidence describing the transient or sustained reaction of the inner core to environment. This is an analytical summary of its pathophysiological changes in reaction to the environmental insults. CONCLUSIONS The application and use of the framework are discussed and propositions are made. The synergized diagnostic platform represents a starting effort to form a unified basis to exchange clinical diagnosis between W Med and C Med. Such framework may facilitate looking for new treatment modalities and results can be compared across different centres.

OBJECTIVE To assess the progress in the treatment of advanced childhood neuroblastoma. METHODS From 1981 to 1996, there were 32 children with neuroblastoma (NB) diagnosed, staged and treated in our institution. There were 4 patients with stage II NB (12%), 5 stage III (16%), 21 stage IV (66%) and 2 stage IV s (6%). The NBs were excised if CT scan indicated that the tumors were operable. For advanced NB, stages III and IV, multiple drug chemotherapy was started first and operability was assessed with serial CT scan examinations. Once the X-ray imaging indicated the tumors were operable, surgical interventions were done. The medical records of the advanced NB were reviewed. RESULTS In the initial period of the study, 9 patients were treated using the VAC protocol [vincristine (vcr), adriamycin (adria) and cyclophosphamide (cyc)]. No patient was convertible to operable and all died with a mean survival of 10 months. OPEC [vcr, cyc, VM26, cisplatin (cis)], Rapid COJEC (carboplatin, VP16, vcr, cis and cyc) and more recently N6 protocol (cyc, adria, vcr, VP16, cis) was used for 17 patients. 80% of them were converted to operable. In 4 patients, surgical specimens showed only necrotic tissue without viable tumor tissue and 6 (35%) tumors were converted to ganglioneuroma or ganglioneuroblastoma. Although 2 (12%) patients died of fungal septicemia and 1 (6%) developed Fanconi's syndrome after chemotherapy, the mean survival period increased to 27 months. In the 10 survivors (60%), 4 had megatherapy with melphalan followed by autologous peripheral blood stem cell (PBSC) transplantation and 2 were waiting for transplantation. CONCLUSIONS There is a high percentage of advanced NB on presentation in Hong Kong. With more potent multiple drug chemotherapy for advanced stage NB there are (1) improvement in the survival of these patients, (2) opportunities for more operations for tumor excision and (3) opportunities for autologous PBSC transplantation for better tumor eradication.

Tined endocardial steroid-eluting leads in the ventricle have demonstrated long-term, very low acute and chronic stimulation thresholds and recently, this work has been extended to the atrium. The objective of this study was to compare two bipolar atrial J leads from one manufacturer: one passive fixation tined lead, and one steroid-eluting lead.

Recent studies showed that a type of insertion/deletion (I/D) polymorphism of angiotensin converting-enzyme (ACE) gene was associated with coronary heart disease (CHD) and essential hypertension (HTN). It was also found that this polymorphism was related to the susceptibility of microvascular complication in type 1 diabetes-nephropathy (DN). We report here 233 Chinese cases to clarify if ACE gene I/D polymorphism attributes to the development of type 2 diabetes and its renal complication.

Data sources All reference data originated from related Chinese- or English-language literature in Chinese journals. Study selection Twenty-three original articles published in 1992-1996 were selected according to the stated purpose and 9 of them were written by myself. Data extraction The present paper dealt with 5 subtopics, i.e. epidemiology, parasitology, pathology, diagnosis, treatment and prognosis. Results Five hundred and eighty-four patients with alveolar echinococcosis (AE) have been reported from 7 provinces or autonomous regions. Human infection rate was 19.2% or 2.8%, and the morbidity was 2.4%-5.0%. The intermediate hosts of Echinococcus multilocularis included 7 species of rodents and 3 species of livestocks, and the final hosts of that were fox, dog or wolf. Diagnosis of AE was chiefly based on imaging examination (ultrasound and CT) and immunological test. The operative resection rate for liver AE was only 10.5% (27/258). Albendazole was a certain remedy for the chemotherapy of AE, and TCM "Xiao-Bao" pill may be a hopeful drug. Conclusion In the past 30 years, a lot of work concerning basic and clinical studies has been done in China and some achievements have been achieved. However, some important problems such as how to conduct further research on molecular biology, how to make early diagnosis, how to improve the chemotherapeutic effect, and how to control the prevalence of AE, need to be studied more deeply in the 21st century.