Abstract:Objective To evaluate the efficacy and safety of defibrase in patients with acute cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial. Methods Patients with acute cerebral infarction within 12 hours of stroke onset were randomly assigned to receive either an initial intravenous infusion of defibrase 15 U plus normal saline 250 mL or 250 mL of normal saline only. Subsequent infusions of defibrase 5 U or placebo (normal saline) were given on the 3rd, 5th, 7th, and 9th day, respectively. Both groups received standard care of acute cerebral infarction. The primary efficacy outcome was functional status (Barthel Index) at 3 months after treatment. Safety outcome were bleeding events and mortality rate. Secondary outcome included Chinese Stroke Scale (CSS) score at 14 days and recurrence rate of stroke at 1 year. Results A total of 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment. There was a significantly greater proportion of favorable functional status (Barthel Index ≥95) in defibrase group than in placebo group at 3 months (52.2% vs. 42.8%, P < 0.01), and the proportion of dependent functional status (Barthel Index ≤60) was a little lower in defibrase group compared with placebo group (27.7% vs. 32.4%). These differences were more obvious among patients who were treated within 6 hours of stroke onset. Patients in defibrase group had better improvement with respect to CSS score than those in placebo group at 14 days (P < 0.05). Recurrence rate of stroke at 1 year was lower in the defibrase group compared with placebo group (6.2% vs. 10.1%, P = 0.053). Patients in defibrase group had higher risk of extracranial bleeding events (4.7% vs. 1.5%, P < 0.01) and a tendency of higher risk of symptomatic intracranial hemorrhage. The hemorrhage incidence was higher in patients with fibrinogen level < 130 mg/dL than ≥130 mg/dL (10.6% vs. 3.8%, P < 0.05). Mortality rate at 3 months were slightly higher in defibrase group than placebo group (5.9% vs. 4.2%). Conclusions The defibrase is effective to improve neurological function and function of daily living for patients with acute cerebral infarction within 12 hours of symptom onset. The efficacy was even better for acute cerebral infarction within 6 hours of onset. The increased risks of intra- and extracranial hemorrhage during defibrase administration were related to the plasma fibrinogen level.
Abstract:Objective To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autolo- gous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoim- mune diseases. Methods Twenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjgren’s syndrome (pSS), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease acti- vity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored. Results Overall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and an- other of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P < 0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation. Conclusion HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.
Abstract:Objective To investigate the relationship between pemphigus vulgaris (PV) and human leukocyte antigen (HLA) in Han nation of northeast China. Methods Standard microcytotoxicity test and polymerase chain reaction-sequence specific primers method were used to detect the HLA classⅠ antigens and HLA-DRB1 and DQB1 alleles in 27 patients with PV and results were compared with control group. Results Gene and phenotype frequencies of HLA-A3, A26(10), B60(40), and B13 (27.99%, 48%; 16.11%, 30%; 23.02%, 41%; 16.11%, 30%, respectively) increased significantly in PV group compared with control (1.01%, 2%; 0.5%, 1%; 4.61%, 9%; 5.13%, 10%, respectively). After P value correction, the difference of A3, A26 (10), and B60 (40) between the two groups was still significant. The gene frequencies of HLA-DRB1*140x (1401, 1404, 1405, 1407, 1408), DRB1*120x, and DQB1*0503 alleles in PV group (42.26%, 25.46%, and 23.02%) were significantly higher than control group (5.09%, 7.74%, and 1.89%). After P value correction, the difference was still significant between the two groups. Conclusion PV significantly relates with HLA in PV patients of Han nation of northeast China.
Abstract:Objective To investigate the techniques and clinical applications of multislice helical computed tomography (CT) colono- graphy in colonic lesions. Methods Fifty-nine patients with malignant lesions of colon underwent volume scanning using multislice helical CT. Four types of reconstruction including CT virtual colonoscopy (CTVC), shaded surface display (SSD), Raysum, and mu- ltiple planar reconstruction (MPR) were used for image post-processing. The results were compared with those of colonos- copy and pathology. Results Multislice helical CT colonography detected 54 colorectal carcinomas, 4 adenomas with focal carcinoma, 1 non-Hodgkin’s lymphoma (NHL). The lesions’ number, size, location, morphology, stricture of intestinal cavity, infiltration, and metastasis were shown satisfactorily by multislice helical CT colonography. Whole colon could be shown in all patients. CT colonography displayed 4 synchronous colonic tumors, 1 ascending colon carcinoma combined with left renal carcinoma among 54 patients with colonic carcinomas. The accuracy of location of CT colonography was 100%. There were 9 cases that CT showed the tumor location was different from the finding of conventional colonoscopy, while all of the CT location were proven exact by operation. CT colonography also displayed the infiltration of serous layer and fatty tissue in 45 cases; 21 cases matched the pathological results in all the 24 cases of suspicious lymph node metastasis, the sensitivity was 87.5%, the specificity was 90.6%; 9 cases hepatic metastasis, 2 ovarian metastasis, and 1 double adrenal gland metastasis. Conclusions Multislice helical CT colonography is effective in preoperative diagnosis, location, stage, and making treatment plan of colorectal carcinoma. It can display the portion not seen during colonoscopy and may have an adjunctive role.
Abstract:Objective To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin (SS), vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP) in plasma and isolated gastric antrum tissue of diabetes mellitus (DM) rat models. Methods Thirty male Sprague-Dawley rats were divided into three groups: control group (n = 10), DM group (n = 10), and erythromycin group (DM models with erythromycin treatment, n = 10). A single dose of streptozotocin (100 mg/kg, dissolved in 0.1 mol/L citric acid buffer, pH4.5) was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be (+++) to (++++) over one week were considered successful DM models. The resting tension, mean contractile amplitude and frequency of spontaneous change in isolated longitu- dinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and ga- stric antrum tissue were measured using radioimmunoassay. Results (1) In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile frequency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension (P < 0.01). (2) Plasma SS, VIP, and MTL concen- trations in DM group were higher than those in control (P < 0.05), while the SP level decreased (P < 0.05). In the gastric antrum, SS of DM group was significantly higher than that of control group (P < 0.01), while SP and MTL levels were lower than those of control group (P < 0.05 and P < 0.01, respectively). However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group (P < 0.05). (3) The blood glucose was lower in erythromycin group than DM group (P < 0.01). Conclusions Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.
Keywords:diabetes mellitus;gastric dysmotility;erythromycin;somatostatin;vasoactive intestinal peptide;motilin;substance P
Abstract:Objective To determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pul- monary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function. Methods Eighteen patients undergoing lung resections for a solitary peripheral carcinoma were classified by lung function as having COPD. Twenty patients with normal lung function served as the control group. Normal lobe bronchioles far away from the lesion site were taken for paraffin section. Goblet cells were identified by AB/PAS staining and the ex- pression of MUC5AC in the paraffin’s section was tested by immunohistochemistry. Results Goblet cell hyperplasia was observed in the COPD group. The positive rate of goblet cell in COPD group (0.20% ± 0.10%) was significantly higher than that in the normal lung function group (0.13% ± 0.06%, P < 0.05). The posi- tive rate of MUC5AC expression in the COPD group (0.27% ± 0.09%) was higher than that in the normal lung function group (0.20% ± 0.10%, P < 0.05). The positive rate of goblet cell in smokers (27.93% ± 9.00%) of the COPD group and normal lung function group was higher than that in non-smokers (17.70% ± 9.37%, P < 0.05), while MUC5AC expression had no significant difference between smokers and non-smokers (17.88% ± 6.44% and 10.88% ± 7.10%, respectively). Conclusion For COPD patients with declined lung function, there were goblet cell hyperplasia and increased expres- sion of MUC5AC. MUC5AC expression up-regulation may due to goblet cell hyperplasia. Smoking may be an important factor for goblet cell hyperplasia.
Abstract:Objective To identify differential genes between normal ovarian epithelium tissue and ovarian epithelial cancer using representational difference analysis of cDNA (cDNA-RDA). Methods cDNA-RDA was performed to identify the differentially expressed sequences between cDNAs from cancer tissue and cDNAs from normal ovarian tissue in the same patient who was in the early stage of ovarian serous cystadeno- carcinoma. These differentially expressed fragments were cloned and analyzed, then sequenced and compared with known genes. Results Three differentially expressed cDNA fragments were isolated using cDNA from normal ovarian tissue as tester and cDNA from cancer tissue as driver amplicon by cDNA-RDA. DPⅢ-1 and DPⅢ-2 cDNA clone showed significant ho- mology to the cDNA of alpha actin gene; DPⅢ-3 cDNA clone showed significant homology to the cDNA of transgelin gene. Conclusion cDNA-RDA can be used to sensitively identify the differentially expressed genes in ovarian serous cys- tadenocarcinoma. Ovarian serous cystadenocarcinoma involves alteration of multiple genes.
Keywords:representational difference analysis of cDNA;ovarian cancer;differential expressed gene;tumor suppressive gene
Abstract:Objective To evaluate the sensitivity and specificity of international classification criteria (2002) for primary Sjgren’s syndrome (pSS) and the role of lower lip biopsy in diagnosis of pSS in Chinese patients. Methods Patients who were diagnosed by the experts/rheumatologists as pSS during 1990-2002 from the Depart- ment of Rheumatology, Peking Union Medical College Hospital were retrospectively collected as experimental group. Patients who were diagnosed as non-pSS connective tissue diseases or non-connective tissue diseases served as control group. Those with a history of head-neck radiation, hepatitis C virus infection, AIDS, lymphoma, sarcoidosis, graft versus host disease (GVHD), and anti-acetylcholine drug use were exempted. Both groups were required to complete question- naires about symptoms such as dry eyes and dry mouth, and complete the objective tests of keratoconjunctivitis and xero- stomia including Schirmer test, corneal staining, unstimulated salivary flow, sialography, lower lip biopsy, and antinuclear antibodies (including anti-SSA/SSB antibodies) test. Results A total of 330 pSS patients were included in experimental group and 185 non-pSS patients in control group. The mean age of both groups matched (47.8 ± 10.9 years vs. 46.2 ± 13.6 years, P > 0.05). The sensitivities of the criteria in pSS patients with lower lip biopsy and in pSS patients without lower lip biopsy were 89.2% and 87.2%, respectively; the overall sensitivity was 88.5%. The specificity was 97.3%. A total of 11.3% pSS patients with negative anti-SSA/SSB anti- bodies were diagnosed as pSS by lower lip biopsy. Conclusion The international classification criteria (2002) for pSS is feasible in Chinese patients. It has high sensitivity and specificity, and may serve as diagnosis criteria in routine clinical practice.
Abstract:Objective To evaluate the improving reliability and safety of thromboendarterectomy and perioperative management for chronic pulmonary thromboembolism. Methods The clinical data of 12 cases with chronic pulmonary thromboembolism, who underwent thromboendarterec- tomy assisted by low flow or circulation arrest with deep hypothermia, were reviewed retrospectively. Results Pulmonary artery pressure decreased 20 to 40 mmHg immediately after surgical procedures in 9 cases. The postoperative pulmonary edema at various degrees happened in 12 cases, among them, 1 died of severe lung infection and pulmonary re-embolism at 19 days postoperation. Computed tomography pulmonary angiography and angiography of 11 cases indicated that the original obstruction of pulmonary artery disappeared. During the follow-up period of 2 months to 5 years, the clinical symptoms and activity was improved. Conclusion Thromboendarterectomy is an effective treatment for chronic pulmonary thromboembolism. The outcome of the surgical procedure needs to be further investigated and followed up regularly according to an evaluative system, because it might be influenced by multiple factors.
Abstract:Objective To introduce a new principle of sellar reconstruction and to evaluate the effectiveness of absorbable gelatin foam and fibrin glue for sellar reconstruction. Methods A total of 176 consecutive patients who underwent surgery for pituitary adenomas, cysts, chordomas, or subdiaphragmatic craniopharyngiomas in the sella turcica between January 2001 and April 2003 at Peking Union Medical College Hospital were enrolled. Different techniques of sellar closure and indications for each specific condition were retrospectively reviewed. Results Seventy-seven (43.7%) patients developed a visible cerebrospinal fluid (CSF) leakage during surgery. Intra- operative CSF leakage were repaired simply with gelatin foam and fibrin glue in 62 (35.2%) patients, and with autologous fat graft and sellar floor reconstruction in 15 (8.5%) patients. Postoperative CSF rhinorrhea occurred only in 1 case. There were no visual deterioration, allergic rhinitis, meningitis, pneumocranium, granulomas, or other complications asso- ciated with the reconstruction procedure. Conclusion The procedure of using gelatin foam and fibrin glue and principle of cranial base reconstruction is safe and effective in preventing postoperative complications following transsphenoidal surgery.
Abstract:Objective To assess the relationships between iodine biological exposure and subclinical thyroid dysfunctions. Methods The cross-sectional survey was performed to obtain the epidemiologic data of population in three communities with different iodine biological exposure: mild iodine deficiency [median urinary iodine concentration (MUI) of 50-99 μg/L], more than adequate iodine intake (MUI of 200-299 μg/L), and excessive iodine intake (MUI over 300 μg/L). Univariate and multivariate analysis (logistic regression analysis) were used to analyze the risk factors of subclinical hypothyroidism and subclinical hyperthyroidism. Results Logistic regression analysis with sex and age controlled suggested that more than adequate iodine intake (OR = 3.172, P = 0.0004) and excessive iodine intake (OR = 6.391, P = 0.0001) increased the risk of subclinical hypothyroidism, while excessive iodine intake decreased the risk of subclinical hyperthyroidism (OR = 0.218, P = 0.0001). Logistic regression analysis including interaction of iodine intake and antibodies [tryroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)] suggested that excessive iodine intake was an independent risk factor of subclinical hypothyroidism (OR = 6.360, P = 0.0001), but independent protect factor of subclinical hyperthyroidism (OR = 0.193, P = 0.0001). More than adequate iodine intake and it’s interaction with TgAb increased the risk of subclinical hypothyroidism independently, in addition, it decreased the risk of subclinical hyperthyroidism at the present of TPOAb. Conclusion Both excessive iodine intake and more than adequate iodine intake could increase risk of subclinical hypo- thyroidism, supplement of iodine should be controlled to ensure MUI within the safe range.
Abstract:Objective To evaluate the effectiveness of three-dimensional computed tomography (3D-CT) guided radiofrequency trige- minal rhizotomy (RF-TR) in treatment of idiopathic trigeminal neuralgia (ITN). Methods From 1999 to 2001, 18 patients with ITN were treated with percutaneous controlled RF-TR. Intraoperative 3D-CT scanning was performed to guide the trajectory of the puncture. After correction of the needle tip according to the CT scans and stimulation effects, 2 to 5 lesions were made for a duration of 60-90 seconds at a temperature of 60℃ to 75℃ depend- ing on the pain distribution and the age of patient. Results The needles located in foramen ovale. Pain alleviated immediately with no serious complication in all patients. The patients were followed up for an average of 31.5 months (range 24-41 months). Acute pain relief was experienced by 17 patients after the procedure, reaching an initial success rate of 94.4%. Early (< 6 months) pain recurrence was observed in 2 patients (11.1%), whereas late (> 6 months) recurrence was reported in 3 patients (16.7%). Thirteen patients had complete pain control, with no need for medication thereafter. Five cases experienced partial pain relief, but required medication at a lower dose than in the preoperative period. Conclusion 3D-CT foramen ovale locations can raise the successful rate of puncture, enhance the safety, and reduce the incidence rate of complication. H
Abstract:Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran- splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg·d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg·kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play im- portant roles in the diagnosis and treatment of rejection.
Abstract:Objective To investigate the expression of Survivin mRNA in lung cancer tissue microarray (TMA) by fluorescence in situ hybridization (FISH) method, and determine the role and significance of it in lung cancer genesis and progress. Methods The expression of Survivin mRNA was detected by FISH method and TMA technology. Fifty-four cases of lung cancer and 10 cases of normal lung tissue were examined. Results Survivin mRNA was expressed in 66.7% (36/54) of lung cancer; the positive ratio of lung cancer was significantly higher than that of normal lung tissue (0/10; χ2 = 15.238, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in poor differentiated cancer (20/24, 83.3%) than moderate and well differentiated cancer (16/30, 53.3%; χ2 = 5.40, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in group with lymph node metastasis (27/32, 84.4%) than without lymph node metastasis (9/22, 40.9%; χ2 = 11.084, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in stage Ⅲ-Ⅳ(12/13, 92.3%) than stage Ⅰ-Ⅱ (24/41, 58.5%; χ2 = 5.066, P < 0.05). Conclusion Survivin mRNA highly expresses in lung cancer, which is related to the progress and malignant behavior. Survivin may play a promoting role in lung cancer genesis and progress and provide a basis for estimating prognosis and treatment.
Keywords:fluorescence in situ hybridization;tissue microarray;Survivin;lung cancer
Abstract:Objective To evaluate the expression of telomerase transcriptional elements-interacting factor (TEIF) in human testis under different status and its relation with human telomerase reverse transcriptase (hTERT) expression. Methods Specific antisera against TEIF were generated by immunization of rabbits with purified recombinated partial TEIF. Samples were assigned to three groups according to their pathological types, including 16 normal testes, 8 atrophic testes, and 6 testicular seminomas. They were subjected to immunohistochemical staining of TEIF and hTERT. Results from both TEIF and hTERT were analyzed semi-quantitatively and compared. Results The expressions of TEIF and hTERT were detected in all samples of normal, atrophic testes, and seminomas. No differences of TEIF expressions among these three groups were observed (P > 0.05). On the contrary, the expressions of hTERT were significantly lower in atrophic testes compared with those of normal testes and seminomas (both P < 0.05). Nevertheless, co-expressions of TEIF with hTERT were revealed to be in normal and malignant cases (P < 0.05) but not in atrophic testes, which generally presented TEIF expression. The cellular distributions of both proteins were similar and mainly in spermatocytes and some Sertoli cells, while were all negative in the interstitial cells and other stromal cells. Conclusions The uniform expressions of TEIF in all these specimens suggest that it may be a marker of testis and its related diseases. The strong expression of hTERT in normal testes and testicular seminomas comparing with the low expres- sion in atrophic testes may suggest a role for telomerase in maintaining proliferation of germ cells.