2004年 · 第117卷第06期

Background We determined the diagnosis of hereditary hemorrhagic telangiectasis (HHT) in a suspected HHT family, identified ALK1 gene mutation and established a gene diagnosis method of HHT. The level of related plasma proteins (transforming growth factor β and thrombomodulin) were also analyzed. Methods Bleeding history and family history were collected; Dilatant nasal mucosal capillaries in proband were observed under nasal cavity endoscope; exons 3, 7, 8 of ALK1 gene in proband and her family members were amplified with polymerase chain reaction (PCR), and the PCR products were analyzed. Using enzyme-linked immunosorbent assay (ELISA), plasma TGF-β1 and TGF-β2 concentrations were measured. Plasma thrombomodulin (TM) level was detected by Western blotting. Results Of all family members, four had epstaxis, two had evident telangiectases on skin or mucosa. Gene screening results showed that C to T substitution at position 1231 in exon 8 of ALK1 gene (CGG→TGG) existed in proband, her affected brother and their father. The mutation did not exist in proband's sister-in-law and nephew. Plasma TGF-β1 concentrations in the affected HHT was 20538, 17194, 13131 pg/ml, while that of normal control and unaffected family members was 15950, 20297, 12836 pg/ml, respectively. Plasma TGF-(32 in HHT patients was 14502, 9550, 10592 and that of normal controls 8579, 20297, 7680 pg/ml respectively. Level of plasma TM was in HHT subjects significantly lower than in normal subjects. Conclusions Chinese HHT individuals have mutant ALK1 gene, a C1231T variation on exon 8 of ALK1 is responsible for HHT clinical phenotypes in this family. ALK1 gene analysis, together with special clinical phenotypes and family history, provides a reliable method in diagnosing HHT. In affected HHT subjects, plasma TGFβ levels were not obviously different from those of normal subject; while plasma TM concentration was significantly lower than that in normal subjects. The significance and mechanism remain to be elucidated. Chin Med J 2004; 117(6):808-812

Background We identified the gene mutations in two Chinese pedigree of type I hereditary protein C deficiency and type I hereditary antithrombin deficiency. Methods The plasma level of protein C activity (PC: A), protein C antigen (PC: Ag), protein S activity, antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) of propositi and two family members were detected using ELISA and chromogenic assay, respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus. Results The plasma PC: A and PC: Ag of propositus 1 was 26% and 1. 43 mg/dl, respectively. The PC: Ag and PC: A of his father were normal. The decreased PC: A level was seen in his mother and 4 of his maternal pedigree. PS: A and AT: A were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in propositus 1 and 8 of his relatives. The plasma AT: A and AT: Ag of propositus 2 was 48. 6% and 10. 4 mg/dl, respectively. The reduced AT: A and AT: Ag levels were found in his father and 5 of paternal pedigree. PC: A, PC: Ag and PS: A were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2. Conclusion The C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary protein C deficiency. The 13387-9G deletion, a novel mutation, can cause antithrombin deficiency and thrombosis. Chin Med J 2004; 117(6):813-817

Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP. Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors. Results The coefficient of variation for intra-batch and inter-batch of the assay were 3. 60% and 8. 35%. The plasma and serum vWF-cp activity in healthy individuals were (78. 79 ±9. 17)‰ ( n = 30) and (79. 47 ±10. 78)% (n =53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83 ± 19.98)%, P < 0. 001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P <0. 03 and P <0. 001, respectively), they were relatively high in comparison with that of TTP patients (P<0. 001). Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors. Chin Med J 2004; 117(6):818-822

Background Off-pump coronary artery bypass grafting is fast-becoming a procedure of choice for elective revascularization in high-risk patients with multi-vessel coronary artery disease. However, the role of off-pump coronary artery bypass grafting for patients with acute coronary syndromes requiring emergency revascularization still requires validation. We present our experience to show the feasibility of off-pump coronary artery surgery as an emergency revascularization technique. Methods From April 2001 to September 2003, emergency (operation within 24 hours after hospitalization) coronary artery bypass grafting without cardiopulmonary bypass (CPB) was performed in 66 patients with a mean age of (66. 9 ± 5. 4) years (range 49-72 years). They presented acute coronary syndromes with 38 patients on platelet glycoprotein Ⅱ b/Ⅲ a receptor antagonists. All patients underwent off-pump coronary artery bypass surgery via sternotomy with the intention of complete coronary revascularization. Results An average of 2. 9 grafts per patient were performed and the posterior descending artery and marginal branches of the circumflex artery were grafted in 83. 3% of the patients. There were 4 events of intraoperative cardiac instability, precipitated by occlusion of right coronary artery or positioning of a cardiomegaly heart, leading to immediate conversion to CPB. The mortality rate was 3% (2/66). Two patients suffered postoperative stroke while three needed hemofiltration for acute renal failure. Post surgery elective coronary angiography (n =46) showed no significant stenosis. Conclusion Emergency off-pump coronary artery surgery with complete revascularization is feasible in patients with acute coronary syndrome with low morbidity and mortality and excellent early results. Chin Med J 2004; 117(6):823-827

Background Immunostimulating agents made from bacterial extracts represent a class of medications that contains antigens derived from several bacterial strains and their potential ability to prevent bacterial infections results from the stimulation of the nonspecific component of the immune system. The present study investigated the effect of the oral immunostimulant Broncho-Vaxom, which includes material from eight different species of bacteria that are frequently present in the lower respiratory tract, on the frequency and severity of acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease (COPD). Methods Ninety patients with chronic bronchitis complicated with COPD were randomly divided into groups A and B. Forty-nine subjects in group A received oral capsules containing 7mg Broncho-Vaxom, while 41 patients in group B received similar placebo capsules. Both groups took one capsule daily for the first 10 days of each month for 3 consecutive months. The frequency of acute exacerbation, symptom scores, and lung function were recorded for the following one year period. Results There was a significant decrease in the incidence, duration, and severity of acute exacerbation, as well as a reduction in the course of antibiotics administered and in the dosage of bronchodilator and mucolytic agent in group A, as compared to group B (P < 0. 05, respectively). Symptom scores for cough, sputum, dyspnea, as well as symptoms observed upon auscultation of the chest also improved significantly in group A as compared to group B (P < 0. 05, respectively). The bacterial clearance rate in sputum cultures from patients who received no antibiotics for the first 3 months was also significantly higher in group A compared to group B (P <0. 01). Conclusions Orally administered Broncho-Vaxom is associated with a decrease in the incidence of acute exacerbation and a decrease in the need for antibiotics and symptomatic relief medications in patients with chronic bronchitis accompanied by COPD. Broncho-Vaxom is also associated with a decrease in symptom scores. Without causing any apparent adverse effects, this drug may also help to eradicate pathogenic bacteria in the airways. Chin Med J 2004; 117(6):828-834

Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome of patients undergoing major abdominal surgery. Methods This study was designed as a multicenter, prospective, randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG, IgM, IgA, CD4, CD8, and CD4/CD8, and the inflammatory response was determined by assessing IL-1α, IL-2, IL-6, IL-10, and TNF-α levels. Infectious complications were also recorded. Results One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9, among patients receiving an immune enhancing diet, IgG, IgA, CD4 and CD4/CD8 levels were significantly higher and TNF-α and IL-6 concentrations were significantly lower compared to the control group. Moreover, among patients receiving an immune enhancing diet, when comparing preoperation to day 9 postoperation levels, increases in IgA, CD4, and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-α concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications. Conclusions Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses. Chin Med J 2004; 117(6):835-839

Background In general, it is very important to understand the state of T cell immune response against tumor cells in leukemia patients and it is especially critical to assess the T cell repertoire of untreated patients. As we know, few studies have dealt with the distribution of oligoclonal T cells in leukemia, so we investigated the distribution and clonality of TCR Vβ repertoire of T cells in patients with chronic myelogenous leukemia (CML) in chronic phase. Methods The complementarity determining region 3 (CDR3) of TCR Vβ24 subfamily genes were amplified in peripheral blood mononuclear cells from 27 cases with CML using reverse transcription-polymerase chain reaction (RT-PCR). In order to observe the distribution of TCR Vβ repertoire, the PCR products were further analyzed by genescan technique to evaluate clonality of the detectable TCR Vβ T cells. The PCR products of the oligoclonal T cells from three cases were analyzed by direct sequencing to define the sequence of CDR3. Results The expression pattern of TCR Vβ repertoire in different individuals are different. Vβ2-21 subfamilies could be detected in CML cases. The frequent usage Vβ repertoire in CML was Vβ1, Vβ2 orVβ13. Most of the PCR products from 27 patients displayed polyclonality, while a part of the PCR products from 21 out of 27 samples displayed clonal expansion pattern. The clonal expanded T cells in CML could be found in Vβ16 subfamilies. The frequent usage of Vβ genes in clonal expansion was Vβ3, Vβ13 or Vβ21. Multiple Vβ clonal expansion was a general phenomenon in the same patient. The CDR3 sequence of Vβ21 oligoclonal T cells from 3 cases showed some difference in splice regions and in the usage of J segments. Conclusions These results indicated that clonal expanded T cells could be found in patients with CML and were tendentious in Vβ3, Vβ13 and Vβ21 subfamilies that may be related to the specific immune response for leukemia cell associated antigen. Chin Med J 2004; 117(6):840-843

Background Continuous positive airway pressure (CPAP) treatment has been proven to be effective in improving the symptoms of coexisting coronary heart disease (CHD) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, it is still unclear whether such improvements are linked to changes in vascular endothelial function. This research was carried out to investigate the effects of CPAP treatment on vascular endothelial function in patients with OSAHS and CHD. Methods Thirty-six patients with moderate or severe OSAHS and CHD undergoing three months of CPAP treatment were recruited for this study. The changes in their morning plasma nitric oxide (NO) and endothelin (ET) levels, NO/ET ratio, total ischemic burden (TIB) of the myocardium, apnea hypopnea index (AHI), and minimal and mean pulse oxygen saturation (SpO2) were compared and analyzed before and during CPAP treatment. Results Compared with the plasma levels of ET [(51.39 ±11.69) ng/L] and NO [(36. 67 ± 11.86) μmol/L], NO/ET (0. 71 ±0. 14), AHI (32. 4 ±7. 9), minimal SpO2[(68. 9 ±11.4)%], and myocardial TIB [ (66. 29 ± 16. 37) mm • min] before treatment, there were significant decreases in ET [(33. 41 ±10. 03) ng/L] (P < 0.05), increases in NO [(59. 89 ± 10.26) μmol/L] and NO/ET (1.79 ± 0.38) (P<0. 01), decreases in AHI (1. 9 ± 0. 5), and increases in minimal Sp02[(90. 6 ± 1. 8) %] (all P < 0. 01) and myocardial TIB [(36. 42 ± 10. 87) mm • min] (P < 0. 05) after three months of CPAP treatment. Conclusion CPAP treatment may play an important role in the improvement and protection of vascular endothelial dysfunction and myocardial ischemia in OSAHS patients with CHD. Chin Med J 2004; 117(6):844-847

Background The aim of this study was to evaluate single fiber electromyography (SFEMG) in the diagnosis of ocular myasthenia gravis (OMG), compared with repetitive nerve stimulation (RNS) and blood concentration of antibody to acetylcholine receptor (AchRAb). Methods SFEMG, RNS and AchRAb titration were measured in 90 patients with OMG (44 men, 46 women). Results Markedly increased jitter and ratio of block in the frontalis and the extensor digitorum communis (EDC) were observed (83. 3% and 61. 1%, respectively). The mean jitter was 43. 6 ± 14. 5 μs, and the percentages of jitter > 55 μs and blocking were 16. 9% ± 19% and 3. 5% ±9. 5%respectively in the EDC. The mean jitter was 64. 3 ±25. 6 ±s, and the percentages of jitter >55 ±s and blocking were 33. 5% ±27. 6% and 29. 3% ±23. 2% respectively in the frontalis. The percentage of abnormal RNS was 27. 8% (25/90). There was an increased AchRAb titration in 29 (32. 2%) of the 90 patients. Increased jitter, blocking was negatively correlated with maximum decrement to RNS (P <0. 01). 11. 4% (4/35) of patients with abnormal RNS and 24. 1 % (7/29) patients with abnormal AchRAb were seen in the patients with normal SFEMG in the EDC. Conclusion SFEMG test showed the highest sensitivity in the diagnosis of OMG. To our knowledge, the three methods (SFEMG, RNS and AchRAb) are complementary in the diagnosis and differential diagnosis of OMG. Chin Med J 2004; 117(6):848-851

Background Stroke unit is the most effective treatment method to benefit stroke patients. Our study is to evaluate the early effectiveness of a hospital stroke unit (SU). Methods Three hundred and ninety-two patients who had suffered from acute strokes and who were admitted to our hospital between December 2001 and January 2003 were recruited for this controlled study. All patients were sent at random to either the SU or the general ward (GW) for treatment. The following indices were measured by: Barthel Index (BI), National Institute of Health Stroke Scale (NIHSS), Oxford Handicap Scale (OHS). Results The mean change in BI score between the day of admission and the day of discharge was 20.00 ±24. 36 for the SU group and 10. 63 ±23. 59 for the GW group. A difference that is statistically significant (P = 0. 000). The mean change in NIHSS score was -2. 01 ±6. 61 for the SU group and 0. 55 ±7. 44 for the GW group. A difference that is also statistically significant (P = 0. 000). Finally, the mean change in OHS score was -0. 74 ±1. 04 for the SU group and -0. 28 ±0. 98 for the GW group, also a statistically significant difference (P = 0. 000). Among SU patients, patient satisfaction was higher (P = 0. 000), the rehabilitation success rate was higher (P = 0. 000), and there were fewer complications (P = 0. 000). Conclusion Compared to GW patients, stroke patients treated in a special SU were able to return to normal daily activities earlier, with better social abilities, and have reduced neurological defects, without increasing the overall economic burden. Chin Med J 2004; 117(6):852-855