2004年 · 第117卷第05期

Background Atrial electrical remodeling (AER) contributes to the maintainance of atrial fibrillation (AF). This study was to compare the effects of Losartan with those of Diltiazem on tachycardia-induced acute AER in rabbits. Methods Twenty-one rabbits paced with maximal atrial capture rate for 3 hours in the right atrium (RA) were randomly divided into saline group, Diltiazem group and Losartan group. After autonomic blockage, we measured atrial effective refractory period (AERP), AERP rate adapting feature, AERP dispersion and RA conduction time at basic cycle lengths (BCLs) of 200 ms and 150 ms at baseline, 0. 5 hour, 1 hour, 2 and 3 hours after rapid atrial pacing. Results In the saline group, there was a prompt decrease in AERP as a result of rapid atrial pacing, and AERP200 and AERP150 were shortened sharply within 0. 5 hour of pacing (30.2 ± 10.5 ms and 24. 1 ± 9. 1 ms, respectively). The AERP did not change dramatically in the Diltiazem and Losartan groups. In the saline group, the value of (AERP200 - AERP150)/50 ms in high RA was 0.17 ±0.08 at baseline and became significantly smaller at 0. 5 hour (0. 08 ± 0. 06), 1 hour (0. 09 ± 0. 06), 2 hours (0. 08 ±0. 04) and 3 hours (0. 09 ±0. 05) (all P <0. 05), suggesting a reduction of rate adaptation of AERP. The value of (AERP200 - AERP150)/50 ms in high RA did not change during the 3 hours of pacing in both Diltiazem and Losartan groups. In the saline group, AERP dispersion increased significantly at 2 and 3 hours (P <0. 05). However, Diltiazem could not prevent the increase of AERP dispersion at 3 hours (P < 0. 05). During Losartan infusion, the AERP dispersion was no longer increased after rapid atrial pacing. There was no significant difference in RA conduction time among the three groups. Conclusion Like calcium antagonist Diltiazem, Losartan could prevent AERP shortening and preserve rate adaptation of AERP after rapid atrial pacing. Losartan is more effective than Diltiazem in inhibiting the increase of AERP dispersion. Chin Med J 2004; 117(5):643-646

Backgroud Recent studies in adult hearts have indicated that KATP channels in the inner mitochondrial membrance are responsible for the protection. And we investigated whether opening of mitochondrial KATP channels (mKATP) could provide myocardial protection for immature rabbits and determined its role in cardioprotection. Methods Thirty-four 3 -4-week-old rabbits, weighing 300 -350 g, were divided randomly into five groups: Group I (control group, n = 8); Group Ⅱ [ diazoxide preconditioning group; n = 8; the hearts were pretreated with 100 μmol/L diazoxide for 5 minutes followed by 10-minute wash out with Krebs-Henseleit buffer (KHB)]; Group Ⅲ [diazoxide + 5-hydroxydeconate (5-HD) preconditioning group; n =5; the hearts were pretreated with 100 μmol/L diazoxide and 100 μmol/L 5-HD); Group IV (diazoxide + cardioplegia group; n = 8; cardioplegia containing 100 μmol/L diazoxide perfused the hearts for 5 minutes before ischemia); Group V (diazoxide + 5-HD + cardioplegia group; n = 5; the cardioplegia contained 100 μmol/L diazoxide and 100 μmol/L 5-HD). All hearts were excised and connected to langend Örff perfusion system and passively perfused with KHB at 38℃ under a pressure of 70 cmH2O. After reperfusion, the recovery rate of left ventricular diastolic pressure (LVDP), ± dp/dtmax, coronary flow (CF), the creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) in coronary sinus venous effluent and the tissue ATP were measured. Mitochondria were evaluated semiquantitatively by morphology. Results After ischemia and reperfusion (I/R), the two groups that were treated by diazoxide only (Groups Ⅱ and Ⅳ) had a significant improvement in LVDP, ± dp/dtmax, and CF recovery. AST, LDH, and CK were decreased, and the levels of tissue ATP in the two groups were higher. Mitochondria was protected better in Group IV than in other groups. Conclusions Activating mKATP channels before and during ischemia can similarly protect immature rabbit hearts, and the mechanism is related to the direct protective effect on mitochondria. Opening of mKATP channel during ischemia provides a better protection for mitochondria than it does before ischemia. Chin Med J 2004; 117(5):647-651

Background Mutations in the cardiac sodium channel gene (SCN5A) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction diseases. Recent studies have shown that polymorphisms in the SCN5A gene also play an important role in the manifestation of disorders involving cardiac excitability. In this study, we investigated the polymorphisms of the SCN5A gene in Han Chinese and its relation to Brugada syndrome (BS). Methods Genomic DNA was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada syndrome patients by means of standard procedures. All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning using an ABI Prism 377 DNA sequencer. Results A total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han Chinese population, including 3 novel ones: G87A (A29A), 4245 + 82A > G, and G6174A. The allele frequencies of each SNP in the Han Chinese population were as follows: G87A (A29A) 27. 5%, A1673G (H558R) 10.4%, 4245 + 82A > G 32.8%, C5457T (D1819D) 41.3%, and G6174A 44. 9%. S1102Y and 10 other SNPs identified in other ethnic populations were not detected in this study. There was no significant difference in the allele frequency of A1673G (H558R) between different ethnic populations (all P > 0. 5). On the other hand, the allele frequency of C5457T (D1819D) among Han Chinese was similar to its frequency among Japanese (P > 0. 5), but higher than that among Americans (P < 0. 005). The allele G1673 (R558) was over-represented in BS patients compared to controls (P < 0.005), but there was no significant difference in genotype frequencies at this locus. There were also no differences in either the allele or genotype frequencies of the 4 other identified SNPs when comparing BS patients with healthy controls. Conclusions The distribution of SCN5A SNPs may vary between different ethnicities. The polymorphism of A1673G might be associated with BS and may contribute to a susceptibility to BS in Han Chinese. Chin Med J 2004; 117(5):652-656

Background Obstructive sleep apnea affects up to 2. 9% of children. This study was to determine demographic and clinical characteristics of a group of children with obstructive sleep apnea syndrome (OSAS) as defined by sleep polysomnography (PSG). Methods A prospective study was conducted in a public-funded general hospital in Hong Kong of China. Children confirmed to have OSAS by PSG were followed up between January 1997 and December 1998. Tonsillectomy and adenoidectomy (T&A) was offered to those with moderate to severe OSAS, and medication was offered to those with mild OSAS. All children were followed up regularly in the sleep clinic and sleep PSG was repeated for those with marked relapse in symptoms. Results Eighty-nine children (64 boys and 25 girls, mean age 7 years) were confirmed to have OSAS out of 352 children who underwent PSG during the study period. The most common symptoms of OSAS were snoring (100%) and sweating (81%) during sleep and nasal blockage (61%) and sleepiness (34%) during daytime. Severe OSAS occurred in 15 children. Moderate OSAS occurred in 33 children. Forty-one children had mild OSAS. Forty-nine children underwent T&A, 5 (boys, <5 years) out of whom were found to have recurrent OSAS within 1 year. Conclusion A male predominance has been found in a group of Hong Kong children with OSAS. Boys undergoing T&A at an early age (<5 years) will be more likely to develop repeated OSAS. Chin Med J 2004; 117(5):657-660

Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113→His), exon 4 (His139→Arg) and GSTP1 polymorphism in exon 5 (lle105→Val) in 100 COPD patients and 100 age- and sex-matched healthy controls. Results The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2. 96 (95% CI 1. 24 - 7. 09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1. 00; and when COPD patients were smokers (current smokers and exsmokers), the OR was less than 1. 00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls. Conclusions mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population. Chin Med J 2004; 117(5):661-667

Background Polycythemia vera (PV) is a malignant disorder of hemaopoietic stem cells which is characterized by clonal hyperproliferation and a low rate of apoptosis. This study was to assess endogenous erythroid colony (EEC) formation in the bone marrow of PV patients and determine its clinical significance. Methods The bone marrow mononuclear cells of 26 patients with PV, 2 patients with secondary erythrocytosis (SE), and 19 normal controls were cultured by Marsh's method for EEC evaluation, and the clinical significance was evaluated. Results EECs appeared in 25 patients with PV but not in 2 patients with SE and 19 normal controls. The number of EECs and the EEC ratio [EEC/erythropoietin (EPO)-dependent colony forming unit-erythroid (CFU-E)] in PV patients positively correlated with hemoglobin (Hb) levels. Their EEC number did not correlate with white blood cell (WBC) counts, platelet (PLT) counts, or leukocyte alkaline phosphatase (LAP) scores. Their EEC did not correlate with serum EPO levels. Fifteen patients with PV were treated with hydroxyurea (Hu) and/or interferon-alpha (IFN-α). Their EEC ratio before treatment positively correlated with the treatment time required for complete remission (CR) and negatively correlated with the time before relapse. The EEC numbers of 7 PV patients treated with Hu/IFN-α decreased after the blood cell counts dropped to normal levels. There was a positive correlation between the EEC ratio and the incidence of attacks of vascular thrombosis in PV patients. The numbers of apoptosised bone marrow mononuclear cells in PV patients were lower than those in normal controls. The EEC numbers of PV patients negatively correlated with the rate of apoptosis of bone marrow mononuclear cells. Conclusions EEC formation is characteristic in PV patients. EEC number in PV patients positively correlates with Hb levels, the time required for CR, and the incidence of attacks of vascular thrombosis. EEC number negatively correlates with the time before relapse. Bone marrow suppressive treatment might decrease EEC number. Thus, EEC number is a sensitive and specific parameter reflecting the abnormal hematopoietic clone burden induced by polycythemia vera. EEC number is an important diagnostic parameter for PV patients. Chin Med J 2004; 117(5):668-672

Background Blood transfusion has been found to be a devastating factor for outcomes of hepatectomy. This study was to assess the value of major hepatectomy without blood transfusion. Methods We retrospectively studied 51 patients who had undergone major hepatectomy without blood transfusion, including 29 patients with primary liver cancer, from August 1997 to December 2000. Sixty patients undergoing major hepatectomy with blood transfusion including 48 patients with primary liver cancer served as controls. Hepatectomy was performed through normothermic interruption of the porta hepatis. Intraoperative ultrasonography was performed to define tumor margins, and an ultrasound dissector was used to dissect liver parenchyma. Results In the study group, the operative mortality and morbidity and 1-, 2-, and 3-year recurrence rates were 0%, 9. 8%, 24. 1%, 27. 6% and 31. 0%, respectively. In the control group, they were 3. 3%, 28. 3%, 43. 5%, 54. 3% and 58. 7%, respectively. Significant differences were seen in morbidity and recurrence rates of patients with liver cancer between the two groups (P <0. 05). Conclusion Major hepatectomy without blood transfusion can reduce postoperative morbidity and recurrence rate of patients with liver cancer. Chin Med J 2004; 117(5):673-676

Background This study examined the prevalence of depressive symptoms among elderly immigrants from Mainland China to Canada and the impact of various psychosocial factors as predictors of the number of depressive symptoms reported by the elderly Chinese immigrants. Methods The participants were 444 elderly immigrants who migrated from Mainland China to Canada. They were a part of a random sample of 2272 elderly Chinese living in the communities and took part in a face-to-face interview to answer questions in an orally administrated questionnaire. The depressive symptoms of the participants were measured by a Chinese version of the Geriatric Depression Scale. Data obtained from the 444 elderly Chinese immigrants was analyzed to assess the impact of various psychosocial factors on the number of depressive symptoms that they reported. Results The findings indicated that 23. 2% of the elderly immigrants were assessed to have some depressive symptoms. When other predicting variables were adjusted, elderly immigrants with more chronic illnesses, less positive attitude towards ageing, poorer physical health, less adequate financial situation, lower level of ethnic identification as Chinese, more service barriers, lower level of life satisfaction, shorter length of residency in Canada and those who lived alone tended to have more depressive symptoms. Conclusions The findings indicate that the prevalence rate of depressive symptoms among our elderly immigrant sample is higher than the one reported in a general elderly population. While further research is recommended to examine the reasons for such a difference, culturally appropriate health services, including health promotion programs, should be promoted to reduce mental health disparities. Chin Med J 2004; 117(5):677-683

Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR). Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone. This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively. Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaPas-AR. LNCaP cells containing empty vector pLXSN served as LNCaPNeo. LNCaP and LNCaPNeo were taken as controls. In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively. Results Growth of LNCaPas-AR was inhibited significantly (P < 0. 05) compared with that of LNCaP and LNCaPNeo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively. No difference was seen between LNCaP and LNCaPNeo (P > 0. 05). Microscopic observation showed that LNCaP and LNCaPNeo cells grew well, but only few LNCaPas-AR cells were alive. Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer. Chin Med J 2004; 117(5):684-688

Background Previous studies have suggested that nomogram can simplize complicated calculations of several varibles. A simple nomogram was constructed to estimate absorption rate coefficient (ka) by using the peak time (tpeak) and the elimination rate coefficient (ke) of drugs administered orally. Methods The nomogram was based on the plasma concentration-time (C-T) curve equation and the function relation between tpeak, ka and ke. A mathematical analysis was presented for the construction of single chart nomogram. To check the degree of accuracy of the developed nomogram, we used it to analyze retrospective profiles of 46 drugs and compared the ka values obtained graphically and those calculated by numerically solving the descriptive equation. In addition, we measured the carbocisteine concentration of 18 healthy volunteers by HPLC with fluorescence detection. To analyze performance error, the measured carbocisteine concentrations were compared with predicted concentrations by the ka obtained from the nomograms along with the other pharmacokinetic parameters. Results The estimated of ka values from nomograms were in very close proximity with the numerical values. The performance error was as follows: median performance error (MDPE) and median absolute performance error (MDAPE) were 1.32% and 18. 15%, respectively. Conclusions The developed nomogram is accurate and reliable. The size of performance error meets the demand of clinical pharmacokinetics. Therefore, the nomograms can offer another convenient and easy method for rational individualized dosage regimens. Chin Med J 2004; 117(5):689-694