2003年 · 第116卷第12期

Objective To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes. Methods Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg • kg-1 • d-1)for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents. Results Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of lCa,L was reduced from 12. 8 ±0. 7 pA/pF in the sham-operated cells,to 7. 7 ±0. 8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9±1.0 pA/pF). After IMI treatment, the density of lKs,tail was enhanced from 2. 5 ±0. 1 pA/pF in hypertrophic cells to 4. 7 ±0. 6 pA/pF (n=7, P <0. 01), which was similar to the sham-operated cells. The densities of lto and IK1 were significantly increased in IMI-treated cells, from 3. 8 ±0. 4 pA/pF and 3. 7 ±0. 5 pA/pF in the hypertrophic cells to 6. 4 ±0. 8 pA/pF and 6. 5 ±0. 3 pA/pF, respectively, but the lKr densities were not different in the three groups. Conclusion IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of lCa, L, lKs, lt0 and IK1 in hypertrophic cells. Chin Med J 2003; 116(12): 1795-1798

Objective To investigate changes in the delayed rectifier K+ channel (Kv) function and the regulation of Kv by the protein kinase C (PKC) pathway in bronchial myocytes from asthmatic rats. Methods The Kv currents and membrane potentials in bronchial myocytes from asthmatic rats and from controls were observed, using whole cell voltage- and current-patch clamp techniques. Results Bronchial myocytes from asthmatic rats showed a significant reduction in Kv-current density(51. 6 ±9. 4 pA/pF, n=14, P <0. 01) in comparison with those from control rats (72. 4 ±12. 3 pA/pF, n=14) at+50 mV. The current-voltage relationship curve exhibited a significant downward shift. Bronchial myocytes from asthmatic rats had no significantly different capacitances (P>0. 05), but had more positive membrane potential (P <0. 01) compared with those from controls. 1 μmol/L phorbol 12-myristate 13-acetate, a PKC activator, caused an obvious reduction in Kv-current density (P <0. 01) and a significant downward shift in the current-voltage relationship curve, an effect which was partly abolished by 1 µmol/L Ro31 -8220 (a PKC inhibitor); 1 μmol/L phorbol 12-myristate 13-acetate caused more positive membrane potential (Em), from -36. 8 ±5. 7 mV to -30. 4 ±7. 3 mV, in rat bronchial myocytes (P <0. 05). This effect was partly abolished by 1 μmol/L Ro31 -8220. Conclusions Bronchial myocytes from asthmatic rats have inhibited Kv function, more positive membrane potential, and higher excitability, all of which can also be induced by PKC activation. These characteristics may contribute to the development of airway hyperreactivity in asthma. Chin Med J 2003; 116(12): 1799-1803

Objective To investigate the expression of inducible heme oxygenase (HO-1) gene in pulmonary artery smooth muscle cells (PASMCs) exposed to hypoxia, and the influence of carbon monoxide(CO) on the proliferation of PASMCs under hypoxic conditions. Methods Primary culture of rat PASMCs were passed every 3 days, and the 3 - 5 passages were used. After exposure to hypoxic conditions (95%N2, 5%CO2) 0, 12, 24 and 48 hours, the level of HO-1 mRNA was examined by reverse transcriptase polymerase chain reaction (RT-PCR). The volume of COHb in the medium was measured spectrophotometrically. The cyclic guanosine mono¬phosphate (cGMP) concentration of cell extracts was determined by radioimmunoassay. PASMCs were divided into 5 groups, cultured under normoxia and hypoxia and treated with hemin, hemoglobin(Hb) and exogenous CO respectively. Then 3-(4, 5-cimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay and immunocytochemical staining were used to study the energy metabolism and the expression of proliferating cell nuclear antigen (PCNA) in PASMCs. Flow cytometry was used to analyze the cell cycle of PASMCs. Results After exposure to hypoxic conditions for 12, 24, and 48 hours, the HO-1 mRNA increased by 2. 7%, 5. 7%and 27. 1 %respectively (P <0. 01). The carboxy-hemoglobin (COHb) in the medium increased by 13. 8%, 31. 0%and 93. 1%(P <0. 01); the cGMP concentrations were 2. 7,4. 0 and 6. 8-fold compared with the control group (P <0. 01 and P <0. 05). In comparison with the control group, the value of MTT colorimetric assay, the immunocytochemical staining of PCNA and the percentages of PASMCs in S and G2M phases in the hypoxic group were significantly higher (P <0. 01). After treatment with Hemin and CO, the results of the above analysis decreased significantly(P <0. 01 and P <0. 05), but increased significantly after treatment with Hb (P <0. 01 and P<0. 05). Conclusions The expression of HO-1 gene in PASMCs is upregulated by hypoxia and the production of endogenous CO is elevated as well. The endogenous CO suppresses the proliferation of PASMC in an autocrine way. Both the induction of endogenous CO by Hemin and the treatment with exogenous CO can suppress the proliferation of rat PASMCs of under hypoxic conditions. Chin Med J 2003; 116(12): 1804-1809

Objective To explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy. Methods Therapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12HIV-1 -infected subjects: Group 1 (G1) had 5 patients with CD4 T-cell counts≥500/µl at baseline, Group 2 (G2) had 5 patients with CD4 at 499-200/µl and Group 3 had 2 patients with CD4 <200/µl(not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD4 cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria(at day 10 and 1, 3, 6, 12, 18 and 24 months). Results Levels of plasma tumor necrosis factor-a (TN F-α), soluble TNF-a receptor-2 (sTNF-RII),neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P=0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD4/CD8 ratio and CD25+ and CD4+ CD25+ percentages increased but HLA-DR+percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD4 counts and percentages during 2-year follow-up. Percentage of apoptotic CD4 cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during malaria but the viral load returned to baseline levels 1-3 months after cure of malaria and remained near baseline levels for up to two years. Conclusions Part of the mechanisms of malariotherapy is to induce high levels of cytokine activities and subsequently the changes of T-lymphocyte subsets and phenotypes in HIV-infected patients. These findings suggest that malariotherapy may treat HIV-1 -infected patients whose CD4 baselines are in the range of 500-200/μl. Chin Med J 2003; 116(12): 1810-1820

Objective Accuracy of diagnostic methods for detecting Helicobacter pylori (H. pylori) infection among patients with bleeding peptic ulcers has not been thoroughly investigated. The aim of this study was to compare the diagnostic tests and their combined usage in detection of H. pylori infection in patients with bleeding gastric ulcers and without the use of nonsteroidal anti-inflammatory drugs. Methods A total of 57 patients who presented with bleeding gastric ulcers by endoscopy were enrolled. The status of H. pylori was identified by performing the rapid urease test (RUT), histology and 13C-labeled urea breath test (UBT). The criteria for having H. pylori infection was a minimum of two positive tests. Results The prevalence of H. pylori infection in our patient group was 80. 7%. Among the three tests used: RUT, histology, and UBT, sensitivities were 56.5%, 97.8%and 100%, while specificities were 100%, 45. 5%and 81. 8%, respectively. The overall accuracies of the tests were 78. 3%, 71. 6%and 90. 9%, respectively. Although UBT obtained significantly higher accuracy than histology (P=0. 02) as opposed to RUT (P=0. 11), UBT had significantly higher sensitivity than RUT (P <0. 001). In terms of combining any two of the three tests, more accuracy (98. 9%) was achieved when both UBT and histology were used to confirm the diagnosis of the other. Conversely, failure to use combined tests generated the potential of missing a proper H. pylori diagnosis. Conclusions UBT is superior to the other two tests in bleeding gastric ulcers. RUT lacks sensitivity for detection of H. pylori infection. However, the concomitant use of UBT and histology seems to be more accurate when gastric ulcers present with bleeding. Chin Med J 2003; 116(12): 1821-1826

Objective To investigate retrospectively the efficacy of cyclosporine A (CsA) in the treatment of membranous lupus nephropathy (MLN). Methods Twenty-four patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were treated with CsA in combination with prednisone. CsA was given at a starting dosage of 5 mg • kg-1 • d-1 for 3 months, with a 1mg • kg-1 • d-1 reduction every month and then maintained at a dosage of 2 mg • kg-1 • d-1. The dosage of oral prednisone differed from person to person according to levels of extra-renal activity. Clinical efficacy and adverse reactions were retrospectively analyzed. Complete remission was defined as having a urinary proteinuria level (Upr) of <0. 4 g/d, and normal serum albumin and serum creatinine (SCr) levels, without SLE activity. Partial remission was defined as having a UPr decrement> 50%of baseline value and a serum albumin value of 30 -35 g/L, without SLE activity. No response was defined as having a Upr decrement <50%of baseline value and>2. 0 g/d, or as a deterioration of renal function, or as having active SLE. Results One patient could no longer undergo follow-up, and the other 23 patients were treated with CsA and followed up for 6 -36 months (mean 16. 8 ±8. 4 months). The mean starting dosage of CsA was 4. 7 ±0. 5) mg • kg-1 • d-1 and the trough level of the whole blood CsA was 248 ±110) μg/L. Twelve patients (52. 2%) achieved complete remission, 10 patients (43. 3%) achieved partial remission after CsA treatment, and one patient showed no response. At different CsA treatment timepoint, the complete remission rates were 17. 4%(3rd month), 21. 7%(6th month), 40%(12thmonth), 88. 9%(18th month) and 100%(24th month) respectively. SCr elevation, when within a normal limit was not observed in most patients during early CsA administration, and at the end of the follow-up all the patients had a normal SCr. Relapse occurred in 33. 3%of the patients after withdrawing CsA for 4 -24 months. No chronic CsA renal toxicity was observed in 4 patients who had a repeat renal biopsy after CsA treatment for 6-24 months. Conclusions CsA could be regarded as an effective therapy for patients with membranous lupus nephropathy, but its adverse effects, especially its nephrotoxicity, should be carefully monitored during CsA treatment. Chin Med J 2003; 116(12): 1827-1830

Objective To investigate the increased podocyte permeability by evidence of adriamycin (AD) and its molecular mechanism. Methods In this study, we explored the direct effects of AD on cultured mouse podocytes and the potential protection effects of Dexamethasome (Dex). Results After 24-hour AD (5 x 10-7 mol/L) treatment, albumin passage through podocyte monolayers was increased by 2. 27-fold (P <0. 01) . AD caused a 62%decrease in Zonula Occluden -1 (ZO-1) protein (P <0. 05), suggesting that AD might increase podocyte permeability by disrupting tight junctions. Dex (1 x 10-6 mol/L), co-administered with AD, protected podocytes from AD-induced increased albumin passage. This may be linked with an increased P-cadherin protein level to 1. 93 fold of control (P<0. 01). Conclusions AD has a direct, detrimental effect on podocyte permeability, probably through disrupting tight junctions; Dex could protect against AD-induced high podocyte permeability by upregulating adherent protein P-cadherin. Chin Med J 2003; 116(12): 1831-1835

Objective To explore the experimental method of obtaining position emission tonogiaphy (PET)imaging evidence of changes in cerebral function by puncturing the Stomach 36 (ST36, Zusanli)acupoint. Methods Data on changes of cerebral glycometabolism were obtained from six healthy male volunteers with positron emission tomography. Visual experimental evidence, as well as statistical parametric mapping (SPM), was gathered while puncturing the ST36 (Zusanli, right leg) acupoint. Results There was increased glycometabolism in the hypothalamus, head of the caudate nucleus,temporal lobe, the sinistral cerebellum, postcentral gyrus, and brain stem while the acupoint ST36was being punctured. Conclusions Acupuncture on ST36 can lead to increase in glycometabolism in the vegetative nerve centers, which is correlated with gastric function. Visual experimental evidence of ST36 acupuncturing on functional gastrointestinal disorder was obtained in our study. Chin Med J 2003; 116(12): 1836-1839

Objective To determine the distribution of aortic arch and intra/extracranial cerebral arterial atherosclerosis in Chinese patients who had suffered acute ischemic strokes. Methods Eighty-nine patients with acute ischemic strokes were included in this study. Transesophageal echocardiography (TEE) was used to evaluate potential sources of embolisms in the aortic arch and in the heart; duplex ultrasound was used for the carotid artery; and intracranial Doppler(TCD) imaging was used for the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and basilar artery (BA). An atherosclerotic lesion in the aortic arch was defined as normal (0); mild plaque (1); moderate plaque (2); and protruding plaque or mobile plaque (3). A lesion in the carotid artery was considered a plaque if the maximal carotid plaque thickness was 1. 2 mm. TCD results were deemed abnormal if flow velocity was either greater or lower than normal, and, in the case of the MCA, if an asymmetry index above 21 %was measured. Results Of the 89 patients, 52 (58. 43%) patients showed evidence of aortic arch atherosclerosis(AAA), including 11 (12. 36%) patients graded mild, 18 (20. 22%) patients graded moderate, and 23 (25. 84%) patients graded severe. Of the 23 patients with severe AAA, AAA was determined to be an important potential embolic source in 14 patients. Forty-nine (50. 56%) patients had carotid arterial plaques (CAPs). The incidence of carotid plaques was higher among patients with AAA than among patients without AAA (71. 15%vs 21. 62%, OR=3. 291, 95%CI=1. 740 -6. 225, P<0. 001). TCD abnormalities affecting the MCA were found in 54 (60. 67%) patients. Differences in incidence of TCD abnormalities between patients with AAA and without AAA (69. 23%vs 48. 65%) were not significant(OR=1. 423, 95%CI=0. 976 -2. 076, P=0. 05). There was a higher incidence of AAA in older, male patients with a history of diabetes and smoking. Conclusions AAA is an important potential source of cerebral embolic strokes. The presence of carotid arterial plaques correlates with AAA incidence. Most of carotid artery lesion were plaques other than severe stenosis, it may be the character of carotid atherosclerosis of stroke patients. It appears that atherosclerosis does not mainly occur in the intracranial arteries in stroke patients as thought before. Aged, male, diabetes, and smoking are important risk factors to the AAA. Chin Med J 2003; 116(12): 1840-1844

Objective To investigate the etiology, pathology, and mechanism of pathogenesis of Moyamoya disease. Methods A total of 15 human autopsies were analyzed. In addition, in order to create an animal model of the disease, 21 Japanese rabbits were divided randomly into two groups and subjected to injections of horse serum either intravenously or locally in the area of the sympathetic ganglia. Pathological and immunohistochemical characteristics were observed. Results The pathological features of the autopsies and the animal models both involved intima hyperplasia and stenosis or even occlusion of the lumen in the terminal ends of the internal carotid artery and the anterior and middle cerebral arteries. Disconnections or even breakages of the inner layer of the lumen were also observed, without an obvious inflammatory response. Hyperplasic smooth muscle cells of the medial membrane had extended inward through broken portions of the internal elastic lamina, with intima cell hyperplasia resulting in lumen stenosis. The hyperplastic vascular walls were positive for IgG and IgM. Conclusions The etiology of Moyamoya disease may involve allergic angiitis. A possible mechanism is that proximal portions of the circle of Willis first develop chronic stenosis or occlusion, leading to compensatory small vessel proliferation, which perforates into the cerebral parenchyma. Chin Med J 2003; 116(12): 1845-1849

Objective To observe the clinical effects of lesionectomies combined with bipolar coagulation of the surrounding cortex (BCSC) on symptomatic epilepsy. Methods The effectiveness of lesionectomies combined with BCSC (71 patients) and of lesionectomies alone (78 patients) were compared in follow-up surveys conducted 2-5 years(average of 37 months) post-operation. Results Treatment in the BCSC group was significantly more effective than in the lesionectomy group(P<0.01). Meanwhile, patients in the BCSC group suffered no permanent post-operative complications. Conclusion Lesionectomy combined with BCSC is a new, effective and safe treatment for symptomatic epilepsy. Chin Med J 2003; 116(12): 1930-1932

Objective To investigate the association of fasting and postpiandial triglyceride with carotid intima-media thickness among type 2 diabetic patients in southeast China. Methods A total of 78 type 2 diabetic patients from southeast China were recruited. All the subjects underwent a standardized mixed-meal test (SMMT) and an oral glucose tolerance test. Carotid intima-media thickness (IMT) was measured by color doppler ultrasound examination. Results Postprandial triglyceride (PTG) after SMMT increased significantly in type 2 diabetic patients. The carotid IMT in patients with postprandial hypertriglyceridemia was sinificantly greater than that in patients with postprandial normal-triglyceridemia (0. 90 mm vs 0. 81 mm, P <0. 05), which remained significant after adjustment for fasting TG and HDL-c levels, and the IMT in patients with fasting hypertriglyceridemia only had tendency to increase compared to patients with fasting normal-triglyceridemia (0. 87 mm vs 0. 84 mm, P>0. 05). Conclusion The results suggest that postprandial hypertriglyeridemia may be an independent risk factor of early atherosclerosis in type 2 diabetes. Chin Med J 2003; 116(12): 1933-1935

Objective To investigate hypoxia-inducible factor 1α (HIF-1α) protein expression in normal prostates(NP), benign prostatic glandular hyperplasia (BPH), and prostate adenocarcinoma (Pca). Methods HIF-1α protein expression was determined by immunohistochemistry in formalin-fixed and paraffin-embedded specimens obtained from 13 cases of NP, 28 cases of BPH, and 34 cases of Pca. In cases of Pca, the relationship between HIF-1α protein expression and certain clinicopathological factors, such as clinicopathologic stage and Gleason score, was evaluated. Results NP manifested no immunoreactivity, whereas Pca and BPH showed significantly increased HIF-1 a protein expression. A significantly higher expression was observed in Pca specimens compared with BPH samples. In Pca, no significant relationship between HIF-1 a protein expression and clinicopathological factors was found. Conclusion Our findings of increased HIF-1 a protein expression in BPH and Pca specimens suggests the potential role of this protein in BPH and Pca. Chin Med J 2003; 116(12): 1936-1939

Objective To discuss the relationship between the onset of peptic ulcers (PU) and meteorological factors (MF). Methods In reviewing records from 17 hospitals in the city of Nanning from 1992 to 1997, we found 24, 252 cases of PU in 104, 121 samples of gastroscopic examinations. We then calculated the detectable rate of PU (DRPU) during each season every five days (FD) and made a correlated analysis with the seasonal MF during the same period in Nanning. Finally, we made a multiple regressive correlated analysis of DRPU and the 5MF for the same period of the year. A forecast model based on the MF of the previous FD was established. The real value and the forecast value was being tested and verified. Results From 1992 to 1997, the DRPU is: winter and spring>summer and autumn (P <0. 005). There is a close relationship between the DRPU and the average temperature (AT), the average highest temperature (AHT), the average lowest temperature (ALT), average air pressure (AAP)and the average dew point temperature (ADT) of the five days of the same period of the year (the correlated coefficients are -0. 5348, -05167, -0. 5384, 0. 4579 and -0. 4936, respectively), with P <0. 01. The AT, AHT, ALT, AAP and ADT of the previous FD are of great value in forecasting the onset of PU, with its real value and forecast value corresponding to 66. 6%. Conclusions There exists a close relationship between DRPU and the AT, AHT, ALT, AAP and ADT of the FD for the same period. A mid-term medical meteorological forecast of the onset of PU can be made more accurately and reliably according to the close relation betweenthe DRPU and some MF of the previous FD. Chin Med J 2003; 116(12): 1940-1942

Objective To report the surgical techniques and results of an 8-year follow-up study of 42 patients with a modified orthotopic ileal neobladder restoring normal anatomical relationship. Methods Total cystoprostatectomy was performed extraperitoneally. A 45 - 50 cm segment of the ileal loop was isolated, detubularized, and reconfigured into an "M"-shape to form a pouch. Bilateral ureters were implanted by inserting 1 cm distal segment into the pouch. The bottom of pouch was opened and anastomosed with the urethra. Results Forty-two patients were followed up for 6 to 96 months, 90. 5%of whom were continent in the daytime, and 85. 7%at night. Two patients had a difficulty in urination. The average volume of the pouch was (361 ±48) ml at 12 months postoperation. Urodynamic examination showed the average peak voiding pressure was (86. 8 ±21. 4) cmH2O. The average maximum flow rate (Qmax) was(18. 4 ±6. 1) ml/s. No remarkable ureter reflux and obstruction were found. No patient was detected to have urethral carcinoma. Conclusions Extraperitoneal cystectomy can avoid the tumor contamination of the abdomen and intestinal interference of the operative field. The ureter-inserting implantation technique is a simple anti¬reflux anastomosis method with less ureter stenosis rate. Isolating the neobladder and ureters from the peritoneal cavity can reduce the postoperative complications, such as adhesive ileus, internal hernia, and urine leakage into the peritoneal cavity. The neobladder is similar to the original bladder in position, volume, shape and anti-reflux ureter connection. Chin Med J 2003; 116(12): 1943-1945

Objective To investigate feasible treatment methods for plantar ulcers in leprosy patients according to the agreement between the Ministry of Health (MOH) of China and the Leprosy Mission International(LMI). Methods A total of 2599 complicated foot ulcers in 1804 leprosy cases underwent surgic treatment. Plastic fixation and supports were used, dressings were changed regularly, and protective footwear and modified insoles were provided. Results Of the 2599 foot ulcers 1446 (55. 64%) healed. The cure rate of the patients treated in leprosy hospitals was 71. 31 %, with 219 (15. 15%) recurrences of foot ulcers. The recurrence rate of those who lived at home was 18. 35%. Conclusions Comprehensive treatment of foot ulcers has a high cure rate and a low recurrence rate. Reduction of workload, avoidance of long distance walking, intensification of education on foot self-care and provision of financial support are the main measures for preventing a recurrence of foot ulcers. Chin Med J 2003; 116(12): 1946-1948