Volume 113 · Issue 05 · 2000

Objective To assess the clinical significance of radionuclide techniques in evaluating dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (CAD-CM). Methods 28 patients with DCM and 55 patients with CAD-CM were studied. All patients underwent 99mTc-MIBI myocardial perfusion SPECT and 18F-FDG myocardial metabolic PET. 78 patients had 99mTc-RBC radionuclide ventriculography and 68 patients had coronary angiography. Results The results of 23 patients (82%) with DCM showed mild and non-segmental distribution perfusion abnormalities. 52 patients with CAD-CM (95%) showed perfusion abnormalities that distributed along the coronary vessel territories. Significant perfusion defects were found in 4 patients with DCM (14%) and 45 patients with CAD-CM (82%) (P < 0.01). The average perfusion score was 4.5 ± 2.6 in DCM and 9.6 ± 2.5 in CAD-CM and the area of diminished perfusion was significantly smaller in DCM than in CAD-CM (P < 0.001). Two patients with DCM and 18 patients with CAD-CM had metabolic defects. The patterns of perfusion/metabolic imaging showed mismatch in most patients with CAD-CM but match in most patients with DCM. The LVEF in patients with DCM and CAD-CM was both decreased but the decreases were not statistically different between DCM and CAD-CM. The RVEF in patients with DCM was significantly lower than that in patients with CAD-CM (32.4% ± 13.9% vs 40.9% ± 15.4%, P < 0.05). Conclusion The radionuclide techniques are helpful for distinguishing DCM from CAD-CM. The segmental perfusion abnormality and RVEF are the most important factors for differentiation of DCM from CAD-CM. Chin Med J 2000; 113(5): 392-395

Objective To assess the value of scintimammogrphy with both 99mTC - MIBI and 99mTc - MDP in detecting breast cancer. Methods A total of 35 women with clinical findings of suspicious breast lesions were studied with both 99m Tc MIBI and 99m Tc - MDP scintimammography. All patients underwent surgery within one week and the finaldiagnostic results (histopathological) were obtained. Results Eighteen of 35 abnormalities of breast were pathologically confirmed as breast cancer and 17 as benign lesions. In this group of patients studied, the sensitivity, specificity and accuracy of 99m Tc - MIBI scintimammography were 77.8%, 88.2% and 82.9%, respectively and those of 99m TC - MDP scintimammography were 72.2%, 88.2% and 80.0%, respectively. There was no significant diffference between 99m TC - MIBI and 99m Tc - MDP scintimammography. Conclusion This study showed the high diagnostic accuracy of both 99m TC - MIBI and 99m TC - MDP scintimammography in detecting breast cancer. Both can be used as non - invasively assess breast cancer invasiveness before surgery. Chin Med J 2000; 113(5) : 400 - 403

Objective To evaluate the hypoxia-avid agent 99mTc-HL91 (99m Tc labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) as the tracer of tumor "hot spot" imaging and the influence of tumor necrosis on the image. Methods After injection of 99mTc-HL91, 6 nude mice bearing human breast cancer MCF-7 and 18 nude mice bearing human pancreatic adenocarcinoma were subjected to gamma camera imaging, postmortem analysis, and autoradiography and imaging of tumor sections. Results The image of tumor was identified 1 hour after injection of 99mTc-HL91. Images demonstrated gradually increased 99mTc-HL91 uptake in the tumor 1 -12 hours after injection (P < 0.05 - 0.001). Six hours after injection, the radioactivity ratios of tumor to thorax and tumor to head were higher than 2.1. Six hours after injection, the radioactivity ratios of tumor to brain, muscle, blood, heart, lung and kidney in pancreatic adenocarcinoma bearing nude mice were 101 .0 ± 114.7, 30.0 ± 30.3, 19.9 ± 21.9, 14.4 ± 15.1, 3.71 ± 2.41 and 0.46 ± 0.26, respectively, and the radioactivity ratios in breast cancer MCF-7 bearing nude mice were close to these figures. The radioactivity of non-necrotic tumor was 3.77 times that of necrotic tumor. However, the radioactivity ratios of tumor to liver, intestine and stomach were lower than 1.3. Autoradiographs and images of tumor sections showed that the radioactivity was higher in the region of solid tumor than in the necrotic region. Conclusion 99mTc-HL91 via gamma camera positively identifies regional tumor in nude mice bearing human cancer. 99mTc-HL91 retention is lower in necrotic tumor than in non-necrotic tumor. The low radioactivity ratio of tumor to abdominal organs limits the application of 99mTc-HL91 in detecting abdominal tumors. Chin Med J 2000; 113(5): 404-407

Objective To evaluate the change in D2 receptors and their relationship with dopamine (DA) content in experimental hemi-parkinsonism rats before and after electro-acupuncture (EA) treatment. Methods 1251 -IBZM D2 receptor cerebral autoradiographic analysis, HPLC-ECD detection of DA and its metabolites, homovanillic acid (HVA), 3, 4-dihydroxyphenylacetic acid (DOPAC) were used to study their levels in striatum in pre-EA, EA and EA control group. Results The DA, HVA and DOPAC levels in striatum of the lesioned side in the EA group were elevated compared to the pre-EA and EA control group (P < 0.05). For the EA group, the striatum/cerebellum 125Ⅰ -IBZM uptake ratio of the lesioned side was 8.04 ± 0.71, (29.34% ± 4.83%) more than that of the contralateral side (P < 0.05), while no significant difference was observed as compared with that in the pre-EA group (8.09 ± 0.52, 30.12% ± 4.53%, higher than that of the intact side P > 0.05). It was lower than the EA control group (8.61 ± 0.63, P < 0.05), and the latter was (38.63% ± 3.71%) higher than that in its contralateral side (P < 0.05). Conclusion 6-OH-DA lesions in the substantia nigra and ventral tegmental areas induce an up-regulation of striatal D2 binding sites. EA treatment could elevate the DA level of the lesioned side striatum and prevent D2 receptor up-regulation in rats with experimental hemi-parkinsonism. Chin Med J 2000; 113(5): 408-411

Objective To investigate the relationship between spontaneous echo contrast (SEC) and left atrial appendage (LAA) blood flow velocity using transesophageal echocardiography (TEE) during percutaneous balloon mitral valvotomy (PBMV) in patients with atrial fibrillation and sinus rhythm. Methods Thirty-five patients (21 in sinus rhythm and 14 in atrial fibrillation) with rheumatic mitral stenosis underwent PBMV with intraoperative transesophageal echocardiography monitoring. We measured LAA blood flow velocities and observed the left atrium for various grades of SEC (from 0 = none to 4 = severe), before and after each balloon inflation. Results Left atrial appendage maximal emptying velocity (LAA MEV) was reduced from 35 ± 14 cm/s to 6 ± 2 cm/s at peak balloon inflation and increased to 40 ± 16 cm/s after balloon deflation. Comparison of the values before balloon inflation and after balloon deflation showed that LAA velocities were significantly lower (P < 0.001). During balloon inflation, both maximal emptying velocity (MEV) and maximal filling velocity (MFV) were significantly decreased, compared to those before inflation and after balloon deflation (P < 0.01). And both MEV and MFV were significantly higher after balloon deflation relative to those before balloon inflation. Patients with atrial fibrillation had significantly lower MEV and MFV before and during balloon inflation and after balloon deflation than patients with sinus rhythm. At peak balloon inflation, new or increased SEC grades were observed during 54 of 61 (88%) inflations and unchanged during 7 (12%) inflations. SEC grades were reduced after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%) and remained unchanged after 6 deflations (10%). At peak balloon inflation, left atrium spontaneous echo contrast (LASEC) grade 4 was observed during 14 of 27 (93%) inflations in the atrial fibrillation patients, significantly higher than in patients with sinus rhythm (8 of 34, 24%; P < 0.05). LASEC completely disappeared after 16 of 34 deflations (47%) in the patients with sinus rhythm, significantly higher than in the atrial fibrillation patients (2 of 27 deflations; P < 0.01). The mean time to achieve maximal SEC grade (2.5 ± 1.2 s) correlated with the mean time to trough LAA velocities (2.3 ± 1.1 s) after balloon inflation. Both the time to lowest LAA velocity and the time to highest LASEC were significantly longer in the patients with sinus rhythm than in the atrial fibrillation patients (2.6 ± 1.1 s vs 1.7 ± 1.0 s, P < 0.05 and 2.8 ± 1.4 s vs 1.9 ± 1.3 s, P < 0. 05, respectively). Upon deflation, the mean time to lowest SEC grade (2.9 ± 1.8 s) correlated with the mean time to achieve maximal LAA velocities (2.7 ± 1.6 s). Both intervals are significantly shorter in the patients with sinus rhythm than in the atrial fibrillation patients (2.0 ± 1.6 s vs 3.5 ± 1.5 s, P < 0.01 and 2.2 ± 1.7 s vs 3.6 ± 1.6 s, P < 0.05). Conclusion Reducing the blood flow velocity in the human left atrium by balloon occlusion of the mitral valve may enhance SEC, whereas restoring blood flow after balloon deflation would cause enhanced echogenic blood to disappear or decrease in both groups of patients. Patients with atrial fibrillation demonstrate more severe blood stagnation of the left atrial body and appendage during transient balloon inflation at mitral valve orifice and slower recovery from the stagnation, decreasing to a lesser extent after balloon deflation, when compared to patients with sinus rhythm. Chin Med J 2000; 113(5): 412-417

Objective To examine the effect of different concentrations of aristolochic acid I (AAI) in inducing apoptosis of cultured porcine renal cell line LLC-PK1 and to investigate the relationship between intracellular free calcium concentration ([ Ca+ +]i) and LLC-PK1 apoptosis induced by AAI and the influence of a calcium antagonist, lacidipine on apoptosis and [Ca+ +]i. Methods LLC-PK1 cells were treated in different groups: a. the normal group without treatment; b. the group with AAI alone (0.01 g• L-1, 0.02 g• L-1, 0.04 g•L-1, 0.08 g•L-1); c. the group with lacidipine alone (10 ng• L-1, 102 ng•L-1, 103 ng•L-1); d. the group with AAI (0.04 g • L-1) plus lacidipine (10 ng • L-1, 102 ng•L-1, 103 ng • L-1). Light microscopy, agarose gel electrophoresis, Annexin-V-Flous apoptosis detection kit and flow cytometry using propidium iodide staining to identify or quantify the apoptosis of LLC-PK1 cells. Mean [Ca+ +]i was measured by laser confocus microscopy using Fluo-3/AM staining. Results A series of morphologic changes that were characteristic of apoptosis, Annexin-V-Flous staining positive apoptotic cells and "DNA ladder" were identified in AAI (0.02 g•L-1 - 0.08 g•L-1) treated LLC-PK1 cells. Quantitative analysis of apoptotic cells showed that the percentage of apoptotic cells in AAI (0.02 g• L-1, 0.04 g• L-1 or 0.08 g• L-1) group was significantly higher than that in normal group (5.3%. 48.5%, 78.7% vs 2.6%, P < 0.001 ). Mean [Ca+ + ]i was significantly higher in cells treated with AAI (0.04 g•L-1) than that in normal cells (58.01 ± 18.89 vs 22.66 ± 4.78, P < 0.001). In group treated with AAI plus lacidipine (102 ng • L-1, 103 ng • L-1), mean [Ca+ +]i was significantly lower than that treated with AAI alone (35.47 ± 12.85, 28.55 ± 10.16 vs 58.01 ± 18.89, P < 0.001). And the percentage of apoptotic cells in group treated with AAI plus lacidipine (102 ng•L-1, 103 ng • L-1) was also significantly lower than that treated with AAI alone (19.0%, 27.8% vs 34.7%, P < 0.001). Conclusions High concentrations of AAI may induce apoptosis of LLC-PK1 cells. The mean [Ca+ +]i in AAI-treated LLC-PK1 cells was increased significantly, sugguesting that the increase of [Ca+ +]i may be related to apoptosis in LLC-PK1 cells. Lacidipine may decrease the raised mean [Ca+ + ]i levels caused by AAI and the percentage of apoptotic cells, and lacidipine may ameliorate AAI-induced apoptotic damage by inhibiting the increase of [Ca+ + ]i in LLC-PK1 cells. Chin Med J 2000; 113(5): 418-424

Objective To observe the changes in hypertensive cerebral arteriosclerosis and the incidence of stroke in rats following treatment with Tanakan, a preparation of Ginkgo Biloba (GB). Methods Using two-kidney, two clip renovascular hypertensive rats (RHRs) as animal models - we investigated changes in these hypertensive arteriosclerosis-associated factors: A Ⅰ, A Ⅱ, ALD, ET, SOD and cGMP. Blood levels were observed after oral administration of GB, at both early and late stages of hypertension. Results The degree of arteriosclerosis was more severe in both RHRs control and the later treated group than in the early treated group, with blood levels of A Ⅰ, A Ⅱ, ALD and ET in the former two groups significantly elevated. The degree of arteriosclerosis in the early treated group decreased and the blood levels of A Ⅰ, A Ⅱ, ALD and ET in this group decreased nearly to normal levels. The blood levels of SOD and cGMP were also elevated in the early treated group. Conclusions These results reveal that it is important to treat hypertension as soon as possible, in order to reduce the occurrence of stroke. Chin Med J 2000; 113(5): 425-428

Obkective To determine whether genetic factors may work in concert with autoimmune factors in the pathogenesis of Guillain-Barre syndrome (GBS). Methods We determined the differences in the distribution of HLA alleles between GBS patients and normal controls. HLA-DQA, -DQB and -DRB alleles were typed by the sequence specific primer polymerase chain reaction (PCR-SSP) methods in 47 GBS, 7 patients with Campylobacter jejuni (CJ) enteritis and 50 normal controls. Results There were no differences in the frequency of HLA-DQA, -DQB and -DRB among GBS group, CJ group, normal controls and GBS subgroups with respect to recent CJ infection, GM1 IgG and GM1 IgM antibodies (P > 0.05). There was an increasing tendency of DQA1 * 0301 (P = 0.056, RR = 2.991) in the subgroup with GM1 IgG antibodies and DQA1 * 0302 (P = 0.087, RR = 3.587) in the subgroup with recent CJ infection. No difference was found among GBS, CJ enteritis patients and normal controls. Conclusions The increasing tendency of the two alleles suggests that there may be some relation between genetic factors and immunological factors, but a definite conclusion waits for more cases. Chin Med J 2000; 113(5): 429-432

Objective To detect oral administration of recombinant human insulin to nonobese diabetic (NOD) mice for preventing them from diabetes and insulitis and to detect the effects of oral administration of insulin on Fas and Fas ligand expression on islet of Langerhans. Methods Sixty-four female NOD mice were divided into two groups. One group (34) was orally administered recombination human insulin 1 mg in 500 μl PBS and the other (30) 500 μl PBS only at age of 5 weeks old, twice a week for the first week, then weekly until 30 weeks of age. Results Oral administration of insulin to female NOD mice can significantly suppress diabetes and insulitis. The insulitis was less severe in the group fed with insulin than that in the control group (score of insulitis: 1.25 ± 0.45 vs 3.0 ± 0.76 at 16 weeks of age, P < 0.01). We examined Fas ligand and Fas expression on islets of Langerhans in both groups of NOD mice by using immunohistochemical techniques. We find that Fas only expressed on islets when the mice suffered the diabetes, whereas Fas ligand expressed on islets of the mice fed with insulin at 16 and 20 week of ages. We did not find Fas ligand positive staining on the islet feeding with PBS. Conclusion We speculated that oral insulin may induce Fas ligand expression on the islets and plays a role in protecting the pancreatic β-cell from autoimmune destruction. These results show that oral insulin affected autoimmune diabetes and insulitis in NOD mice. The immune mechanism of oral tolerance is closely related to the change of Fas ligand and Fas system. Chin Med J 2000; 113(5): 433-436

Objective To clarify whether genetic variants of the renin-angiotensin system (RAS) contribute to the development of diabetic nephropathy (DN) in the Chinese. Methods Totally 173 Chinese subjects of Han nationality from Shanghai were classified into! control, DN (-) and DN (+) groups. The latter was subdivided according to diabetic duration at the onset of DN and the stage of DN. Genotyping of five polymorphic sites in four key genes of the RAS: the AGT-T174M, AGT-M235T and AGTR1 genotypes were determined by PCR/restriction enzyme digestion. The insertion/deletion (I/D ) and [ACAC] n-STR microsatellite polymorphic markers were used for ACE and REN genotyping, respectively. Statistical analysis showed comparisons of gene frequencies between any two groups were made with Fisher's exact test or Chi-square test. Logistic regression analysis was performed to identify predictors of DN. Results The frequencies of ACE-DD genotype and ACE-D allele were much higher in DN(+) group than in DN (-) group (0.25 vs 0.05, 0.47 vs 0.29, respectively), so were the frequencies of TT genotype and T allele in AGT-M235T (0.73 vs 0.54, 0.85 vs 0.68, respectively). DN (+) DUR < 5 years group had greatly increased frequencies of AGT-M235T allele and ACE-DD genotype in comparison with DN(-) group (0.92 vs 0.68 and 0.28 vs 0.05. respectively). Logistic regression analysis further identified these two genes as contributing factors to DN. Although AGTR1 and AGT-T174M genotyping analysis revealed differences in frequency distribution between DN (+) and DN (-) or control groups, logistic regression analysis failed to implicate them in the development of DN. Conclusions Our study revealed RAS genes, ACE and AGT-M235T but not AGT-T174M, AGTR1 or REN genotypes, as contributing factors for DN in type 2 diabetes mellitus in Chinese. Chin Med J 2000; 113(5): 437-441