2000年 · 第113卷第01期

Objective To investigate the occurrence and extent of apoptosis in the course of restenosis. Methods The experimental models of vessel narrowness and intima thickness were established in minipigs' iliac arteries by balloon injury and specimens were retrieved on the 1st, 3rd, 6th, 12th and 30th days for dynamic observation. Apoptotic smooth muscle cells (SMCs) were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results Apoptotic SMCs occurred only in the thickened intima 12 days after injury accompanied with the proliferative SMCs, the percentage of apoptosis was 1.94% ± 0.42% on the 12th day and 1.36% ± 0.31 % on the 30th day respectively. The low frequency of apoptosis compared with the proliferative SMCs was a feature in the restenotic pathology. Conclusions Apoptosis participates in the pathogenetic process of intimal thickening and its level was low compared with proliferation. The findings suggest that attempts to modulate apoptosis after vessel injury constitute a theoretical approach to the prevention of restenosis. Chin Med J 2000; 113(1): 10-13

Objective To evaluate the efficacy and safety of excimer laser coronary angioplasty (ELCA) with adjunctive balloon angioplasty in patient with in-stent restenosis. Methods ELCA was performed in 20 patients of in-stent restenosis. All patients were symptomatic and had class Ⅲ - Ⅳ angina. ELCA was performed with the Spectranetics CVX-300 System. The laser catheter of Vittesse C (concentric) and E (eccentric) with diameter of 1.4 - 2.0 mm was used. Results Laser catheter crossed all stenotic stents without difficulty. The lesion length was 4.6-51.2 mm, mean 20.7 ± 13.7 mm, including 14 lesions > 10 mm. Laser treatment alone increased minimal lumen diameter (MLD) from 0.3 ± 0.3 mm to 1.4 ± 0.3 mm (P < 0.0001) and improved the diameter stenosis from 88.8% ± 10.0% to 46.0% ± 8.0% (P < 0.0001). Adjunctive balloon angioplasty further increased minimal lumen diameter to 2.3 ± 0.7 mm and reduced diameter stenosis to 14.2%±8.2% (P < 0.0001). At follow-up (1-17 months, mean 8.9±5.7 months), 17 (85%) patients had remained asymptomatic, 3 (15%) patients had mild to moderate exertional angina, 1 (5%) patient received CABG. Conclusion ELCA with adjunctive percutaneous transluminal coronary angioplasty (PTCA) is an efficient and safe technique to debulk tissue in the patient with in-stent restenosis. The incidence of procedural related complication was low and ELCA may be used as a good method for in-stent restenosis treatment. Chin Med J 2000; 113(1): 14-17

Objective To study the alteration of Na+ -Ca2+ exchange in rat cardiac sarcolemmal membrane during phases of septic shock. Methods Sepsis was induced by cecal ligation and puncture (CLP). Na+ -Ca2+ exchange was assayed by radioactive analysis. Results Na+ -dependent 45Ca2+ uptake was decreased by 62% - 69% in late phase of sepsis, whereas it was not affected in early phase of sepsis. Na+ -Ca2+ exchange stimulated by 5'guanylyl imidodiphosphate [Gpp (NH) p] was decreased by 65.7% in late phase of sepsis but unaltered in early phase of sepsis. Two agonists (angiotensin Ⅱ and phenylephrine) coupled to Gq and a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) all inhibited Na+ -Ca2+ exchange in late phase of sepsis. Na+ -Ca2+ exchange activities induced by phosphorylation of Na+ -Ca2+ exchange were decreased in late phase of sepsis, whereas inhibition of Na+ -Ca2+ exchange by dephosphorylation was increased both in early and late phases of sepsis. Conclusion The alteration of Na+ -Ca2+ exchange during different phases of sepsis might be related to the activities of Gq, protein kinase C, and phosphorylation/dephosphorylation. Chin Med J 2000; 113(1): 18-21

Objective To investigate the tumor necrosis factor alpha (TNFα) and nitric oxide synthase (NOS) in gastric mucosa of patients with Helicobacter pylori (H. pylori) infection. Methods In supernatants of homogenized antral mucosal biopsy specimens taken from 32 H. pylori positive and 24 H. pylori negative patients with chronic active gastritis and 12 H. pylori negative normal controls, TNFα levels and NOS activity were measured by means of radioimmunoassay and the oxidation of oxyhaemoglobin to methaeglobin by nitric oxide was monitored spectrophotometrically. The presence of chronic active gastritis in biopsy specimens was graded using Rauws' gastritis scores. Results Gastritis scores in specimens of gastritis with and without H. pylori infection were in a similar spectrum but higher than those in normal controls. TNFa levels and NOS activity were significantly higher in H. pylori positive gastritis (TNFα 5.42 ± 2.77 fmol/mg pro, NOS 246.8 ± 70.7 pmol • mg pro-1 • min-1) than those in H. pylori negative gastritis (TNFα 2.67 ± 2.18 fmol/mg pro, NOS 159.0 ± 71.4 pmol • mg pro-1 • min-1) and normal control specimens (TNFα 2.50 ± 2.00 fmol/mg pro, NOS 122.8 ± 57.6 pmol • mg pro-1 • min-1, P < 0.01, respectively). In H. pylori positive gastritis, NOS activity showed positive correlations with gastritis scores (n = 32; r = 0.658, P < 0.01) and TNFa levels (r = 0.427, P < 0.01). Gastritis scores (from 5.3 ± 2.5 to 2.4 ±1.6, P < 0.05), TNFα levels (from 6.02 ± 3.64 fmol/mg pro to 3.21 ± 2.97 fmol/mg pro, P < 0.05) and NOS activity (260.7 ± 70.8 pmol •mg pro-1 • min-1 to 172.6 ± 81.9 pmol • mg pro-1 • min-1, P < 0.01) were markedly decreased in 16 patients after eradication of H. pylori. NOS activity was further more increased after mucosa incubation with TNFa (1.0 nmol/L) in vitro for 24 hours, and the effect was inhibited significantly by the arginine analogue L-NMMA but not by the calcium chelating agent EDTA in specimens obtained from 12 H. pylori positive patients. Conclusion The results suggest that gastric mucosal TNFa and NOS may contribute to the pathogenesis of H. pylori associated gastritis. The enhanced NOS activity expressing the inducible isoform in H. pylori infected gastric mucosa is probably derived from the macrophages, and induced by some cytokines such as TNFα.

Objective To investigate the effect of salt intake on the circadian rhythm of blood pressure and the characteristics of ambulatory blood pressure (ABP) in salt-sensitive (SS) subjects. Methods Twenty-three normotensive subjects and forty-three patients with essential hypertension were included in this study. Salt sensitivity was determined with a chronic dietary salt loading test and an acute venous saline loading test, respectively. 24-hour ABP measurements were performed twice in normotensive subjects when they were on a high salt diet and when they had a low salt diet. Blood and urine samples were collected for measurement of plasma norepinephrine concentration (PNE), plasma renin activity (PRA), angiotensin Ⅱ, aldosterone, erythrocyte sodium content and urinary sodium excretion. 24-hour ABP readings were also obtained in patients with essential hypertension when antihypertensive drugs were discontinued for at least 2 weeks. Results High salt intake attenuated the circadian rhythm of blood pressure in SS normotensive subjects, and the nocturnal decline in blood pressure was smaller in SS patients with essential hypertension than in salt-resistant (SR) patients. The level of PNE was higher and the suppression of PRA was smaller in SS subjects than in SR subjects when they had a high salt diet, and the urinary sodium excretion decreased and the erythrocyte sodium content increased significantly in SS subjects on high salt intake. Conclusions High salt intake caused an abnormal circadian rhythm of blood pressure in SS subjects. The blunted nocturnal decline in blood pressure may be a characteristics of SS patients with essential hypertension. Chin Med J 2000; 113(1): 22-26

Objective To investigate whether albumin can be substituted by mannitolum in cirrhotic patients with tense ascites treated by paracentesis. Methods Sixty-eight patients admitted to this therapeutic procedure were randomly assigned to receive intravenous albumin (36 patients ) and mannitolum (32 patients) infusion. In repeated large-volume paracentesis (3-6 L/day), intravenous albumin 20 g or intravenous 20% mannitolum 250 ml were added. Results In 24 and 48 hours after paracentesis the mean value of electrolytes, liver and renal functions and various indicators of systemic circulation either in Group 1 or in Group 2 cases were found without changes (P > 0.05). As compared with that before paracentesis, the diameter of spleen vein was increased significantly (P < 0.05). The complications occurring after paracentesis were similar in both groups. Conclusions It was suggested that paracentesis with intravenous infusion of mannitolum is an effective and safe method in treating cirrhotic patients with tense ascites. Chin Med J 2000; 113(1): 27-30

Objective To investigate whether inactivation of pl6 gene is frequent in nasopharyngeal carcinoma (NPC) biopsies and whether the pl6 gene may play a role in NPC carcinogenesis. Methods In the present study, the expression of the pl6 gene in 14 NPC biopsies was detected by immunohistochemistry method, and the possible deletion of the exon la and 2 of the pl6 gene was also detected in these biopsies by comparative multiplex PCR-Southern blotting with an attempt to understand the mechanism of pl6 gene down regulation. To further understand the role of the pl6 gene in NPC carcinogenesis, a full-length wild-type pl6 cDNA was introduced into NPC cell line HNE1 with p16 gene down-regulation by electroporation. Seven G418-resistant clones were isolated. PCR was used to detect the integration of the exogenous pl6 cDNA and Northern blotting was used to detect the expression of the pl6 gene in 4/7 clones. Finally the growth suppression of the positive clone was detected twice by cytometry and xenografts. Results It was found that 12/14(85%) NPC biopsies lacked pl6 expression, but only 2/14 (14%) biopsies contained exon 2 deletion. In four stable transfectant clones, only one showed integration of exogenous pl6 cDNA with pl6 mRNA expression increasing. Comparaed to the HNE1 cell line and the transfectant clones without integration of exogenous pl6 cDNA, this transfectant clone showed: (a) a longer doubling time; (b) an accumulation of cells in G1 phase; (c) longer latent period of tumor formation in nude mice. Conclusion These data suggested that the pl6 gene is frequently inactivated in NPC, but the deletion of exons la and 2 of the pl6 gene can not account for high frequent lack of pl6 expression. In addition to the deletion, methylation and mutation must contribute to the alteration of the pl6 gene expression. The direct evidence that the pl6 gene may play a role in NPC was provided by the gene transfer experiment. Up-regulation of pl6 expression can inhibit the growth and tumor formation of NPC cells. All these data show that the pl6 gene is a functional tumor suppressor gene in NPC and takes part in promoting the malignant phenotype reversion of NPC cells.

Objective To study the incidence of Graves' disease and the associated factors. Methods Totally 100 123 people aged 15 to 79 years in Daqing area were surveyed epidemiologically. The investigation was conducted for two years. Results All 301 patients with Graves' disease were first diagnosed, with 74 (1.6‰) males and 227 (4.1‰) females. The total incidence was 3.0‰, showing significant differences between ages and between occupations. Investigation of 18 associated factors for Graves' disease by using the logistic multivariate regression analysis showed the pathological factors of the virus infection history, psychological stimulation, food, drugs, family history, education and distribution. Conclusion This study may suggest the theoretical evidence for prevention and treatment of Graves' disease. Chin Med J 2000; 113(1): 31-34

Objective To investigate the characteristics of mutations in exon 3 - 20 of Wilson disease (WD) gene and their consequences in Chinese population. Methods Sixty unrelated normal Chinese and forty-four unrelated WD patients were studied. Genomic DNA was prepared from peripheral blood leukocytes by a salt-out method. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently direct sequencing were used to identify the mutations and polymorphisms of WD gene. Results Ten different mutations have been found, accounting for 52% of the mutant genes. Five of them are identified as novel missense mutations. Mutations Arg778Leu, Thr935Met and Ala874Val were represented respectively in 28.4%, 6.8% and 3.4%of WD chromosomes. The remaining mutations were found rare and limited to one or two patients. A total of 11 patients were homozygous for a single mutation, and 17 patients were in a compound heterozygous state with or without a known mutation. Conclusion In Chinese, WD seems to result from two or three relatively common mutations and a large number of rare mutations. Arg778Leu and Thr935Met might be hotspots of mutation in Chinese population. The results indicated that the feature of mutations of WD gene is different between Chinese and the Western. Instead of exon 14 and exon 18, we had to select exon 8 and exon 12 first to detect mutations of WD gene in Chinese. It is of great importance to establish a direct diagnostic method for WD. This study improves our knowledge on functional domains of the WD gene, and helps elucidate the wide spectrum of manifestations of the disease as well. Chin Med J 2000; 113(1): 40-43

Objective To investigate the effect of Q-switched alexandrite laser irradiation on dermal melanocytes of nevus of Ota. Methods Multiple biopsies were carried out on 4 patients with nevus of Ota before and after laser irradiation. Altogether 11 samples were examined under light microscope and 14 under transmission electron microscope. Results Immediately after laser irradiation, the dermal melanocytes were destroyed, the melanosomes were degenerated with central vesicle formation within most of them, and intradermal round vacuoles appeared. The epidermis remained intact. Three months to 1 year after irradiation, the degenerated melanosomes and cell debris were scavenged mainly by macrophages. Dermal melanocytes gradually decreased. No fibrosis was found. Conclusion Q-switched alexandrite laser can selectively destroy dermal melanocytes of nevus of Ota and treat the disease safely. Chin Med J 2000; 113(1): 49-52

Objective To estimate the effect of borderline hypertension on the left ventricular hypertrophy and left ventricular diastolic function. Methods Doppler echocardiography was performed and ambulant blood pressure (ABP) was monitored in 92 borderline hypertensive (BH) patients and 36 normotensive subjects, and the following parameters were detected: left ventricular end-diastolic dimension (LVDd), interventricular septal thickness (IVST), posterior wall thickness (PWT), rapid filling phase and late diastolic filling phase peak flow velocity (E and A), the ratio of E/A, isovolumic relaxation time (IVRT), decelerating time (DT) of E peak and internal dimension of left atriuum (LAD) . Left ventricular mass (LVM) was calculated by Devereux equation: LVM(g) =0.8 x 1.04[(LVDd + IVST + PWT)3 -LVDd3] + 0.6. Left ventricular mass index (LVMI, g/m2) was calculated by dividing the value of LVM by body surface area. The upper limits of normal of LVMI were 125 g/m2 for men and 120 g/m2 for women. The ABP's parameters were calculated according to the original readings: (1) average 24-hour blood pressure; (2) daytime and nighttimeblood pressure; (3) blood pressure load values (the percentage of SBP > 140 mm Hg and DBP > 90 mm Hg during daytime or SBP > 120 mm Hg and DBP > 80 mm Hg during night-time); and (4) the ratio of nighttime and daytime blood pressure. Results The left ventricular hypertrophy was found in 17 of 92 BH patients (18.5%). In the study group, 76 cases presented a "dipper pattern" ABP curve, and only 12 of them (15.8%) had LVH, however, 5 (31%) of the other 16 cases with "no-dipper pattern" had LVH. The LVMI in BH group was significantly higher than in normotensives (107.2±13.5 g vs 92.5±11.6g, P <0.01), and it was closely correlated with daytime SBP and load value of daytime's SBP (r = 0.30 and 0.28, respectively, P < 0.01), it also correlated to the 24-hour SBP and night/day SBP ratio (r = 0.25 and 0.22, respctively, P < 0.05). The left ventricular diastolic function was obviously damaged in BH group, compared with those in the normotensive group, all items which reflect the LVDF except IVRT were significantly higher in BH group (P < 0.05 - P < 0.01), which reveals that BH patients have developed insufficient LVDF. Conclusions The study suggests that left ventricular structure and function are impaired in BH patients. SBP level and the day-night rhythm disorder are responsible for the left ventricular involvement. Since BH patients can develop LVH and insufficiency of LVDF which has increased the risk of cardiovascular diseases, it is necessary for us to strengthen the medical care of the BH population to stratify the risk factors and give them adequate directions and reasonable treatments.

Purpose To summarize the main achievements of the control of malaria in the People's Republic of China. Data sources The data are from national case reporting system (1955 - 1998), and bibliographic reviews of textbooks and review articles. Study selection Successes in control and research of malaria were identified and selected to address the stated purpose. Data extraction In the past 50 years, large-scale malaria control activities were conducted in the country, relying on primary health care networks and community participation. The control of malaria was implemented according to the time- and locality-oriented approaches. As a result, remarkable success has been achieved. By the end of 1998, there were 31.3 thousand malaria cases in China, with a morbidity of 0.25 per ten thousand, which dropped by 99% in comparison with that in the 1950s. Results Most of the original hyper-endemic areas became meso- or hypo-endemic and for most of the previously meso- or hypo-endemic areas, the disease became sporadic. Malaria distribution and epidemic pattern also demonstrated great changes. Conclusions Malaria control in China has been considerably successful in the past 50 years, which coincides with the target of the World Health Organization's "Health for all by the year 2000". Chin Med J 2000; 113(1): 89-92