不稳定性心绞痛病人白细胞变形能力、粘附功能和白细胞CD18表达的变化

目的：探讨白细胞流变性、粘附性与急性心肌缺血的关系，为不稳定性心绞痛（ＵＡ）的治疗提供理论参考。方法：４７例不稳定性心绞痛病人，其中男２９例，女１８例。自发型心绞痛１６例，心肌梗死后心绞痛２２例，初发劳力型心绞痛９例。采用红细胞变形能力测定仪、血栓血小板粘附两用仪和酶联免疫吸附法（ＥＬＩＳＡ）分别检测了４０例健康人和４７例不稳定性心绞痛病人心绞痛发作期和缓解后２４小时的白细胞滤过指数（ＩＦ）、白细胞粘附率（ＬＡＲ）和白细胞不同组别第１８（ＣＤ１８）表达。结果：不稳定性心绞痛病人白细胞变形能力（ＬＤ）明显降低，白细胞粘附功能（ＬＡＦ）和白细胞ＣＤ１８表达明显增加（Ｐ＜０．００１，Ｐ＜０．０１），心绞痛发作时，ＬＤ降低和白细胞粘附功能、白细胞ＣＤ１８表达增高较心绞痛缓解后２４小时更明显（Ｐ＜０．００１），且白细胞滤过指数、白细胞粘附率和白细胞ＣＤ１８表达之间均呈正相关（Ｐ＜０．０１）。心绞痛发作时和缓解后２４小时，自发型心绞痛白细胞滤过指数、白细胞粘附功能和白细胞ＣＤ１８表达较心肌梗死后和劳力型心绞痛变化更明显（Ｐ＜０．０１）。结论：心肌缺血与白细胞流变性和粘附性改变有一定关系     

Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a most efficient monocyte attractant and CCR1 agonist

Chemokines are proinflammatory cytokines that play a role in leukocyte migration and activation. Recent reports showed that RANTES (regulated on activation normal T-cell expressed and secreted chemokine), eotaxin, macrophage-derived chemokine (MDC), and stromal cell-derived factor-1 (SDF-1) are NH(2)-terminally truncated by the lymphocyte surface glycoprotein and protease CD26/dipeptidyl peptidase IV (CD26/DPP IV). Removal of the NH(2)-terminal dipeptide resulted in impaired inflammatory properties of RANTES, eotaxin, MDC, and SDF-1. The potential CD26/DPP IV substrate macrophage inflammatory protein-1beta (MIP-1beta) and the related chemokine, LD78alpha (ie, one of the MIP-1alpha isoforms), were not affected by this protease. However, CD26/DPP IV cleaved LD78beta, a most potent CCR5 binding chemokine and inhibitor of macrophage tropic human immunodeficiency virus-1 (HIV-1) infection, into LD78beta(3-70). Naturally truncated LD78beta(3-70), but not truncated MIP-1beta, was recovered as an abundant chemokine form from peripheral blood mononuclear cells. In contrast to all other chemokines processed by CD26/DPP IV, LD78beta(3-70) had increased chemotactic activity in comparison to intact LD78beta. With a minimal effective concentration of 30 pmol/L, LD78beta(3-70) became the most efficient monocyte chemoattractant. LD78beta(3-70) retained its high capacity to induce an intracellular calcium increase in CCR5-transfected cells. Moreover, on CCR1 transfectants, truncated LD78beta(3-70) was 30-fold more potent than intact LD78beta. Thus, CD26/DPP IV can exert not only a negative but also a positive feedback during inflammation by increasing the specific activity of LD78beta. CD26/DPP IV-cleaved LD78beta(3-70) is the most potent CCR1 and CCR5 agonist that retains strong anti-HIV-1 activity, indicating the importance of the chemokine-protease interaction in normal and pathologic conditions. (Blood. 2000;96:1674-1680)     

高低密度脂蛋白胆固醇对血小板免疫活化的影响及氟伐他汀的干预作用

目的 观察高低密度脂蛋白胆固醇对体内及体外血小板膜PAC-1和CD40L表达的影响及氟伐他汀的干预作用并探讨可能的机制.方法 以低密度脂蛋白胆固醇正常的健康对象为对照,通过流式细胞仪检测高低密度脂蛋白胆固醇患者服用氟伐他汀前后血小板膜PAC-1和CD40L表达阳性率变化;高低密度脂蛋白胆固醇血浆体外孵育健康血小板及低密度脂蛋白胆固醇直接孵育血小板并用氟伐他汀干预,流式细胞仪、RT-PCR及Westen blotting法检测血小板膜PAC-1和CD40L表达阳性率及血小板总CD40L mRNA及蛋白含量.结果 高低密度脂蛋白胆固醇患者PAC-1和CD40L表达较对照组显著升高(9.47%±1.96%比5.73%±1.20%、3.04%±0.62%比1.87%±0.49%,P均<0.01),服用氟伐他汀一个月后随低密度脂蛋白胆固醇浓度降低,血小板膜PAC-1和CD40L表达阳性率均有不同程度降低(7.29%±1.35%比 9.47%±1.96%、2.17%±0.53%比3.04%±0.62%,P均<0.01);体外高低密度脂蛋白胆固醇血浆较低密度脂蛋白胆固醇正常血浆更能促进血小板膜PAC-1和CD40L的表达(10.47%±1.39%比6.39%±1.23%、3.19%±0.73%比1.87%±0.47%,P均<0.01),氟伐他汀在体外未能显著抑制血小板膜PAC-1和CD40L表达(10.39%±1.41%比10.47%±1.39%、3.21%±0.69%比3.19%±0.73%,P均>0.05);单纯高低密度脂蛋白胆固醇在体外亦不能显著增加血小板膜PAC-1和CD40L的表达(3.99%±1.74%比3.87%±1.63%、0.83%±0.46%比0.77%±0.44%,P均>0.05),而高低密度脂蛋白胆固醇+ADP组血小板膜PAC-1、CD40L表达阳性率较ADP组显著增高(17.73%±2.09%比11.31%±2.12%、4.17%±0.71%比2.91%±0.69%,P<0.05),氟伐他汀的体外作用不显著;低密度脂蛋白胆固醇对血小板总CD40L mRNA和蛋白表达无明显影响,但高低密度脂蛋白胆固醇能够显著促进ADP活化血小板CD40L蛋白表达(1.63±0.19比1.40±0.21,P<0.05),氟伐他汀体外不能抑制这一作用.结论 高低密度脂蛋白胆固醇在体内体外均能够促进血小板膜PAC-1和CD40L的表达,氟伐他汀在体内能抑制这一作用;低密度脂蛋白胆固醇本身不能够活化血小板免疫功能,但能够促进活化血小板,氟伐他汀体外无抑制血小板免疫活化的作用.     

Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome

BACKGROUND: The pathophysiology of severe acute respiratory syndrome (SARS) is at present poorly understood, but advanced age and serum total lactate dehydrogenase (LD) activity >300 U L(-1) have been associated with adverse clinical outcomes. Blood leucocytes and lymphocyte subsets were reported to decrease, respectively, in 47% and up to 100% of 38 patients in Beijing. However, their prognostic implications have not been thoroughly investigated. OBJECTIVE: To investigate serum total LD, LD isoenzymes, and other parameters including blood lymphocyte subsets as prognostic indicators in SARS patients for adverse clinical outcomes in terms of admission to intensive care unit (ICU) and death. DESIGN: Retrospective analysis. SUBJECTS AND METHODS: A total of 109 patients with a clinical diagnosis of SARS according to the modified World Health Organization case definition of SARS were recruited from two major acute hospitals in Hong Kong. They were either involved in the initial outbreak of SARS, or cases from the community outbreak of Amoy Gardens between 10 March and 5 May 2003. The clinical diagnosis was subsequently confirmed by serological test and/or molecular analysis. Serum total LD and LD isoenzyme activities, complete blood picture with total leucocyte count and differential counts, absolute counts of CD3+, CD4+, CD8+, natural killer cells and B lymphocytes were measured daily upon admission. Receiver operating characteristic curve analysis was used to determine and compare different cut-offs for various biochemical and immunological parameters at peak serum total LD concentration in predicting adverse clinical outcomes. RESULTS: Of a total of 109 patients, 41 were admitted to ICU and 42 died. Of 42 fatal patients, 24 died in ICU and 18 died in general medical wards. Age was found to be an independent prognostic indicator for death with an area under curve (AUC) of 0.96 [95% confidence interval (CI) = 0.90-0.99] but not for admission to ICU [AUC = 0.61 (CI = 0.51-0.70)]. Whilst serum total LD could only achieve AUC of 0.68 (CI = 0.59-0.77) for predicting death, LD1 isoenzyme was found to be the best biochemical prognostic indicator with AUC of 0.84 (CI = 0.75-0.90), sensitivity of 62% (CI = 46-76%), specificity of 93% (CI = 83-98%) at cut-off activity of > or =80 U L(-1). CD3+, CD4+, CD8+ and natural killer cell counts were promising immunological prognostic indicators for predicting admission to ICU with AUC of 0.94 (CI = 0.86-0.98), 0.91 (CI = 0.81-0.96), 0.93 (CI = 0.85-0.98), and 0.87 (CI = 0.76-0.94), respectively. CONCLUSIONS: Apart from age, serum LD1 activity was the best prognostic indicator for predicting death in patients with SARS compared with serum total LD activity, haemoglobin concentration, leucocyte and lymphocyte counts. Its release could possibly be from blood erythrocytes and body tissues other than the myocardium. Blood CD3+, CD4+, CD8+ and natural killer cell counts were found to be good prognostic indicators for predicting admission to ICU in patients with SARS compared with age, leucocyte count and LD isoenzymes. The suppressed CD3+, CD4+, CD8+, and natural killer cell counts were also implicated in the pathophysiology of SARS. Patients with increased serum LD1 should be closely monitored to ensure prompt management, and preparation for admission to ICU could be planned ahead for patients with suppressed lymphocyte subsets.     

Live donor renal transplantation in Australia 1964-1999: an evolving practice

Abstract
Background:  Australia has a low cadaver organ donor (CD) rate by international standards, leading to the increasing use of live donor (LD) renal grafts.
Aims:  To review the Australian experience with LD transplants from 1964 to 1999.
Methods: Data were obtained from the Australian and New Zealand Dialysis and Transplant Registry. Survival was assessed by the Kaplan−Meier method.
Results:  A total of 1584 LD and 10 252 CD transplants was performed between 1964 and 1999. While the CD rate dropped over the last decade, the LD rate increased, maintaining the overall transplan­tation rate. Only 3.6% of grafts before 1980 were LD, increasing to 28.4% during 1995−1999. Patient and graft survival of LD grafts was superior to CD grafts. Most LD grafts were from live related donors (LRD), most commonly parents or siblings. The number of transplants from live unrelated donors (LURD) has risen (1980−1989, n  = 6; 1990−1999, n  = 143), ­primarily due to more spousal donation, with no ­difference in survival between LRD and LURD groups. Grafts from older donors (>50 years of age) increased, with no graft survival difference between donors <50 years and donors >50 years. LD transplants performed prior to commencement of dialysis increased, with survival similar to grafts performed after dialysis.
Conclusion: The pattern of renal transplantation in Australia has changed, with increasing numbers of LD transplants, growing use of unrelated and older donors, and more transplants before dialysis commences. Long-term patient and graft survival advantages have been maintained, supporting the growing use of live donors to expand the donor pool. (Intern Med J 2002; 32: 569−574)     

Atherogen lipid profile in HIV-1-infected patients with lipodystrophy syndrome

Background: Cases of lipodystrophy syndrome and metabolic disorders have been described since the onset of highly active antiretroviral therapy in HIV-infected patients. The aim of our study was to estimate the prevalence of lipodystrophy (LD) and to define the associated lipid profile of these patients. Methods: The following were determined for each patient: lipid profile (cholesterol and its subfractions, atherogenicity ratios, and triglycerides), blood glucose, and immunovirological markers (CD4(+) cell count and plasma viral load). Patients were classified into two groups on the basis of whether or not they presented with clinical signs of LD. Results: Among 233 HIV-infected patients included in the study, 61 cases (26.1%) of lipodystrophy (LD) were noted. Compared with non-LD patients (NLD), LD patients were older men (P<10(-4)) with a lower CD4(+) lymphocyte cell count (P<0.007) and more often at the AIDS stage (P<10(-3)) (OR=3.2 (95% CI: 1.47-6.2)). Multivariate analysis showed a correlation between LD cases and age (10 years older) (OR=1.78 (95% CI: 1.23-2.57), P<0.002) and the decrease in CD4(+) cell count (100 CD4(+)/mm(3) lower) (OR=1.31 (95% CI: 1.09-1.58), P<0.004). An analysis of lipid subfractions and atherogenicity ratios clearly indicated a proatherogenic lipid profile for the LD patients. Conclusions: The underlying physiopathological mechanism of LD is still unknown. However, the lipid profile of HIV-1-infected patients with a LD syndrome appears to place these patients at an increased risk of progression of atherosclerosis.     

Duodenosis linfocítica: estudio etiológico y formas de presentación clínica

IntroductionLymphocytic duodenosis (LD) is a characteristic lesion in the initial phases of celiac disease (CD) but can be associated with many other entities. The aim of this study was to evaluate the prevalence of distinct causes of LD and possible differences in clinical presentation according to etiology.MethodsA retrospective study was performed that included 194 patients diagnosed with LD (more than 25 intraepithelial lymphocytes per 100 epithelial cells). A preestablished strategy to evaluate the cause of the disease was followed that included celiac serology (antitransglutaminase antibodies), HLA-DQ2/DQ8 genotypes, diagnosis of Helicobacter pylori and small intestinal bacterial overgrowth (SIBO). Diagnosis of CD was established on the basis of clinical and histological response to a gluten-free diet in patients with positive serology or compatible findings on HLA–DQ2 (at least one of the alleles) or -DQ8 (both alleles) study.ResultsThe most frequent cause of LD was CD (39%), followed by SBBO (22%), H.pylori (14%), CD and SIBO (12%), and other causes (13%). Most of the patients (83%) had a compatible HLA-DQ2 or -DQ8 genotype. In these patients, the most frequent diagnosis was CD (46%), while in the absence of HLA-DQ2/DQ8, the most frequent diagnoses were SIBO (44%) and H. pylori (22%). CD was the most frequent diagnosis in patients referred for dyspepsia, diarrhea and anemia, while H. pylori was the most frequent diagnosis in patients with abdominal pain.ConclusionsThe most common causes of LD in our environment are CD, followed by SIBO and H. pylori infection.     

低剂量与传统剂量糖皮质激素治疗成人原发免疫性血小板减少症疗效和安全性比较

目的 :比较低剂量与传统剂量糖皮质激素治疗成人原发免疫性血小板减少症(ITP)的疗效和安全性。方法:对2011年1月1日至2013年8月31日在本院就诊的初治和既往激素敏感的复发ITP患者(n=49)给予口服醋酸泼尼松0.5 mg/(kg·d),治疗3~4周,随后激素缓慢减量。同期接受醋酸泼尼松传统剂量[1 mg/(kg·d)]治疗的患者作为对照组(n=46)。随访资料收集截止期2014年8月31日。动态观察血小板计数,并监测生化指标、出血症状,记录不良事件。结果:低剂量组和传统剂量组治疗总体有效率(ORR)分别为81.6%和82.6%,其中初治的有效率分别为73.0%和80.0%,复发的有效率分别为94.7%和86.7%,2组间均没有统计学差异。2组患者血小板计数达到≥50×109/L和≥100×109/L中位时间均为2周,无统计学差异。血小板计数≥50×109/L维持时间大于6个月和12个月者,低剂量组分别为51.0%和30.6%,传统剂量组分别为45.7%和34.8%,没有统计学差异。2组患者治疗后出血表现均显著改善(均P<0.001)。结论:低剂量糖皮质激素治疗成人ITP疗效与传统剂量者相当,患者耐受性好。     

Leukocyte Filtration Does Not Affect Lymphocyte Subpopulations and NK Cell Function in Recipients of Blood Transfusions

Background and objectives: The possible immunosuppressive action of blood transfusion has aroused great interest recently, particularly with respect to its effects on tumor growth and recurrence rate of malignant disease. Materials and methods: The effect of blood transfusion on lymphocyte subpopulations and NK cell function preoperatively and 6 months postoperatively was studied in 129 patients treated with elective surgery for colorectal malignancy. Forty-two patients (33%) received blood transfusions, 21 of them randomly allocated to receive leukocyte-depleted blood products. Investigation was by means of conventional laboratory methods. Results: In 21 patients receiving a median of 3 units of non-leukocyte-depleted blood products (NLD), a significant reduction in CD4+ lymphocytes (44% vs. 40%, p < 0.01) occurred. In contrast, no significant changes in CD4+ lymphocytes were observed in the 21 patients transfused with leukocyte-depleted blood products (LD). However, with respect to lymphocyte subpopulations and NK cell function, differences between the NLD and LD groups were not significant. There was a marginal decrease in HLA-DR+ lymphocytes in the NLD patients without a history of previous transfusion. Conclusions: There seems to be no major change in lymphocyte subpopulations and NK cell function 6 months after blood transfusion. Thus we cannot confirm our previous findings of a reduced number of CD20+ cells after blood transfusion.     

Low-dose prednisolone therapy for idiopathic thrombocytopenic purpura

Prednisolone (PSL) is widely used for the treatment of idiopathic thrombocytopenic purpura (ITP). We compared the effects of a relatively low dose (0.5 mg/kg/day, LD group) of PSL and the conventional dose (1.0 mg/kg/day, CD group) on 59 ITP patients. Twenty-six patients were treated with low-dose PSL, and 23 patients with the conventional dose. No statistically significant difference was observed in the complete remission rates for the LD group (35%) and the CD group (39%). However, the mean duration of hospitalization was significantly (p < 0.001) shorter for LD group patients than for patients in the CD group (20 days versus 50 days, respectively). In conclusion, low-dose PSL may be as effective as the conventional dose and capable of reducing the cost of hospitalization, thus, improving the quality of life for patients with ITP.     

Two-stage candidate gene study of chromosome 3p demonstrates an association between nonsynonymous variants in the MST1R gene and Crohn's disease

BACKGROUND: Genomewide linkage studies identified chromosome 3p21 as an IBD locus. Genomewide association studies have supported this locus and the Wellcome Trust Case Control Consortium (WTCCC) study narrowed it to a 0.6 Mb region. Our objectives were to perform a 2-stage candidate gene association study of the 3p locus and to identify linkage disequilibrium (LD) between significant single-nucleotide polymorphisms (SNPs) and an Oxfordshire subset (n = 282) of the WTCCC as well as the HapMap SNPs. METHODS: A total of 197 SNPs in 53 genes from the 3p locus were genotyped on the Illumina platform in a screening cohort of 469 Crohn's disease (CD) patients and 461 controls. Significant associations were then genotyped on the iPLEX platform in the original as well as a second cohort of 139 CD patients, 670 ulcerative colitis (UC) patients, and 1131 controls. All cases and controls were Caucasian and from the Oxfordshire region of the UK. RESULTS: An intronic SNP rs1128535 in the TRAIP gene was associated with CD in the screening and validation cohorts (combined [n = 608] P = 0.0004 [corrected 0.002], odds ratio [OR] 0.77, 95% confidence interval [CI], 0.67-0.89]). No association was seen for UC. Epistasis was seen with the common CARD15 mutations (P = 0.00003 [corrected 0.0006], OR 0.48, 95% CI, 0.34-0.68). No LD was demonstrated with the WTCCC SNPs. Strong LD was demonstrated with 2 nonsynonymous HapMap SNPs in the MST1R gene in an adjacent LD block to the peak WTCCC association, suggesting a distinct association signal. CONCLUSIONS: The LD with these functional MST1R variants implicate this gene as having a possible role in CD pathogenesis.     

Short-term safety and efficacy of human GH replacement therapy in 595 adults with GH deficiency: a comparison of two dosage algorithms

The aim of GH replacement therapy in GH-deficient adults is to optimize response with minimum incidence of adverse reactions, but optimal therapy regimens are still to be established. This two-arm parallel study examined effects of two GH dose algorithms in adults with GH deficiency of adult or childhood onset. Patients on low dose (LD; n = 302) received GH at 3 microg/kg per day for 3 months increasing to 6 microg/kg per day for 3 months, and those on conventional dose (CD; n = 293) started on 6 microg/kg per day for 3 months increasing to 12 microg/kg per day for 3 months. The proportion of patients completing therapy was greater for the LD group than the CD group for the first 3 months (93.0% vs. 88.1%; P = 0.037) and overall for the 6 months (90.7% vs. 84.0%; P = 0.013). Both dose groups showed significant increases in lean body mass and decreases in fat mass for all time points. Percent increase in lean body mass was less with LD than CD over the first 3 months (2.43 +/- 4.33 vs. 3.58 +/- 4.69%; P = 0.006) but not overall for the 6-month period (4.38% +/- 5.34% vs. 5.21% +/- 5.99%; P = 0.141). Percent decrease in fat mass was less with LD than CD for the first 3 months (-2.81% +/- 7.81% vs. -5.53% +/- 8.64%; P < 0.001) and overall for the 6-month period (-6.35% +/- 9.42% vs. -9.45% +/- 12.07%; P = 0.006). IGF-I SD score increased less with LD than CD for 0 to 3 and 0 to 6 months, although for IGF-binding protein-3 SD score, there was no significant difference between doses at any time. Arthralgia was the only adverse event that occurred significantly less frequently with LD than with CD. Calculated changes based on gender and onset indicated greater changes in males than females for body composition, but there was little difference in GH-related adverse events between males and females. The lower starting dose with dose titration appeared more favorable, but differences in response between genders and onset of GH deficiency need to be taken into account when setting an individual dose regimen.     

Synergic effect of metabolic syndrome and lipodystrophy on oxidative stress and inflammation process in treated HIV-patients

The aim of this study was to assess the effect of lipodystrophy (LD) associated to metabolic syndrome (MS) on oxidative stress and inflammation in a cohort of 243 HIV-infected patients with MS, all of them under three different antiretroviral regimens. We collected immunovirological, biochemical and metabolic data, as well as anthropometric measurements. In addition, cardiovascular risk was also assessed by means of Atherogenic Index of Plasma (API) and Framingham Risk Score. The MS-LD patient set was characterized by a lower initial lymphocyte CD4 count and CD4/CD8 ratio and a higher initial viral load than the group without LD. We also found worse lipidic and glycaemic profiles (with lower HDL-cholesterol and higher triglyceride and glucose levels) in the MS-LD group. BMI, systolic blood pressure and Framingham score were significantly increased compared to MS-Non LD. In addition, patients with MS and LD had significantly higher levels of carbonylated proteins, lipid peroxidation, IL-6 and IL-8, as well as a significant decrease in the levels of leptin, adiponectin and antioxidant activities of catalase, super oxide dismutase and glutathione associated enzymes. In MS-LD HIV-1 patients, a significant negative correlation was found between Framingham Risk Score and the antioxidant biomarkers, however a positive association was found between API and protein-C reactive and carbonylated proteins. Segregating by ART, the above-mentioned conditions were worse within the MS-LD group whose treatment contained protease inhibitors, such as lopinavir. In conclusion, HIV-1 infected patients treated for at least six months, especially with regimens including PIs, showed a worsening of inflammatory process and oxidative stress.     

Social isolation in HIV-infected patients according to subjective patient assessment and DEXA-confirmed severity of lipodystrophy

This study was designed to investigate the persistence of lipodystrophy (LD)-related social distress and isolation in HIV-infected patients in the current era, according to confirmatory dual energy X-ray absorptiometry (DEXA) measurements. Cross-sectional interview data were collected from 168 HIV-positive adult patients taking more than 2 years of antiretroviral therapy (133 cases with LD diagnosed a mean of 7.2 years before; 35 without LD, controls). Mean time of HIV infection was 16.2 years (2.1–27.3), and the mean time of exposure to highly active antiretroviral therapy of 11.7 years (2.1–21.1). The presence and severity of LD, confirmed by DEXA measurements, correlated with social isolation through a validated scale, including avoidance of social relationships, sex, work, or sport activities. In comparison with control patients, social distress was observed for patients having moderate body changes. The significant correlation between LD and social isolation was irrespective of age, CD4+ count, HIV RNA level, AIDS diagnosis, time of HIV infection, anxiety, or depressive symptoms. These results confirm that patient assessment of LD is correlated with whole-body DEXA scan, and they highlight the role of LD as an independent cause of social isolation even after years of the diagnosis.     

白细胞变形能力和粘附功能与急性心肌梗塞病情相关性

白细胞变形能力和粘附功能与急性心肌梗塞病情相关性刘成玉１曲彦２纪新强３滕青４谭润鸾１（１．青岛医学院诊断学教研室２６６０２１２．青岛市市立医院２６６０２１３．青岛医学院预防医学教研室２６６０２１４．青岛市浮山医院２６６０７１）ＴｈｅＣｏｒｅｌａｔｉｏ...     

冠心病患者白细胞变形能力和粘附功能及细胞粘附分子表达的变化

为探讨白细胞变形能力、粘附功能和细胞粘附分子与冠心病的关系，检测了188例冠心病患者和68例健康人外周血白细胞滤过指数、粘附率、白细胞CD18表达和血清可溶性细胞间粘附分子-1浓度变化。结果发现，冠心病病人白细胞滤过指数、粘附率、白细胞CD18表达及可溶性细胞间粘附分子-1浓度均明显增高，与对照组比较差异有极显著性意义（P＜0．001）。急性心肌梗塞病人各指标增高较不稳定心绞痛和陈旧性心肌梗塞更明显（P＜0．001）、冠心病病人白细胞滤过指数、粘附率与白细胞CD18表达和可溶性细胞间粘附分子-1浓渡呈正相关（r=0．679～0．764，P＜0．001），白细胞滤过指数与粘附率呈正相关（r=0.663，P＜0．001）。提示白细胞变形能力降低，粘附功能和CD18表达及可溶性细胞间粘附分子-1浓度增高，参与了冠心病的发生，且与病情变化有关。     

垂体泌乳素瘤下丘脑多巴胺调节功能的评价

本文以卡比多巴 左旋多巴(CD LD)和灭吐灵(MCP)试验,观察了11例垂体泌乳素(PRL)瘤和7例健康女性血TSH和LH水平的变化,同时与血PRL的变化作比较。结果表明PRL瘤患者血PRL不被CD LD抑制,但其TSH和LH可被显著抑制,并与正常组相似。患者血PRL对MCP的反应低减,而TSH和LH的反应却显著高于正常组,其升高幅度与血PRL基础值呈正相关。提示,PRL瘤患者下丘脑多巴胺调节功能正常,并存在多巴胺与PRL间反馈机制,以致下丘脑多巴胺含量相对过多。     

Automated CD61 immunoplatelet analysis of thrombocytopenic samples

Revision of the current decision point for prophylactic platelet transfusion in thrombocytopenic patients requires the availability of a method that is able to provide accurate platelet counts to as low as 1 x 109/l. This study is the first to evaluate the immunoplatelet method (CD61-Imm) of the haematological analyser Cell-Dyn 4000 in direct comparison with the flow cytometric procedure. Additionally CD61-Imm results were compared with CD4000 optical (Plto) counts in the ranges 20-547 x 109/l (n = 127) and 1-35 x 109/l (n = 107). The immunoplatelet and Plto results were in good agreement between 20 x 109/l and 547 x 109/l, but for samples of < 25 x 109/l the Plto tended to overestimate the counts. We determined the limits of detection (LD) and quantification (LLQ) for all three methods using standard statistical procedures. The LD for the flow cytometric CD41a method was 0.02 x 109/l compared with 0.009 x 109/l and 1.73 x 109/l for the CD61-Imm and Plto methods respectively. The LLQCV = 15% for the CD41a method was 1.8 x 109/l compared with 1.6 x 109/l and 18.0 x 109/l for the CD61-Imm and Plto procedures. In conclusion, (i) the CD61-Imm method performance is at least equivalent to the reference flow cytometric method, and (ii) in severe thrombocytopenia the CD61-Imm count is superior to the Plto count.     

Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome

Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV(+)) patients who were followed during 18 months of HAART. A dramatic polarization to TNF-alpha synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF-alpha synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF-alpha and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF-alpha synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-alpha. Interestingly, we observed that LD is associated with a more dramatic TNF-alpha dysregulation, and positive correlations were found between the absolute number of TNF-alpha CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF-alpha synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV(+) patients.     

Mitochondrial involvement in antiretroviral therapy-related lipodystrophy

OBJECTIVES: The management of HIV infection has greatly improved during recent years essentially because of the appearance of new antiretroviral drugs. Highly active antiretroviral therapy (HAART) has achieved important reductions of viraemia and significant recoveries of CD4(+) cell counts in HIV-infected patients. Nonetheless, cases of HIV-infected individuals experiencing lipodystrophy (LD) are being increasingly reported. The purpose of this work was to analyse whether the presence of mitochondrial abnormalities is a frequent feature in LD, since we previously detected mitochondrial abnormalities in an HIV-patient. The second main objective was to study whether LD could be associated with a specific drug. DESIGN: Seven HIV patients presenting LD and five HIV non-LD controls participated in the study. LD patients met the following criteria: (1) LD was their only clinical abnormality, (2) LD was clinically relevant, (3) compliance with antiretroviral treatment was higher than 90% and (4) patients did not have personal or familial history suggestive of mitochondrial disease or neuromuscular disorder. METHODS: Histological stainings, histo-enzymatic reactions, enzymatic and respiratory activities of mitochondrial respiratory chain complexes, and mitochondrial DNA (mtDNA) depletion and rearrangements were examined on muscle mitochondria. RESULTS: Structural muscle abnormalities, mitochondrial respiratory chain dysfunction or mtDNA deletions were detected in all HIV lipodystrophic patients. CONCLUSIONS: The mitochondrial abnormalities found suggest that mitochondrial dysfunction could play a role in the development of antiretroviral therapy-related lipodystrophy.