Coronary risk factors in newly diagnosed and previously diagnosed type 2 diabetic men with myocardial infarction

Risk factors for coronary artery disease in 131 known non-insulin-dependent (type 2) diabetic patients is compared to that in 115 newly diagnosed type 2 diabetic subjects and in 316 non-diabetic patients. The subjects, all Indian men aged 21-60 years, represent consecutive survivors of myocardial infarction and were investigated 3-4 months after their acute episode. A group of 524 healthy Indian men aged 21-60 years were included as controls. Significant differences in parameters measured were noted when all diabetic and non-diabetic patients were compared to the control group. Diabetic patients were older than the non-diabetic patients and with significantly higher frequency of hypertension and hypertriglyceridaemia, whilst smoking and family history of coronary artery disease were elicited more frequently in the non-diabetic patients. Mean concentrations of serum total cholesterol and lipoproteins in the diabetic and non-diabetic men were similar, whereas serum triglyceride concentrations were significantly higher in the diabetic patients. Newly diagnosed and known diabetic patients did not differ with respect to the risk factors examined. Clusters of various combinations of hypertension, obesity, hypertriglyceridaemia and low HDL-cholesterol values were encountered more frequently in diabetic patients when compared to non-diabetic patients, whilst no significant differences were observed when the two groups of diabetic subjects were compared. In conclusion, this study has demonstrated that in men with myocardial infarction there are significant differences between diabetic and non-diabetic patients with respect to certain risk factors. However, newly diagnosed diabetic men have similar risk profiles to their known diabetic counterparts.     

Restricted immunoglobulin VH region repertoire in chronic lymphocytic leukemia patients with autoimmune hemolytic anemia

Between 10% and 25% of chronic lymphocytic leukemia (CLL) patients have episodes of autoimmune hemolytic anemia (AIHA) during the course of their disease. The anti-erythrocyte autoantibodies in most cases are polyclonal and express a different heavy chain isotype than the malignant clone, indicating that they are secreted by normal autoreactive B lymphocytes. To further investigate the pathogenesis of the AIHA in CLL, we analyzed the lg heavy (H) chain variable region genes expressed by leukemic cells from CLL patients with and without AIHA. Two VH genes were preferentially expressed by the leukemic cells in the CLL cases with AIHA and were present in 9 of the 12 investigated cases. The 51p1/DP-10 gene was expressed in 5 of these cases and was absent in the control group of 12 consecutive CLL cases without AIHA, whereas the DP-50 gene was present in 4 CLL-AIHA cases and only once in the control CLL group. A strikingly similar H-chain CDR3 region that contained a single reading frame of the DXP4 DH gene segment, and N- encoded proline at the DH/JH boundary, and a tyrosine-rich region encoded by the JH6 gene segment was observed in four CLL-AIHA cases. The preferential expression of two VH gene segments and a particular CDR3 region by the leukemic cells of patients with AIHA suggests that the antibodies produced by the CLL cells are directly involved in the pathogenesis of the hemolytic anemia.     

非转流小型猪原位肝移植模型的建立及评价

目的:建立标准化程度高、重复性和稳定性好的小型猪原位肝移植模型。方法:实验于2004-06/2006-02在南方医科大学南方医院动物研究所完成。选用健康中国版纳小型猪36只,按随机数字表法分为供、受体各18只,施行非转流小型猪原位肝移植手术18例。在非体外静脉转流的条件下行同种异体原位肝移植术,严格控制动物无肝期时间,应用套管法吻合胆总管,另外加强围手术期的处理,使无肝期的血压维持在满意水平。监测动物无肝期时间、手术时间、失血量、输血量及动物存活期;术中监测动物的血液动力学及动脉血气分析、生化指标变化;猪死后当天行尸体解剖明确死亡原因。结果:成功建立非转流小型猪原位肝移植模型18只,均纳入结果分析,无脱失。①实验动物无术中死亡,术后当天死亡1只,死亡原因为急性肺水肿;术后第2天死亡1只,死亡原因为胆总管吻合口胆瘘。术后7d存活率为88.9%。②手术时间、无肝期时间、术中失血量及输血量分别为(179.61±14.27)min,(27.28±3.43)min,(422.22±66.91)mL及(444.44±51.13)mL。③与无肝前期相比,实验动物无肝期平均动脉压、中心静脉压、pH值及碱剩余明显下降(P<0.05￣0.01),心率及血清钾水平显著升高(P<0.01);手术结束时平均动脉压及中心静脉压恢复,经药物调整后血清钾水平下降,pH值逐渐恢复。结论:非转流条件下的小型猪原位肝移植模型是肝移植实验的理想动物模型。     

Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria

The polymorphic frequency of the gene for beta s-globin involved in the generation of sickle trait and sickle cell anemia in the human population is caused by the enhanced resistance of sickle trait individuals to Plasmodium falciparum malaria, as supported by epidemiologic and in vitro studies. However, the mechanism for the protective effect of sickle hemoglobin in vivo has not been fully defined. The generation of transgenic mice expressing high levels of human beta s- and alpha-chains has allowed us to study this phenomenon in vivo in an experimental model. We infected the transgenic beta s mice with two species of rodent malaria and found a diminished and delayed increase in parasitemia as compared with controls. This is in contrast to our previous studies involving the introduction of a beta A transgene, which does not alter the infection. The use of this model allowed us to address the question of the mechanism of protection against malaria in mice expressing sickle hemoglobin. We find that splenectomy of transgenic mice completely reverses the protection against Plasmodium chabaudi adami infection. The results reported have shown a relationship between the presence of the beta s gene product and partial resistance to malaria in an experimental model in vivo and shows that the spleen plays an important role in this protection.     

Elevated prolidase activity in keloids: correlation with type I collagen turnover

BACKGROUND: Keloid pathogenesis involves an altered balance of extracellular matrix metabolism, mainly accumulation of type I collagen. This could be due to excessive synthesis or decreased degradation of matrix, or a combination of both processes. Prolidase, an imidodipeptide-cleaving cytosolic enzyme, plays an important role in the collagen catabolic process by recycling proline for collagen synthesis. Collagen accumulation in keloids is due to an imbalance in the steady state of collagen turnover. OBJECTIVES: To investigate prolidase activity and its role in the steady state of collagen turnover between normal skin and keloid tissue and their derived fibroblasts. METHODS: Ten sets of keloid and normal skin tissues and their derived fibroblasts were employed. Measurements were made of tissue prolidase activity, free proline level, and concentrations of the collagen synthesis product aminoterminal propeptide of type I procollagen (PINP) and the collagen degradative product carboxyterminal telopeptide of type I collagen (ICTP). Also, synthesis of collagens type I and III and matrix metalloproteinases 1 and 2 was investigated using Western blot analysis. RESULTS: Keloid tissues had a significant increase in prolidase activity, up to fourfold that in normal skin. The elevated prolidase activity was accompanied by an increase in tissue PINP and ICTP concentrations in keloid; in addition, the collagen turnover index (PINP/ICTP) was higher in keloids. CONCLUSIONS: The combination of elevated prolidase activity and associated higher collagen synthesis to degradation ratio in keloids suggests a possible metabolic process for the excessive accumulation of type I collagen in keloids.     

蝙蝠葛苏林碱的抗致心律失常性迟后除极

应用标准微电极技术，探讨蝙蝠葛苏林碱(Ds)对豚鼠心室乳头肌迟后除极(DAD)和触发活动(TA)的影响。DS 50 um01.L^-1可消除哇巴因和咖啡因引起的TA，抑制异丙肾上腺素诱发TA。使低K⁺高Ca²⁺、苯肾上腺素诱导TA的发生率分别由 100，75％降低到9.1及22.2％，显著抑制上述因素诱发的DAD。表明Ds对DAD和TA有良好的抑制作用。     

Influenza and Respiratory Virus Surveillance,Vaccine Uptake,and Effectiveness at a Time of Cocirculating COVID-19: Protocol for the English Primary Care Sentinel System for 2020-2021

BackgroundThe Oxford–Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) are commencing their 54th season of collaboration at a time when SARS-CoV-2 infections are likely to be cocirculating with the usual winter infections.ObjectiveThe aim of this study is to conduct surveillance of influenza and other monitored respiratory conditions and to report on vaccine uptake and effectiveness using nationally representative surveillance data extracted from primary care computerized medical records systems. We also aim to have general practices collect virology and serology specimens and to participate in trials and other interventional research.MethodsThe RCGP RSC network comprises over 1700 general practices in England and Wales. We will extract pseudonymized data twice weekly and are migrating to a system of daily extracts. First, we will collect pseudonymized, routine, coded clinical data for the surveillance of monitored and unexpected conditions; data on vaccine exposure and adverse events of interest; and data on approved research study outcomes. Second, we will provide dashboards to give general practices feedback about levels of care and data quality, as compared to other network practices. We will focus on collecting data on influenza-like illness, upper and lower respiratory tract infections, and suspected COVID-19. Third, approximately 300 practices will participate in the 2020-2021 virology and serology surveillance; this will include responsive surveillance and long-term follow-up of previous SARS-CoV-2 infections. Fourth, member practices will be able to recruit volunteer patients to trials, including early interventions to improve COVID-19 outcomes and point-of-care testing. Lastly, the legal basis for our surveillance with PHE is Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002; other studies require appropriate ethical approval.ResultsThe RCGP RSC network has tripled in size; there were previously 100 virology practices and 500 practices overall in the network and we now have 322 and 1724, respectively. The Oxford–RCGP Clinical Informatics Digital Hub (ORCHID) secure networks enable the daily analysis of the extended network; currently, 1076 practices are uploaded. We are implementing a central swab distribution system for patients self-swabbing at home in addition to in-practice sampling. We have converted all our primary care coding to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) coding. Throughout spring and summer 2020, the network has continued to collect specimens in preparation for the winter or for any second wave of COVID-19 cases. We have collected 5404 swabs and detected 623 cases of COVID-19 through extended virological sampling, and 19,341 samples have been collected for serology. This shows our preparedness for the winter season.ConclusionsThe COVID-19 pandemic has been associated with a groundswell of general practices joining our network. It has also created a permissive environment in which we have developed the capacity and capability of the national primary care surveillance systems and our unique public health institute, the RCGP and University of Oxford collaboration.