Studies on the effect of vanadate on endocytosis and shape changes in human red blood cells and ghosts

When amphipathic cationic drugs are added to intact human RBCs, the RBCs first undergo a stomatocytic shape change and then, if relatively large amounts of drug are added and if the metabolic state of the RBC is appropriate, endocytic vacuoles form. Vanadate has a structural similarity to the transition state of phosphate, which presumably accounts for its ability to inhibit phosphohydrolases, although other actions of vanadate have been described. Vanadate inhibited three forms of drug-induced endocytosis in intact RBCs despite the fact that the three drugs chosen (primaquine, chlorpromazine, and vinblastine) are known to have differing requirements for RBC ATP. Vanadate also inhibited the stomatocytic shape change produced by primaquine, chlorpromazine, and vinblastine, but not the stomatocytosis produced by low pH. Vanadate had no effect on RBC echinocytosis produced by lysophosphatidylcholine. In studying endocytosis in hypotonic, leaky, "white" ghosts, we discovered that vanadate inhibited only the endocytosis produced by Mg-ATP and not the endocytosis produced by manipulations that directly attack the cytoskeletal proteins. These findings suggest that ATP hydrolysis has a role in some forms of amphipathic cation-induced stomatocytosis and endocytosis in intact RBCs. In addition, studies in ghosts support the idea that Mg-ATP does indeed produce "energized" endocytosis dependent on utilization or hydrolysis of ATP.     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Outcome of catheter ablation in the very elderly-insights from a large matched analysis

BackgroundAblation emerged as first line therapy in the treatment of various arrhythmias. Nevertheless, in older patients (pts), decision is often made pro drug treatment as more complications and less benefit are suspected.HypothesisWe hypothesized that different kind of ablations can be performed safely regardless of the pts age.MethodsWe enrolled all pts aged >80 years (yrs) who underwent ablation for three different arrhythmias (atrial flutter [AFL], atrioventricular nodal re‐entry tachycardia [AVNRT], ventricular tachycardia [VT]) between August 2002 and December 2018. Procedural data and outcome were compared with matched groups aged 60 to 80 years and 40 to 60 years, respectively. Periprocedural and in‐hospital complications were analyzed.ResultsThe analysis included 1191 patients (397 pts per group: 63% AFL, 23% AVNRT, 14% VT) who underwent ablation. Acute success was high in all types of arrhythmias irrespective of age (>80, 60‐80, 40‐60 years: AFL 97%/98%/98%, AVNRT 97%/95%/97%, VT 82%/86%/93%). Rate of periprocedural complications were similar in all groups treated for AFL and AVNRT. For VT ablations significant differences were noted between pts > 80 or 60 to 80 years and those aged 40‐60 years (16.1%/14.3%/3.6%). Most complications were infections and groin haematoma. No strokes, iatrogenic atrioventricular blocks and deaths related to the ablation occurred.ConclusionAblation appears safe in pts > 80 years. Success rates were comparable to matched younger cohorts. A significant difference was observed for VT patients.     

Corrigendum

Introduction

In the mid-1990s, Cambodia faced one of the fastest growing HIV epidemics in Asia. For its achievement in reversing this trend, and achieving universal access to HIV treatment, the country received a United Nations millennium development goal award in 2010. This article reviews Cambodia’s response to HIV over the past two decades and discusses its current efforts towards elimination of new HIV infections.

Methods

A literature review of published and unpublished documents, including programme data and presentations, was conducted.

Results and discussion

Cambodia classifies its response to one of the most serious HIV epidemics in Asia into three phases. In Phase I (1991–2000), when adult HIV prevalence peaked at 1.7% and incidence exceeded 20,000 cases, a nationwide HIV prevention programme targeted brothel-based sex work. Voluntary confidential counselling and testing and home-based care were introduced, and peer support groups of people living with HIV emerged. Phase II (2001–2011) observed a steady decline in adult prevalence to 0.8% and incidence to 1600 cases by 2011, and was characterized by: expanding antiretroviral treatment (coverage reaching more than 80%) and continuum of care; linking with tuberculosis and maternal and child health services; accelerated prevention among key populations, including entertainment establishment-based sex workers, men having sex with men, transgender persons, and people who inject drugs; engagement of health workers to deliver quality services; and strengthening health service delivery systems. The third phase (2012–2020) aims to attain zero new infections by 2020 through: sharpening responses to key populations at higher risk; maximizing access to community and facility-based testing and retention in prevention and care; and accelerating the transition from vertical approaches to linked/integrated approaches.

Conclusions

Cambodia has tailored its prevention strategy to its own epidemic, established systematic linkages across different services and communities, and achieved nearly universal coverage of HIV services nationwide. Still, the programme must continually (re)prioritize the most effective and efficient interventions, strengthen synergies between programmes, contribute to health system strengthening, and increase domestic funding so that the gains of the previous two decades are sustained, and the goal of zero new infections is reached.     

重复胃镜检查的原因分析

0　引言　胃镜检查是上消化道疾病诊断的重要方法之一 .了解重复胃镜检查的原因及结果 ,有利于探讨疾病发生发展的基本规律 ,有利于发现诊断和治疗中存在的问题 ,从而提高对消化疾病的诊治水平 .1　材料和方法1.1　材料　随机抽检 1996 / 1998胃镜检查资料为调查对象7812例 ,其中行 2次以上胃镜检查者 937例 .调查内容包括性别、年龄、职业、主要症状和体征、病程、初步诊断、内镜检查时间、次数、内镜诊断、病理诊断、确诊时间 .1.2　方法　回顾性调查上述材料的临床特征 .列表统计研究对象一般情况的分布状况 ,计算各年龄段比例构成 ,各病…     

Childhood cardiac function after twin-to-twin transfusion syndrome – a 10-year follow up

Aim:  To perform a 10-year follow up of cardiac structure and function after twin-to-twin transfusion syndrome (TTTS) – a severe foetal circulatory complication associated with myocardial hypertrophy in the recipient twin.
Methods:  Cardiac dimensions, systolic and diastolic function as assessed by echocardiography including flow and tissue Doppler velocimetry in 22 healthy survivors of TTTS with a mean age of 9.6 (7.2–11.8) years.
Results:  The donor and recipient twin did not show any differences in end-diastolic ventricular size, interventricular septum thickness, diameter of right ventricular outflow tract, cardiac valves, coronary arteries or in systolic blood flow velocities. However, compared with the donors, the recipients had significantly lower E/A ratios because of lower E-waves in both mitral (−0.15 ± 0.10, p < 0.01) and tricuspid (−0.09 ± 0.07, p < 0.01) valves, indicating reduced early diastolic ventricular fillings compared with donors.
Conclusion:  At school age, twins surviving TTTS had a cardiac structure and function within normal range. There were no differences in heart structure or systolic ventricular function between twins but, compared with the donor twin, we found a reduced early diastolic function in the recipient.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.