马来酰亚胺苯甲氨酯聚乙二醇修饰膜蛋白掩盖AB和RhD抗原制备通用血型红细胞

聚乙二醇(PEG)上的活性基团结合在红细胞表面掩盖血型抗原是制备通用血型红细胞的途径之一,这些PEG链有很强的水合作用,能覆盖红细胞表面的大片区域,阻断血型抗原与抗体结合。甲基氧PEG-5000(mPEG-5000)是常用的红细胞修饰剂,主要修饰蛋白上的氨基基团。在氯化氰脲酸(CnCl)催化下,mPEG-5000与红细胞膜上氨基形成共价键连接,掩盖Rh抗原和A或B抗原。CnCl-PEG-5000浓度越高,血型抗原的覆盖效果越好。由于微环境下A和B血型抗原处无氨基基团或者氨基基团不能被CnCl-PEG-5000修饰,不能完全阻断抗-A、B与A和B血型抗原结合。本文报道…     

Rapid achievement of the child survival millennium development goal: evidence from the Navrongo experiment in Northern Ghana

OBJECTIVE: To determine the impact of deploying nurses and volunteers to village locations on demographic and health outcomes. METHOD: We implemented an experimental design that emphasizes the value of aligning community health services with traditional social institutions that organize village life. Data for this analysis come from the Navrongo demographic surveillance system, a longitudinal database that tracks fertility, mortality, and migration events over time. The experiment uses conventional demographic methods for estimating mortality rates from longitudinal demographic surveillance registers. RESULTS: Posting nurses to community locations reduced childhood mortality rates by over half in 3 years and accelerated attainment of the childhood-survival millennium development goal (MDG) in the study areas relative to trends observed in comparison areas. CONCLUSION: Results from the Navrongo experiment demonstrate that community health and family planning programmes can have an impact on childhood mortality. Posting nurses to communities can dramatically accelerate the pace of progress in achieving the childhood-survival MDGs. Community-volunteer approaches, however, have no additional impact, a finding that challenges the child survival value of international investment in volunteer-based health programmes. The total cost of the intensive arm of the project is less than $10 per capita per year. Navrongo research thus demonstrates affordable means of attaining the child survival MDG agenda with existing technologies.     

The way forward

Good public-health decisionmaking is dependent on reliable and timely statistics on births and deaths (including the medical causes of death). All high-income countries, without exception, have national civil registration systems that record these events and generate regular, frequent, and timely vital statistics. By contrast, these statistics are not available in many low-income and lower-middle-income countries, even though it is in such settings that premature mortality is most severe and the need for robust evidence to back decisionmaking most critical. Civil registration also has a range of benefits for individuals in terms of legal status, and the protection of economic, social, and human rights. However, over the past 30 years, the global health and development community has failed to provide the needed technical and financial support to countries to develop civil registration systems. There is no single blueprint for establishing and maintaining such systems and ensuring the availability of sound vital statistics. Each country faces a different set of challenges, and strategies must be tailored accordingly. There are steps that can be taken, however, and we propose an approach that couples the application of methods to generate better vital statistics in the short term with capacity-building for comprehensive civil registration systems in the long run.     

Mefloquine treatment for uncomplicated falciparum malaria in young children 6-24 months of age in northern Ghana

Mefloquine (MQ) single dose 20 mg/kg treatment of falciparum malaria was evaluated in 186 children of 6-24 months of age in northern Ghana. There were 15 RII/RIII-type parasitologic failures, all with Day 2 MQ blood levels significantly lower than children whose parasitemias cleared before Day 7 and remained clear through 28 days. Predictors of RII/RIII parasitologic response were vomiting after MQ dosing, Day 2 MQ levels < 500 ng/mL, and undetectable Day 2 levels of the carboxymefloquine metabolite. There were 50 cases of delayed RI parasitologic failure, but 71% of these cases had undetectable Day 28 blood levels of MQ and drug levels in the remaining 29% ranged below the 620 ng/mL level that suppresses MQ sensitive strains of P. falciparum. Drug levels among infants that tolerated MQ well were not associated with age, weight, hemoglobin, parasitemia, and pre-existing symptoms of vomiting or diarrhea. An observed recurrent parasitemia of 34,400 trophozoites/microL against a MQ blood concentration of 550 ng/mL was taken as indication of tolerance to suppressive levels of the drug at this location.     

Expression of human neutrophil proteins in acne vulgaris

Background In acne vulgaris patients, the presence of a dysregulation of the production of innate and specific antimicrobial peptides has been postulated. Objective This study aims to determine whether human neutrophil proteins (HNP) 1–3 are expressed in acne patients. Materials and methods HNP 1–3 expression was investigated in 35 acne patients treated with isotretinoin and in 25 healthy subjects. At the beginning of the study, two skin biopsies were taken from acne patients; one biopsy was taken from an established pustule and one from uninvolved skin, and the biopsies were repeated after treatment. Only one biopsy was obtained from controls. Results The statistical analysis showed that pustular lesions of acne patients had significantly higher levels of perivascular and interstitial HNP 1–3 expression when compared with the biopsy of uninvolved skin of these patients (P = 0.003, P = 0.001, respectively) and with that of healthy controls (P = 0.007, P = 0.014, respectively). Isotretinoin treatment achieved a decrease in the perivascular and interstitial HNP 1–3 expression of pustular lesions (P = 0.01, P = 0.001, respectively). Conclusion Our current study demonstrates the novel observation that a recently identified antimicrobial peptide, HNP 1–3, is expressed in neutrophils of acne inflammation but not in uninvolved skin of these patients. These results suggest that HNP 1–3 may contribute to the development of inflammatory lesions of acne.     

Validity of data-derived algorithms for ascertaining causes of adult death in two African sites using verbal autopsy

background Verbal autopsy (VA) is used to ascertain causes of death using information obtained from bereaved relatives. Causes of death can be ascertained from VA questionnaires by a panel of physicians or from predefined algorithms. In a previous study, we developed data-derived algorithms using VA data from 796 adult deaths in hospitals in Tanzania, Ethiopia, and Ghana (primary sites). These computerized algorithms accurately estimated the cause-specific mortality fractions (CSMFs) for deaths due to injuries, meningitis, TB/AIDS and diarrhoeal diseases in the primary sites. Since the same data were used to generate and to validate the algorithms, the accuracy of our algorithms may have been overestimated. We report here on the validity of the algorithms when they were applied to VA data from two secondary sites in Ghana and Tanzania. Here, 'validity' is taken to mean the degree to which the algorithms replicated the physician-generated CSMF for major causes of death, when applied to the same VA data. methods VA interviews were conducted in two secondary sites: in Navrongo, Ghana, on 406 adult deaths, where three local physicians independently reviewed the questionnaires and assigned a cause of death. In Morogoro, Tanzania, VA interviews were conducted on 209 adult deaths, and a panel of physicians independently reviewed the VA questionnaires together with the hospital death certificates or hospital records to determine the cause of death. The CSMF obtained using each algorithm was compared with the CSMF obtained using physician review. results For injuries and meningitis, the algorithms and physician review estimated a similar CSMF in the Morogoro and Navrongo data. For TB/AIDS, the algorithm estimated a similar CSMF as the physicians in Morogoro. The algorithm for diarrhoeal diseases did not agree closely with the physicians in Morogoro or Navrongo. conclusions In general, our data-derived algorithms for assigning causes of death due to injuries, meningitis, and TB/AIDS estimated a similar CSMF as the physicians in the secondary sites. Recommendations for further validation and refinement are discussed. Computerized algorithms offer a potentially quick, affordable, and feasible method for assigning causes of death in mortality surveillance or studies using VA.     

Malaria: current status of control,diagnosis, treatment,and a proposed agenda for research and development

Rolling back malaria is possible. Tools are available but they are not used. Several countries deploy, as their national malaria control treatment policy, drugs that are no longer effective. New and innovative methods of vector control, diagnosis, and treatment should be developed, and work towards development of new drugs and a vaccine should receive much greater support. But the pressing need, in the face of increasing global mortality and general lack of progress in malaria control, is research into the best methods of deploying and using existing approaches, particularly insecticide-treated mosquito nets, rapid methods of diagnosis, and artemisinin-based combination treatments. Evidence on these approaches should provide national governments and international donors with the cost-benefit information that would justify much-needed increases in global support for appropriate and effective malaria control.     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

Impact of Hepatitis B Virus Infection,Non-alcoholic Fatty Liver Disease,and Hepatitis C Virus Co-infection on Liver-Related Death among People Tested for Hepatitis B Virus in British Columbia: Results from a Large Longitudinal Population-Based Cohort Study

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine–Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.