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Aims/Introduction Glycemic control in type 1 diabetes can be challenging, and is influenced by many factors. This study aimed to investigate glycemic control and its associated factors in Chinese people with type 1 diabetes. Materials and Methods This cross‐sectional study included 779 participants with type 1 diabetes selected from hospital records review, outpatient clinics and inpatient wards. Data were collected through face‐to‐face interviews, medical records and venous blood samples. Multiple logistic regression analysis was carried out to determine factors associated with glycemic control. Results Among 779 participants, 49.2% were male. The median age was 24 years (interquartile range 14–36 years). The median age at diagnosis of diabetes was 17 years (interquartile range 10–28 years) and the median duration of diabetes was 4 years (interquartile range 1–8 years). The mean ± standard deviation hemoglobin A1c was 9.1 ± 2.5%. Nearly 80% of participants had inadequate glycemic control (hemoglobin A1c ≥7.0%). Multivariable analysis showed that age at diagnosis of diabetes ≤20 years, living in a rural location, low household income, low intake of fruit and vegetables, low level of physical activity, low adherence to insulin, and low utilization of insulin pump were independent risk factors for poor glycemic control (hemoglobin A1c ≥9.0%). Conclusions Inadequate glycaemic control is common among people with type 1 diabetes in China. Efforts should be made to control the modifiable risk factors, which include low intake of fruit and vegetables, low level of physical activity, and low adherence to insulin for the improvement of glycemic control. Appropriate use of insulin pump among type 1 diabetes should be encouraged., This study found that inadequate glycemic control is prevalent among people with type 1 diabetes in China, and several factors contribute to poor glycemic control.

In the months following my mother’s death I searched for outlets for my grief. There were factual obituaries to be written, but I wanted to write something at a deeper level, as a way of trying to ...

Aims To examine whether the age profile of people with Type 1 diabetes differs from that of the general population and in what manner, and to study the clinical characteristics related to metabolic disorders among people with Type 1 diabetes in China. Methods We sequentially enrolled 849 people with Type 1 diabetes from hospital records review, inpatient wards and outpatient clinics. Data were collected via face-to-face interviews, medical records and venous blood samples. Beijing census data for 2011 were used to provide the general population statistics. Descriptive analysis of the results and tests for differences were performed. Results The median (interquartile range) age at diagnosis of diabetes was 16 (9-28) years and the duration of diabetes was 4 (1-8) years. The mean ± sd HbA1c concentration was 76±28 mmol/mol (9.1±2.5%). Compared with the general population, the population with Type 1 diabetes comprised more young individuals and fewer elderly individuals. The overall prevalence of metabolic syndrome among those with Type 1 diabetes was 10.1% (95% CI 7.9-12.2). People with metabolic syndrome were older and were diagnosed with diabetes at an older age. Hypertension and dyslipidaemia were more common in obese individuals with Type 1 diabetes than in their non-obese counterparts. Conclusions Compared with the general population, people with Type 1 diabetes comprised more young and fewer elderly individuals. The prevalence of metabolic syndrome in the Type 1 diabetes population was 10.1%. Hypertension and dyslipidaemia were more prevalent in obese than non-obese individuals.

Cardiopulmonary bypass (CPB) facilitates the repair of cardiac lesions in adults and children. Surgical mortality has decreased with improvements in technique allowing for the successful repair of complex heart defects in neonates of increasingly low body weight and gestational age. The physiological effects of CPB are more significant in children. The presence of intracardiac shunts and other anatomic variants further complicates CPB in patients with congenital heart disease. Special techniques and monitors are often necessary. Protocols are often established within individual institutions to standardize the approach to CPB. The anesthesiologist caring for the patient must understand the physiology of CPB to facilitate the initiation and separation from bypass, and to be able to treat complications. Evidence supporting a particular technique of CPB in pediatric population is still largely from uncontrolled or nonrandomized trials, observational studies, extrapolation from adult studies, and expert opinion. The heterogeneity of congenital heart disease makes randomized controlled trials or meta-analyses challenging, and thus they are limited in the literature.

Initially described in 1948 by Hertert thromboelastography (TEG) provides a real-time assessment of viscoelastic clot strength in whole blood. Rotational thromboelastometry (ROTEM) evolved from TEG technology and both devices generate output by transducing changes in the viscoelastic strength of a small sample of clotting blood (300 µl) to which a constant rotational force is applied. These point of care devices allow visual assessment of blood coagulation from clot formation, through propagation, and stabilization, until clot dissolution. Computer analysis of the output allows sophisticated clot formation/dissolution kinetics and clot strength data to be generated. Activation of clot formation can be initiated with both intrinsic (kaolin, ellagic acid) and extrinsic (tissue factor) activators. In addition, the independent contributions of platelets and fibrinogen to final clot strength can be assessed using added platelet inhibitors (abciximab and cytochalasin D). Increasingly, ROTEM and TEG analysis is being incorporated in vertical algorithms to diagnose and treat bleeding in high-risk populations such as those undergoing cardiac surgery or suffering from blunt trauma. Some evidence suggests these algorithms might reduce transfusions, but further study is needed to assess patient outcomes.

Aims The paucity of data on Type 1 diabetes in China hinders progress in care and policy-making. This study compares Type 1 diabetes care and clinical outcomes in Beijing and Shantou with current clinical guidelines. Methods The 3C Study was a cross-sectional study of the clinical practices and outcomes of people with Type 1 diabetes. The study sequentially enrolled 849 participants from hospital records, inpatient wards, and outpatient clinics. Data were collected via face-to-face interviews with patients and health professionals, the Summary of Diabetes Self-Care Activities, medical records, and venous blood samples. Care was audited using ISPAD/IDF indicators. Data underwent descriptive analysis and tests for association. Results The median age was 22 years (IQR = 13–34 years), and 48.4% of the sample had diabetes less than six years. The median HbA1c was 8.5% (69 mmol/mol) (IQR 7.2–10.5%), with significant regional variance (p = 0.002). Insulin treatment was predominantly two injections/day (45% of patients). The highest incidence of diabetic ketoacidosis was 14.4 events/100 patient years among adolescents. Of the 57.3% of patients with LDL-C > 2.6 mmol/L, only 11.2% received treatment. Of the 10.6% considered hypertensive, 47.1% received treatment. Rates of documented screening for retinopathy, nephropathy, and peripheral neuropathy were 35.2%, 42.3%, and 25.0%, respectively. The median number of days of self-monitoring/week was 3.0 (IQR = 1.0–7.0). There were significant differences in care practices across regions. Conclusions The study documented an overall deficit in care with significant regional differences noted compared to practice guidelines. Modifications to treatment modalities and the structure of care may improve outcomes.

Aim To describe coverage, cost and care of type 1 diabetes (T1D) in 2 regions of China – Beijing and Shantou – including: Estimating the numbers of people with T1D diabetes. Estimating the economic burden of T1D and financial barriers to care. Identifying scale of necessary government investment to improve health care coverage. Defining the burden of disease based on clinical outcomes. Describing the education and care experience of people with T1D with comparison to selected clinical practice guidelines. Describing the information processes associated with diabetes care and education. Methods This is a mixed-methods descriptive study with three arms – coverage, cost and care. It is taking place in 4 tertiary hospitals, 3 secondary hospitals and 4 primary health facilities in Beijing, and 2 tertiary hospitals, 2 secondary hospitals and 2 primary health centres in Shantou, China. Two additional hospitals are involved in the coverage arm of the study. T1D participants are recruited from a 3-year list generated by each hospital and from those attending the outpatient clinic or admitted to the inpatient ward. Participants also include health care professionals and government officials. To determine coverage of care, a list of people with T1D is being developed including information on diagnosis, age, sex and vital status. The age and sex distribution will be compared with the expected distribution. To estimate the economic burden of T1D three groups of costs will be calculated – direct medical costs, direct non-medical costs and indirect costs from different perspectives of analysis (patients and their families, health system, insurer and societal perspective). The data are being collected from people with T1D (patient–parents face-to-face interviews), hospital billing departments, medical records and government officials using a combined “top-down, bottom-up” approach developed to validate the data. Quality of life is assessed using the EQ-5D tool and burden of disease is measured based on clinical outcomes and complications. Standard care will be defined, costed and compared to the cost of current care identified within the study to determine the investment required to improve outcomes. The third arm includes three components – health policy, clinical care and education, and information management. Face-to-face, semi-structured interviews are conducted with people with T1D (for those [7] . Clinical outcomes and self-care activities will be analysed for associations with care and education. Information management and care processes will be described using the Standard for Integration Definition for Function Modelling (IDEF0) [8] . Progress to date At the time of writing (early October) the 3-year case list includes 1269 people with type 1 diabetes from Beijing and 481 people for Shantou, a total of 1750. In addition, two hundred and twenty people with T1D or their parents participated in face-to-face interviews in Beijing and 183 in Shantou, a total of 403. Practical preliminary conclusions Key implementation considerations were identified early in the project. Project success is dependent on strong local partnerships with local opinion leaders and key officials. It is important that a physician is the first point of contact to build the case list and recruit participants. July, August and January are peak months for recruiting school-age children in the Children's Hospital as this is school vacation period when they are more likely to attend clinics.

The Gulf of Mexico Alliance (GOMA) was tasked by the five Gulf State Governors to identify major issues affecting the Gulf of Mexico (GoM) and to set priorities for ameliorating these problems. One priority identified by GOMA is the need to improve detection methods for water quality indicators, pathogens and microbial source tracking. The United States Environmental Protection Agency (USEPA) is tasked with revising water quality criteria by 2012; however, the locations traditionally studied by the USEPA are not representative of the GoM and this has raised concern about whether or not the new criteria will be appropriate. This paper outlines a number of concerns, including deadlines associated with the USEPA Consent Decree, which may prevent inclusion of research needed to produce a well-developed set of methods and criteria appropriate for all regulated waters. GOMA makes several recommendations including ensuring that criteria formulation use data that include GoM-specific conditions (e.g. lower bather density, nonpoint sources), that rapid-testing methods be feasible and adequately controlled, and that USEPA maintains investments in water quality research once the new criteria are promulgated in order to assure that outstanding scientific questions are addressed and that scientifically defensible criteria are achieved for the GoM and other regulated waterbodies.

Summary Background There are no methodologically rigorous studies of the incidence of stroke in sub-Saharan Africa. We aimed to provide reliable data on the incidence of stroke in rural and urban Tanzania. Methods The Tanzania Stroke Incidence Project (TSIP) recorded stroke incidence in two well defined demographic surveillance sites (DSS) over a 3-year period from June, 2003. The Hai DSS (population 159 814) is rural and the Dar-es-Salaam DSS (population 56 517) is urban. Patients with stroke were identified by use of a system of community-based investigators and liaison with local hospital and medical centre staff. Patients who died from stroke before recruitment into the TSIP were identified via verbal autopsy, which was done on all those who died within the study areas. Findings There were 636 strokes during the 3-year period (453 in Hai and 183 in Dar-es-Salaam). Overall crude yearly stroke incidence rates were 94·5 per 100 000 (95% CI 76·0–115·0) in Hai and 107·9 per 100 000 (88·1–129·8) in Dar-es-Salaam. When age-standardised to the WHO world population, yearly stroke incidence rates were 108·6 per 100 000 (95% CI 89·0–130·9) in Hai and 315·9 per 100 000 (281·6–352·3) in Dar-es-Salaam. Interpretation Age-standardised stroke incidence rates in Hai were similar to those seen in developed countries. However, age-standardised incidence rates in Dar-es-Salaam were higher than seen in most studies in developed countries; this could be because of a difference in the prevalence of risk factors and emphasises the importance of health screening at a community level. Health policy makers must continue to monitor the incidence of stroke in sub-Saharan Africa and should base future funding decisions on such data. Funding The Wellcome Trust.

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis 'DOTS' model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A(1c) (HbA(1c)) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.

The prevalence of Parkinson's disease (PD) varies worldwide from 7 to 450 per 100,000, and appears low in sub-Saharan Africa (SSA) but few data exist. We conducted a prevalence study of PD in rural Tanzania. A door-to-door study was conducted in the Hai district project area (population 161,071), using a screening questionnaire followed by structured history and examination of positive responders. Diagnosis was based on the UK PD Society Brain Bank Criteria. 33 (23 men) cases of PD were detected, with mean age 74 years (range 38-94). One patient died before the prevalence date. 78% were previously undiagnosed and untreated. Mean duration of symptoms was 5 years, and median Hoehn and Yahr stage 3. Crude prevalence rates were 30/100,000 (men), 11/100,000 (women) and 20/100,000 (combined). The direct age-standardized prevalence rates compared with the UK population were 64/100,000 (men), 20/100,000 (women) and 40/100,000 (combined). These rates are higher than previously reported from SSA, but still lower than the developed world. Many PD patients in SSA may never be diagnosed or treated, with consequent reduction in their life expectancy and quality of life. With the world population ageing PD is predicted to become an increasing problem.

Diabetes is a major contributor to the global burden of mortality and morbidity. The International Diabetes Federation (IDF) uses a transparent reproducible methodology to generate global and country level estimates of diabetes prevalence in adults (20-79 years). However, the methodology produces point estimates and no uncertainty measurements have been reported. To estimate the potential sources of uncertainty in the prevalence estimates and their magnitude, we performed two separate analyses: (1) a simulation study to access raw data uncertainty; (2) a bootstrap analysis of the sensitivity of the global prevalence estimate to the study selection process In the simulation study, we drew 500 random samples inside of the 95% confidence interval (CI) range for each raw point estimate given in the data sources. Then, these samples were used in the IDF estimation procedure as conducted for the original data. To access the sensitivity of a global probability magnitude to a selection of studies, we employed the bootstrap analysis. In a loop, one of all the selected studies was randomly picked up and removed from the list; the global prevalence was calculated on a base of remaining studies. The simulation study produced an uncertainty interval 0.26% wide with the median shifted to the right due to low prevalence values. In the bootstrap analysis, the mean deviance from the point estimate was 0.006% (S.D. = 0.055%, 95% CI was 0.9% wide). However, the most important information was the extreme points in the analysis that composed 0.73% wide range. The total uncertainty interval was constructed as the united area of two measurements and was around 0.9% prevalence wide on the global level. The uncertainty measurement will permit the comparison of IDF results with other sources and over time.

OBJECTIVE: To compare mortality burden estimates based on direct measurement of levels and causes in communities with indirect estimates based on combining health facility cause-specific mortality structures with community measurement of mortality levels. METHODS: Data from sentinel vital registration (SVR) with verbal autopsy (VA) were used to determine the cause-specific mortality burden at the community level in two areas of the United Republic of Tanzania. Proportional cause-specific mortality structures from health facilities were applied to counts of deaths obtained by SVR to produce modelled estimates. The burden was expressed in years of life lost. FINDINGS: A total of 2884 deaths were recorded from health facilities and 2167 recorded from SVR/VAs. In the perinatal and neonatal age group cause-specific mortality rates were dominated by perinatal conditions and stillbirths in both the community and the facility data. The modelled estimates for chronic causes were very similar to those from SVR/VA. Acute febrile illnesses were coded more specifically in the facility data than in the VA. Injuries were more prevalent in the SVR/VA data than in that from the facilities. CONCLUSION: In this setting, improved International classification of diseases and health related problems, tenth revision (ICD-10) coding practices and applying facility-based cause structures to counts of deaths from communities, derived from SVR, appears to produce reasonable estimates of the cause-specific mortality burden in those aged 5 years and older determined directly from VA. For the perinatal and neonatal age group, VA appears to be required. Use of this approach in a nationally representative sample of facilities may produce reliable national estimates of the cause-specific mortality burden for leading causes of death in adults.

We investigated the prevalence of wheeze, self-reported asthma, and asthma care via four cross-sectional surveys among adults and children (5-15 years) in urban and rural populations from Tanzania and Cameroon. Age-standardized prevalence of current wheeze (in the previous year) was 2.2% to 5.0% in adults and 1.9% to 5.2% in children in Tanzania, and 1.3% to 2.5% (adults) and 0.8% to 5.4% (children) in Cameroon. There were no consistent patterns of urban:rural prevalence. Peak flow rates varied with age, peaking at 25-34 years, and were higher in urban areas (age adjusted difference 22-70 L/min) and in the Tanzania populations. Awareness (83%–86% versus 52%–58%) and treatment (43%–71% versus 30%–44%) of asthma was higher among those with current wheeze in rural areas. Use of inhaled drugs, particularly steroids, was rare. Diagnosis by traditional healers (15%) and use of traditional remedies (62% of those recalling any treatment) were common only among self-reported asthmatic patients in rural Cameroon. Asthma is an important clinical condition in sub-Saharan Africa. There were major gaps in clinical care, particularly in urban areas. Sustainable methods for delivering accessible and effective asthma care in sub-Saharan Africa are required.

Monokine induced by IFN-γ (MIG; CXC chemokine ligand (CXCL)9) is important in T lymphocyte recruitment in organ transplantation. However, it is not known whether this chemokine, in addition to its chemotactic properties, exerts any effect on T lymphocyte effector functions. For in vivo studies, we used a previously characterized murine model of chronic rejection. The recipient mice were treated with anti-MIG/CXCL9 Ab; graft-infiltrating cells were analyzed for IFN-γ production. For in vitro studies, exogenous CXCR3 ligands were added to CD4 lymphocytes in MLRs, and the proliferative responses were measured. Separate experiments quantitated the number of IFN-γ-producing cells in MLRs by ELISPOT. Neutralization of MIG/CXCL9, in the in vivo model, resulted in significant reduction in the percentage of IFN-γ-producing graft-infiltrating T lymphocytes. In vitro experiments demonstrated that 1) exogenous MIG/CXCL9 stimulated CD4 lymphocyte proliferation in a MHC class II-mismatched MLR, 2) MIG/CXCL9 also increased the number of IFN-γ-producing CD4 lymphocytes in ELISPOT, 3) neutralization of MIG/CXCL9 in MLR reduced T lymphocyte proliferation, 4) IFN-γ-inducible protein 10/CXCL10 and IFN-inducible T cell α chemoattractant/CXCL11 had similar effects on T lymphocyte proliferation, 5) MIG/CXCL9 stimulated T lymphocyte proliferation in MHC class I- and total MHC-mismatched MLRs, 6) neutralization of CXCR3 reduced MIG/CXCL9-induced T lymphocyte proliferation and the number of IFN-γ-positive spots on ELISPOT, and 7) the proliferative effects of MIG/CXCL9 were mediated via an IL-2-independent pathway and were controlled by IFN-γ. This study demonstrates that MIG/CXCL9 stimulates T lymphocyte proliferation and effector cytokine production, in addition to its chemotactic effects. This novel observation expands our current understanding of MIG/CXCL9 biology beyond that of mediating T cell trafficking.

Donor shortage remains a major obstacle to widespread application of lung transplantation. In region 5, including California, Nevada, New Mexico, Utah, and Arizona, the United Network of Organ Sharing (UNOS) database median waiting time for lung transplant candidates in 2000–2001 exceeded 17 months. The purpose of this study was to determine the impact of liberalization of donor criteria on median waiting time and short-term outcome of lung transplantation. From September 1999 to October 2002, 42 patients underwent lung transplantation from nonstandard donors. The donors were classified as nonstandard due to (1) infiltrate on chest radiograph (n = 33), (2) PaO2 < 300 on FiO2 1.0 and PEEP 5 (n = 3), (3) PaO2 < 100 on FiO2 0.4 and PEEP 5 (n = 3), (4) purulent sputum on bronchoscopy (n = 22), and (5) smoking history greater than 50 pack-years (n = 1). Perioperative characteristics and short-term outcome of this group was analyzed. The median waiting time for this cohort was 114 days (range, 10–1267), as compared with the national UNOS database median waiting time of 24 months between 1996 and 2001. The incidence of ischemia reperfusion injury was 2.3 per cent. None of the recipients developed pneumonia. The median ventilator support time was 2 days (range, 1–95). The median ICU stay and hospital stay were 4 days (range, 2–103) and 14 days (range, 5–194), respectively. The 3-month survival was 97.6 per cent. Selective liberalization of donor lung criteria can decrease the waiting time and is associated with favorable short-term outcome. Utilization of nonstandard lungs can expand the donor pool.

The aim of this review is to summarize the contextual, clinical and health system challenges to the delivery of health care for diabetes in Africa. Planners need to allocate sufficient resources in a context where resources for health in general are insufficient. Choices need to be made between different options for health care within this context and mechanisms are required to facilitate the implementation of the selected options and ensure that quality of care is maintained.

To describe the prevalence of tobacco smoking in an urban East African population while using a simple validation procedure to examine the degree of under reporting in men and women. A cross sectional population based study in adults (15 years and over) with sampling from a well maintained census register. Ilala Ilala, a middle income district of Dar es Salaam, Tanzania. An age and sex stratified random sample of 973 men and women. Self reported smoking status with correction by exhaled alveolar carbon monoxide (EACO). From the 605 participants (response rate 67.9%) age standardised (new world population) smoking prevalence, based on questionnaire and EACO, was 27.0% (95% confidence interval (CI) 20.8% to 33.2%) in males and 5.0% (95% CI 2.8% to 7.2%) in females. The age specific prevalence of smoking was highest in the age group 35-54 years (34.3%) for men and in the over 54 years group (16%) for women. Of those classified as smokers, 7.3% of men and 27.3% of women were reclassified as current smokers based on EACO (> or = 9 parts per million), after they had reported themselves to be an ex- or non-smoker in the questionnaire. The data suggest: (1) high rates of smoking among men in an urban area of East Africa; and (2) the importance of validating self reports of smoking status, particularly among women.

Introduction Diabetes is a serious and increasing global health burden and estimates of prevalence are essential for appropriate allocation of resources and monitoring of trends. Methods We conducted a literature search of studies reporting the age-specific prevalence for diabetes and used the Analytic Hierarchy Process to systematically select studies to generate estimates for 219 countries and territories. Estimates for countries without available source data were modelled from pooled estimates of countries that were similar in regard to geography, ethnicity, and economic development. Logistic regression was applied to generate smoothed age-specific prevalence estimates for adults 20–79 years which were then applied to population estimates for 2013 and 2035. Results A total of 744 data sources were considered and 174 included, representing 130 countries. In 2013, 382 million people had diabetes; this number is expected to rise to 592 million by 2035. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. Conclusion The new estimates of diabetes in adults confirm the large burden of diabetes, especially in developing countries. Estimates will be updated annually including the most recent, high-quality data available.

Gelatinase A (MMP-2), a matrix metalloproteinase (MMP) involved in tumor invasion and angiogenesis, is secreted as an inactive zymogen (proMMP-2) and activated by proteolytic cleavage. Here we report that polymorphonuclear neutrophil (PMN)-derived elastase, cathepsin G, and proteinase-3 activate proMMP-2 through a mechanism that requires membrane-type 1 matrix metalloproteinase (MT1-MMP) expression. Immunoprecipitation of human PMN-conditioned medium with a mixture of antibodies to elastase, cathepsin G, and proteinase-3 abolished proMMP-2 activation, whereas individual antibodies were ineffective. Incubation of HT1080 cells with either purified PMN elastase or cathepsin G or proteinase-3 resulted in dose-and time-dependent proMMP-2 activation. Addition of PMN-conditioned medium to MT1-MMP expressing cells resulted in increased proMMP-2 activation and in vitro invasion of extracellular matrix (ECM), but had no effect with cells that express no MT1-MMP. MMP-2 activation by PMN-conditioned medium or purified elastase was blocked by the elastase inhibitor α1-antitrypsin but not by Batimastat, an MMP inhibitor, showing that elastase activation of MMP-2 is not mediated by MMP activities. The PMN-conditioned medium-induced increase in cell invasion was blocked by Batimastat as well as by α1-antitrypsin, showing that PMN serine proteinases trigger a proteinase cascade that entails proMMP-2 activation: this gelatinase is the downstream effector of the proinvasive activity of PMN proteinases. These findings indicate a novel role for PMN-mediated inflammation in a variety of tissue remodeling processes including tumor invasion and angiogenesis. © 2001 Wiley-Liss, Inc.

Objectives—To determine the age specific prevalence of impairment and disability relating to hemiplegic stroke in one rural area of Tanzania. Methods—During the yearly house to house census of the study population of 148 135 (85 152 aged 15 and over) in August 1994, specific questions were asked to identify those who might be disabled from stroke. People thus identified were subsequently interviewed and examined by one investigator. In those in whom the clinical diagnosis of stroke was confirmed a more detailed interview and examination relating to risk factors and recovery was carried out. Results—One hundred and eight patients, 61 men and 47 women, were identified with a median age of 70 (range 18‐100). Median age at first stroke was 65 years. The age specific rates in this study were lower than previous studies in developed countries. All were cared for at home although 23 (21%) were bedbound. Conclusions—Although prevalence of impairment and disability related to stroke in this population as a whole was low this is mainly explained by the age structure, with less than 6% being aged 65 and over. Age standardised rates for stroke with residual disability were about half those found in previous studies in developed countries. Death from stroke in Africa may be higher but data are limited. With the demographic transition stroke is likely to become a more important cause of disability in sub-Saharan Africa. (J Neurol Neurosurg Psychiatry 2000;68:744‐749)

Summary Background Most data for stroke mortality in sub-Saharan Africa are hospital based. We aimed to establish the contribution of cerebrovascular disease to all-cause mortality and cerebrovascular disease mortality rates in adults aged 15 years or more in one urban and two rural areas of Tanzania. Methods Regular censuses of the three surveillance populations consisting of 307 820 people (125 932 aged below 15 years and 181 888 aged 15 or more) were undertaken with prospective monitoring of all deaths arising in these populations between June 1, 1992 and May 31, 1995. Verbal autopsies were completed with relatives or carers of the deceased to assess, when possible, the cause of death. Findings During the 3-year observation period 11 975 deaths were recorded in the three surveillance areas, of which 7629 (64%) were in adults aged 15 years or more (4088 [54%] of these in men and 3541 [46%] in women). In the adults, 421 (5·5%) of the deaths were attributed to cerebrovascular disease, 225 (53%) of these in men and 196 (47%) in women. The yearly age-adjusted rates per 100 000 in the 15–64 year age group for the three project areas (urban, fairly prosperous rural, and poor rural, respectively) were 65 (95% Cl 39–90), 44 (31–56), and 35 (22–48) for men, and 88 (48–128), 33 (22–43), and 27 (16–38) for women, as compared with the England and Wales (1993) rates of 10·8 (10·0–11·6) for men and 8·6 (7·9–9·3) for women. Interpretation We postulate that the high rates in Tanzania were due to untreated hypertension. Our study assessed mortality over a single time period and therefore it is not posible to comment on trends with time. However, ageing of the population is likely to lead to a very large increase in mortality from stroke in the future.

Two cases of posterolateral corner reconstruction of the knee with postoperative sciatic perineural analgesia using a mixture of clonidine and buprenorphine, are presented. Numeric rating scores for pain with movement were 0-2 out of 10 postoperatively after injection. Gross motor function below the knee was maintained in both cases.

Background: Matrix metalloproteinase-2 (MMP-2), an enzyme involved in tumor invasion, is secreted as an inactive proenzyme and requires interaction with membrane-type 1 MMP (MT1-MMP) for activation. We have previously demonstrated that polymorphonuclear neutrophils (PMNs) release a soluble factor(s) that activates pro-MMP-2. Therefore, we tested the hypothesis that PMN-derived proteinases act in concert with MT1-MMP to activate pro-MMP-2. Methods: Human HT-1080 cells transfected with MT1-MMP cDNA (HT-SE) or the corresponding antisense cDNA (HT-AS) or an empty vector (HT-V), which expressed differing levels of MT1-MMP, were incubated with serum-free, human PMN-conditioned medium with or without proteinase inhibitors. The culture supernatants were analyzed by gelatin zymography. Results: HT-1080 cells expressing basal (HT-V) or low levels (HT-AS) of MT1-MMP secreted MMP-2 in proenzyme form (72 kd). HT-1080 cells with high levels of MT1-MMP (HT-SE) secreted proMMP-2 and a 68 kd intermediate activation product. Addition of PMN-conditioned medium to either HT-SE or HT-V clones resulted in dose-dependent generation of active, 62 kd MMP-2. In contrast, when PMN-conditioned medium was added to HT-AS clones, no MMP-2 activation occurred. Conclusions: PMN-derived serine proteinases act in concert with MT1-MMP to activate proMMP-2. This finding indicates a potential role for inflammatory cells in promoting extracellular matrix breakdown during tumor invasion. (Surgery 1998;124:232-8.)

Aims We estimated the number of live births worldwide and by IDF Region who developed hyperglycaemia in pregnancy in 2013, including total diabetes in pregnancy (known and previously undiagnosed diabetes) and gestational diabetes. Methods Studies reporting prevalence of hyperglycaemia first-detected in pregnancy (formerly termed gestational diabetes) were identified using PubMed and through a review of cited literature. A simple scoring system was developed to characterise studies on diagnostic criteria, year study was conducted, study design, and representation. The highest scoring studies by country with sufficient detail on methodology for characterisation and reporting at least three age-groups were selected for inclusion. Forty-seven studies from 34 countries were used to calculate age-specific prevalence of hyperglycaemia first-detected in pregnancy in women 20–49 years. Adjustments were then made to account for heterogeneity in screening method and blood glucose diagnostic threshold in studies and also to align with recently published diagnostic criteria as defined by the WHO for hyperglycaemia first detected in pregnancy. Prevalence rates were applied to fertility and population estimates to determine regional and global prevalence of hyperglycaemia in pregnancy for 2013. An estimate of the proportion of cases of hyperglycaemia in pregnancy due to total diabetes in pregnancy was calculated using age- and sex-specific estimates of diabetes from the IDF Diabetes Atlas and applied to age-specific fertility rates. Results The global prevalence of hyperglycaemia in pregnancy in women (20–49 years) is 16.9%, or 21.4 million live births in 2013. An estimated 16.0% of those cases may be due to total diabetes in pregnancy. The highest prevalence was found in the South-East Asia Region at 25.0% compared with 10.4% in the North America and Caribbean Region. More than 90% of cases of hyperglycaemia in pregnancy are estimated to occur in low- and middle-income countries. Conclusion These are the first global estimates of hyperglycaemia in pregnancy and conform to the new WHO recommendations regarding diagnosis and also include estimates of live births in women with known diabetes. They indicate the importance of the disease from a public health and maternal and child health perspective, particularly in developing countries.

Introduction Hyperglycaemia is one of the most prevalent metabolic disorders occurring during pregnancy. Limited data are available on the global prevalence of hyperglycaemia in pregnancy. The International Diabetes Federation (IDF) has developed a methodology for generating estimates of the prevalence of hyperglycaemia in pregnancy, including hyperglycaemia first detected in pregnancy and live births to women with known diabetes, among women of childbearing age (20–49 years). Methods A systematic review of the literature for studies reporting the prevalence of gestational diabetes was conducted. Studies were evaluated and scored to favour those that were representative of a large population, conducted recently, reported age-specific estimates, and case identification was based on blood test. Age-specific prevalence data from studies were entered to produce estimates for five-year age groups using logistic regression to smooth curves, with age as the independent variable. The derived age-specific prevalence was adjusted for differences in diagnostic criteria in the underlying data. Cases of hyperglycaemia in pregnancy were derived from age-specific estimates of fertility and age-specific population estimates. Country-specific estimates were generated for countries with available data. Regional and global estimates were generated based on aggregation and extrapolation for 219 countries and territories. Available fertility rates and diabetes prevalence estimates were used to estimate the proportion of hyperglycaemia in pregnancy that may be due to total diabetes in pregnancy – pregnancy in women with known diabetes and diabetes first detected in pregnancy. Results The literature review identified 199 studies that were eligible for characterisation and selection. After scoring and exclusion requirements, 46 studies were selected representing 34 countries. More than 50% of selected studies came from Europe and North America and Caribbean. The smallest number of identified studies came from sub-Saharan Africa. The majority of studies were for high-income countries, although low- and middle-income countries were also represented. Conclusion Prevalence estimates of hyperglycaemia in pregnancy are sensitive to the data from which they are derived. The IDF methodology is a transparent, reproducible, and modifiable method for estimating the burden of hyperglycaemia in pregnancy. More data are needed, in particular from developing countries, to strengthen the methodology.

Canopy interception of incoming photosynthetically active radiation (PAR) is an important factor affecting tree fruit orchard productivity. In traditional multiple-leader training systems, a positive correlation exists between PAR interception and yield. In this study, a sensor-based canopy mapping method was developed for measuring of PAR interception in Y-trellised sweet cherry (Prunus avium L.) orchard. A mobile sensor system capable of measuring PAR data under a constant data spatial resolution was development and used in field PAR data collection in two significantly different canopy stages of dormant (March, 2013) and full canopy (June, 2012). A mathematical model of canopy projecting position correction was developed to correct deformation of canopy projection caused by the sun position (i.e. solar zenith and azimuth angles), on PAR reading recorded at different time. Digital images of ten tree canopies were taken on dormant season to evaluate the accuracy of canopy projection correction. Results showed that the developed sensor system could obtain a 1.0 cm constant spatial resolution within the entire speed range of the mobile platform along the traveling direction. The relative errors of inclinations of 20 distinct segments on digital images and mapping images were from 0.2% to 9.6%, presenting the good performance of the canopy mapping method.

Desmoid tumors (DTs), the commonest extra-intestinal manifestation of familial adenomatosis polyposis (FAP), are monoclonal neoplasms demonstrating fibroblastic - myofibroblastic differentiation; they are locally invasive without metastatic capacity. FAP-associated DT natural history knowledge is limited; we examined patient and tumor characteristics for a FAP-DT cohort and evaluated anti-DT therapy molecular target expression levels (immunohistochemical analyses, FAP-DT tissue microarray; TMA). Forty-four patients were classified as intra-abdominal (IA; n=26), abdominal wall (AW)/extra-abdominal (EA; n=12) or concomitant IA/AW (n=6) based on DT primary diagnosis location. Positive family histories were found in 62% of FAP versus 10% of DT patients. Surgery was the mainstay therapy for AW/EW patients, whereas IA DTs received surgery, chemotherapy, radiotherapy, tamoxifen, NSAIDs, and/or imatinib. Eight of 20 completely resected DTs in the IA and AW/EA groups recurred; 12 of 38 patients in these groups (33%) developed secondary lesions elsewhere. Two intestinal mesenteric DT patients died of disease, three from other cancers, 27 are alive with disease and 12 are alive without disease. All evaluable FAP-DT exhibited nuclear β-catenin, 65% were positive for cyclin D1, and 66% expressed nuclear p53. No ERα expression was observed, but ERβ was expressed in 72%. COX2 was expressed in all evaluable FAP-DTs. KIT was rarely found in DTs but both PDGFRs and their ligands were expressed. Comparing biomarker expression (IA vs. EA DTs), only nuclear ER-ß staining was significantly higher in EA lesions (p=0.0070); no other markers were site informative. Enhanced knowledge of FAP-DT molecular underpinnings will facilitate development of novel therapeutic strategies.

Introduction Diabetes is a major cause of morbidity and mortality and its global prevalence is growing rapidly. A simple and robust approach to estimate the prevalence of diabetes is essential for governments to set priorities on how to meet the challenges of the disease. The International Diabetes Federation has developed a methodology for generating country-level estimates of diabetes prevalence in adults (20–79 years). Methods Using country-level data sources from peer-reviewed studies, national health statistics reports, commissioned studies on diabetes prevalence, and unpublished data obtained through personal communication, we use logistic regression to generate estimates of the prevalence of diabetes. An approach matching countries on ethnicity, geography, and income group is used to fill in gaps where original data sources are not available. The methodology also uses changes in urbanization and population to generate estimates and projections on the prevalence of diabetes in adults. Conclusion Diabetes prevalence estimates are very sensitive to the data from which they are derived. The revised IDF methodology for estimating diabetes prevalence is a transparent, reproducible approach that will be updated annually. It takes data-driven approaches to filling in gaps where data are not available and where assumptions have to be made. It uses a qualification system to rank data sources so that only the highest quality data are used.

Background and purpose To establish post-stroke case fatality rates within a community based incident stroke population in rural Tanzania. Methods Incident stroke cases were identified by the Tanzanian Stroke Incidence Project and followed-up over the next 3–6 years. In order to provide a more complete picture, verbal autopsy (VA) was also used to identify all stroke deaths occurring within the same community and time period, and a date of stroke was identified by interview with a relative or friend. Results Over 3 years, the Tanzanian Stroke Incidence Project identified 130 cases of incident stroke, of which 31 (23.8%, 95% CI 16.5 to 31.2) died within 28 days and 78 (60.0%, 95% CI 51.6 to 68.4) within 3 years of incident stroke. Over the same time period, an additional 223 deaths from stroke were identified by VA; 64 (28.7%, 95% CI 20.9 to 36.5) had died within 28 days of stroke and 188 (84.3%, 95% CI 78.1 to 90.6) within 3 years. Conclusions This is the first published study of post-stroke mortality in sub-Saharan Africa from an incident stroke population. The 28 day case fatality rate is at the lower end of rates reported for other low and middle income countries, even when including those identified by VA, although CIs were wide. Three year case fatality rates are notably higher than seen in most developed world studies. Improving post-stroke care may help to reduce stroke case fatality in sub-Saharan Africa.

To obtain the baseline information for supporting the development of new cherry harvesters for fresh market grade fruits, an investigation was conducted on assessing the performance and efficiency of two existing mechanical harvesters in removing cherry fruits from the trees. One harvester detaches fruits using an inertia force and the other using a vibration force. To gain a comprehensive understanding on the responses of cherry trees to those fruit detaching forces, a series of excited vibration tests were performed in this assessment study. To record the responding acceleration for performing the assessment, a group of single axial accelerometers were installed at different locations on the tree. From field experiment observations it was found that the responses of the limbs were different under different excitation mode. Obtained data further revealed that the vibratory shaker resulted in higher efficiency in fruits removal and less damage on fruit quality than that from the inertia harvester. Obtained results provided some critical information required for designing a more effective mechanical harvester with better produce quality.

This article, the second in a series on the NHS Institute for Innovation and Improvement's eight high impact actions, reviews the roles played by nurses and local organisations in preventing falls among older people through early intervention and the promotion of active lifestyles.

A pair of rapid tests for evaluation of the effectiveness of penetrating sealers in preventing corrosive chloride ions from penetrating concrete have been developed. The tests are designed to yield an indication of the relative performance of a sealer as compared with unsealed concrete. The first test is based on measurement of electrical resistance between two small electrodes created on a concrete surface by use of a highly conductive spray-applied coating. A criterion of 200 k-ohms after 4 minutes of test was selected for differentiating between effective and ineffective sealers. The second test is based on absorption of water into the concrete surface over a four minute period. Development and field trials of the two tests are described. The tests are applicable to both horizontal and vertical surfaces. Applications for the tests include quality control of sealer application, qualification of sealers under field conditions, and monitoring of sealer performance over time in a nondestructive manner.

Regularity of respiration is characteristic of stable sleep without sleep disordered breathing. Appearance of respiratory irregularity may indicate onset of wakefulness. The present study examines whether one can detect transitions from sleep to wakefulness using only the CPAP flow signal and automate this recognition.Prospective study with blinded analysisSleep disorder center, academic institution.74 subjects with obstructive sleep apnealhypopnea syndrome (OSAHS) INTERVENTIONS: n/a.74 CPAP titration polysomnograms in patients with OSAHS were examined. First we visually identified characteristic patterns of ventilatory irregularity on the airflow signal and tested their relation to conventional detection of EEG defined wake or arousal. To automate recognition of sleep-wake transitions we then developed an artificial neural network (ANN) whose inputs were parameters derived exclusively from the airflow signal. This ANN was trained to identify the visually detected ventilatory irregularities. Finally, we prospectively determined the accuracy of the ANN detection of wake or arousal against EEG sleep/wake transitions. A visually identified irregular respiratory pattern (IrREG) was highly predictive of appearance of EEG wakefulness (Positive Predictive Value [PPV] = 0.89 to 0.98 across subjects). Furthermore, we were able to automate identification of this irregularity with an ANN which was highly predictive for wakefulness by EEG (PPV 0.66 to 0.86).Despite not detecting all wakefulness, the high positive predictive value suggests that analysis of the respiration signal alone may be a useful indicator of CNS state with potential utility in the control of CPAP in OSAHS. The present study demonstrates the feasibility of automating the detection of IrREG.

Tests were performed under separate contracts at different times for three manufacturers of ground granulated blast-furnace slag to determine the performance of their products with portland cement. Physical tests were performed on pastes, mortars, and concretes to determine both freshly mixed and hardened properties. The effects of gypsum addition, fineness of slag, and levels of replacement in cement-slag combinations were evaluated. Physical tests performed on pastes and mortars included time of setting, compressive strength, and volume stability. In the mortar compressive strength series, various curing regimens were evaluated with respect to strength development. Included were normal moist curing at 23°C (73°F) and 4.4°C (40°F) and 100% relative humidity, and accelerated atmospheric curing [71°C (160°F)] and 100% relative humidity. Tests conducted on concretes containing slag included compressive strength, freeze-thaw durability, and resistance to deicer chemicals (scaling). Measurements of air-void systems of hardened concretes were made. Results generally show that use of slag can be beneficial without resulting in significant technical problems or adverse construction problems.

Blended cements were prepared from two controlled particle size distribution (CPSD) cements (95% finer than 31 or 23 μm) and one normally ground cement (345 m 2 /kg Blaine), using the same clinker and gypsum. Pastes made with these cements blended with Class F or Class C fly ashes or ground granulated slag, and lesser amounts of ground limestone or silica fume, were tested for flow, strength development, and drying shrinkage. Three CPSD blended cements (two with Class F fly ash and one with slag, all with ground limestone) were selected for mortar and concrete tests along with two normally ground blended cements as controls. All five of these cements yielded mortars at 0.485 water/cement (W/C) with equal flow (121 ′ 2%). Mortar strengths were higher at all ages with the CPSD blends than the controls. The CPSD fly ash blended cement concretes prepared at 0.50 W/C required higher cement contents for 50 to 100 mm slump than did concretes prepared with normally ground blended cement. CPSD blended cements had slightly better compressive and flexural strengths and sulfate resistance than did their normally ground counterparts. Drying shrinkage of the concretes was lower when paste contents were lower, as with the CPSD slag blended cement.

Objectives: To validate verbal autopsy (VA) procedures for use in sample vital registration. Verbal autopsy is an important method for deriving cause-specific mortality estimates where disease burdens are greatest and routine cause-specific mortality data do not exist. Methods: Verbal autopsies and medical records (MR) were collected for 3123 deaths in the perinatal/neonatal period, post-neonatal < 5 age group, and for ages of 5 years and over in Tanzania. Causes of death were assigned by physician panels using the International Classification of Disease, revision 10. Validity was measured by: cause-specific mortality fractions (CSMF); sensitivity; specificity and positive predictive value. Medical record diagnoses were scored for degree of uncertainty, and sensitivity and specificity adjusted. Criteria for evaluating VA performance in generating true proportional mortality were applied. Results: Verbal autopsy produced accurate CSMFs for nine causes in different age groups: birth asphyxia; intrauterine complications; pneumonia; HIV/AIDS; malaria (adults); tuberculosis; cerebrovascular diseases; injuries and direct maternal causes. Results for 20 other causes approached the threshold for good performance. Conclusions: Verbal autopsy reliably estimated CSMFs for diseases of public health importance in all age groups. Further validation is needed to assess reasons for lack of positive results for some conditions.

Background Cause-specific mortality statistics remain scarce for the majority of low-income countries, where the highest disease burdens are experienced. Neither facility-based information systems nor vital registration provide adequate or representative data. The expansion of sample vital registration with verbal autopsy procedures represents the most promising interim solution for this problem. The development and validation of core verbal autopsy forms and suitable coding and tabulation procedures are an essential first step to extending the benefits of this method. Methods and Findings Core forms for peri- and neonatal, child, and adult deaths were developed and revised over 12 y through a project of the Tanzanian Ministry of Health and were applied to over 50,000 deaths. The contents of the core forms draw upon and are generally comparable with previously proposed verbal autopsy procedures. The core forms and coding procedures based on the International Statistical Classification of Diseases (ICD) were further adapted for use in China. These forms, the ICD tabulation list, the summary validation protocol, and the summary validation results from Tanzania and China are presented here. Conclusions The procedures are capable of providing reasonable mortality estimates as adjudged against stated performance criteria for several common causes of death in two countries with radically different cause structures of mortality. However, the specific causes for which the procedures perform well varied between the two settings because of differences in the underlying prevalence of the main causes of death. These differences serve to emphasize the need to undertake validation studies of verbal autopsy procedures when they are applied in new epidemiological settings., A procedure for recording verbal autopsy information was tested in two countries and found to be capable of providing reasonable mortality data. The need to undertake validation studies was also demonstrated., Editors' Summary Background. People living in developed countries take it for granted that when a loved one dies an accurate cause-of-death certificate will be issued. But for two-thirds of the deaths that occur worldwide, there are no certificates. Detailed information about what people die from is unavailable for more than 50% of countries, many of which have high death rates. This information is badly needed for public-health planning, for using scarce health resources wisely, and for monitoring the effect of new health initiatives. One way to improve knowledge about what people die from is a procedure called verbal autopsy (VA). Relatives or caregivers are interviewed about the symptoms experienced by the deceased before their death and the circumstances surrounding their death by trained personnel who use a standard form. Doctors then review the completed VA forms and assign a specific cause of death from a short version of the International Classifications of Diseases, or ICD, an internationally agreed on list of codes for hundreds of diseases. Why Was This Study Done? VA procedures are being developed in many countries, but each step in a VA can be affected by factors that vary from place to place, such as how long after the death the interview is done, the training that interviewers receive, how the questions are worded, and the locally common diseases, which tend to be recognized better than rare diseases. To ensure that the data collected are accurate and comparable between countries and also over time, VA procedures need to be standardized. In this study, the researchers describe their efforts to achieve this through the development and validation of core VA procedures. What Did the Researchers Do and Find? In 2001, the researchers refined the VA forms that were being used in Tanzania for deaths occurring around the time of birth and for deaths occurring in childhood and adulthood. They then translated the forms for use in China, adapting them slightly to allow for cultural differences in how symptoms are described. They also drew up a short list of ICD codes to use in tabulating and validating important causes of death. Then, for four years, they collected VA and medical record information for the same deceased individuals and measured how well the VA procedure agreed with the medical record information in both countries. They found that the procedure could be transferred between China and Tanzania but that it performed rather differently for different causes of death in the two countries. So, in both countries, the procedure accurately recorded tuberculosis, cerebrovascular diseases such as strokes, and transport accidents as causes of death. But some other causes of death were accurately recorded in one country only—generally the common diseases in that country—and many causes of death were inaccurately reported in both countries. What Do These Findings Mean? The researchers use their experience of developing VAs for use in Tanzania and China and the results of this study to make several recommendations about how to develop standardized VA procedures that will yield accurate cause of death. For example, they suggest that the VA form should contain a detailed core symptom duration checklist and only a short space for a narrative history (an open-ended description of the last illness provided by the relative or caregiver) because long narrative histories are hard to standardize. They discuss the need to adapt core VA forms when moving between countries to allow for linguistic differences and colloquial expression and also the need to consider cultural differences between countries—for example, how soon after bereavement a VA interview can occur. Most importantly, they strongly recommend that validation studies like theirs should be routinely done when VA procedures are applied in new countries or if the major cause of death in a country changes because of a new epidemic or health initiative. Provided this is done, write the researchers, although VA procedures can never be as accurate as proper medical certification at the time of death, they should provide important information about the causes of death for the many countries where this information would otherwise be completely missing. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030268. • World Health Organization information on mortality and on the International Classification of Diseases • The United Nations' World Mortality Report 2005 • Information on the Tanzania Ministry of Health Adult Morbidity and Mortality Project, which used the VA procedures on which this study was based • A description of a standard VA method for investigating deaths in infants and children from the World Health Organization • The INDEPTH Network, an organization collecting health statistics from developing countries that provides standardized VA forms • MEASURE Evaluation, a USAID-funded project that, in collaboration with the US Census Bureau and the University of Queensland (Australia), supports countries to implement core VA procedures and sample/sentinel vital registration methods • The Health Metrics Network, a global collaboration focused on strengthening country health information systems to generate sound data for decision-making at country and global levels, is committed to improving sources of vital statistics and cause-of-death data

Background The role of CD8 lymphocytes, in chronic rejection or cardiac allograft vasculopathy (CAV), is incompletely understood. The purposes of this study were to determine whether CD8 lymphocytes, in the absence of CD4 lymphocytes, are capable of causing the intimal lesions of CAV; and if so, to define the effector mechanism(s) of CD8 lymphocytes. Methods We modified a previously characterized major histocompatibility complex class II mismatched murine model of CAV. Wild-type CD8 lymphocytes were transferred to nude mice followed by heterotopic heart transplantation. Recipient mice were then treated with a CD40 activating antibody, which is known to provide help for CD8 lymphocyte activation, in the absence of CD4 lymphocytes. Donor hearts were harvested on day 40 posttransplantation and analyzed for cellular infiltrates and intimal thickening. In separate experiments, isolated perforin -/-, Fas ligand (FasL) -/-, and interferon (IFN)-gamma -/- CD8 lymphocytes were transferred to nude mice followed by identical experimented protocol. Results With adaptive transfer of wild-type CD8 lymphocytes, the donor hearts were infiltrated with activated CD8 lymphocytes and displayed significant intimal lesions. Adoptive transfer of perforin -/- and FasL -/- CD8 lymphocytes to nude mice resulted in similar patterns of CD8 lymphocyte infiltration and similar severity of intimal lesions. The donor hearts from IFN-gamma -/- CD8 lymphocyte reconstituted recipients displayed minimal intimal lesions, although CD8 lymphocytes were present in the allografts. Conclusions Unprimed CD8 lymphocytes in the absence of CD4 lymphocytes can cause intimal lesions of CAV. CD8 lymphocytes production of IFN-gamma, but not the perforin or the FasL-mediated cytotoxicity, is the critical step in the development of intimal lesions.

Background—Chemokine-chemokine receptor interaction and the subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts or cardiac allograft vasculopathy (CAV). In this study, we sought to determine whether blockade of chemokine receptors CCR1 and CCR5 with Met-RANTES affects the development of CAV in a murine model.Methods and Results—B6.CH-2bm12strain donor hearts were transplanted heterotopically into wild-type C57BL/6 mice (myosin heavy chain II mismatch). Recipients were treated daily with either Met-RANTES or vehicle starting on postoperative day 4 and were euthanized on postoperative days 24 and 56. We found that Met-RANTES significantly reduced intimal thickening in this model of chronic rejection and that Met-RANTES markedly decreased the infiltration of CD4 and CD8 T lymphocytes and MOMA-2+monocytes/macrophages into transplanted hearts. Met-RANTES also suppressed the ex vivo and in vitro proliferative responses of recipient splenocytes to donor antigens. Finally, Met-RANTES treatment was associated with a marked reduction in RANTES/CCL5 and monocyte chemoattractant protein-1 gene transcript levels in the donor hearts.Conclusions—Antagonism of the chemokine receptors CCR1 and CCR5 with Met-RANTES attenuates CAV development in vivo by reducing mononuclear cell recruitment to the transplanted heart, proliferative responses to donor antigens, and intragraft RANTES/CCL5 and monocyte chemoattractant protein-1 gene transcript levels. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and may serve as potential therapeutic targets.

T lymphocytes play a critical role in chronic rejection of transplanted hearts, or cardiac allograft vasculopathy (CAV). However, the molecular mediators of T lymphocyte recruitment in CAV are incompletely defined. We hypothesized that the chemokine, monokine induced by interferon-gamma (MIG/CXCL9), which induces T lymphocyte migration in vitro, participates in T lymphocyte recruitment in CAV. In a previously characterized MHC II-mismatched murine model of CAV, intragraft MIG/CXCL9 gene transcript and protein levels increased on days 7, 14, and 24 days after transplantation, paralleling T lymphocyte recruitment and preceding intimal thickening. Antibody neutralization of MIG/CXCL9 significantly reduced CD4(+) T lymphocyte infiltration and intimal thickening in this model. MIG/CXCL9 was produced by graft-infiltrating MOMA-2+ macrophages in early and late stages of CAV. And, although T lymphocytes did not produce MIG/CXCL9, recipient CD4(+) T lymphocytes were required for sustained intragraft MIG/CXCL9 production and CAV development. These findings demonstrate that 1) MIG/CXCL9 plays an important role in CD4(+) T lymphocyte recruitment and development of CAV, 2) MOMA-2+ macrophages are the predominant recipient-derived source of MIG/CXCL9, and 3) recipient CD4 lymphocytes are necessary for sustained MIG/CXCL9 production and CAV development in this model. Neutralization of the chemokine MIG/CXCL9 may have therapeutic potential for the treatment of chronic rejection after heart transplantation.

Objective To estimate the distribution of blood pressure (BP), body mass index (BMI), smoking habits and their associations with socioeconomic status (SES) in an urban population in early epidemiological transition. Methods Cross-sectional survey of the entire population aged 25‐64 years in five branches of Dar es Salaam (Tanzania) through visits to all homes in the study area. Blood pressure was based on the mean of the second and third readings with an automated device. Socioeconomic status was estimated with indicators of education, occupation and wealth. Results In all 9254 people were examined. Age-adjusted prevalence (%) among men/ women aged 35‐64 years was 27.1/30.2 for BP >140/90 mmHg or antihypertensive medication, 13.1/17.7 for BP >160/95 mmHg or antihypertensive medication, 28.0/27.4 for BMI of 25.0‐29.9 kg/m 2 , 6.9/17.4 for BMI >30 kg/m 2 , and 22.0/2.6 for smoking (>1 cigarette per day). Prevalence of categories of drinking frequency and history of diabetes are also reported. After adjustment for covariates, SES was associated inversely with BP and smoking and directly with BMI. Body mass index was associated positively with BP (1.01 and 0.91 mmHg systolic BP per 1 kg/m 2 BMI in men and women, respectively) and inversely with smoking (‐1.14 kg/m 2 in male smokers versus non-smokers). Hypertension treatment rates were low, particularly in people of low SES. Conclusions High prevalence of several cardiovascular risk factors in the urban population of a low-income country stresses the need for early public health interventions and adaptation of the health care infrastructure to meet the emerging challenge of cardiovascular disease. The direct SES-BMI association may drive increasing BMI and BP while the population becomes more affluent.