Counting the dead in China. Measuring tobacco's impact in the developing world.
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China↗
Biomedical subjects
A D Lopez
Publications and source records attributed to A D Lopez.
KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells: morphoregulatory roles in pancreatic islet development.
Cell adhesion molecules (CAMs) are important mediators of cell-cell interactions and regulate cell fate determination by influencing growth, differentiation, and organization within tissues. The human pancarcinoma antigen KSA is a glycoprotein of 40 kD originally identified as a marker of rapidly proliferating tumors of epithelial origin. Interestingly, most normal epithelia also express this antigen, although at lower levels, suggesting that a dynamic regulation of KSA may occur during cell growth and differentiation. Recently, evidence has been provided that this glycoprotein may function as an epithelial cell adhesion molecule (Ep-CAM). Here, we report that Ep-CAM exhibits the features of a morphoregulatory molecule involved in the development of human pancreatic islets. We demonstrate that Ep-CAM expression is targeted to the lateral domain of epithelial cells of the human fetal pancreas, and that it mediates calcium-independent cell-cell adhesion. Quantitative confocal immunofluorescence in fetal pancreata identified the highest levels of Ep-CAM expression in developing islet-like cell clusters budding from the ductal epithelium, a cell compartment thought to comprise endocrine progenitors. A surprisingly reversed pattern was observed in the human adult pancreas, displaying low levels of Ep-CAM in islet cells and high levels in ducts. We further demonstrate that culture conditions promoting epithelial cell growth induce upregulation of Ep-CAM, whereas endocrine differentiation of fetal pancreatic epithelial cells, transplanted in nude mice, is associated with a downregulation of Ep-CAM expression. In addition, a blockade of Ep-CAM function by KS1/4 mAb induced insulin and glucagon gene transcription and translation in fetal pancreatic cell clusters. These results indicate that developmentally regulated expression and function of Ep-CAM play a morphoregulatory role in pancreatic islet ontogeny.
Adult↗
The global burden of disease, 1990-2020.
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Persons with Disabilities↗
Health for all: analyzing health status and determinants.
An analysis of health status and determinants is presented as a basis for health for all renewal and in order to provide a model linking the health for all vision with strategy and action. Equity and gender, at the core of health for all, directly concern health status and the distribution of health determinants. The role of the various transitions (demographic, epidemiological, health risk and technological) is described, the need to strengthen the link between data and decision-making for health is explained, and the range of health determinants--macroeconomic, demographic/nutritional, environmental, tobacco and alcohol and their implications for policy--is outlined.
Epidemiologic Methods↗
Alcohol consumption and mortality among middle-aged and elderly U.S. adults.
BACKGROUND: Alcohol consumption has both adverse and beneficial effects on survival. We examined the balance of these in a large prospective study of mortality among U.S. adults. METHODS: Of 490,000 men and women (mean age, 56 years; range, 30 to 104) who reported their alcohol and tobacco use in 1982, 46,000 died during nine years of follow-up. We compared cause-specific and rates of death from all causes across categories of base-line alcohol consumption, adjusting for other risk factors, and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years. RESULTS: Causes of death associated with drinking were cirrhosis and alcoholism; cancers of the mouth, esophagus, pharynx, larynx, and liver combined; breast cancer in women; and injuries and other external causes in men. The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6). The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers, with little relation to the level of consumption. The overall death rates were lowest among men and women reporting about one drink daily. Mortality from all causes increased with heavier drinking, particularly among adults under age 60 with lower risk of cardiovascular disease. Alcohol consumption was associated with a small reduction in the overall risk of death in middle age (ages 35 to 69), whereas smoking approximately doubled this risk. CONCLUSIONS: In this middle-aged and elderly population, moderate alcohol consumption slightly reduced overall mortality. The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco.
Adult↗
Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study.
BACKGROUND: Plausible projections of future mortality and disability are a useful aid in decisions on priorities for health research, capital investment, and training. Rates and patterns of ill health are determined by factors such as socioeconomic development, educational attainment, technological developments, and their dispersion among populations, as well as exposure to hazards such as tobacco. As part of the Global Burden of Disease Study (GBD), we developed three scenarios of future mortality and disability for different age-sex groups, causes, and regions. METHODS: We used the most important disease and injury trends since 1950 in nine cause-of-death clusters. Regression equations for mortality rates for each cluster by region were developed from gross domestic product per person (in international dollars), average number of years of education, time (in years, as a surrogate for technological change), and smoking intensity, which shows the cumulative effects based on data for 47 countries in 1950-90. Optimistic, pessimistic, and baseline projections of the independent variables were made. We related mortality from detailed causes to mortality from a cause cluster to project more detailed causes. Based on projected numbers of deaths by cause, years of life lived with disability (YLDs) were projected from different relation models of YLDs to years of life lost (YLLs). Population projections were prepared from World Bank projections of fertility and the projected mortality rates. FINDINGS: Life expectancy at birth for women was projected to increase in all three scenarios; in established market economies to about 90 years by 2020. Far smaller gains in male life expectancy were projected than in females; in formerly socialist economies of Europe, male life expectancy may not increase at all. Worldwide mortality from communicable maternal, perinatal, and nutritional disorders was expected to decline in the baseline scenario from 17.2 million deaths in 1990 to 10.3 million in 2020. We projected that non-communicable disease mortality will increase from 28.1 million deaths in 1990 to 49.7 million in 2020. Deaths from injury may increase from 5.1 million to 8.4 million. Leading causes of disability-adjusted life years (DALYs) predicted by the baseline model were (in descending order): ischaemic heart disease, unipolar major depression, road-traffic accidents, cerebrovascular disease, chronic obstructive pulmonary disease, lower respiratory infections, tuberculosis, war injuries, diarrhoeal diseases, and HIV. Tobacco-attributable mortality is projected to increase from 3.0 million deaths in 1990 to 8.4 million deaths in 2020. INTERPRETATION: Health trends in the next 25 years will be determined mainly by the ageing of the world's population, the decline in age-specific mortality rates from communicable, maternal, perinatal, and nutritional disorders, the spread of HIV, and the increase in tobacco-related mortality and disability. Projections, by their nature, are highly uncertain, but we found some robust results with implications for health policy.
Adolescent↗
Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.
BACKGROUND: Prevention and control of disease and injury require information about the leading medical causes of illness and exposures or risk factors. The assessment of the public-health importance of these has been hampered by the lack of common methods to investigate the overall, worldwide burden. The Global Burden of Disease Study (GBD) provides a standardised approach to epidemiological assessment and uses a standard unit, the disability-adjusted life year (DALY), to aid comparisons. METHODS: DALYs for each age-sex group in each GBD region for 107 disorders were calculated, based on the estimates of mortality by cause, incidence, average age of onset, duration, and disability severity. Estimates of the burden and prevalence of exposure in different regions of disorders attributable to malnutrition, poor water supply, sanitation and personal and domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension, physical inactivity, use of illicit drugs, and air pollution were developed. FINDINGS: Developed regions account for 11.6% of the worldwide burden from all causes of death and disability, and account for 90.2% of health expenditure worldwide. Communicable, maternal, perinatal, and nutritional disorders explain 43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%; neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs worldwide. The ten leading specific causes of global DALYs are, in descending order, lower respiratory infections, diarrhoeal diseases, perinatal disorders, unipolar major depression, ischaemic heart disease, cerebrovascular disease, tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor water, and sanitation and personal and domestic hygiene. INTERPRETATION: The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children. The substantial burdens of neuropsychiatric disorders and injuries are under-recognised. The epidemiological transition in terms of DALYs has progressed substantially in China, Latin America and the Caribbean, other Asia and islands, and the middle eastern crescent. If the burdens of disability and death are taken into account, our list differs substantially from other lists of the leading causes of death. DALYs provide a common metric to aid meaningful comparison of the burden of risk factors, diseases, and injuries.
Adolescent↗
Regional patterns of disability-free life expectancy and disability-adjusted life expectancy: global Burden of Disease Study.
BACKGROUND: Information on non-fatal health outcomes of disease and injury has been largely neglected in health planning because of the conceptual and definitional complexity of measuring morbidity and disability in populations. One of our major objectives was to quantify disability for inclusion in health policy debates. We analysed these health outcomes in terms of disability-free life expectancy (DFLE) and disability-adjusted life expectancy (DALE). METHODS: Published and unpublished data were systematically reviewed to estimate the incidence, prevalence, and duration of 483 disabling sequelae of 107 diseases and injuries. To ensure internal consistency of these estimates, a software programme (DISMOD) was applied many times until consistent parameters were identified. The severity of disability, on a scale of 0 (perfect health) to 1 (death), was measured in a deliberate manner by the person-trade-off method. Spearman's and Pearson's correlation coefficients were used to measure disability weights among groups. Prevalence of seven classes of disability was back-calculated from the distribution of each disabling sequela across disabilities. Prevalence for each class of disability for different age-sex groups was used to calculate seven forms of DFLE and DALE based on Sullivan's method. FINDINGS: Prevalence of most disability classes is highest in sub-Saharan Africa and lowest in established market economies. Low-severity disabilities (class I and class II) are the most common. The expectation at birth of class I disability ranges from 6.5 years in established market economies to 14.7 years in sub-Saharan Africa, and for class II disabilities, from 8.5-18.4 years. DFLE varies significantly among regions: DFLE for class I disabilities at birth ranges from 9.9 years in sub-Saharan Africa to 47.7 years in established market economies for females and DFLE for class V disabilities ranges from 43.4 years for men in sub-Saharan Africa to 74.8 years for women in established market economies. The proportion of expected life span at birth lived with disability adjusted for severity, varies from about 8% in established market economies to 15% in sub-Saharan Africa, with little difference between men and women. In high-income regions, nearly 90% of expected disability is due to non-communicable diseases and most of the remainder to injuries. In poorer regions, almost half of expected disability is due to communicable diseases and injuries. INTERPRETATION: The higher proportion of lifespan spent disabled in high-mortality populations is consistent with the compression of morbidity hypothesis. The threshold definition of disability used substantially affects the results of DFLE, DALE, which incorporates severity weights for disabilities, is a useful summary measure of the burden of disability and mortality.
Adolescent↗
Mortality by cause for eight regions of the world: Global Burden of Disease Study.
BACKGROUND: Reliable information on causes of death is essential to the development of national and international health policies for prevention and control of disease and injury. Medically certified information is available for less than 30% of the estimated 50.5 million deaths that occur each year worldwide. However, other data sources can be used to develop cause-of-death estimates for populations. To be useful, estimates must be internally consistent, plausible, and reflect epidemiological characteristics suggested by community-level data. The Global Burden of Disease Study (GBD) used various data sources and made corrections for miscoding of important diseases (eg, ischaemic heart disease) to estimate worldwide and regional cause-of-death.patterns in 1990 for 14 age-sex groups in eight regions, for 107 causes. METHODS: Preliminary estimates were developed with available vital-registration data, sample-registration data for India and China, and small-scale population-study data sources. Registration data were corrected for miscoding, and Lorenz-curve analysis was used to estimate cause-of-death patterns in areas without registration. Preliminary estimates were modified to reflect the epidemiology of selected diseases and injuries. Final estimates were checked to ensure that numbers of deaths in specific age-sex groups did not exceed estimates suggested by independent demographic methods. FINDINGS: 98% of all deaths in children younger than 15 years are in the developing world. 83% and 59% of deaths at 15-59 and 70 years, respectively, are in the developing world. The probability of death between birth and 15 years ranges from 22.0% in sub-Saharan Africa to 1.1% in the established market economies. Probabilities of death between 15 and 60 years range from 7.2% for women in established market economies to 39.1% for men in sub-Saharan Africa. The probability of a man or woman dying from a non-communicable disease is higher in sub-Saharan Africa and other developing regions than in established market economies. Worldwide in 1990, communicable, maternal, perinatal, and nutritional disorders accounted for 17.2 million deaths, non-communicable diseases for 28.1 million deaths and injuries for 5.1 million deaths. The leading causes of death in 1990 were ischaemic heart disease (6.3 million deaths), cerebrovascular accidents (4.4 million deaths), lower respiratory infections (4.3 million), diarrhoeal diseases (2.9 million), perinatal disorders (2.4 million), chronic obstructive pulmonary disease (2.2 million), tuberculosis (2.0 million), measles (1.1 million), road-traffic accidents (1.0 million), and lung cancer (0.9 million). INTERPRETATION: Five of the ten leading killers are communicable, perinatal, and nutritional disorders largely affecting children. Non-communicable diseases are, however, already major public health challenges in all regions. Injuries, which account for 10% of global mortality, are often ignored as a major cause of death and may require innovative strategies to reduce their toll. The estimates by cause have wide Cls, but provide a foundation for a more informed debate on public-health priorities.
Adolescent↗
Analysis of a human fetal pancreatic islet cell line.
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Antigens, Polyomavirus Transforming↗
Ex vivo expansion of human pancreatic endocrine cells.
Cell transplantation as a therapy for type 1 diabetes is facilitated by ex vivo cell expansion of pancreatic beta-cells without loss of differentiative characteristics. The aim of this study was to determine the optimal conditions for in vitro growth of functional human pancreatic endocrine tissue. We examined the mitogenicity of matrixes from a variety of cell lines; proliferation was greater in cells growing on matrixes from bladder carcinoma cell lines, especially in monolayers grown on matrix from the human cell line HTB-9. After 14-day culture, there was a more than 100-fold proliferative increase, which was augmented to a more than 200-fold when hepatocyte growth factor/scatter factor was added; however, hepatocyte growth factor/scatter factor induced a rapid decrease in insulin content. Without the growth factor, fetal cell monolayers expanded 4-fold with no insulin loss; however, after 12-fold expansion, the insulin levels decreased to 40% of those in unexpanded cells. Adult islet cells expanded 3-fold without insulin loss. After 5-fold expansion, insulin levels decreased by 25% compared to those in free floating islets while retaining a normal response to secretagogues. Together, these results indicate that HTB-9 matrix provides the best stimulatory effect on replication of human endocrine cells, with little loss of in vitro function.
Adult↗
Functional beta-cell mass after transplantation of human fetal pancreatic cells: differentiation or proliferation?
The scarcity of human adult islets available for transplantation in IDDM makes the use of human fetal pancreatic cells desirable. Human fetal pancreatic cells grow and differentiate after transplantation in nude mice. It is unclear whether proliferation of preexisting endocrine cells or differentiation of precursor cells is mainly responsible for the increased islet mass and if beta-cell enrichment before transplantation enhances the functional outcome of the graft. To answer these questions, we transplanted purified human fetal islets, islet-like cell clusters (ICCs), and fresh tissue under the kidney capsule of nude mice. Insulin content was highest in the fresh tissue but fell rapidly during culture as either fetal islets or ICCs. Although fetal islets contained fourfold more insulin than ICCs before transplantation, the insulin content of the resulting grafts was the same after 3 months in vivo. The degree of stimulation after glucose challenge was comparable; however, more tissue was needed to generate the fetal islets. Grafts of fresh tissue also had similar total insulin contents, but when normalized to DNA, insulin concentration was significantly higher in the grafts from cultured tissue. Moreover, there were distinct morphological differences; the grafts from fresh tissue were more fibrous, with prominent ductal and cystic elements. Grafts from cultured tissue were two- to threefold enriched in endocrine tissue when compared with grafts originating from fresh tissue. These results suggest that islet cells identified in the grafted ICCs are mainly derived through differentiation of endocrine precursors and that cultured ICCs are more preferable than either fetal islets or uncultured tissue for transplantation.
Age Factors↗
Trehalose: a cryoprotectant that enhances recovery and preserves function of human pancreatic islets after long-term storage.
The scarcity of available tissue for transplantation in diabetes and the need for multiple donors make it mandatory to use an optimal cryopreservation method that allows maximal recovery and preservation of beta-cell function. We have developed a method to cryopreserve islets with excellent survival of endocrine cells. Current methods use DMSO as cryoprotectant. Our method involves introducing both DMSO and the disaccharide trehalose into the cells during cooling. Uptake and release of trehalose occurred during the thermotropic lipid-phase transition measured in pancreatic endocrine cells between 5 degrees and 9 degrees C, using [14C]trehalose. Recovery of adult islets after cryopreservation with 300 mmol/l trehalose was 92 vs. 58% using DMSO alone. In vitro function, in terms of insulin content and release in response to secretagogues, was indistinguishable from fresh islets. Grafts from islets cryopreserved with trehalose contained 14-fold more insulin than grafts from islets cryopreserved without trehalose. Results with human fetal islet-like cell clusters (ICCs) were more pronounced: recovery from cryopreservation was 94%, compared with 42% without trehalose. Complete functionality of fetal cells was also restored; tritiated thymidine incorporation and insulin content and release were similar to fresh tissue. After transplantation in nude mice, there was a 15-fold increase in insulin content of grafts from ICCs cryopreserved with trehalose compared with ICCs cryopreserved without trehalose. Thus, the addition of trehalose to cryopreservation protocols leads to previously unobtainable survival rates of human pancreatic endocrine tissue.
Adult↗
The utility of DALYs for public health policy and research: a reply.
The WHO Advisory Committee on Health Research (ACHR), through its DALY Review Group, has recently criticized the use of disability-adjusted life years (DALYs). To suggest that the use of DALYs should be discouraged as an aid in health resource allocation may, however, be premature, since it enhances informed debate on the social values that influence resource allocation, identifies health problems that may be neglected, and points to the strengths and weaknesses of existing health information systems.
Persons with Disabilities↗
Evidence-based health policy--lessons from the Global Burden of Disease Study.
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Cost of Illness↗
Mortality from smoking worldwide.
Estimates are made of the numbers and proportions of deaths attributable to smoking in 44 developed countries in 1990. In developed countries as a whole, tobacco was responsible for 24% of all male deaths and 7% of all female deaths, rising to over 40% in men in some former socialist economies and 17% in women in the USA. The average loss of life for all cigarette smokers was about 8 years and for those whose deaths were attributable to tobacco about 16 years. Trends in mortality attributable to tobacco differed between countries. In some the mortality in middle age (35-69 years) had decreased by half in men since 1965; in others it was continuing to increase. In women, the proportion was mostly increasing, almost universally in old age. Mortality not attributable to smoking decreased since 1955 in all OECD (Organization for European Collaboration and Development) countries, by up to 60% in men and more in women. No precise estimate can be made of the number of deaths attributable to smoking in undeveloped countries, but the prevalence of smoking suggests that it will be large. In the world as a whole, some 3 million deaths a year are estimated to be attributable to smoking, rising to 10 million a year in 30-40 years' time.
Adolescent↗
The incremental effect of age-weighting on YLLs, YLDs, and DALYs: a response.
When disability-adjusted life years (DALYs) were first formulated, the effect of age-weighting on years of life lost due to death at each age as well as the different effect on short- and medium-term disability were taken into consideration. While there is considerable scope for discussion on the actual values that are incorporated into DALYs, the present article argues that once the values have been chosen we should accept the consequences of the choice.
Age Factors↗