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Biomedical subjects

A D Lopez

Publications and source records attributed to A D Lopez.

At least 19 recordsLinked to original sources

Mortality from tobacco in developed countries: indirect estimation from national vital statistics.

Prolonged cigarette smoking causes even more deaths from other diseases than from lung cancer. In developed countries, the absolute age-sex-specific lung cancer rates can be used to indicate the approximate proportions due to tobacco of deaths not only from lung cancer itself but also, indirectly, from vascular disease and from various other categories of disease. Even in the absence of direct information on smoking histories, therefore, national mortality from tobacco can be estimated approximately just from the disease mortality statistics that are available from all major developed countries for about 1985 (and for 1975 and so, by extrapolation, for 1995). The relation between the absolute excess of lung cancer and the proportional excess of other diseases can only be approximate, and so as not to overestimate the effects of tobacco it has been taken to be only half that suggested by a recent large prospective study of smoking and death among one million Americans. Application of such methods indicates that, in developed countries alone, annual deaths from smoking number about 0.9 million in 1965, 1.3 million in 1975, 1.7 million in 1985, and 2.1 million in 1995 (and hence about 21 million in the decade 1990-99: 5-6 million European Community, 5-6 million USA, 5 million former USSR, 3 million Eastern and other Europe, and 2 million elsewhere, [ie, Australia, Canada, Japan, and New Zealand]). More than half these deaths will be at 35-69 years of age: during the 1990s tobacco will in developed countries cause about 30% of all deaths at 35-69 (making it the largest single cause of premature death) plus about 14% of all at older ages. Those killed at older ages are on average already almost 80 years old, however, and might have died soon anyway, but those killed by tobacco at 35-69 lose an average of about 23 years of life. At present just under 20% of all deaths in developed countries are attributed to tobacco, but this percentage is still rising, suggesting that on current smoking patterns just over 20% of those now living in developed countries will eventually be killed by tobacco (ie, about a quarter of a billion, out of a current total population of just under one and a quarter billion).

Adult

The use of digital image processing to quantitate angiogenesis induced by basic fibroblast growth factor and transplanted pancreatic islets.

We have used digital image processing as a technique to quantify the formation of blood vessels in situ in response to the application of either an angiogenic peptide, basic fibroblast growth factor, or isolated pancreatic islets. The peptide or the islets were placed under the rat kidney capsule. For in vivo microscopy fluorescein-labeled dextran was injected intravenously and video images were made as deemed appropriate. Images to be analyzed were selected manually, digitized, and stored in a computer for processing. The calculation of the total vessel length per area was called the microvascular index. Three weeks after the transplantation of 200 islets, the microvascular index was fairly constant and did not change significantly when the same measurements were performed 1 week later. In another experiment, pellets containing 0.5 micrograms of basic fibroblast growth factor produced an angiogenic response no different from that of a control pellet. At a dose of 1 microgram, however, the response was statistically significant after 1 week. These data indicate that digital image processing may be a useful method to quantitate the angiogenesis induced by local administration of angiogenic stimulants.

Animals

Angiogenic peptides in pancreatic islet transplantation to diabetic rats.

To overcome the deleterious effects of hyperglycemia on islet transplantation, we have used recombinant basic fibroblast growth factor (FGF), an angiogenic peptide, concurrently with the intrasplenic placement of neonatal islets in severely diabetic rats. In both experimental and control rats, a minipump, secured to the spleen with a small indwelling catheter, delivered either the basic FGF at 10 ng/hr, or only the diluent. The rate of cure in the animals receiving the islets plus the peptide was significantly higher (70%) than in control rats (20%). This difference (P less than 0.05), could not be attributed to direct effects of the peptide on islet function or to increased islet cell replication. We believe that these results may be best explained as an enhancement by basic FGF of the angiogenic process in the transplant islets.

Administration, Topical

Competing causes of death. A review of recent trends in mortality in industrialized countries with special reference to cancer.

In most industralized countries, the last two decades or so have been characterized by a further significant reduction in mortality. Summary measures of mortality, such as the age-standardized death rate, have declined in parallel with reductions in CVD mortality. Yet, cancer mortality over all ages has risen in the majority of industralized countries. However, this rise in cancer mortality has been accompanied by a rise in the average age at death from the disease, suggesting further progress in deferring death. How much of the observed increase in cancer mortality for such sites as the brain, as well as for multiple myeloma, is real is difficult to determine. Certainly, for countries such as the United States, where mortality from ill-defined causes and ill-defined cancer sites has not fallen, it is quite probable that the increase in death rates largely reflects a real increase in cancer risk. There can be little doubt that the rise in lung cancer mortality is a real trend and this has repeatedly been shown to mirror, with an appropriate lag period, previous changes in cigarette consumption. On the other hand, for some countries, such as France, Japan, and Italy, there have been very substantial postwar declines in mortality rates from ill-defined causes, and hence any increase in mortality from diseases for which diagnostic precision is known to have improved must be viewed with some caution. The reductions in CVD mortality have also been accompanied by a rise in the average age at death and a decline in the proportion of all deaths attributable to CVD. There have thus been fewer CVD deaths and these deaths are increasingly postponed to higher ages. This is reflected by the widespread decline in summary indices of premature mortality, such as the age-standardized death rate at ages 35 to 74 years. On the other hand, cancer death rates at these ages have risen in several countries, suggesting that at least some of the "younger" persons "saved" from dying from CVD are now succumbing to cancer. The suggestion that previous cigarette smoking has "claimed" the majority of "saved" lives from CVD is supported by the evidence on mortality trends for major sites of cancer. (The principal site of the disease for which mortality in males at ages 35 to 74 years rose in most countries substantially is lung cancer, which accounts for the vast majority of the rise in overall cancer mortality where it has occurred.) These conclusions would be strengthened if one could demonstrate parallel trends based on incidence data.(ABSTRACT TRUNCATED AT 400 WORDS)

Accidents, Traffic

The use of cause-of-death statistics for health situation assessment: national and international experiences.

About 80 countries or areas regularly report detailed cause-of-death data to WHO based on the International Statistical Classification of Diseases, Injuries, and Causes of Death (ICD). These data refer to about 35% of all deaths estimated to occur in the world, although the actual coverage may be somewhat higher due to the representativeness of data-collection schemes in countries such as China. These data are systematically validated and documented by WHO before their dissemination, principally through publication in the World health statistics annual. This article describes the collection and use of these data by WHO for assessing the global and regional health situation, and for monitoring trends in health status. In addition, several issues in the use of mortality data and the ICD for national health situation assessment are discussed, including the need for documenting the quality and coverage of cause-of-death statistics, identifying biases and evaluating mortality trends.

Cause of Death

Who dies of what? A comparative analysis of mortality conditions in developed countries around 1987.

The developed countries are often viewed as being relatively homogeneous in terms of health conditions. This is not the case, however. Whilst the overall level of life expectancy in these countries (73.7 years) is well in excess of that observed in the majority of developing countries, there are nonetheless very substantial differences in health status among and between the developed countries. Female life expectancy is typically 6-8 years longer than that of males. The gap in life expectancy between Japan and some countries of Northern Europe, on the one hand, and the nations of Eastern Europe on the other, is of the same order of magnitude. Of the 11 million deaths reported in the developed countries each year, roughly 5.5 million or almost exactly 50% are attributable to cardiovascular diseases. Of these deaths, 2.4 million are coded to ischaemic heart disease and 1.5 million to stroke (cerebrovascular disease). Cancer (all forms) accounts for 2.3 million deaths (21%), 500,000 of which are due to lung cancer alone. External causes of death claim 750,000 lives each year in the developed countries, with suicide and motor-vehicle accidents each accounting for around 180,000 deaths. This pattern of mortality, when viewed in conjunction with the epidemiological evidence about the principal risk factors associated with these causes of death, strongly suggests that national health-for-all strategies must continue to emphasize individual health consciousness as the primary means of achieving national health goals.

Age Factors

Causes of death: an assessment of global patterns of mortality around 1985.

Cause-of-death statistics are available for virtually the entire population of the developed world (1.17 billion in 1985) and thus estimates of the mortality pattern in these countries can be made with some confidence, notwithstanding the artefacts which arise due to differences in diagnostic and certification practices between countries. In the developing countries, cause-of-death estimation is much more difficult due to the paucity of mortality statistics. Nonetheless, there are several sources of information on mortality, ranging from surveillance systems and small-scale community studies to complete vital registration, which can be exploited to estimate mortality patterns. Of the 50 million deaths which occur throughout the world each year, roughly 39 million (78%) occur in developing countries. For the developing countries as a whole, infectious and parasitic diseases are estimated to have accounted for almost one-half of all deaths in 1985. Diarrhoeal diseases, acute respiratory diseases (primarily pneumonia) and tuberculosis each claimed about 3-5 million deaths in the developing world in the mid-1980s, with a further 2.6 million due to measles and whooping cough. Perinatal conditions are estimated to have been responsible for a little over 3.2 million deaths in 1985 in developing countries, one-quarter of which were due to neonatal tetanus alone. Maternal causes claimed the lives of about 0.5 million women. At the same time, the chronic diseases are emerging as a leading cause of death in several regions of the developing world, particularly Latin America and East Asia. Circulatory and specific degenerative diseases are estimated to have caused about 6.5 million deaths in 1985. Chronic lung diseases and cancer are each thought to have claimed about 2.5 million lives in 1985. External causes also probably accounted for 2.0-2.5 million deaths.

Australia

Enhancement of pancreatic islet cell monolayer growth by endothelial cell matrix and insulin.

The roles of glucose and insulin in the promotion of DNA synthesis in pancreatic islet cell monolayers were assessed using a variety of in vitro conditions. Several substrates including collagen, poly-l-lysine, Matrigel, and the extracellular matrix produced by cultured bovine endothelial cells (BCEM) were compared for their ability to promote monolayer growth. Islets grown on BCEM in combination with medium RPMI 1640 supplemented with 22.2 mM glucose or 10 micrograms/ml insulin gave the best results as determined by new DNA synthesis. The new-form monolayers were free of contaminating fibroblasts. These results suggest that insulin is critical to pancreatic islet growth when the cells are attached to biocompatible matrices.

Animals

Decrease in the number of neonatal islets required for successful transplantation by strict metabolic control of diabetic rats.

We have investigated the influence of glycemic control on the number of transplanted neonatal islets needed to cure streptozotocin (STZ)-diabetic rats. Intrasplenic transplantation of 1000 neonatal islets to a group of STZ-diabetic rats with poor glycemic control cured only 30% of the rats. In a second group, insulin at doses of 10-15 U/day given for 5 days after transplantation improved the cure rate to 72%. Normalization of blood glucose by a previous transplant to the kidney capsule produced cure in 100% of the rats. The above results were obtained despite the fact that isolated adult islets, when compared with neonatal islets, were larger, contained more protein and DNA--and, in response to glucose stimulation, released more insulin than neonatal islets. These experiments show that neonatal islets are an excellent source of endocrine replacement tissue when transplanted intrasplenically, and that the number of islets needed to cure experimental diabetes is significantly reduced by normalization of the metabolic milieu in the recipient.

Animals

Hypertension in developing countries.

Population surveys carried out since the 1970s in 15 developing countries including 23 population groups show that the prevalence of hypertension ranges from as low as 1% in some African countries to over 30% in Brazil. A trend analysis of the mortality statistics for 35-74 year-olds from 16 countries in which data are available shows a downward trend in mortality from hypertension and cerebrovascular diseases in most of these countries. In spite of the current low prevalence in some countries, the total number of hypertensives in the developing world is high, and a cost assessment of possible antihypertensive drug treatment indicates that developing countries cannot afford the same drug treatment levels as developed countries.

Adult

An in vivo model for study of the angiogenic effects of basic fibroblast growth factor.

We have investigated the angiogenic effects of basic fibroblast growth factor following its implantation in slow release beads under the kidney capsule. The presence of basic fibroblast growth factor in the subcapsular space induced a marked angiogenic response maximal at 1 microgram dose per kidney. Histological examination at the site of treatment failed to reveal evidence of an inflammatory response, thus supporting the observation that basic fibroblast growth factor alone can stimulate in vivo neovascularization. Beads pretreated with saline or with human growth hormone had no angiogenic effect. Because of the readily accessible location in the retroperitoneal space, the ease of drug delivery, and the marked vascular proliferation seen in response to FGF, our results suggest that the kidney capsule is an excellent model for study of the physiological role played by FGF and related peptides in promoting angiogenesis in vivo.

Animals