Longevity Health and Wellness Protocol

Get Younger Tomorrow Reversing 20 Years Of Aging

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The Search For Longevity Genes

Aging research throughout the first three epochs of gerontology was primarily concerned with describing general aspects of the process covering all levels of biological organization, from the molecular to the organismal. The data collected spawned a large number of theories (covered in chapter 2) touching on all aspects of cellular structure and function, as well as changes that may occur at the physiological level. Although these theories were crucial for producing advances in the discipline, they failed to produce a clear picture of fundamental mechanisms responsible for the aging process. However, beginning in 1993 with the NIA program to isolate aging genes, there has been a great surge in the genetic analysis of aging and a better understanding of the molecular mechanisms, signaling pathways, and physiological processes that promote longevity. Thus, with the beginning of the current epoch and the launching of comprehensive genome sequencing projects, the goal of gerontology...

Mouse Longevity Genes

Where it performs a longevity function. Consequently, human lag-1 may be thought of as a human longevity gene, although much work is needed to confirm its function in humans. Perhaps the most striking similarity between longevity genes in humans and lower organisms is the yeast sgs-1 gene and the human wrn gene. The sgs-1 gene codes for a helicase and, when mutated, can accelerate the aging process. Werner's syndrome, described previously, is a disease in humans that is also associated with accelerated aging. The gene responsible for this disease, called wrn, has been identified. The protein product of the wrn gene is a helicase, not the same helicase encoded by the sgs-1 gene, but a member of the same family, possessing a similar function. Mutations in these two genes provide dramatic evidence in support of the connection between life span and genetic stability.

Longevity Population Pressure and Warfare

The largest effect of agriculture and a steady food supply was on population size and density. This major demographic change is the result of an increase in expectation of life at birth. As soon as this average longevity reaches about 20 years, the population starts to rise. Families would become larger, and many more children would survive to become reproducing adults. If the number of offspring increases by 10 , per generation, then the population rises exponentially, and will double in less than eight generations. More females would reach the end of menaupause, stop reproducing and care for grandchildren or other family members. In these settled communities there was no longer the driving force of migration, which was common during the hunter - gatherer period. is, threat and bluster, rather the real violence which results in much loss of life, although head hunting amongst enemies certainly occurred. We see the emergence of warriors, who spend a lot of time making weapons and...

Mutants Who Live Longer

A demonstrative precedent that mutations can really be favorable for longevity has been furnished by Hekimi and coworkers 204,205 , who studied the nematode Caenorhabditis elegans. A mutant worm with two damaged genes was obtained living 5.5 times longer than the wild type. It would be interesting to study mutations in homologous genes already found in other organisms (from yeast to man).

Problems With Life Expectancy and Quality Adjusted Life Expectancy as Measures Used to Set Health Policy

Life expectancy in the absence of an intervention is a function of current age and sex and, in most populations, of race. When life expectancy is used as the measure of effectiveness, an intervention that prolongs life will have the smallest effect on the estimated gain in life expectancy in the group with the shortest life expectancy. Thus, the cost per year of life gained will be greatest in the group with the shortest life expectancy in the absence of the intervention. When cost-effectiveness evaluates a choice between alternative therapies for example, a choice between two different types of pneumococcal vaccine in the elderly, this theoretical problem does not pertain. When, however, cost-effectiveness analysis is used to guide choices between an intervention for a person with a short life expectancy and similar interventions for persons with a longer life expectancy, use of life expectancy as an outcome will discriminate against the group whose life expectancy is shortest...

Adjusting the Measure of Life Expectancy

The measurement of preferences for health states was discussed in Chapter 8. Application of these techniques results in assignment of a value to time spent in each health state. This value is often called Q. The Q factor for each health state is to adjust the life expectancy for each health state by multiplying the amount of time spent in each health state by the Q factor for that health state. In the simplest case, the disease causes a consistent reduction in quality of life over all remaining years of life expectancy and the intervention returns quality of life to what it would have been in the absence of disease. Quality-adjusted life expectancy for those with the disease is calculated by multiplying life expectancy for those with the disease by Q. Quality-adjusted life expectancy for those with the intervention is calculated by multiplying life expectancy in the absence of the disease by 1.0. The difference between the two estimates is used as the denominator in the...

Vacterl Syndrome Life Expectancy

With improved surgical techniques and paediatric intensive care facilities, many patients with ARM now live relatively normal lives, with a near-normal life expectancy. Therefore, sexual function and fertility are of increasing importance. Sexual function may be impaired for several reasons

Limits On Life Expectancy And Future Prospects

Rectangularization Mortality

Because we do not understand the mechanisms of biological aging or the reasons for aging, estimating the limits of human life expectancy is highly empirical. There is a strong evolutionary and genetic influence on life expectancy (7-9). The forces of natural selection decrease with advancing age because, in natural populations, few individuals survive past the reproductive ages. Therefore, among the survivors, random mutations (alleles) will accumulate and their detrimental effects will be expressed after reproductive activity has ceased. In recognition of those ideas, Williams (10) proposed an antagonistic pleiotropy hypothesis, which suggests that disadvantageous genes in a population will not be selected against if they arise after the reproductive phase that is required to maintain the population. A related theory is that of the disposable soma theory (11), the concepts of which were summarized by Holliday (12) as follows Finch (9) has reviewed the relationships between life-span...

Measuring Life Expectancy

Life expectancy is defined by actuaries as the average future lifetime of a person. It is usually estimated for persons of a specific age, sex, and race. Actuarial methods to estimate life expectancy are based on specialized statistical lifetable functions that rely on data on mortality rates specific for age, sex, and race. The age-, sex-, and race-specific mortality rates are based on death certificate data and census data. In very rare cases, life expectancy for interventions has been compared directly in a randomized trial or in a follow-up study. In these rare cases, the empirically measured information on life expectancy from the relevant studies can be used directly. More often, available information on life expectancy in persons with a disease is in the form of overall mortality rates, 5-year survival rates, or median survival. The available information on interventions consists of a measure of the relative risk or the odds of mortality in those who have the intervention...

Myths of Life Extension

Ever since humans became fully aware that they will get old and die, individuals must have wondered about the possibility of extending longevity, or achieving immortality on earth. This has resulted in innumerable myths relating to supposed examples of life-extension, one of the most notable being the 969 year lifespan of Methuselah, as recorded in the Bible. Christian fundamentalists are liable to say that in those days people lived much longer than they do today These are many other claims, and far too many to list here. The Guiness Book of Records has stated that maximum lifespans of people and animals are some of the hardest records to document. Some of the claims of human longevity have occurred in the 20th century, and as in some cases they were initially accepted by scientists, and they provide good examples of how people are deceived. Many people living in the Caucasus region of the ex-Soviet Union claimed their ages were over 120 years, or even 160 years. There was even a...

The Modulation of Longevity

Chapter 9 discussed the mythical claims, ancient and modern, that humans can have very long lifespans. This one is devoted to the various ways in which ageing and longevity can be modulated, including either an increase or a decrease. We know that there are at least three major components that determine the expectation of life at birth. One is the species itself, because in mammals maximum lifespan varies by at least 30-fold, and if we accept the reports of extreme longevity in some whales, probably 60-fold. The second is the environment, which can obviously limit natural lifespan through predation, starvation and disease. Even in a protected environment of a zoo, the environment, including food, and possibly the opportunities for normal well-being and behaviour, are likely to influence longevity. The third, is an intrinsic variation of the determinants of longevity within the animal itself. We saw in Chapter 1 that identical twins do not have have identical lifespans, and even more...

The Evolution of Human Longevity

From a simple biological standpoint, it is remarkable that Homo sapiens is the longest lived terrestrial mammalian species. The largest, such as the elephant, hippopotomas and rhinoceros, have long lifespans, but not as long as human beings. There are herbivores which are much larger than man, and also carnivores, but their lifespans are well under half the human one. Scientists studying ageing have correlated brain size, or the ratio of brain weight to body weight, with lifespan. There is in fact a good reason why, at least for humans, there should be an association of brain size with longevity, and this will be explained in this chapter. Another feature of human ageing is the well known fact that women have a longer expectation of life than men, by 5-7 years in developed countries. This has so far never been satisfactorily explained, but I suggest an explanation here. There are two major evolutionary features of ageing. The first is the reason for the evolution of ageing per se,...

Longevity

In Western societies with good health care the expectation of life at birth is now about four times higher than in primitive ones more than 80 years for females, and just a few years shorter for males. There is not much infant mortality, and most subsequent mortality in the following decades is due to accidents, suicide, homicide, or occasional intrinsic disease, such as cancer. For a population, the shape of the survival curve is like that shown in Figure 1A. It is clear that the force of mortality starts to increase only quite late in life. With constant annual mortality, the survival curve is 'exponential' as shown in Figure 1B. Through history a major factor that increased longevity was the development of agriculture, which ensured a much more reliable supply of food. Even so, civilisations as advanced as the ancient Romans and Greeks had survival curves that were not very different from exponential, as shown in Figure 2. There was high infant mortality and expectation of life at...

DNA Structure Inspires New Theories

Gerontologists of the second epoch quickly realized that the genetic code and the events of protein synthesis gave them, for the first time, testable theories of the aging process. The first, proposed by Deham Harman in 1956, was the free radical theory, and the second, proposed by Leslie Orgel in 1963, was the error catastrophe theory. Both of these theories (described in chapter 2) suggest that aging is caused by errors in biosynthesis, due either to free radicals or to inherent error frequencies associated with transcription and translation. In either case, according to the theories, the result is a buildup of dysfunctional proteins that damage normal cellular functions, thus reducing cell viability with time. The error catastrophe theory was first tested on bacteria, experimental organisms introduced to gerontology during the early years. To further test this theory and the free radical theory, gerontologists of the However, many investigators were quick to realize that even...

The History Of Gerontology

Gerontology is a branch of the biological sciences devoted to the study of the aging process and its effects on cells and organisms. Philosophers and scientists have been interested in this subject for thousands of years, but this history will be confined to the modern era, extending back no further than the late 1800s. The history of gerontology, like many other branches of biological research, may be divided into four epochs. The first, covering the early years, began around 1870 with the invention of the compound microscope and ended in the 1950s. The second epoch began with the discovery of the DNA double helix in 1952 and extended to the early 1970s. The third epoch began with the introduction of recombinant DNA technology in 1973, ending in the early 1990s. The current epoch, known as the postgenomic era, began with the formation of a genome sequencing consortium in 1990 and continues to the present day.

Genes and Programmed Aging

Community, the animal's intelligence, the number of offspring, and the pressure the animal experiences from its predators, are all taken into account. The final life span seems to be a balance of all these forces and, given these forces, may be the best deal the organism can hope for. There would be no point to nature's producing a fruit fly that could live a thousand years, because their predators eat them all in a matter of days. Scientists might try producing a fly that could live that long, but what in the world would an animal with that level of intelligence do for all that time This is not just a whimsical point. There is a very strong correlation between longevity and the weight of the brain Smart animals live longer than dumb animals (with two exceptions, noted in chapter 1).

Hormone Imbalance Theory

Processing Resources Theory Aging

Additional evidence in support of the role of the hypothalamus in the aging process comes from the observation that the levels of pituitary hormones, with the exception of ACTH, gradually decrease with age. The overall effect of this change is believed to be the loss of vigor, physical strength, and endurance that is typical in an aging human. Accordingly, many attempts have been made to reverse these effects with hormone therapies that include GH, estrogen, or testosterone supplements. While these therapies have alleviated some of the symptoms of old age, they have not been able to reverse the aging process. With our limited knowledge of the cell and the complexities of physiological and endocrinological systems, there are real dangers associated with hormone therapies. Estrogen supplements can minimize bone thinning in menopausal women, but constant exposure to this hormone can lead to breast cancer. Similarly, androgen supplements in men can increase vigor and physical strength,...

Recombinant Technology Revolutionizes the Field

Expression studies observe the transcription of a gene to produce messenger RNA (mRNA) and the resulting translation of mRNA into protein. Because most mRNA is automatically translated into protein, conducting an expression study involves determining the amount of mRNA being produced by a specific gene. The information gained by doing so is extremely important because all cellular processes are ultimately controlled by the differential expression of various genes. Some genes in some cells always stay off, whereas some are always on (constitutive expression), and some turn on or off as conditions demand (regulative expression). One theory of aging suggests that the aging process is caused by subtle disruptions in the normal control of gene expression. At first, gerontologists tried to test this assumption by examining the protein products of translation with two-dimensional (2-d) protein electrophoresis, a technology introduced in 1977. But 2-d elec-trophoresis can detect only a few...

Error Catastrophe Theory

In its original formulation, the error catastrophe theory focused on protein synthesis, which apparently can tolerate a high error frequency. Consequently, many scientists began to wonder if errors in the genome, or possibly a defective regulation of the genes, might be responsible for the aging process. After all, cells avoid an error catastrophe at the trans-lational level because they can always try again with a fresh mRNA from a good gene. But if the genes themselves are damaged, or programmed for senescence, the outcome would be a gradual decline in cell vigor and the eventual death of the organism.

Antioxidants

According to the free radical theory of the aging process, antioxidants should help reduce some of the symptoms associated with cellular senescence. Experiments with mice and rats have failed to substantiate this claim. However, there is some evidence suggesting that antioxidants such as vitamin C and E may reduce the threat of Alzheimer's disease by dissolving beta-amyloid plaques (deposits). In addition, research on longevity genes (described in chapter 6) has shown that some of these genes code for proteins that minimize oxidative damage to cells and tissues. This could mean that the failure of previous experiments to substantiate the free radical theory may be the fault of the experimental procedure and, thus, not a true test of the theory.

Summary

The search for longevity genes has identified four physiological processes that influence life span. They are metabolic control, resistance to stress, gene dysregulation, and genetic stability. Evidence supporting the involvement of metabolic control comes from the roles of lag-1 in yeast, daf-2 in nematodes, indy and sod-1 in Drosophila, and prop-1 in mice. Resistance to stress is a function of several longevity genes, such as ras-2, daf-12, mth, and p66shc. Gene dysregulation, as a mechanism of aging, has been clearly demonstrated in yeast with the isolation of three histone deacytlase genes, rpd-3, hda-1, and sir-2. Finally, the relationship between genetic stability and life span is indicated by the effects of sgs-1 mutants in yeast and the human disease known as Werner's syndrome, which is associated with accelerated aging and is caused by the gene wrn, a homolog of sgs-1. This collection of genes, small though it is, has given a powerful boost to gerontological research and...

Antiaging Medicine

The treatment of the aging process and of the diseases associated with it is difficult and highly controversial. Many scientists believe there is no such thing as a treatment that will reverse the aging process. Indeed, in 2002, a coalition of 51 gerontologists and biologists took an unprecedented step of publishing a paper that was sharply critical of antiaging medicines and the companies that market them. The following is an excerpt from their position statement The paper gives a thorough overview of what scientists have learned about the aging process and presents detailed arguments against the use of various therapies, particularly those involving hormone supplements, which can be dangerous if used without the supervision of a physician. Most antiaging products, however, are no more dangerous than sunscreens, skin creams, perfumes, and over-the-counter treat To a great extent, the controversy between the gerontologists and the cosmetic industry is reminiscent of the general clash...

Gene Therapy

Antiaging medicines, such as estrogen or testosterone supplements, do not reverse the aging process, nor do they alleviate all symptoms associated with a loss of those hormones. This is due to the age-related changes that occur in all the cells of the body. Old cells do not respond to hormones the same way they did when they were younger. Hormone receptors in the membranes of every cell change with time, as does the translation machinery that uses mRNA to synthesize proteins. Success with treating age-related diseases will always be limited until the health of each cell in the body can be restored a big job, but not inconceivable. Cloning technology has shown that it is possible to reprogram a highly differentiated nucleus to assume the functional status of an undifferentiated embryonic cell. Nuclear transfer, the method used to clone Dolly the sheep, is really a form of cellular rejuvenation. When a nucleus from an adult cell is placed inside an enucleated egg, the environment of the...

Agerelated Diseases

Growing old holds many pleasures, but for someone with Alzheimer's disease (AD), it can be a confusing and often frightening experience. The image of an absentminded elderly man or woman has been with us for a long time. People today are in the habit of thinking that this is the natural consequence of growing old, but gerontologists (scientists who study the aging process) have taught us to be cautious of this stereotype. Old people may be slower at certain tasks, but they are not necessarily senile or any more absentminded than a 20-year-old. Aging makes us more susceptible to certain diseases, but those diseases are not an inevitable consequence of growing old. Several other age-related diseases are described in this chapter, but none are so devastating as AD.

The Early Years

To study the structure and function of individual cells in a way that was never before possible. While many microbiologists of the time concentrated on studying the link between disease and microbes, many others began studying the life cycle of bacteria and protozoa in the hope it would shed some light on the aging process. These studies were descriptive in nature that is, the researcher observed the behavior of the cells and recorded it without subjecting the system to experimental procedures that would modulate the rate of the aging process. Thus it was that light microscopy, biochemistry, histochemistry, and histology became the basic tool kit for gerontologists during the early years of scientific research in this field. Scientists at that time believed they had all the techniques that were needed to fully understand the structure and the function of cells and animals. They were only partly right. The techniques of that day made it possible for scientists to gain a basic...

Concluding Remarks

With the exception of the role of telomeres in aging, all the theories just described have been with us for more than 40 years, and during that time gerontologists have subjected those theories to thousands of experiments in the hope of gaining a better understanding of the aging process. But today we do not understand the underlying mechanism of aging any better than we did when those theories were first formulated. This is not a criticism of the many outstanding scientists who devoted their research lives to this problem, but a recognition of the tremendous complexities involved in the aging process. Aging is the puzzle of all centuries, and its resolution will take an effort that will dwarf all other biological research projects to date. Microarray analysis provides an extremely powerful method for analyzing the aging process in an unbiased manner. That is, until the genome project was completed, gerontologists, using available theories as a guide, had to make an educated guess as...

The Road Ahead

In 1900 life expectancy for the average North American was only 45 years. This has increased to the current expectancy of 80 years primarily because of a dramatic reduction in infant mortality, cures for various diseases, better hygiene, and better living conditions. This increase occurred despite the enormous number of deaths per year from cigarette smoking. A further increase of 20 to 30 years is expected if cures are found for cancer and cardiovascular disease. Beyond that, advances in life Developing therapies that will reverse the aging process, allowing individuals to grow younger, is theoretically possible, but the realization of that goal will likely turn out to be the most difficult challenge that biologists have ever faced. The production of aging therapies will require a fusion of animal cloning, gene therapy, and stem cell technologies. But even these technologies, as powerful as they are, will not be enough. Gaining a deep understanding of the basic mechanisms of aging...

Geriatrics

The World Health Organization (WHO) places health issues on a continuum from disease to impairment to disability to handicap. Geriatrics is a branch of the biomedical sciences devoted to helping the elderly (65+ years old) deal with the effects of age. The geriatric approach does not try to reverse the aging process but rather to minimize its consequences by reducing or inhibiting the progression to disability. This effort, conducted in hospitals, clinics, and nursing homes, is based on a broad range of therapies that are grounded in the biological, psychological, and social sciences.

Drug Therapy

Geriatric patients are often prescribed a large number of drugs to deal with the many disorders they suffer from. However, as indicated above, there are usually effective nonpharmacological therapies available that should be attempted before resorting to drugs. All geriatric patients need a careful and thorough review of the drugs they are prescribed to ensure they are necessary and that there is no change of potentially dangerous drug interactions. Effective drug therapy is often hampered by faulty diagnosis. Older patients may underreport symptoms, or their complaints may be vague and multiple. In addition, symptoms of physical diseases may overlap with psychological illness. Consequently, making the correct diagnosis and prescribing the appropriate drugs is a very difficult task in geriatric medicine. Finally, the aging process alters the elderly patient's ability to deal with drugs physiologically. This deficit occurs primarily at the liver and at the kidneys.

Telomeres

The telomeres in human fibroblasts are long enough to permit about 50 rounds of DNA replication. That is, the cell can divide about 50 times in culture. This is often referred to as the Hayflick limit, after Leonard Hayflick, the scientist who was the first to notice that normal cells cannot divide indefinitely in culture. Cancer cells, on the other hand, can divide indefinitely, and from them scientists isolated an enzyme called telomerase that restores the telomeres after each cell division. If the telomerase gene is added to normal fibroblasts, they are no longer bound by the Hayflick limit and can divide indefinitely, like an immortal cancer cell. The transformation of normal fibroblasts with the telomerase gene was conducted for the first time in 1998 at the Geron Corporation, a biotechnology company. The results generated a tremendous amount of excitement, for they seemed to imply that reversal of replicative senescence would be followed very quickly by the reversal of the aging...

Nematode

A nematode is a very small round worm that inhabits the sole and sometimes the digestive tracts of mammals. Mammalian parasite nematodes are known as pinworms. The nematode C. elegans is a popular research organism among developmental biologists and gerontol-ogists. Several longevity genes have been identified in C. elegans, most of which are involved in an insulin-like signaling pathway (see table). At the head of this pathway is the insulin-like receptor, encoded by the gene daf-2. shifts the entire physiology of the animal from active behavior to something resembling hibernation in mammals. Hibernation behavior in nematodes is known as a diapause state. Nematode diapause is characterized by a shift from active glucose metabolism (i.e., burning calories) to storage functions, such as the deposit of fat. The animal's activity level drops, and the life span is increased by nearly 80 percent. Thus daf-2 is a negative regulator of life span it is an example of the kind of gene that...

How Is Information Reported

Cancer incidence rates are often reported either as actual counts at a given point in time or are expressed as age-adjusted rates. Simply reporting the raw number of new cases annually provides some information concerning the magnitude of the disease incidence within a population. Unfortunately, this approach does not take into account the number of patients at risk for developing cancer. The age distribution of populations changes over time. Western countries, for example, generally have a greater number of elderly people compared to most developing nations. As more people live longer, the risk of developing prostate cancer increases. This will be especially true when the large baby boom generation enters its seventh and eighth decades. As a consequence, the absolute number of new cancer cases may increase but the relative incidence rate may increase, decrease, or remain constant.

Pathophysiology Of Acute Aortic Syndromes

Cardiovascular disease is the leading cause of death in most Western societies and is increasing steadily in many developed countries. Aortic diseases constitute an emerging share of this burden. New diagnostic imaging modalities, longer life expectancy in general, longer exposure to elevated blood pressure, and the proliferation of modern noninvasive imaging modalities have all contributed to the growing awareness of acute and chronic aortic syndromes. Despite recent progress in recognition of both the epidemiological problem and diagnostic and therapeutic advances, cardiology and the medical community in general are far from comfortable in understanding the spectrum of aortic syndromes and defining an optimal pathway to manage aortic diseases1-13. This chapter reviews the etiology of aortic wall disease, natural history, and the pathophysiology of the complexity of acute aortic syndromes.

Incidence Of Dementia

During the past decade new cases of dementia developing during the follow-up of non-demented individuals from earlier prevalence studies or based on longitudinal studies of normal volunteers, have provided data concerning the incidence of AD and dementia, i.e. the number of new cases per year (Figure 2.2). An exponential increase with age (Jorm and Jolley, 1998) is apparent in this semi-log plot, again with doubling of incidence, prompting the question of what happens to the incidence of dementia after age 95. The regression line in this figure is based upon the values from the Canadian Study of Health and Aging (2000) and values from a Eurodem meta-analysis of four studies (Letenneur et al., 2000). Figure 2.2 also includes data from additional incidence studies (Copeland et al., 1992 Gussekloo et al., 1995 Fichter et al., 1996). There is some variability between sites, which may reflect the smaller numbers of new cases observed in incident studies as compared to prevalent cases....

How Do Incidence Rates Vary by Patient Age at Diagnosis

For much of the 1980s, the mean age of diagnosis was approximately 72 years for Caucasians and 70 years for African Americans.5 Since the introduction of PSA testing, the mean age at diagnosis has fallen. As of 1994, the mean age at diagnosis among Caucasians was 69 years and 67 years among African Americans. These statistics suggest that prostate cancer is being diagnosed in the late 1990s approximately 2.5 years earlier than it was a decade ago. Because of this abrupt increase in the lead time of diagnosis, patients can expect to live an additional 2.5 years after their diagnosis compared to reports from a decade ago. To attribute improvements in longevity to aggressive intervention with either surgery or radiation, researchers must allow for a 2.5-year lead time when making comparisons with historic series.

Prophylactic Mastectomy

Schrag and colleagues55 discuss the decision analysis involved in prophylactic mastectomy and oophorectomy and life expectancy outcome among patients with BRCA1 and BRCA2 germ-line mutations. They found that, on average, a 30-year-old woman harboring such a mutation would gain from 2.9 to 5.3 years of life expectancy from prophylactic mastectomy and from 0.3 to 1.7 years from prophylactic oophorectomy. These findings were dependent upon their cumulative risk of cancer. Gains in life expectancy also would decline with age at the time of prophylactic surgery. They would be minimal for a 60-year-old woman. Importantly, in women aged 30, an oophorectomy may be delayed for 10 years with minimal loss of life expectancy. This would allow women to complete their families. These investigators concluded that On the basis of a range of estimates of the incidence of cancer, prognosis, and efficacy of prophylactic surgery, our model suggests that prophylactic mastectomy provides substantial gains...

Adaptation to Cancer

According to the American Cancer Society (ACS), cancer is an umbrella term for a group of diseases characterized by uncontrolled growth and spread of abnormal cells.'' Not counting some highly prevalent, rarely fatal forms of skin cancer, the most common cancers are (in order of prevalence) prostate, lung, colon rectal, and bladder (for men) and breast, colon rectal, lung, and uterus (for women). For both men and women, lung cancer causes the most deaths. Although it kills far fewer people than CVD, cancer is perceived as more dangerous, destructive, and deadly. In reality, the survival rate for cancer has been climbing steadily throughout this century. Taking a normal life expectancy into consideration, the ACS estimates that 50 of all people diagnosed with cancer will live at least 5 years. Nevertheless, cancer remains the second-leading cause of death and is associated with significant pain and disability.

Apolipoprotein E In Downs Syndrome

In adults with DS, all studies have consistently found that the presence of the apoE-e2 allele increases longevity and reduces risk of dementia (Hardy et al., 1994 Royston et al., 1994 Schupf et al., 1996 Tyrrell et al., 1998 Sekijima et al., 1998 Lai et al., 1999). In two studies employing survival analysis, the presence of an apoE-e4 allele was associated with earlier onset of AD (Schupf et al., 1996 Lai et al., 1999) (Figure 3.2). Negative findings have been reported in studies with small sample sizes and, importantly, failure to consider differences in the age at onset of dementia among those with and without an e4 allele. Since the effect of the e4 allele is not expressed until midlife, inclusion of sufficient numbers of adults over 50 years of age and analysis using survival methods that can adjust for age and years of follow-up are important methodological considerations. In sum, in DS, as in the general population, the presence of the e2 allele is protective, while the...

Azidothymidine See AZT

AZT (azidothymidine) A synthetic pyrimi-dine dideoxynucleoside analog that inhibits replication of retroviruses, including HIV by interfering with DNA synthesis mediated by the viral reverse transcriptase. AZT-5'-triphosphate interacts preferentially with reverse transcriptase rather than cell DNA poly-merase. The use of this drug by oral administration in vivo is recommended for reducing viral load, restoring T cell function, and prolonging life in persons with clinical AIDS. It is also recommended for use in HIV-infected pregnant women in order to reduce the risk of transmission of HIV to the baby. The drug is toxic to dividing cells such as bone marrow cells, and drug-resistant HIV mutants arise readily the benefits of AZT therapy need to be balanced against these opposing factors. Synonyms 3'-azido-2',3'-dideoxythymi-dine AZT azidothymidine retrovir zidovudine.

Surgery Specific Considerations

Asymptomatic AAA allows time for a complete cardiac evaluation. Moreover, elective AAA is by definition prophylactic and is only rational if the patient has a reasonable life expectancy. Thus, the threshold for obtaining additional cardiac testing should be lowered as the indication for intervention becomes less absolute, particularly as patients reach extremes of chronological or physiological age with modest-sized aneurysms. More importantly, because these considerations require surgical judgement, clinical evaluation of cardiac risk should not be delegated entirely to the cardiologists or medical consultant.

Horn Cattell Theory in the KAIT

Than Horn's extended ability model, which divides cognitive abilities into nine discrete abilities (Horn, 1989 Horn & Hofer, 1992). Kaufman and Kaufman believed that assessing the broader Gf-Gc abilities would enhance the value of the KAIT as a clinical measure of adolescent and adult problem-solving ability. They contended that assessing each ability distinctly in its purest form (as is done in Horn's extended model) would serve to decrease the practical utility of the test by making the tasks less relevant to problems encountered in real life (Kaufman & Kaufman, 1997). Furthermore, they adhered to David Wechsler's deep-seated belief that the best way to develop a clinically rich instrument is to offer complex measurement of a few broad constructs rather than many narrow constructs (Kaufman, 2000). Wechsler asserted that too much fragmentation of constructs led to narrow abilities that are not optimally suited for assessing human intelligence. Because Wechsler was Alan...

Engagement in Cognitive Activities and Maintenance of Intelligence

The relationship between aging and intelligence is reviewed in this chapter, with the key question being the nature of the relationship between measures of crystallized ability (such as V-IQ and VCI) and fluid ability (such as P-IQ and POI) to the normal aging process. Although Schaie and his colleagues have conducted the most exhaustive and excellent investigations of this topic, their general conclusion of small declines occurring relatively late in life were based on the group-administered, highly speeded, and old PMA test. Of more importance for clinicians are the relationships to advancing age of the scores yielded by individually administered tests of intelligence such as the WAIS-III and KAIT (and the WJ III see the section on CHC Abilities across the Life Span in Chapter 14). Gf and Gv tasks. Also, the interpretation of maintained and vulnerable abilities needs to incorporate research and theory on numerous other factors as well, such as working memory, executive functions,...

Does IQ Decline with Advancing Age A Cross Sectional Approach

To answer the crucial questions that pertain to the relationship between adults' IQs and the aging process, we have integrated the results of both cross-sectional and longitudinal investigations of this relationship. These different types of studies are treated in the sections that follow, with emphases on the pros and cons of each style and on an integration of the findings from both kinds of empirical investigation.

Age and Intelligence across the Adult Life Span

Spans the broad 16-89-year age range. These WAIS-III analyses are discussed later in this chapter, and are integrated with the results of similar analyses conducted on the WAIS-R (Kaufman, 1990, pp. 212-222 Kaufman et al., 1989) and Kaufman tests (Kaufman & Horn, 1996 Kaufman et al., 1996 Wang & Kaufman, 1993), to gain insight into generational differences in the relationship of IQ to the aging process and into theoretical perspectives on these changes. The findings from Schaie's (1983b) landmark 21-year cohort-sequential Seattle longitudinal study, though based on the nonclinical PMA test, are also integrated into this discussion. However, to be consistent with the focus of this text, this chapter consistently emphasizes aging data obtained from studies of Wechsler's and Kaufman and Kaufman's individually administered intelligence tests for adults. In contrast to these tests, group-administered instruments like the PMA are subject to individual differences in test-taking...

Theory of GAs With Endogenous Fitness

In many of the scientific models we have looked at, fitness is not externally imposed but instead arises endogenously it is reflected, for example, by the longevity and the fertility of an individual. Up to now, almost all work in GA theory has assumed exogenous rather than endogenous fitness functions. Holland (1994) has recently done some theoretical work on GA behavior with endogenous fitness in the context of Echo, using notions such a flow-matrix for describing the transmission of useful genetic building blocks from generation to generation. This is only a first step in theoretically analyzing such systems.

Nutritional Indications

The prerequisites for this procedure are a functionally intact GI tract and meaningful longevity of the patient. Nutritional support for patients suffering from cerebrovascular accidents, senile dementia, brain tumors, amyotrophic lateral sclerosis, trauma, and sequelae of extensive neurologic surgery, are the most common nutritional indications for PEG placement. Other appropriate indications include tumors of the oral cavity, head and neck tumors, and severe facial trauma leading to alteration or obstruction of the

Does Arterial Stiffness Predict Atherosclerotic Coronary Events

Coronary heart disease is a major cause of death and morbidity. Due to the increased longevity of most developed societies, there is an increasing overlap between arteriosclerosis associated with normal vascular ageing and atherosclerosis associated with cardiovascular risk factors. There is therefore a need for improvements, both in the early identification of individuals at risk, and in cardiovascular risk stratification. Arterial stiffness is an important determinant of cardiovascular risk and can now be measured simply and non-invasively in large populations. This review will therefore focus on the current evidence as to the predictive value of arterial stiffness in relation to coronary events and also on the possible pathophysiological mechanisms linking arterial stiffness and atherosclerosis.

Resolution of the Paradox

The colonisation of land by plants and animals inevitably lead to the huge biodiversity we see today, namely, innumerable plant species with different morphologies, life styles and ecological niches, and animals which feed on plants, or on each other, adapting to an ever-increasing range of habitats. Vertebrates become the largest land and marine animals, and their body plans are incompatible with indefinite survival. Even the longest-lived, such as whales or giant tortoises, survive only a minute fraction of evolutionary time. The warm blooded vertebrates, mammals and birds, eventually become the most successful land animals, and in both groups adults retain a constant body size, and exhibit the characteristic features of ageing. Humans age because they evolved from species that already had an ageing mechanism, or set of mechanisms, built into their body plans. Interestingly, humans evolved a greater longevity because they became the most successful in colonising the environment (as...

Measurement Of Quality

Calculation of QALYs is confounded by several factors.80,97 For instance, estimates of the future value of an outcome measure may vary with the circumstances prevailing at the time of assessment (e.g., acute pain) or with the patient's age (e.g., the elderly often place great value on the ability to live independently).Thus, quality of life may be more important than longevity.98 Calculation of QALYs may also be affected by gender, ethnicity, socioeconomic status, religious beliefs, and other factors that affect attitudes about health care. Adjusting outcome measures to account for health status and severity of illness before treatment can also be difficult.99

Sequencing Concomitant Vascular Procedures

In the very elderly patient with concomitant aortic aneurysm and cardiovascular disease, the higher risk situation is handled first. Left main left main equivalent coronary disease, unstable angina, recent myocardial infarction with destabilization would all be indications for coronary bypass to precede aneurysm repair. Significant 3-vessel coronary artery disease with good ejection fraction is a judgment call aneurysmorrhaphy can be safely performed in urgent situations (i.e., aneurysms that are extremely large, painful or acutely contained ruptures). Conversely, and particularly if the aneurysm is small and or recently diagnosed, elective coronary bypass followed by aneurysm repair is prudent. Nonurgent aortic disease in conjunction with significant coronary artery disease, reduced ejection fraction (particularly to < 30 ) and salvageable myocardium would indicate the need for coronary bypass first. This treatment algorithm is based on the ability to improve ejection fraction and...

How Many Genes

Two major facts are non-controversial, first, that the DNA contains all the instructions for making a human being, and second, genes specify the structure of all the different proteins in our body. Since each mammalian species has a maximum lifespan, preceded by a period of senescence, there must be genes that in some way control ageing and longevity. Some believe that ageing is genetically programmed, or even more strongly, that there must be a programme for ageing. This view is far too simplistic, and I have cited the ageing of teeth as a simple illustration. The size and structure of teeth is genetically determined, but teeth wear down or decay with use. Teeth are indeed programmed to last a lifetime, but if, hypothetically, they were not used In spite of the major conclusion that very large numbers of genes influence in one way or another an animals lifespan, it is commonly believed that there are a few critical gerontogenes which really determine lifespan. One reason is that gene...

Oxidative Stress From Secondary to Primary Event

Original descriptions of oxidative stress (Martins et al. 1986 Smith et al. 1991) were dismissed as epiphenomena (Mattson et al. 1995), based on the notion that plaques and NFT were long-lived and hence expected to accumulate oxidative damage similar to in other long-lived proteins such as collagen (Monnier and Cerami 1981). Amyloid-P in vitro was found to be toxic via an oxidative mechanism (Yankner et al. 1989), placing oxidative stress as a secondary event. This toxicity in vitro is related to its ability to bind to iron (Schubert and Chevion 1995 Rottkamp et al. 2001). Cell culture studies aside, what happens in vivo Proponents of the longevity notion were somewhat correct long-lived proteins do accumulate oxidative damage. However, the majority of the oxidative damage that is found in AD is short-lived. Indeed, oxidized RNA is markedly increased in neurons in AD (Nunomura et al. 1999) and Down syndrome

Antimicrobial Therapy

A number of factors should be considered when choosing appropriate antimicrobial agents. They should be effective against all target organism(s), induce little or no resistance, achieve sufficient levels in the infected site, have minimal toxicity, and have maximum stability and longevity.

The Road to Discovery

In 1990, Caleb Finch published a masssive review of research on ageing, Longevity, Senescence and the Genome, with a text of nearly 700 pages, and about 4000 cited publications. Although it can be regarded as a tour de force, it did not come to any firm conclusions It soon became apparent that the maintenance of the body does not only depend on the accuracy of sythesis of large molecules. There are many other maintenance mechanisms, as described in Chapter 3. So it became obvious that the totality of maintenance depends on a substantial proportion of all the energy resources available to an animal. When scientists started to compare maintenance mechanisms in animals with different life spans, it became clear that they were more effective or efficient in long-lived ones than shortlived ones, In other words, there is a direct correlation between maintenance and longevity, as described in Chapter 6.

Reasons for some Parasites Causing Detrimental Effects

The following reasons can be advanced to explain why parasites may become more pathogenic and reduce the longevity of their hosts under certain circumstances. Firstly, selective pressure will favour parasites modifying the behaviour of the intermediate host if this results in increasing the probability of it being eaten by the definitive host. In such cases it may be said that the parasite gene is being phenotypically expressed in the host's body and Dawkins (1990) gives many examples of this phenomenon. In this case, the intermediate hosts are acting as vehicles for transmission, rather than for reproduction.

Characterization of mammary epithelial stem cells

Further characterization of mammary epithelial stem cells has been aided greatly by cross fertilization from studies of other adult stem cell systems. For example, examination of the patterns of deoxyribonucleic acid (DNA) label retention in the study of stem cells in the skin and small intestine has now been applied to the mammary epithelium (36,37). This technique involves administration of a DNA label, usually tritiated thymidine (3H-dT) or a halogenated thymidine analogue such as bromodeoxyuridine (BudR), to the animal and then determination of which cells retain the label at subsequent time points. The label is taken up only by cells actively synthesizing DNA at the time of treatment. In cells that continue to divide, the DNA label will be progressively diluted such that, after a few divisions, levels are reduced to below the level of detection. However, in cells that do not continue to divide, the label will be retained. As quiescence and longevity are considered stem cell...

Ageing and the Angels

In this Chapter and Chapter 8, I have attempted to explain both the evolution of human longevity, and the social consequences of the increased awareness of natural death from old age. Darwinism successfully challenged the authority of contemporary religions. Although socio-biologists such as Edward Wilson have provided speculations about the evolution of human religions, I believe that one can go further and provide a much more rational explanation of origins of religion.

Community palliative care

Few things in general practice are more important and more rewarding than enabling a patient to die peacefully at home. For GPs, district nurses, and others in the primary health care team (PHCT), this is an important and intrinsic part of their work. They deliver most palliative care to patients and generally do this in a sound and effective way, especially when they are backed by appropriate specialist support. People now live longer with serious illness, with most of the time spent living normally at home, so providing good community based care is vital. Sensitively facing the reality of dying and making a plan for the final stage of life is as important in end of life care as planning for pregnancy and labour are in antenatal or early life care. Yet this pre-emptive planning is often omitted, resulting in a tendency towards reactive, crisis led care that does not always meet the needs of dying patients. The paradox is that although most of the final year of life is spent at home,...

Caroline H Bridgewater Margaret F Spittle

There are many new developments in the understanding of the pathogenesis of AIDS-related malignancies and in the future these will inform new therapies. In the last few years alone highly active antiretroviral therapy (HAART) has had a great impact on the incidence and natural history of some of these malignancies. As opportunistic infections are more easily treated and patients live longer the malignancies are likely to become relatively more common. The incidence of AIDS-related malignancies varies within the different population groups with HIV and as affected groups evolve there will doubtless be a change in the incidence of malignancies seen in the UK. With these rapid changes optimal treatment strategies are controversial and patients should be entered into clinical trials.

Unwilling but essential test subjects

Corneal transplants, safer methods of blood transfusion, anticoagulants, diphtheria vaccines and kidney dialysis all came about in the early 20th century as a result of medical research involving animals. Prior to this time, Type 1 diabetes was regarded as nothing less than a death sentence, but life-saving insulin was developed through experiments on dogs, rabbits and mice. While countless benefits have obviously been derived for humans, it must also be pointed out that even today's pets live longer and far healthier lives due to the parallel development of vaccines and treatments that are now standard in veterinary medicine.

Physical Function An Important Geriatric Concept

The number of older persons living with physical disability increases dramatically with increasing age. Data from the US National Health Interview Survey of Disability show that of the women aged 65 years and older, 18.8 needs help with (instrumental) activities of daily living at home, which is 10.9 in men (3). At the age of 85 years or older, 54.8 of the women and 36.9 of the men are needing help with (instrumental) activities of daily living. One of the key paradoxes in gerontology is that although women live longer than men, they live with more physical disability at older age. This is for a large part caused by the fact that the prevalence of nonlethal but disabling chronic diseases is generally higher in older women than in older men.

ABC of arterial and venous disease Vascular complications of diabetes

Adults with diabetes have an annual mortality of about 5.4 (double the rate for non-diabetic adults), and their life expectancy is decreased on average by 5-10 years. Although the increased death rate is mainly due to cardiovascular disease, deaths from non-cardiovascular causes are also increased. A diagnosis of diabetes immediately increases the risk of developing various clinical complications that are largely irreversible and due to microvascular or macrovascular disease. Duration of diabetes is an important factor in the pathogenesis of complications, but other risk factors for example, hypertension, cigarette smoking, and hypercholesterolaemia interact with diabetes to affect the clinical course of microangiopathy and macroangiopathy.

Quality Adjusted Life Yearsan Outcome Measure in Cost Effectiveness Analysis

Calculation of quality-adjusted life expectancy involves, first, the estimation of life expectancy and the amount of life spent in various health states. Second, it is necessary to measure the value that individuals or society place on the time spent in each health state. These two pieces of information are used to estimate quality-adjusted life-years by multiplying the amount of time spent in each health state by the measure of value for time spent in that health state.

Differential diagnosis Other glycogen storage diseases

In GSD II (infantile form) death occurs before 1 year of age, in the childhood form before 25 years. In infantile GSD III death occurs before 4 years, childhood and adult forms survive longer. GSD V has a normal life expectancy. In other forms of GSD life expectancy may be normal unless severe myoglobinuria and muscle necrosis occurs.

Measuring Preferences for Health States

Preference-based measures of health status are necessary to estimate quality-adjusted life expectancy. The methods that are used most often to measure preferences for health states are the standard gamble, the time trade-off, and direct scaling methods. gamble. The certain outcome is the health state to be rated. The gamble has two possible outcomes the best health state (usually complete health), which is described as occurring with a probability, p or an alternative state, the worst state (usually death), which is described as occurring with a probability of 1 - p. The probability, p, is varied until the rater is indifferent between the indifferent between the alternative that is certain and the gamble that might bring the better health state. The gamble is repeated for all of the health states that are to be rated. The points of indifference associated with each health state are the values used in the scale of health preferences. Values from 0.0 to 1.0 are assigned to each health...

Differential diagnosis HMSN Charcot Marie Tooth disease

WDM and MBDM are slowly progressive and do not affect life expectancy. In contrast, MIDM progresses more rapidly and affected patients may be nonambulatory within 10 years from the onset of symptoms. DBM has a rapid progression and affects respiratory, bulbar, and proximal muscles. The disorder may be associated with cardiac arrythmias.

Monitoring HIV infection

Counting CD4 lymphocyte numbers (the CD4 count) is an important part of monitoring HIV infection. A progressive downward trend in CD4 cells reflects disease progression and decreased life expectancy, even in the absence of symptoms. Epidemiological studies have firmly correlated distinct ranges of CD4 cell counts with risk of particular opportunist infections. Recent data show that monitoring either the absolute CD4 lymphocyte count or the ratio of CD4 to CD8 cells, the 4 8 ratio, are both equally good at monitoring progression in HIV infection. p2 microglobulin and neopterin are molecules shed from activated lymphocytes serum levels increase with progressive HIV infection and can be a useful adjunct to CD4 counts in monitoring.

Elements Of Costeffective Nonemergency Surgical Care

The citizens of industrialized nations generally enjoy a high level of health, and the positive correlation between life expectancy and per capita income is one of the best-known relationships in international development.1 Yet many of these nations also face major challenges in controlling the cost and improving the quality of health care.The United States has attempted to control these costs through price controls (in the Nixon era), prospective payment (in the Reagan era), and managed care (in the Clinton era), but none of these measures have had any long-term success see Table 1 .2'3 A consequence of the ongoing growth in health care expenditures is that health care then increasingly competes with other social goals (e.g., education) for some of the same funds. The anguish of having to choose one social goal over another can be rationalized when the expenditures on the chosen goal produce demonstrable improvements. Thus, if increased health spending generates measurably better...

Locally Advanced Breast Cancer

Integration of systemic chemotherapy and or hormonal therapy with surgery and irradiation is considered the standard of care in the treatment of locally advanced breast cancer (LABC). Because the greatest risk for patients with LABC is the development of distant metastases and subsequent death, the goals of surgery are to provide maximal locoregional control with minimal disfigurement and to permit accurate staging to determine prognosis. Breast conservation surgery is sometimes possible after tumor downstaging with induction chemotherapy, but close cooperation between the medical and surgical oncologists and the radiation therapist is required to determine the feasibility of this option. Similarly, the surgeon must be familiar with the natural history of LABC to assess the advisability of major resections of either persistent advanced primary disease or locoregional recurrences. If life expectancy is very short, as is the case with patients who have bulky visceral disease or...

The Burden of Knowing

Physicians began writing about families with unusually high numbers of cancers more than a century ago. For decades such reports were treated as little more than medical curiosities, but as life expectancy soared (since 1900 the average life expectancy for white women born in the United States has climbed from 45 to 78, and it continues to rise) and we learned more about the diseases of old age, and our knowledge of pathology and genetics grew, the evidence that a significant fraction of breast cancer (and many other cancers) occurred in people who were born with a strong genetic predisposition mounted.

The Renaissance and the Scientific Revolution

As an era of scientific and philosophical interest, if not therapeutic advances, the Renaissance is a time of special importance for medicine. The death rate circa 1500 was about three times the present level, and life expectancy was perhaps half that of modern Europe. War, famine, and epidemic disease appeared so often that fears of the imminent end of the world were widespread. However, the exact relationship between the Renaissance and the renaissance of medicine is extremely complicated. It is possible to speak of a long medical renaissance that began in the twelfth century, a distinct medical renaissance of the sixteenth century, and a medical revolution of the seventeenth century.

Idiopathic Portal Hypertension

It is crucial to properly diagnose IPH from a prognostic and management point of view. With proper management of variceal bleeding and splenomegaly and its associated thrombocytopenia, life expectancy is no different from healthy individuals. Its course is stable over many years and not associated with cirrhosis or hepatic neoplasms. There is a high initial success rate for the management of bleeding varices whether banding or sclerotherapy is used, which approaches 90 to 95 . Rebleeds are uncommon (3 ) but are managed equally successfully. Emergent portosystemic shunts are rarely required (< 10 of acute bleeds), with TIPS having proven to be an effective approach. Splenomegaly can be also treated effectively with percutaneous intra-arterial embolization of a portion of the spleen (initially 25 to 50 with reevaluation).

Inheritance And Genetic Mapping Of The

Extensive breeding studies excluded a recessive mode of inheritance and indicated that the Campus syndrome is an autosomal dominant disorder with a germline mutation in the healthy founder boar Campus (Tammen et al., 1999). This explains the unusual segregation rate of 8.7 among the offspring and an increased frequency of affected piglets among the offspring of affected sows. In view of the short life expectancy discussed above, breeding with the affected animals was limited and efforts to raise male affected animals for the collection of sperm failed. The expression of the tremor is obviously independent from the genetic back

Methodologic Considerations in the Development of Measures of Health Status and Health Related Quality of Life

A number of measures used in outcome studies attempt to simultaneously assess physical, social, and emotional aspects of health. These measures are often called measures of general health status, generic measures of health status, or measures of health-related quality of life. The description of generic measures of health status as measures of quality of life coincides with the growing emphasis on economic analysis in the evaluation of interventions. Many economic evaluations attempt to derive measures of quality-adjusted life expectancy. Many researchers believe that all measures that are called measures of quality of life are suitable for use in cost analysis and that all of them can be used to derive estimates of quality-adjusted life expectancy. Measures of health status can be categorized as being preference-based and nonpreference-based methods. In practice, only preference-based measures of quality of life can be used in to estimate quality-adjusted life expectancy in an...

Assessment of Physical and Mental Happiness

Generic instruments now exist that are aimed at evaluating a patient's level of productive assimilation into his or her environment. The Short Form-36 (SF-36) is designed to assess physical and mental happiness in eight domains of health (1) physical function (10 items) (2) physical role limitations (4 items) (3) bodily pain (2 items) (4) vitality (4 items) (5) general health perceptions (5 items) (6) emotional role limitations (3 items) (7) social function (2 items) and (8) mental health (5 items). The underlying assumption is that mental and physical functions are readily separable aspects of health, but of course, this is not really the case.52'53 Predictably, patients' responses on the SF-36 tend to be strongly influenced by the type of operation they had. For example, a patient who has undergone total hip arthroplasty will feel better immediately one who has undergone lung resection for cancer may not feel particularly well immediately afterward but, ideally, will be relieved of...

Chemotherapy and Radiation Therapy

Radiation therapy alone has definite benefits in relieving symptoms. Pain and bleeding can be treated with low dose radiation therapy in about 75 of patients however, palliation is often of short duration and is expected to last only about 3 to 9 months. Radiation therapy is thus most useful to patients with advanced disease and short life expectancy. By itself, it offers no survival benefit. A positive effect on long term survival can only be attained with the addition of chemotherapy. External beam and intraoperative radiation therapy combined with surgery has been attempted to improve palliation in patients with locally recurrent rectal cancer. Available evidence suggests that this is most beneficial in patients with negative margins at resection (Lindel et al, 2001). There are separate chapters on rectal cancer (see Chapter 98, Curative Intent Management of Rectal Cancer), abdominal radiation (see Chapter 100, Abdominal Radiation) and on colorectal cancer adjuvant and chemotherapy...

Effects of Early Detection on Cancer Mortality

In addition, there is significant indirect epidemiologic evidence suggesting that screening may indeed have a profoundly beneficial effect on survival and mortality. For instance, data from the SEER program indicates that the 5-year relative survival rates from prostate carcinoma have improved from 66.7 between 1974 and 1976 to 79.6 in the interval from 1983 to 1990.64 In a separate analysis of SEER data, a 20 increase in relative survival from carcinoma of the prostate from 1985 to 1993 compared to the period 1973 to 1980 was revealed.65 In addition, a decision model developed by the American College of Physicians suggests that, with appropriate treatment, the use of screening to detect organ-confined cancers in men between the ages of 50 and 69 years may increase life expectancy by up to 3 years.11 Finally, in 1996, the National Center for Health Statistics reported an estimated 6.3 decrease in mortality from prostate cancer in the United States from 1991 to 1995.66 Therefore, while...

Paul J Thuluvath Md Frcp and Cary H PattMD

Sive drugs, costs, and the immediate surgical mortality are considered, this patient may be better off with conservative treatment. Similarly, a noncirrhotic patient with primary sclerosing cholangitis (PSC) may request preemptive transplantation because of the fear of developing a cholangio-carcinoma. This patient's lifetime risk of developing cancer is around 15 , and the mortality associated with LT in the first 5-years is around 20 . This patient should be educated about the expected outcome and discouraged from early transplantation until the patient develops serious complications or when prediction models (eg, Mayo Model) suggest that the patient's life expectancy is < 2 years without transplantation. Although mortality is an important consideration, the quality of life is equally important. Patients who may not fulfill all criteria for LT may be transplanted for intractable pruritis, fatigue, repeated bouts of cholan-gitis, and hepatic encephalopathy. In this review, we will...

Medical Practice In Modern China

By the 1980s, China had established a health care system that is generally conceded to be a model for other developing countries. Sensitive measures of health in Shanghai in 1980, such as infant mortality and life expectancy at birth, compared favorably with New York City. Western visitors were impressed by Chinese experiments in medical education and the restructuring of medical practice, which obligated the physician to share diagnostic and therapeutic responsibilities with a newly empowered array of lay and paramedical personnel. Preventive medicine and basic primary health care were provided by legions of ''barefoot doctors,'' midwives, and nurses. The use of herbal remedies, acupuncture, and moxibustion remains the core of medical practice, but

Robert J Nejat MD Christopher W Johnson MD Mitchell C Benson MD

The American Cancer Society (ACS) estimates that there will be 179,300 new cases of prostate cancer diagnosed in 1999, making it the most commonly diagnosed malignancy among men in the United States. In addition, a projected 37,000 men will die this year secondary to prostate cancer. As a result, the ACS and the American Urological Association (AUA) have put forth guidelines recommending that annual serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE) be offered to men aged 50 and older who have at least a 10-year life expectancy. The PSA and DRE should also be offered to younger men at high risk for developing prostate cancer, such as African American men or men with a strong family predisposition to the disease (two or more affected first-degree relatives, e.g., father, brother). Information should be provided to patients regarding the risks and benefits of intervention.1

Management options

Infection, e.g. with fungi or other atypical organisms. Neurological manifestations are especially important to anaesthetists and include neuropathy, encephalopathy, meningitis, focal brain lesions, dementia, myelopathy and myopathy. In addition, HIV-positive subjects' life expectancy is increased by taking prophylactic highly active antiretroviral therapy (HAART). These drugs may cause blood dyscrasias, gastrointestinal disturbances, neurological and hepatic impairment and increased drug metabolism via hepatic enzyme indication. Prior to any anaesthetic intervention all patients must therefore be assessed carefully for evidence of organ system impairment.

Indications For Surgery

Parathyroidectomy appears to decrease the risk of subsequent complications such as osteoporosis, renal dysfunction, nephrolithiasis and, perhaps, hypertension. Although some metabolic problems can be partially reversed after successful parathyroidectomy (osteoporosis, renal impairment, nephrolithiasis, and gout), others, such as hypertension, usually do not improve. Asymptomatic patients also appear to receive the same metabolic benefits on bone, renal dysfunction, and other systems as symptomatic patients.27-31 They also return more quickly to a normal life expectancy after successful parathyroidectomy.22-24 Parathyroidectomy prevents the subsequent development of hypercalcemic crises, eliminating the need to manage hypercalcemia when patients are hospitalized for other serious, unrelated medical problems.

The Choice Of Adjuvant Therapy And The Biology Of The Tumor And Of The Patient

Though the biology of the tumor is important, so too is the biology of the patient in the choice of adjuvant systemic therapy. Age is the most important factor. There is little data on the efficacy of chemotherapy in patients over the age of 70 years of the 19,000 reviewed in the EBCTCG chemotherapy overview, there were only 600 women over 70 years. They could draw no conclusion as to the value of chemotherapy in that age group.19 Chemotherapy should be reserved for women over 70 years with poor prognostic tumors containing no hormone receptor, with a reasonable life expectancy, and that are physiologically in excellent health. It is important to emphasize, however, that being over 70 years should not a priori exclude a woman from consideration of chemotherapy. In the younger postmenopausal groups, chemotherapy is clearly beneficial alone or when added to tamoxifen. Nevertheless, it should not be universally given. The EBCTCG trial analyzed the same randomized trials where they found...

The Impact Of Parkinsonism On Healthrelated Quality Of Life

Some analogies can usefully be drawn from Hr-QoL studies in PD. The degree of disability in atypical parkinsonism is at least as great as in PD and depression occurs in all atypical parkinsonian disorders (29,30). It is therefore likely that these factors are also important in atypical parkinsonian disorders. However, these are likely not to be the only difficulties encountered by patients with atypical parkinsonism in whom, frequently, many systems are affected. The impact of features such as greater autonomic dysfunction, higher rate of falls, behavioral changes, or cognitive impairment, will depend on the type of atypical parkinsonism. In addition, the shortened life expectancy, greater disability, lack of response to treatment, associated nonmotor features, cognitive impairment, and behavioral disturbances in atypical parkinsonian disorders will all impact on patients' subjective evaluation of their Hr-QoL. On the other hand, symptoms that occur less frequently in atypical...

Posttest discussion points when giving an HIVpositive result

Whilst recognising the seriousness of the diagnosis, you should avoid speculating about a patient's life expectancy, stressing that each individual case is different and that strategies to extend survival and new treatment therapies are being developed and tested at a rapid pace. The fact that they are diagnosed in a first world country will mean that treatment options are readily available and expert care is available.

Invasive Therapy Surgery

Surgical therapy is the principal modality used for treatment of rectal cancer with curative intent. Yet it is only one of many modalities used in palliative therapy. Although many options are available for the palliation of cancer of the intra-abdominal colon, such as abdominal colectomy, segmental resection, internal bypass, or fecal diversions, surgical palliation of rectal cancer is technically more difficult and options are more limited. This is due to the anatomic restrictions of the pelvis and the fact that there is more commonly fixation of the tumor to major structures like the iliac vessels, prostate, bladder, or nerve roots. Operative palliative therapy is indicated in patients that are able to tolerate surgery and with the intent of providing relief or improvement of symptoms while maintaining normal function. Indications include bowel obstruction, perforation of the rectum, formation of rectal fistulas to the vagina, bladder or prostate, bleeding, pain, and local...

From the amyloid protein A4 to isolation of the first Alzheimers disease gene amyloid A4 precursor protein APP

As life expectancy continues to increase, so will the prevalence and incidence of Alzheimer's disease (AD) in our elderly population by 2050, as many as 14 million AD cases are expected in the USA, alone. AD is characterized by global cognitive decline in association with specific brain pathological lesions, neuronal loss, and synaptic pruning. The disease takes its name from Dr. Alois Alzheimer, a German psychiatrist who in the fall of 1906 suggested that specific physical aberrations in the brain were driving dementia in his female patient, Auguste D (Alzheimer 1907a). Alzheimer had been treating Auguste D since she was first admitted at age 51 to the Hospital for the Mentally Ill and Epileptics in Frankfurt for frenzied delirium. Shortly after the patient's death at age 56, Alzheimer presented the results of his post-mortem examination of her brain at a meeting in Tubingen. He wisely took advantage of Camillo Golgi's new silver staining technique to examine the neurons in his...

Clinical Significance or Insignificance of Prostate Cancer

The efficacy of screening is a crucial but unresolved question. The American Urological Association convened the Prostate Cancer Clinical Guidelines Panel to analyze the literature regarding available methods for treating locally confined prostate cancer. The panel concluded that outcomes data are inadequate to make valid comparisons of treatment. In a similar literature review, Wasson et al.18 were unable to find definitive evidence concerning the efficacy of treatment of localized disease. Both groups cited the large number of weak study designs that allowed selection biases affecting choice of treatment and patient selection. Only one small randomized prospective trial has been completed assessing radical prostatectomy.18-20 This trial involved 111 men with early stage prostate cancer randomized to radical prostatectomy and placebo versus placebo alone. This trial with small size and low power showed a statistically indistinguishable life expectancy in both arms.

Should Everyone Be Tested

The most exciting dividend of the cloning of the CF gene has been the tremendous impact it has had on driving creative approaches to new treatments. Thankfully, the health and life expectancy of patients with CF has, because of new antibiotics and better management of the risk for pneumonia, improved steadily for the last 30 years. Children born with CF today have an even chance to live into their late 30s, but advances have slowed, the disability can be severe, and the costs of care are high. For example, patients with end-stage cystic fibrosis are the people who most often undergo lung transplants or heart-lung transplants.

Encephalomyopathies s ee also

A heterogeneous group of multisystem diseases, the basis of which involves abnormalities of the mitochondrial metabolic pathways.They form part of a group now known as the OXPHOS (oxidative phosphorylation) diseases (Shoffner 1996).The OXPHOS diseases are associated with deletions and mutations of mitochondrial DNA, which is maternally inherited, or less commonly, nuclear DNA, which is not. Such mutations may also be part of the ageing process and Parkinson's disease. In aerobic metabolism, adenosine triphosphate is produced by the mitochondrial respiratory chain and oxidative phosphorylation systems. A variety of enzyme-protein complexes are involved, complexes I-V, that are located in the mitochondrial inner membrane. Mutations may result in dysfunctional aerobic metabolism and a large number of organs can be affected. There may be characteristic pathological muscle changes seen in mitochondrial myopathies. When some muscle fibres are stained with a special Gomori stain, 'ragged red...

Body Architecture

With regard to ageing, teeth are a very instructive component of the body. After milk teeth are discarded, the larger adult teeth replace them. These teeth are subject to wear and tear, and also to bacterial attack. Although they contain nerves and a blood supply, they are essentially mechanical structures which cannot be expected to last forever. In the case of humans, the existence of dentists allow them to last much longer than they would normally do alternatively they can be replaced with artificial teeth. This is a clear case of intervention in the normal ageing process, which I will discuss more fully later on. Teeth show very clearly that the distinction which is often made between programmed ageing, and ageing through wear and tear, is quite artificial. Our genes determine the size, strength and structure of teeth. That is clearly part of the programme for development. The teeth, however, are subject to wear and tear, so gradually lost their normal structures. Clearly the...

ApoE4 A case of evolutionary underperformance

Anorectal Malformation Pathophysiology

1) ApoE4, with its polymorphisms at amino acid sites 112 and 158, represents the ancestral form of the apoE gene (Finch and Stanford 2004). Homo sapiens only recently acquired the apoE3 and apoE2 allelic variants. All the other mammals and primates examined so far (except humans) are apoE4 carriers. Interestingly, the apoE2 allele, which was shown to confer some protection again AD, also happens to be over-represented in human centenarians (Blanche et al. 2001 Frisoni et al. 2001), clearly pointing toward a role in longevity and successful aging.

Choledochojejunostomy and Cholecystojejunostomy

Mobilization Ligament Treitz

For any patient with a life expectancy of greater than 6months, surgical biliary bypass can provide durable palliation for jaundice. The preferred surgical method for palliative treatment of biliary obstruction is a side-to-side anastomosis, because it allows the possibility of making a large anastomosis, and of draining the intrahepatic bile duct as well as the part of the bile duct distal to the anastomosis. If local anatomy does not allow a side-to-side anastomosis, an end-to-side anastomosis should be made taking into account the possibility of stasis of pancreatic juice in the pancreatic part of the bile duct. Absolute and Relative Life expectancy less than 6months (preferred method of treatment transmural Preoperatively, one should consider whether the morbidity and mortality of the surgical procedure outweigh the life expectancy of the patient. Often one is confronted with inoperability during exploration. In such situations, biliary bypass can be performed as a palliative...

Clinical Development of CV706 and CV787

A Phase I trial of CV706 was initiated in 1998 at the Brady Urological Institute of the Johns Hopkins Oncology Center under the direction of Jonathan Simons, MD, and Ted DeWeese, MD. The patient population consists of men with locally recurrent prostate cancer with rising PSA levels following definitive external beam irradiation. Men in this category are usually left untreated or receive androgen ablation therapy as serum PSA levels rise significantly above 10 ng mL. On average, these men have a life expectancy of 3 years. The virus was administered under spinal anesthesia using the brachytherapy template

Current Role Of Surgical Shunts

Chronic Pancreatitis Life Expectancy

The management of a complex disease such as portal hypertension requires a multidisciplinary effort, and each specialist has a defined role and contribution gastroenterologist (overall management of the liver disease, medical management of variceal hemorrhage, sclerotherapy or variceal banding), vascular transplant surgeon (surgical shunting, liver transplantation), and interventional radiologist (TIPS). The treatment of each patient should be selected based on the severity of the underlying liver disease, the amount of functional liver reserve and his life expectancy. There is little doubt that patients with severe liver dysfunction should not undergo surgical porta-systemic shunting as a high likelihood of perioperative mortality, and encephalopathy can be expected. Such patients are best managed with sclerotherapy or TIPS as a bridge to an eventual liver transplantation, which is the definitive treatment for both the portal hypertension, and liver dysfunction. If the patient is not...

Preoperative abnormalities

Vital capacity decreases progressively, and when it falls below 700 ml, the risk of death is high. Diaphragmatic weakness occurs and blood gases may show hypoventilation and hypoxia in the later stages of the disease. Once diurnal hypercapnoea develops, life expectancy is less than 1 year (Simonds et al 1998).

Physiology The Unity ofCompanies 2003 Form and Function Third Edition

Transducer Any device that converts one form of energy to another, such as a sense organ, which converts a stimulus into an encoded pattern of action potentials. transgenic bacteria Genetically engineered bacteria that contain genes from humans or other species and produce proteins of that species used commercially to produce clotting factors, interferon, insulin, and other products. translation The process of enzymatically reading an mRNA molecule and synthesizing the protein encoded in its nucleotide sequence. transmission electron microscope (TEM) A microscope that uses an electron beam in place of light to form high-resolution, two-dimensional images of ultrathin slices of cells or tissues capable of extremely high magnification. triglyceride (try-GLISS-ur-ide) A lipid composed of three fatty acids joined to a glycerol also called a triacylglycerolor neutral fat. fig. 2.19 triiodothyronine (T3) (try-EYE-oh-doe-THY-ro-neen) A thyroid hormone with three iodine atoms, secreted in...

Occlusive Disease of the Upper Abdominal Aorta

Chronic Mesenteric Ischemia Treatment

Which can effectively control the blood pressure in most patients with renovascular hypertension. The second is the evolving success of balloon angioplasty and stenting in the revascularization of atherosclerotic renal artery lesions. We believe both of these treatments complement rather than replace surgical management and extend the spectrum of disease that can be effectively managed. Although antihypertensive medications may effectively reduce blood pressure in renovascular hypertension, they do not prevent progression of the lesion and resulting ischemic nephropathy. Hunt and Strong compared medical and surgical management of renovascular hypertension and found that medical management had poorer overall survival, greater late incidence of renal failure and progression of lesions to occlusion.5 Medical management of renovascular hypertension in patients with documented bilateral renal artery lesions, particularly when ACE inhibitors are required for pressure control, is associated...

Endovascular Treatment

Aortic Dissection Uncovered Stent

Subclavian artery and the absence of mural thrombus or calcifications or hemorrhage on the aortic wall at the neck site. Several studies reported the artificial creation of an aortic neck, covering the left subclavian artery with the stent graft, with or without previous subclavian to carotid transposition or bypass grafting. However, subclavian-to-carotid transposition is an invasive adjunctive procedure that carries the risk of mortality and stroke (4.2 ), while the abrupt closure of the left subclavian artery may evolve into chronic or acute subclavian steal syndrome. The risk of vertebral ischemia and cerebellar infarction is reported up to 13 for interventional treatment of intracranial aneurysm treated by vertebral ligation. Therefore, we may expect the same rate of complication for endovascular coverage of the left subclavian artery with a stent graft. Moreover, the long-life expectancy of the uncovered part of the stent graft to the left carotid artery is a potential source of...

Mucopolysaccharidoses MPS

A group of inherited connective tissue syndromes that result from enzyme deficiencies. The mucopolysaccharides (or glycoaminoglycans) are constituents of connective tissue, and are made up of repeating disaccharide units connected to protein.They are normally broken down in the cell lysosomes to monosaccharides and amino acids. In the absence of certain enzymes, accumulation of intermediate products of degradation process takes place.These substances increase cell size and cause impairment of function.The effects depend upon the enzyme defect, and the specific organs involved.The disease progresses with age, and life expectancy is greatly reduced.

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