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[Serum carcinoembryonic antigen doubling time in patients with recurrent gastrointestinal carcinoma and its relationship to tumor biology and life expectancy].

BACKGROUND: The present study was done to determine if carcinoembryonic antigen (CEA) concentration doubling time can predict the course of disease in patients with adenocarcinoma of the gastrointestinal tract and characterize tumor biology. METHODS: CEA doubling times were determined from semilogarithmic plots of CEA concentration time courses in 20 patients with recurrent gastric cancer and 17 with recurrent colorectal cancer. RESULTS: Gastric and colorectal carcinomas showed mean CEA doubling times of 229 days and 85 days, respectively. There were no significant differences with regard to patient age, tumor size, gross appearance and histological differentiation. However, women had shorter CEA doubling times than did men. Flow cytometric analysis showed that tumors with a higher proportion of cells in S-phase (> or = 15%) had significantly shorter CEA doubling times than those with a lower S-phase fraction (< 15%). There was a significant correlation between the CEA doubling time and the length of survival after the initial CEA concentration increase in patients with recurrent gastric and colorectal carcinomas. CONCLUSIONS: CEA doubling time predicts life expectancy in patients with adenocarcinoma of the gastrointestinal tract. Differences in survival time are closely associated with variations in the biological aggressiveness of individual tumors.

Aged↗

The spontaneous course of small abdominal aortic aneurysms. Aneurysmal growth rates and life expectancy.

Since abdominal ultrasonography has become a routine diagnostic procedure, increasing numbers of small asymptomatic abdominal aortic aneurysms are detected incidentally. Of 128 patients (108 male, 20 female) with abdominal aortic aneurysms, 96 patients were observed clinically and by repeated ultrasound studies for an average of 3.47 years, adding up to a total observation period of 333 patient-years. Among these 96 patients, 72 had small aneurysms (averaged diameters less than 5 cm). Three of them were lost to follow up. None of the remaining 69 patients died from rupture, 20 died from other causes and 8 patients were successfully operated. Of the patients with a large aneurysm one was lost to follow up. Five patients of the remaining 23 died as a result of rupture, 7 were successfully operated. The average growth rate of small aneurysms was 0.18 cm/year, whereas the larger aneurysms showed a growth rate of 0.28 cm/year (diameter). The survival rate of patients with small aneurysms was 94% after one year, 80% after 3 years, and 73% after 5 years, indicating that life expectancy is reduced in patients with an aneurysm of the abdominal aorta, but not because of complications of the aneurysm.

Adult↗

DNA oxidative damage and life expectancy in houseflies.

The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8-hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence.

8-Hydroxy-2'-Deoxyguanosine↗

Life expectancy of children in vegetative and minimally conscious states.

We determined estimates of survival in children, 3-15 years of age, in the vegetative state (VS) (n = 564), immobile minimally conscious state (MCS) (n = 705), and mobile MCS (n = 3,806). Data were extracted from the annual Client Development Evaluation Reports of the California Department of Developmental Services between 1988 and 1997 using the operational definitions for these three states on the basis of 15 descriptive behavioral categories. Patients were also categorized according to the following four etiologies: acquired (traumatic and nontraumatic) brain injury; perinatal/genetic; degenerative; and unknown/undetermined. The percentage of patients surviving 8 years was 63%, 65%, and 81%, for the VS, immobile MCS, and mobile MCS, respectively. Children in the VS and MCSs with acquired brain injury had lower mortality rates and those with degenerative diseases the highest mortality rates. We observed little difference in survival between patients in the VS and immobile MCS, suggesting that the presence of consciousness is not a critical variable in determining life expectancy. Furthermore, survival was much greater for patients in the mobile MCS than for those in the immobile MCS, suggesting that mobility is more important in predicting survival than the level of consciousness.

Adolescent↗

Large-scale hormone replacement therapy and life expectancy: results from an international comparison among European and North American populations.

OBJECTIVES: An analysis was performed to determine the risks and benefits of a 10-year hormone replacement therapy regimen that had been applied to all women at 50 years of age in 8 countries. METHODS: Cumulative mortality with and without hormone replacement therapy over 20 years was estimated, with both current and predicted total and disease-specific secular mortality trends and the influence of a generational cohort effect taken into account. RESULTS: In countries with high ischemic heart disease frequency and predictable relative predominance of ischemic heart disease rates over breast cancer rates for the next 20 years, hormone replacement therapy could result in benefits with regard to overall mortality; this advantage decreases in younger-generation cohorts. In countries in which breast cancer mortality predominates over ischemic heart disease in early postmenopause and in which the predictable trends for both diseases reinforce this condition, a negative effect on overall mortality would be observed. In the United States, the effect of large-scale hormone replacement therapy would change over time. CONCLUSIONS: The long-term effect of hormone replacement therapy on life expectancy of postmenopausal women may vary among countries.

Age Distribution↗

Changes in the life expectancy of patients with severe haemophilia A in Finland in 1930-79.

Important advances have been made in the treatment of haemophilia during the past 30 years. We have analysed the data of all the known 163 patients with severe haemophilia A living in Finland in 1930-79 in order to study changes in the prognosis of severe haemophilia A. During the period of 50 years the mean age at death of the patients has increased from 7.8 years in 1930-39 to 25.5 years in 1970-79 and the annual death rate has markedly decreased in all age groups. The decline has been greatest in patients under 10 years of age. In this age group the annual death rate decreased from over 50 per thousand in 1930-39 and 1940-49 to 4.8 per thousand in 1970-79. The prognosis of patients with inhibitors has remained poor, however. Five of the six deaths during the last decade occurred in patients with inhibitors. The overall annual death rate of patients without inhibitors was only 1.2 per thousand in 1970-79, suggesting that at the present time the life expectancy of patients who do not develop inhibitors does not markedly differ from that of the general male population.

Adolescent↗

Drinking water, mortality, and life expectancy: an assessment of the east-west mortality gap in Europe.

The role of the drinking water in public health has been recognised for many years. Recent ecological studies of mortality rates in Slovakia when compared to indicators of environmental pollution have shown surprising results--areas with greater air pollution seem to have lower total mortality rates. This paradox may be explained by a number of other factors, including urban/rural occupational conditions, socio-economic status, access to health care, and perhaps drinking water. Overall population access to safe drinking water is about the same between East and West Europe, but more careful evaluation suggest at least one important difference. About 35.7% of the people in Central and Eastern European countries do not have 100% access to safe drinking water in their rural areas, compared to only 18.7% of the rural populations in Western Europe who do not have full access to safe drinking water. This study examines access to safe drinking water, assesses overall drinking water quality, and utilises an index of drinking water quality to perform correlation with total mortality, selected chronic diseases which have been associated with drinking water contamination, and life expectancy at birth. These methods are applied to data for East-West Europe, Slovakia, and detailed urban-rural comparisons for three areas of Slovakia (Trnava, Banská Bystrica, and Kosice).

Adolescent↗

Life expectancy among people with cerebral palsy in Western Australia.

This report describes trends, predictors, and causes of mortality in persons with cerebral palsy (CP) using individuals identified by the Western Australian Cerebral Palsy Register and born between 1958 and 1994. Two thousand and fourteen people were identified (1154 males, 860 females), of whom 225 had died by 1 June 1997. Using date-of-death data, crude and standardized mortality rates were estimated and predictors of mortality sought using survival analysis stratified by decade of birth, description of impairments, and demographic and perinatal variables. For those born after 1967, the cause of death profile was examined over time. Mortality exceeded 1% per annum in the first 5 years and declined to age 15 years after which it remained steady at about 0.35% for the next 20 years. The strongest single predictor was intellectual disability, but all forms of disability contributed to decreased life expectancy. Half of those with IQ/DQ score <20 survived to adulthood, increasing to 76% with IQ/DQ score 20-34, and exceeding 92% for higher scores. Severe motor impairment primarily increased the risk of early mortality. Despite there being 72 persons aged from 25 to 41 years with severe motor impairment in our data set, none had died after the age of 25 years. Infants born after more than 32 weeks' gestation were at significantly higher risk of mortality than very preterm infants, accounted for by their higher rates of intellectual disability. No improvements in survival of persons with CP were seen over the study period despite advances in medical care, improved community awareness, and the increasing proportion of very preterm births among people with CP. This may be the result of improved neonatal care enabling the survival of infants with increasingly severe disabilities.

Adolescent↗

Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study.

BACKGROUND: In the studies of left ventricular dysfunction (SOLVD), enalapril reduced mortality in patients with symptomatic but not asymptomatic left ventricular systolic dysfunction during the trial. We did a 12-year follow-up of SOLVD to establish if the mortality reduction with enalapril among patients with heart failure was sustained, and whether a subsequent reduction in mortality would emerge among those with asymptomatic ventricular dysfunction. METHODS: Of the 6797 patients previously enrolled in the SOLVD prevention and treatment trials, we ascertained the subsequent vital status of 5165 individuals who were alive when the trials had been completed. Follow-up was done through direct contacts in Belgium and linkages with national death registries and federal beneficiary or historic tax summary files in the USA and Canada. FINDINGS: Follow-up was 99.8% (6784/6797) complete. In the prevention trial, 50.9% (1074/2111) of the enalapril group had died compared with 56.4% (1195/2117) of the placebo group (generalised Wilcoxon p=0.001). In the treatment trial, 79.8% (1025/1285) of the enalapril group had died compared with 80.8% (1038/1284) of the placebo group (generalised Wilcoxon p=0.01). The reductions in cardiac deaths were significant and similar in both trials. When data for the prevention and treatment trials were combined, the hazard ratio for death was 0.90 for the enalapril group compared with the placebo group (95% CI 0.84-0.95, generalised Wilcoxon p=0.0003). Enalapril extended median survival by 9.4 months in the combined trials (95% CI 2.8-16.5, p=0.004). INTERPRETATION: Treatment with enalapril for 3-4 years led to a sustained improvement in survival beyond the original trial period in patients with left ventricular systolic dysfunction, with an important increase in life expectancy.

Angiotensin-Converting Enzyme Inhibitors↗

Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin.

Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the beta-subunit of beta-hexosaminidase. GM2 ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the GM2 gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N-butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease.

1-Deoxynojirimycin↗

Life expectancy in primary myelodysplastic syndromes: a prognostic score based upon histopathology from bone marrow biopsies of 569 patients.

The retrospective evaluation of bone marrow biopsies of 569 patients with primary myelodysplastic syndrome--pMDS--revealed 256 refractory anemias--RA--, 52 refractory anemias with ringed sideroblasts--RARS--, 133 refractory anemias with excess of blasts--RAEB--, 52 refractory anemias with excess of blasts in transformation--RAEB-t--, and 53 chronic myelo-monocytic leukemias--CMMOL--according to FAB-criteria, 23 patients were not otherwise specified (myelodysplastic syndrome: not otherwise specified--MDS.NOS--). RARS-patients had the best prognosis (median survival 41.9 months, incidence of leukemia 3.8%), followed by RA-patients (26.5 months, 16.4%), MDS.NOS-patients (22.4 months, 21.7%), CMMOL-patients (12.5 months, 49.1%). RAEB- and RAEB-t-patients had the worst prognosis (median survival time 8.5 and 4.6 months, incidence of leukemia 42.1% and 57.7%, respectively). But the survival times showed a considerable range in each FAB-subgroup with 0-154 months in RA or 0-52 months in CMMOL. To forecast life expectancy more precisely, a scoring system was developed using nine histopathological parameters, among which the three most important ones were determined: quantity of myeloblasts, myelofibrosis and ALIP's. The scoring system allows a determination of three risk groups with significantly different survival times. It is valid also for patients without increase of myeloblasts (< 5% myeloblasts in the bone marrow) and identifies high-risk MDS patients in this group. By this proposed scoring system, a prognostic approval in primary MDS can be achieved applying histopathology without regarding further methods herewith presenting a system which could be considered independently from hematologic, cytological or laboratory data.

Adult↗

Mean life expectancy of Old World screwworm fly, Chrysomya bezziana, inferred from the reproductive age-structure of native females caught on swormlure-baited sticky traps.

The reproductive status of native (wild) screwworm fly, Chrysomya bezziana, caught on swormlure-baited sticky traps in Papua New Guinea is described. A total of 1122 females and 25 males were trapped. Of these females 595 were scored for insemination status and stage of ovarian development (on a scale of 2-10) of which 20% were in suitable condition for assignment to first, second and third ovarian cycles. Of the nulliparous females, only 17% were inseminated at stage 3 of ovarian development, 70% at stage 4, 93-97% at stages 5 and 6, and all of stages 7-10 (gravids). All parous females were inseminated. More than half of the captured females were parous (58%) and only 7% of the total were gravid. Proportions of females in ovarian cycles 1, 2 and 3 were 41%, 50% and 9% respectively. Survival of female Ch.bezziana in the laboratory was adequately described by lognormal and Gompertz survival functions, for both of which the mortality rate is an increasing function of reproductive age. Analysis of the reproductive age distribution of native females estimated their mean life-expectancy at 9 days under the prevailing mean field temperature of 26.5 degrees C. This equates to completion of 1.7 ovarian cycles and an estimated mean lifetime fecundity of 146 female progeny. The survival models, which also allowed responsiveness of females to swormlure-baited traps (female trappability) to vary according to their stage of ovarian development, indicated significant age-dependent trapping bias. These findings are compared with similar data for the New World screwworm fly, Cochliomyia hominivorax.

Animals↗

Association of mutations in the hemochromatosis gene with shorter life expectancy.

BACKGROUND: To investigate whether the frequency of carriers of mutations in the HFE gene associated with hereditary hemochromatosis diminishes with age as an indication that HFE mutations are associated with increased mortality. It is of value in the debate concerning screening for hereditary hemochromatosis to determine the significance of heterozygosity. METHODS: Genotyping for mutations in exons 2 and 4 of the HFE gene using denaturing gradient gel electrophoresis in 1784 participants aged 45 to 100 years from 4 population-based studies: all 183 centenarians from the Danish Centenarian Study, 601 people aged 92 to 93 years from the Danish 1905 Cohort, 400 aged 70 to 94 years from the Longitudinal Study of Aging Danish Twins, and 600 aged 45 to 67 years from a study of middle-aged Danish twins. RESULTS: All participants (N=1784) were screened for mutations in exon 4, and a trend toward fewer heterozygotes for the C282Y mutation-the mutation most often associated with hereditary hemochromatosis-was found. This was significant for the whole population (P=.005) and for women (P=.004) but not for men (P=.26). A group of 599 participants was screened for mutations in exon 2, and there was no variation in the distribution of mutations in exon 2 in the different age groups. CONCLUSIONS: In a high-carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy.

Age Distribution↗

Normal life expectancy and thrombosis-free survival in aspirin treated essential thrombocythemia.

Focusing on platelet-mediated erythromelalgia as a specific, presenting, and single sign of essential thrombocythemia (ET) we were able to define the characteristic peripheral blood and bone marrow findings in ET patients. From 1974 to 1986 we treated 20 symptomatic ET patients with microvascular circulation disturbances including erythromelalgia (N = 18), atypical or typical transient ischemic attacks (N = 6), or acute coronary ischemic syndrome (N = 3) with aspirin and one course of busulfan. The mean platelet counts before and after busulfan treatment were 1,009 (range 545-1,525) and 241 (range 159-315) x 10(9)/L, respectively. After induction of a complete remission, treatment with busulfan and aspirin was discontinued until symptoms returned. All 20 patients remained asymptomatic as long as ET was in maintained remission (platelet < 350 x 10(9)/L) for 4 to 61 (mean 36) months. Eight patients became symptomatic and 4 patients remained asymptomatic at relapse of ET after a follow-up period of 19 to 61 and 31 to 46 months, respectively. Platelet counts at time of symptomatic relapse in the 8 patients were 410, 450, 490, 500, 515, 545, 548, and 635 x 10(9)/L and at time of asymptomatic relapse in 4 ET patients 577, 600, 648, and 725 x 10(9)/L. Based on these observations, since 1986 we followed the strategy to treat ET patients with aspirin as long as the platelet count was between 400 and 1,000 up to 1,250 x 10(9)/L. Clear indications to reduce the platelet count were bleeding, aspirin side effects, and platelets counts above 1500 x 10(9)/L. This nonleukemogenic or least toxic approach in ET is the rationale behind the normal life expectancy and subsequent thrombosis-free survival in 68 ET patients after a mean follow-up period of 6.2 years.

Acute Disease↗

Life expectancy in differentiated thyroid cancer: a novel approach to survival analysis.

In differentiated thyroid carcinoma 10-year survival rates amount to 80-95%. Because age at diagnosis varies widely, these survival rates strongly depend on age at presentation. The aim of the present study was to analyse the attributable risk factors, including therapy per se, on survival in thyroid cancer after proper adjustment for the baseline mortality rate in the general population and to elucidate the adverse treatment effects on survival. Initial treatment in 504 patients consisted of thyroidectomy and 131I ablation. High-dose 131I was administered for residual disease. Patients in complete remission underwent an annual physical examination and thyroglobulin measurements during TSH suppression. Survival time was studied after transformation to standardised survival time to adjust for the baseline mortality rate in the general population. Median follow-up since diagnosis was 9 years. The 10-year overall survival was 83% and disease-specific survival 91%. After initial treatment, persistent disease occurred in 75 patients (15%). In univariate analysis, T4, N1, M1 status and Hürthle cell type were prognostic for persistent and recurrent disease. Age was not prognostic for recurrent disease in multivariate analysis. The standardised survival time was not altered in disease-free patients. However, patients with persistent disease had a median standardised survival time of only 0.60 (95% confidence interval 0.47;0.72), ranging from 0 to above 1, independent of initial tumour status or age. The cumulative proportion of persistent disease was at least 20% of the whole group. Disease-free patients after thyroid carcinoma have a normal residual life span. In contrast, in cases of persistent disease the life expectancy ranges widely with its median being reduced to 60%. Overall, treatment including radioiodine is safe but unsuccessful in 20% of the patients. Age is not a disease-specific risk factor and should not be used as an independent factor in treatment algorithms.

Adult↗

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.

Adolescent↗