Biomedical subjects

T Seeman

Publications and source records attributed to T Seeman.

At least 19 recordsLinked to original sources

PubMed2006

[Hereditary form of thrombotic thrombocytopenic purpura].

BACKGROUND: Thrombotic thrombocytopenic purpura is characterized by microvascular platelet clumping resulting in thrombocytopenia, microangiopathic hemolysis, neurological abnormality, and renal dysfunction. Similar manifestations also occur in patients with the hemolytic uremic syndrome or other types of disorders. Recent studies demonstrate that severe deficiency of the von Willebrand factor cleaving metalloprotease, ADAMTS 13, causes thrombotic thrombocytopenic purpura. Aim of our study was to characterize gene defects causing inherited type of disease. METHODS AND RESULTS: We investigated nine patients with recurrent type of disease with familiar origin and twelve relatives. Samples were taken in a remission of disease. We measured activity of ADAMTS13 (vWF-CP) with modified method of the quantitative immunoblotting of degraded vWF multimers. Mutation screening was carried out by sequencing all 29 exons and flanking intron regions of the ADAMTS13 gene. Five distinct mutations were found. Three of them are novel. CONCLUSIONS: Mutation analysis of the ADAMTS 13 gene brought interesting results in eight patients. We found a one single base frameshift insertion, 4143insA in 8 of 9 unrelated individuals. This investigation represents an advantage in the differential diagnosis of disease since the thrombotic thrombocytopenic purpura phenotype in childhood can be variable and rapid detection of mutation is helpful for the recurrence prevention.

ADAM Proteins↗

PubMed2006

[Arterial hypertension in children and adolescents].

Hypertension is one of the main risk factors of cardiovascular diseases. Hypertension in childhood is defined as blood pressure > or = 95. percentile for healthy children population. The prevalence of hypertension in childhood is considerably lower than in adults and is about 1%. The aetiology of hypertension in childhood differs from adult population--in children secondary forms are more common than primary, however, in adolescents primary form already prevails. In general, the younger the child and the higher the blood pressure, the more probably it is a secondary form of hypertension. The most common causes of secondary hypertension are renal diseases (renoparenchymal or renovascular). Cardiac diseases (aortic isthmus stenosis), endocrinopathies, central nervous system disorders or use of hypertensinogenic drugs are less frequent causes of secondary hypertension. Each child with hypertension has to be carefully examined; the extent of the examination depends on the age of the child and severity of hypertension. The main task for the investigation is to exclude or reveal secondary form of hypertension, which could be causally treated (e.g. angioplasty in renal artery stenosis). Treatment of hypertension is non-pharmacological and pharmacological (angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, diuretics, angiotensin receptor blockers).

Adolescent↗

PubMed2006

[Improved control of hypertension and its effect on graft function in children after renal transplantation].

BACKGROUND: Hypertension in patients after renal transplantation (RTx) is associated with impaired graft functions and graft survival. Control of hypertension in children after RTx is low--only 20-50 % of children have well controlled hypertension. The aim of this interventional study is to improve blood pressure control and to investigate whether the improved control will improve the graft survival. METHODS AND RESULTS: 36 children after RTx (mean age 13.9 +/- 4.4 years, time after RTx 2.7 +/- 2.4) fulfilled the inclusion criteria. Ambulatory blood pressure monitoring (ABPM) and graft function were examined. In children with uncontrolled hypertension, the dose and number of antihypertensive drugs were increased to reach BP <95th centile. ABPM was repeated after 12 months. After 12 months day-time and night-time BP dropped non-significantly, however prevalence of uncontrolled hypertension improved significantly from 42 % to 34 % (p<0.05). Number of antihypertensive drugs increased from 2.1 +/- 0.9 to 2.4 +/- 0.8 drugs per patient (p<0.05), namely that of ACE-inhibitors (from 19% to 27%, p<0.05). Graft function decreased by 3.6 ml/min/1.73m2/year (p<0.05). CONCLUSIONS: This 12 months interventional trial demonstrated that control of hypertension in children after RTx can be improved by increasing number of prescribed antihypertensive drugs. The decline of graft function was lower comparing with previous trials.

Adolescent↗

PubMed2005

Proteinuria in children after renal transplantation.

Proteinuria is associated with poor long-term allograft as well as patient survival among adults after renal transplantation. In children, there are no studies focusing primarily on posttransplant proteinuria. The aim of this cross-sectional study was to investigate the prevalence of and possible risk factors associated with proteinuria. Thirty-three children (mean age of 13.7 +/- 4.3 years; mean time after renal transplantation = 2.3 +/- 2.2 years) were eligible for the study. There was an 82% prevalence of proteinuria (> or =96 mg/m2/d) with nephrotic range proteinuria (> or =960 mg/m2/d) in 12% of children. The mean urinary protein excretion was 256 +/- 299 mg/m2/d (range = 47 to 1264). Children with hypertension, as defined by ambulatory blood pressure monitoring, showed significantly higher proteinuria than normotensive children (382 +/- 435 vs 163 +/- 79 mg/m2/d, P < .05). Children with a history of a previous acute rejection episode showed significantly higher proteinuria than children who never had an episode (416 +/- 445 vs 165 +/- 91 mg/m2/d, P < .05). Children with proteinuria did not show statistically different graft function than children without proteinuria. No statistically significant correlation was observed between proteinuria and ambulatory blood pressure values or graft function. In conclusion, proteinuria is a frequent finding also in children after renal transplantation; it is associated with hypertension and a history of rejection episodes.

Adolescent↗

PubMed2004

Ambulatory blood pressure monitoring in children after renal transplantation.

Arterial hypertension is a common complication in children after renal transplantation and the control of hypertension is often difficult. This retrospective investigates the prevalence and rate of control of hypertension using ambulatory blood pressure monitoring (ABPM) in 45 children (mean age 14.1 +/- 4.3 years, mean time after renal transplantation 2.2 +/- 2.7 years), all on cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil plus daily steroids. The overall prevalence of hypertension was 82%. None of the transplanted children had normal blood pressure without antihypertensive therapy (ie, spontaneous normotension). Twenty percent of children had untreated hypertension, 18% had controlled hypertension, and 62% had uncontrolled hypertension. Prevalence of the nondipping phenomenon was 53%. The mean number of antihypertensive drugs (without diuretic monotherapy) in treated patients was 1.9 drugs per patient. The prevalence of arterial hypertension in children after renal transplantation is high and the control of hypertension is often unsatisfactorily low.

Adolescent↗

PubMed2004

Renal concentrating capacity is linked to blood pressure in children with autosomal dominant polycystic kidney disease.

Impaired glomerular filtration rate (GFR) is a risk factor for the development of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD). However, markers of tubular function were not tested whether they are linked to hypertension or blood pressure (BP) level. The aim of our study was to investigate the relationship between renal concentrating capacity and BP in children with ADPKD. Fifty-three children (mean age 11.8+/-4.4 years) were investigated. Standardized renal concentrating capacity test was performed after nasal drop application of desmopressin, BP was measured by ambulatory BP monitoring (ABPM). Renal concentrating capacity was decreased in 58 % of children. The prevalence of hypertension was significantly higher in children with decreased renal concentrating capacity (35 %) than in children with normal renal concentrating capacity (5 %) (p<0.05). Significant negative correlations were found between renal concentrating capacity, ambulatory BP and number of renal cysts (r = -0.29 to -0.39, p<0.05 to p<0.01). In conclusion, the concentrating capacity is decreased in about half of the patients and is linked to BP. Decreased renal concentrating capacity should be considered.

Adolescent↗

PubMed2001

Ambulatory blood pressure monitoring in children with unilateral multicystic dysplastic kidney.

UNLABELLED: Multicystic dysplastic kidney (MCDK) is one of the most common congenital renal anomalies. Arterial hypertension is a potential complication of MCDK. Blood pressure (BP) has so far been measured only casually and the frequency of hypertension has been estimated to be between 0%-8%. Ambulatory blood pressure monitoring (ABPM) provides more precise information on BP than the casual BP measurement. The aim of this study was to investigate the BP profile in children with MCDK using ABPM. A group of 25 children (16 girls), with a mean age of 7.8 years (range 3.8-17.7 years) were investigated. ABPM was performed using the oscillometric SpaceLabs 90207 device. Hypertension was defined as mean systolic and/or diastolic BP during the day and/or in the night exceeding 95th percentile for ABPM. Five (20%) children showed hypertension, two of them had combined daytime and night-time hypertension and three had isolated nocturnal hypertension, although daytime BP was between the 90th-95th percentile in two of them. Children with ultrasonographical and/or laboratory signs of contralateral kidney abnormalities showed a higher incidence of hypertension than those without abnormalities (two of four versus 3 of 21). The mean night-time systolic and diastolic BP of children with MCDK was significantly higher than in healthy children (+ 0.50 and + 0.54 SDS, respectively, P = 0.012 and 0.03, respectively). Three of the hypertensive children were already nephrectomised. All five hypertensive children showed ultrasonographical and/or laboratory signs of contralateral kidney abnormalities. Hypertensive children had significantly higher microalbuminuria than normotensive children (6.9 +/- 3.2 mg/mmol creatinine versus 1.8 +/- 0.7, P = 0.03). The nocturnal BP fall (dip) was attenuated in five children, only one of whom was hypertensive. CONCLUSION: Arterial hypertension in children with multicystic dysplastic kidney is seen more often if based on ambulatory blood pressure monitoring than on casual blood pressure recordings. The main risk factor for developing hypertension is contralateral kidney damage. Ambulatory blood pressure monitoring should be performed in children with multicystic dysplastic kidney, especially in those with contralateral kidney abnormalities.

Adolescent↗

PubMed2001

Frailty in older adults: evidence for a phenotype.

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

Aged↗

PubMed2000

Importance of generativity for healthy aging in older women.

This article reviewed increasing evidence that remaining physically, cognitively, or socially active confers health benefits by delaying or preventing the onset of disease and disability in older adults. The desire to be generative, or to make a difference, has long been considered an important developmental objective in later years in order to give meaning to one's life, and may provide the necessary impetus for older women to initiate and maintain health-promoting activities. Because the prevalence of disability is greatest in older women, it is critical to find ways to maximize their opportunities for generative activity to promote healthier life-styles. Unfortunately, those who stand to gain most from the promotion of generative roles face many limiting factors, including low education, financial dependence and poverty, primary care-taking responsibilities, social isolation, and low self-efficacy. These obstacles may be too difficult and pervasive for an individual to overcome by oneself. Rather, these challenges need to be addressed through progressive changes in social programs that acknowledge the contributions that older adults can make in later years. Decreasing the structural lag between current social and demographic realities of older women's roles with increasing age will become ever more critical as a growing proportion of older women and men transition from a job outside the home to retirement.

Aged↗

PubMed2000

Higher basal cortisol predicts verbal memory loss in postmenopausal women: Rancho Bernardo Study.

BACKGROUND: In animals, higher endogenous or exogenous corticosteroids cause neuronal dysfunction, damage, and loss, especially in the hippocampus. In humans, high cortisol levels have been linked to memory impairment. OBJECTIVE: To prospectively examine the relation between morning basal cortisol level and change in cognitive performance during an average follow-up of 2 years. DESIGN: Longitudinal cohort. SETTING: Geographic community in southern California. MEASUREMENTS: Between 1984 and 1987, blood for basal morning cortisol was obtained along with pertinent medical, behavioral, and physical covariates from 749 post-menopausal women, mean age 72 years, who were not taking corticosteroids or postmenopausal hormones. Cognitive function was assessed in 502 women in the period from 1988 to 1991 and repeated in 136 women in the period from 1991 to 1993. RESULTS: In both age- and multiply adjusted linear regression models, higher baseline cortisol was a significant predictor of worsened category fluency. No other cognitive domain tested was related to cortisol. CONCLUSIONS: These results support the hypothesis that subtle dysregulation of cortisol axis is related to memory loss. Interventions that block this pathway may provide new therapeutic options to prevent cognitive decline.

Aged↗

PubMed2000

A prospective study of the effect of fracture on measured physical performance: results from the MacArthur Study--MAC.

OBJECTIVE: To examine the impact of fractures on measured physical performance and to assess whether specific fractures have unique sequelae. SUBJECTS: 762 men and women, aged 70 to 79 at baseline, who were part of the MacArthur Study of Successful Aging. DESIGN: A longitudinal case-cohort: those with prevalent fractures at baseline were excluded; cases were persons with a medically diagnosed hip, arm, spine, or wrist fracture during the follow-up period (1988-1995). MEASURES: Eight physical performance tests: turning a circle, walking fast, chair stands, timed tap, tandem stand, grip strength, single leg stand, and balance (average of single leg and tandem stands) measured at baseline and follow-up. ANALYSIS: Two fracture groups were defined: (1) those with incident wrist fractures (n = 7) and (2) those with a fracture of the hip, arm, or spine (combined fractures group, n = 16). Change in physical performance was analyzed using crude, age-adjusted, and multiply-adjusted ANCOVA models. RESULTS: The combined fracture group demonstrated statistically significant (P < .05) declines seven of eight of the performance tests compared with individuals without fractures. In contrast, individuals with wrist fractures did not experience a statistically significant decline in any performance measure compared with the no fracture group. CONCLUSIONS: Relative to those without fractures, individuals with a hip, arm, or clinical spinal fracture show similar global declines in physical performance, whereas those with wrist fracture demonstrate no physical performance decrements.

Aged↗

PubMed2000

The effect of race and health-related factors on naming and memory. The MacArthur Studies of Successful Aging.

OBJECTIVES: The purpose of the analyses was to examine the impact of health-related variables on race differences in neuropsychological functioning (Boston Naming Task). METHODS: Using cross-sectional data from the MacArthur Successful Aging Study, the authors examined the relationship of demographic characteristics, health status, health habits, physical functioning, and speed of performance to naming and incidental recall of items from the Boston Naming Task. Participants were 1,175 healthy African American and European American older persons 70 to 79 years old. RESULTS: Regression analyses indicated that although race differences persisted for confrontational naming after controlling for demographic and health factors, there was no effect due to race for incidental recall scores or for savings scores for recall. DISCUSSION: The racial differences found in test performance may reflect differences in cultural appropriateness of the material rather than differences in ability.

Black or African American↗

PubMed2000

A health and demographic profile of noninstitutionalized older Americans residing in environments with home modifications.

OBJECTIVES: In this analysis the authors investigate the demographic characteristics, the health conditions/events, and the disabilities of community-dwelling Americans 70 years of age and older that are associated with residing in environments with specific home modifications. METHODS: Data from a large population-based study of the elderly are used to estimate logistic regression equations that reveal profiles of older individuals who are likely to have distinct home modifications. RESULTS: Having diseases such as diabetes and stroke, having experienced a hip fracture, a fall or a joint replacement, and having greater limitations with activities of daily living raise the likelihood of having home modifications. Low income, Hispanic, and African American elderly appear underrepresented among those with modifications. DISCUSSION: The authors conclude that specialized housing alternatives will be an increasingly important issue in the future as individuals aim to achieve and maintain the delicate balance between their functional ability and their living environment.

Activities of Daily Living↗

PubMed2000

[Renal transplantation in children in the Czech Republic].

The aim of the study is to review results of pediatric renal transplantation in center in Prague, Czech Republic. Results are compared with the registry data from Europe and United States. Patients, who underwent RTx at the University Hospital Motol, Prague (Czech Republic) between 1977 and the end of 1999, were analyzed. Since 1977 128 Rtx from cadaveric donors were performed in children in mean age 12.8 +/- 4.1 years. In 1977-1987, patients were treated with prednisone and azathioprine, and since 1988, cyclosporine A, added to prednisone and azathioprine. Sequential quadruple immunosuppression was used only in few highly sensitized patients. Acute graft rejections were treated with methylprednisolone pulses, antithymocyte globulin and monoclonal antibodies OKT3, in selected cases. In 1988 and 1999 cyclosporine A was replaced by tacrolimus as initial immunosuppression in some patients. The number of Tx ranged between 5 and 13 per year. Patients and graft survival were significantly lower in the first time period 1977-1987 with a median patients 5-year survival rate of only 50% and graft survival 30%. In the last period (1988-1999) 5-year patients survival is 90% and 5-year graft survival is 68% (p = 0.01). Two cases of posttransplant lymphoproliferative disease were diagnosed so far. One of them died several months after RTx, the other received cytostatic therapy for Hodgkin tumor and graft function was maintained. Main causes of graft failure were chronic rejection followed by acute steroid resistant rejections, severe cytomegalovirus infections, noncompliance, vascular thrombosis, and recurrence of original disease.

Adolescent↗

PubMed1999

[Blood pressure, functional and morphological study of kidneys in children with autosomal dominant polycystic kidney disease].

BACKGROUND: Autosomal dominant polycystic kidney disease is one of the most common inherited disorders with a prevalence of 1:1000 and is responsible for cca 10% of end-stage renal disease in adult patients. Renal insufficiency is a rare symptom of ADPKD in children, however, there are some symptoms, which can occur already in childhood. The aim of this study was to detect early signs of renal damage and to reveal the blood pressure profile in children with ADPKD using ABPM (ambulatory blood pressure monitoring). METHODS AND RESULTS: 32 children (aged 3.4-19.4 years, mean age 12.3)-carriers of PKD-gene with normal GFR, diagnosed on the basis of a positive family history and characteristic ultrasound features, and in 21 cases also indirect DNA analysis revealed positive results. 11/32 children (34%) presented arterial hypertension detected by ABPM (values higher than 95th centile of normal individuals). The mean of ABPM values of all patients was significantly higher than normal children (p < 0.01), 76% patients had values above the 50th centile. Signs of renal damage (proteinuria, microalbuminuria, decreased renal concentrating capacity, pathological excretion of tubular markers) were found in 22-64% of investigated children. Significantly higher renal volume and renal length were found in more than 1/3 of the children, renal volume and length higher than the mean of healthy children in about 90% of patients and a significant correlation between ABPM parameters and renal length and volume (p < 0.05). CONCLUSIONS: The results of this study show, that the signs of renal damage and arterial hypertension occur relatively often in children with ADPKD despite still normal GFR. This justifies the early diagnosis of ADPKD especially as it reveals the most important treatable complication of ADPKD-arterial hypertension. These findings emphasise the importance of early diagnosis in children from families with ADPKD. Probably, early treatment of hypertension could even postpone the otherwise common end-stage renal damage in adult patients with ADPKD. Careful follow up of all children with ADPKD is strongly recommended, above all the blood pressure should be controlled.

Adolescent↗

PubMed1999

Abolished nocturnal blood pressure fall in a boy with glucocorticoid-remediable aldosteronism.

Glucocorticoid-remediable aldosteronism (GRA) is a rarely recognised cause of arterial hypertension. We report the features of a 13-year-old boy with hypertension (casual blood pressure (BP) 140-180/95-110 mm Hg) discovered during a routine paediatric check. Ambulatory BP monitoring (ABPM) revealed significant hypertension with an abolished nocturnal BP fall (mean daytime BP 155/108 mm Hg, mean night-time BP 156/104 mm Hg, nocturnal BP fall 0/4%) which was indicative of secondary hypertension. Despite triple antihypertensive drug therapy the hypertensive control was unsatisfactory. Laboratory tests revealed hypokalaemia (3.0 mmol/l), suppressed plasma renin activity (0.012 nmol/l/h) and high plasma aldosterone (1.190 nmol/l). The diagnosis of primary hyperaldosteronism was established and GRA was further confirmed by the presence of the chimaeric GRA-gene and dexamethasone therapy was initiated. During the next 2 months of dexamethasone therapy all three antihypertensive drugs were discontinued and BP remained under control with restoration to a normal nocturnal BP fall (mean daytime BP 129/77 mm Hg, mean night-time BP 113/64, nocturnal BP fall 12/17%). A change of therapy from dexamethasone to spironolactone was necessary due to the side effects of corticosteroids after 3 months. Spironolactone alone (0.8-2 mg/kg/day) was able to control the BP sufficiently. In conclusion, to our knowledge, this is the first reported case of abolished nocturnal BP fall in a patient with genetically proven GRA. This study indicates that GRA can cause severe hypertension even in children, associated with an abolished nocturnal BP fall. GRA thus should be excluded in all hypertensive patients with circadian BP rhythm disturbances.

Adolescent↗

PubMed1999

Variation in the impact of social network characteristics on physical functioning in elderly persons: MacArthur Studies of Successful Aging.

OBJECTIVES: Social support and social networks have been shown to exert significant effects on health and functioning among elderly persons. Although theorists have speculated that the strength of these effects may differ as a function of sociodemographic characteristics and prior health status, few studies have directly tested the moderating effects of these variables. METHODS: Longitudinal data from the MacArthur Study of Successful Aging were used to examine the effects of structural and functional social support on changes in physical functioning over a 7-year period, measured by the Nagi scale, in a sample of initially high-functioning men and women aged 70 to 79 years. Multiple regression analyses were used to test the main effects of social support and social network variables, as well as their interactions with gender, income, and baseline physical performance. RESULTS: After controlling for potential confounding effects, respondents with more social ties showed less functional decline. The beneficial effects of social ties were stronger for respondents who were male or had lower levels of baseline physical performance. DISCUSSION: The effects of social support and social networks may vary according to the individual's gender and baseline physical capabilities. Studies of functional decline among elderly persons should not ignore this population variation in the effects of social networks.

Activities of Daily Living↗

PubMed1999

Protective and damaging effects of mediators of stress. Elaborating and testing the concepts of allostasis and allostatic load.

Stress is a condition of human existence and a factor in the expression of disease. A broader view of stress is that it is not just the dramatic stressful events that exact their toll but rather the many events of daily life that elevate activities of physiological systems to cause some measure of wear and tear. We call this wear and tear "allostatic load," and it reflects not only the impact of life experiences but also of genetic load; individual habits reflecting items such as diet, exercise, and substance abuse; and developmental experiences that set life-long patterns of behavior and physiological reactivity (see McEwen). Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation, but in the long run allostatic load causes changes in the body that lead to disease. This will be illustrated for the immune system and brain. Among the most potent of stressors are those arising from competitive interactions between animals of the same species, leading to the formation of dominance hierarchies. Psychosocial stress of this type not only impairs cognitive function of lower ranking animals, but it can also promote disease (e.g. atherosclerosis) among those vying for the dominant position. Social ordering in human society is also associated with gradients of disease, with an increasing frequency of mortality and morbidity as one descends the scale of socioeconomic status that reflects both income and education. Although the causes of these gradients of health are very complex, they are likely to reflect, with increasing frequency at the lower end of the scale, the cumulative burden of coping with limited resources and negative life events and the allostatic load that this burden places on the physiological systems involved in coping and adaptation.

Adaptation, Physiological↗