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Biomedical subjects

T Harris

Publications and source records attributed to T Harris.

At least 145 records · Page 8Linked to original sources
PubMed1994

Body mass index, weight change, and risk of mobility disability in middle-aged and older women. The epidemiologic follow-up study of NHANES I.

OBJECTIVE: As disability is highly prevalent among older women, is costly, and affects the quality of life, preventable causes of disability must be identified. In this study, we investigated the relationship between the body mass index (BMI), weight change, and the onset of disability in older women. DESIGN: Prospective cohort study. SETTING: The nationally representative US epidemiologic follow-up study of the National Health and Nutrition Examination Survey (NHANES) I (1971 through 1987). PATIENTS: White women classified as young-old (mean age 60 years at baseline, mean age 65 years at follow-up) and old-old (mean age 76 years at baseline, mean age 80 years at follow-up). MAIN OUTCOME MEASURES: The relative odds for the onset of mobility disability associated with tertiles of past BMI (measured 8 to 16 years prior to disability ascertainment) and current BMI (measured 2 to 5 years prior to disability ascertainment) and with weight change between the two weight measurements. RESULTS: In both cohorts, women in the high past BMI group (> 27 in the young-old and > 28.1 in the old-old cohort) had a twofold increase in the risk for disability compared with women in the low past BMI group. High current BMI was as strongly related as past BMI to risk of disability in the young-old women; it was not as strong a predictor in old-old women. In the old-old group only, women who experienced a weight loss of more than 5% had a twofold increase in risk of disability compared with weight-stable women. These results were adjusted for age, smoking, education, and study time and were not importantly modified with the addition into the models of single or multiple health conditions. CONCLUSIONS: These prospective data suggest that high BMI is a strong predictor of long-term risk for mobility disability in older women and that this risk persists even to very old age. However, the paradoxical increase in risk associated with weight loss in the old-old women requires further study. Programs to prevent overweight may have potential for decreasing disability in women.

Aged↗
PubMed1994

Proteinuria as a biomarker: risk of subsequent morbidity and mortality.

A standard laboratory renal assessment, concentration of albumin in urine, has been suggested as a biomarker of renal damage, but little data exist on its ability to predict health outcomes in the general population. This 16-year follow-up study of a general population evaluated the utility of this assessment to predict subsequent serious health consequences. Four percent of men and 2% of women aged 45-74 years exhibited proteinuria in a cross-sectional screening of an ambulatory population, with the percentage increasing with age. The finding of proteinuria was predictive of serious health consequences, with adjusted relative risks for subsequent mortality of 1.71 for men and 1.84 for women and adjusted relative risks for renal disease incidence of 3.46 in men and 1.39 in women. Controlling for those factors which might be associated with proteinuria and even excluding early cases did not alter these findings. These data support that causal proteinuria should be considered as a marker for risk of poor health outcomes.

Adult↗
PubMed1994

Determinants of change in total cholesterol and HDL-C with age: the Framingham Study.

OBJECTIVE: The purpose of the study was to assess the determinants of change of total cholesterol and high density lipoprotein cholesterol (HDL-C) change in an adult population. METHODS: The prospective cohort was examined at baseline and eight years later. A total of 2,222 men and 2,677 women age 20-79 years at baseline were included. Analyses were performed in 15-year age groups, and persons with cardiovascular disease or cancer during the observation period were excluded. RESULTS: In longitudinal analyses, body mass index (BMI) and plasma total cholesterol levels of each rose in concert among younger age groups, whereas levels declined in older individuals. Mean levels of BMI and total cholesterol peaked at a later age in women than in men. The corresponding changes in HDL-C were negative at all ages, and greater declines were seen in the elderly. A decrease in plasma total cholesterol was highly associated with greater age and a decrease in body mass index over the study interval, whereas the decline in HDL-C was proportional to change in body mass index. These changes remained significant after adjustment for baseline age and change in alcohol intake, cigarette consumption, diuretic use, and oral estrogen use. CONCLUSIONS: The rise in plasma total cholesterol among apparently healthy young men and women and its fall in the elderly are significantly associated with similar trends for obesity. The key determinants of a decline in HDL-C are an increase in obesity and advancing age itself. A decline in total cholesterol and in HDL-C is particularly common among the elderly, and it can be expected to occur without specific dietary or pharmacologic intervention.

Adult↗
PubMed1994

The third National Health and Nutrition Examination Survey: contributing data on aging and health.

The third National Health and Nutrition Examination Survey (NHANES III, 1988-94) is the most recent in a series of national examination studies conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention. Prior to NHANES III the upper age limit was 74; the upper age limit was removed for NHANES III. Persons 60 years and older in the black and Mexican American populations, and those 60-69, 70-79, and 80 years and older in the white population were oversampled. The NHANES III component for older persons provides a multidimensional overview of physical health status and aspects of functional health status. The key components for older persons are: Osteoporosis, arthritis, nutrition, cardiovascular disease, pulmonary disease, and physical, cognitive, and social function.

Activities of Daily Living↗
PubMed1994

Mitogenic actions of endothelin-1 and epidermal growth factor in cultured airway smooth muscle.

1. Hyperplasia of airway smooth muscle contributes to the increase in bronchomotor responsiveness that characterizes asthma. We have investigated the mitogenic potential of endothelin-1 (ET-1) and epidermal growth factor (EGF) in guinea-pig cultured airway smooth muscle and the relationship of these actions to tyrosine phosphorylation and increases in intracellular calcium (Ca2+i). 2. ET-1 stimulated DNA and protein synthesis and also increased cell number, but these mitogenic actions were small compared with those of EGF. 3. ET-1 and EGF increased the level of tyrosine phophorylation of a range of proteins with apparent molecular weights between 80 and 100 kDa and also increased phosphorylation of a single protein of 33 kDa. 4. Ca2+i levels were increased by both ET-1 and EGF. However, concentrations of EGF three orders of magnitude higher than those having mitogenic actions or increasing protein tyrosine phosphorylation were required. ET-1 was a more potent stimulant of increases in intracellular calcium than of mitogenesis. 5. We conclude that elevation of Ca2+i is unlikely to be an important signal for the mitogenic action of EGF. It is suggested that stimulants at the EGF receptor (EGF and transforming growth factor alpha) may play a role in the airway smooth muscle hyperplasia in asthma.

Animals↗
PubMed1994

Self-reported causes of physical disability in older people: the Cardiovascular Health Study. CHS Collaborative Research Group.

OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community-dwelling older people. DESIGN: Cross sectional analyses of data obtained in an observational cohort study. SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA. PARTICIPANTS: 5201 community-dwelling people > or = 65 years old. RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status. CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.

Activities of Daily Living↗
PubMed1994

The burden and outcomes associated with dehydration among US elderly, 1991.

OBJECTIVES: Dehydration has been underappreciated as a cause of hospitalization and increased hospital-associated mortality in older people. This study used national data to analyze the burden and outcomes following hospitalizations with dehydration in the elderly. METHODS: Data from 1991 Medicare files were used to calculate rates of hospitalization with dehydration, to examine demographic characteristics and concomitant diagnoses associated with dehydration, and to analyze the contribution of dehydration to mortality. RESULTS: In 1991, 6.7% (731,695) of Medicare hospitalizations had dehydration listed as one of the five reported diagnoses, a rate of 236.2/10,000 elderly Medicare beneficiaries. In 1991, Medicare reimbursed over $446 million for hospitalizations with dehydration as the principal diagnosis. Older people, men, and Blacks had elevated risks for hospitalization with dehydration. Acute infections, such as pneumonia and urinary tract infections, were frequent concomitant diagnoses. About 50% of elderly Medicare beneficiaries hospitalized with dehydration died within a year of admission. CONCLUSIONS: Hospitalization of elderly people with dehydration is a serious and costly medical problem. Attention should be focused on understanding predisposing factors and devising strategies for prevention.

Age Factors↗
PubMed1994

Granulocyte and granulocyte-macrophage colony-stimulating factors exert differential effects on neutrophil platelet-activating factor generation and release.

The haemopoietic recombinant human cytokines granulocyte and granulocyte-macrophage colony-stimulating factor (rhG-CSF and rhGM-CSF) are used to facilitate recovery of bone marrow function following cytotoxic chemotherapy. Recent clinical experience indicates that rhG-CSF is better tolerated than rhGM-CSF. Thus, we have compared the priming effects of rhG-CSF and rhGM-CSF on superoxide anion (O2-) generation and platelet-activating factor (PAF) synthesis by neutrophils. During a 60-min incubation of neutrophils with rhGM-CSF (1 nM) or recombinant human tumour necrosis factor-alpha (rhTNF-alpha; 0.3 nM), cell-associated PAF levels increased, and upon stimulation with FMLP (100 nM) there was a striking amplification of PAF formation (8-13-fold) and release (24-36-fold). In contrast, in rhG-CSF (1 nM)-primed cells, there was no increase in cell-associated PAF levels and neither PAF synthesis nor PAF release was amplified following stimulation with FMLP. On the other hand, each of rhG-CSF, rhGM-CSF or rhTNF-alpha increased subsequent FMLP (100 nM)-induced O2- generation (by 89%, 166% and 115%, respectively). These results suggest the existence of distinct intracellular signalling pathways for cytokine priming. Furthermore, some of the more severe adverse reactions to the administration of rhGM-CSF may be a result of the biosynthesis and/or release of the potent inflammatory mediator, PAF.

Arachidonic Acid↗
PubMed1994

The fundholding fandango.

General practitioner fundholding allows flexible use of resources at the coal-face, provides incentives to alter practice such as prescribing within cash limits and forces hospitals to be more responsive to general practitioner demands. However, the additional administrative costs both in time and money, the fragmentation of purchasing power compounded by a lack of expertise and experience in contracting, and the poor information and financial systems which exist in the National Health Service are severe constraints. A suggested way forward is to delegate responsibility for running the scheme, including the contracting and billing, to district health authorities offering more flexible budgets to all practices and extending the scheme as local information systems allow. This will reduce fragmentation of purchasing power and administrative costs and re-establish local accountability. It will also give the general practitioner more time to see and treat patients, who will see the system as being fairer.

Budgets↗
PubMed1993

Number of pregnancies and the subsequent risk of cardiovascular disease.

BACKGROUND: Whether increasing parity or gravidity is a risk factor for coronary heart disease has been debated, but the question remains unresolved. METHODS: We tested the association between the number of pregnancies and a variety of cardiovascular end points in two groups of women who had completed childbearing. One group comprised 2357 women who were followed for 28 years through the Framingham Heart Study, and the other 2533 women followed for at least 12 years through the first National Health and Nutrition Examination Survey National Epidemiologic Follow-up Study (NHEFS). RESULTS: The rates of coronary heart disease were higher among multigravid women than among women who had never been pregnant, in both the Framingham Heart Study and the NHEFS, but in both studies, the higher rates were statistically significant only in women with six or more pregnancies. For the women in the Framingham Study, the rate ratio adjusted for age and educational level in the group with six or more pregnancies (as compared with women who had never been pregnant) was 1.6 (95 percent confidence interval, 1.1 to 2.2). For the women in the NHEFS, the same adjusted rate ratio was 1.5 (95 percent confidence interval, 1.1 to 1.9). Adjustments for other known cardiovascular risk factors, including weight, did not markedly alter this risk. The rate of total cardiovascular disease was also significantly higher among multigravid women in the Framingham Study than in the women who had never been pregnant. CONCLUSIONS: In two prospective American studies, having six or more pregnancies was associated with a small but consistent increase in the risk of coronary heart disease and cardiovascular disease. Whether gravidity itself or some other unmeasured factor accounts for the increase in risk that we observed requires further investigation.

Aged↗
PubMed1993

Prolonged isoproterenol treatment alters immunoregulatory cell traffic and function in the rat.

The mechanisms by which the sympathetic nervous system modulates functional parameters of the immune system have not been fully defined. In vivo, acute and chronic beta 2-adrenergic stimulation have been shown to have dramatic but opposing effects on circulating lymphocyte number and subset distribution in humans. In vitro studies have suggested impairment of numerous lymphocyte effector functions in the presence of catecholamines. To better define the effects of short and long term beta-adrenergic stimulation on lymphocyte migration patterns between circulating and splenic pools, as well as function, we infused rats with either low or high doses of isoproterenol over various time intervals. Specifically, we determined the number and subset composition of peripheral blood and splenic lymphocytes in addition to assessing responsivity to the T cell mitogen concanavalin A and antibody production. As a measure of in vivo lymphocyte proliferation, we also monitored the effect of these infusions on the number of peripheral blood lymphocytes and splenocytes and the splenic weight. Isoproterenol led to dose-dependent, short-lived decrements in mitogen-induced lymphocyte proliferation with concomitant decreases in circulating and splenic lymphocyte number in a subset-specific manner. Analysis of the distribution of circulating and splenic subtypes with isoproterenol treatment suggests definite but limited influences on beta-adrenergic stimulation on immunoregulatory cell traffic. We conclude that beta-adrenergic stimulation in the rat model leads to a dose-dependent, transient effect on lymphocyte proliferation and migration patterns. The relative lack of functional beta-receptors on rat lymphocytes and the propensity for early sustained receptor desensitization on exposure to agonist may account for qualitative differences seen between rats and humans.

Animals↗
PubMed1993

Screening for osteoporosis by bone densitometry: a stratified intervention approach.

We have performed computer modelling of the relationship between bone mass, age and hip fracture in a conditional probability model using a national population of 100,000 postmenopausal women aged 50 who have their bone density measured once. The computer model very closely reproduced the actual number of fractures in a Western Australian population. Intervention to bone loss completely in subjects with the lowest bone density (below 1 SD below the mean) would prevent 0.42 of a hip fracture per patient treated if the whole population were treated. Halving the rate of bone loss in the whole population would reduce hip fracture by two-thirds. These data suggest that hormone replacement therapy, which is the most effective therapy for preventing bone loss but which has the most side effects, should be focused on subjects with bone mass below 1 SD below the mean. The remainder of the population could be targeted with a public health campaign based on the lifestyle factors of increased dietary calcium and exercise which have been shown to slow but not stop bone loss.

Bone Density↗
PubMed1993

Molecular genetic analysis of the ABO blood group system: 1. Weak subgroups: A3 and B3 alleles.

We have determined the nucleotide sequences of the coding region in the last two coding exons of ABO genes (which occupy 91% of the soluble form of A1 transferase) from 7 individuals with weak subgroup phenotypes. Four of the individuals had an A3 phenotype and 3 individuals had a B3 phenotype. We determined the nucleotide sequences based on PCR followed by subcloning and DNA sequencing of the amplified fragments. Two cases of the A3 allele and 1 case of the B3 allele were found to contain a single-base substitution which resulted in an amino acid substitution. However, no other cases of A3 and B3 alleles were found to contain differences in this region. This finding demonstrates for the first time heterogeneity among these weak subgroups at the nucleotide level.

ABO Blood-Group System↗
PubMed1993

Molecular genetic analysis of the ABO blood group system: 3. A(X) and B(A) alleles.

We have employed a PCR approach to determine the nucleotide sequences of the coding region in the last two coding exons of the histo-blood group ABO genes from one A(X) and one B(A) individual. Compared with A1 alleles, the (A(X)) allele has a single nucleotide substitution (T-->A at nucleotide 646) resulting in an amino acid substitution (phenylalanine-->isoleucine at amino acid 216). Compared with B alleles, the B(A) allele has two nucleotide substitutions (T-->C at nt. 657 and A-->G at nt. 703) resulting in an amino acid substitution (serine-->glycine at aa. 235). The amino acid substitution resulting from this B(A) allele is located at the second of the four amino acid substitutions which discriminate human A and B transferases, and the amino acid residue (glycine) is identical to that of A transferase suggesting the involvement of this amino acid or its surrounding area for the recognition and/or binding of the donor nucleotide sugars.

ABO Blood-Group System↗
PubMed1993

Hip fracture rates in Hong Kong and the United States, 1988 through 1989.

OBJECTIVES: Prior studies have suggested that hip fracture rates are substantially lower in Asian countries than in the United States. However, comparisons have been limited by unavailability of recent data, differences in case definition, lack of data from similar time periods, and small sample sizes. This study sought to examine trends by age and sex, with separate statistics for those aged 85 or older. METHODS: Hospital discharge data were used to obtain hip fracture incidence in Hong Kong and the United States from 1988 through 1989. RESULTS: Within each population, women had higher hip fracture rates than men. Fracture rates in the United States were significantly higher for both sexes than rates in Hong Kong. For persons over the age of 80, rates of hip fracture among White US males exceeded those for Hong Kong women. Inclusion of transferred cases in hip fracture rates minimized differences between the countries. CONCLUSIONS: Despite increasing hip fracture rates in Hong Kong, those rates are still substantially lower than the rates in the United States. Identifying factors responsible for this variation may prove useful in the search for preventive strategies.

Aged↗