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Biomedical subjects

E J Atkinson

Publications and source records attributed to E J Atkinson.

At least 37 records · Page 2Linked to original sources

Association of a myeloperoxidase promoter polymorphism with multiple sclerosis.

Myeloperoxidase (MPO) generates hypochlorous acid and other reactive oxygen intermediates leading to tissue damage. MPO is expressed in macrophages-microglia in multiple sclerosis (MS) lesions. A G-->A substitution that abolishes an SP1 transcription factor consensus sequence in the promoter reduces gene expression. We studied the association of the genetic variant with MS. We did not find an association with gender, age at onset, susceptibility to, or the course and severity of MS in a population-based sample of 122 patients from Olmsted County.

Adult↗

Cross-sectional versus longitudinal evaluation of bone loss in men and women.

We evaluated age- and sex-specific differences in bone density at a variety of skeletal sites in a population-based sample of 348 men (age 22-90 years) and 351 women (age 21-93 years) by dual-energy X-ray absorptiometry. Several patterns of age-related bone loss were observed, but adjustments for height (or, where possible, calculation of bone mineral apparent density) dampened the apparent rate of bone loss from most skeletal sites as judged from cross-sectional measurements at baseline. Cross-sectional data also overestimated the rate of bone loss observed longitudinally over 4 years at many sites, particularly the hip and spine; conversely, in some forearm regions, cross-sectional rates of loss underestimated the bone loss seen prospectively. Longitudinal rates of bone loss were generally greater among individuals age 70 years or older compared with younger men and women, but some of the latter effect was due to a greater proportion of younger women on hormone replacement therapy, whose rate of bone loss was generally less. These observations highlight the limitations of cross-sectional data for defining the patterns of bone loss over life at different skeletal sites.

Absorptiometry, Photon↗

The epidemiology of ovarian cancer: a population-based study in Olmsted County, Minnesota, 1935-1991.

PURPOSE: To determine trends in incidence and survival between 1935 and 1991 and to evaluate risk factors for ovarian cancer among Olmsted County, Minnesota women. METHODS: All newly diagnosed cases of ovarian cancer among Olmsted County women in 1975-1991 were identified using the medical records linkage system of the Rochester Epidemiology Project. In order to assess trends, incidence rates in the subset of Rochester women were compared with Rochester rates for 1935-1974. Survival was evaluated by the Kaplan-Meier product-limit method. A case-control analysis of risk factors compared Olmsted County women with invasive epithelial ovarian cancer and an age-matched group of women from the community by logistic regression. RESULTS: Altogether, 129 Olmsted County women were newly diagnosed with ovarian cancer in 1975-1991. The age-adjusted (to 1970 United States whites) incidence rate was 22.5 per 100,000 person-years. Median survival from initial diagnosis was 3.7 years. Compared to an equal number of controls, the 103 women with invasive epithelial disease were more likely to be nulliparous (odds ratio [OR] 1.9; 95% CI 0.95-3.9) but less likely to have a history of thyroid disease (OR 0.4; 95% CI 0.2-0.8), hypertension (OR 0.4; 95% CI 0.1-0.9) or nonsteroidal estrogen use (OR 0.5; 95% CI 0.2-0.9). Prior hysterectomy (OR 0.5; 95% CI 0.2-0.9) and unilateral oophorectomy (OR 0.2; 95% CI 0.04-0.7) were also associated with reduced risk. CONCLUSION: The incidence of ovarian cancer in this community in 1975-1991 was little changed from rates 20 years earlier. There has been some improvement in survival from ovarian cancer in this population compared to 1935-1974, but still less than 50% survive for 5 years. Prior hysterectomy and unilateral oophorectomy appear protective for ovarian cancer.

Adult↗

Clinical utility of routine screening for abdominal aortic aneurysm during echocardiography.

BACKGROUND: The aim of this study was to determine the clinical utility of transthoracic echocardiography (TTE) as a screening method for the detection of abdominal aortic aneurysms (AAA). PATIENTS AND METHODS: Each patient who was referred to the echocardiography laboratory TTE was included into the study. After complete cardiac assessment the abdominal aorta was evaluated. Patients with a known, a clinically suspected, or a previously operated AAA were excluded. RESULTS: During the study period, 14,876 patients underwent TTE. 13,166 (88.5%) of the patients were 50 years and older. Of these 6953 (52.8%) were men and 6213 (47.2%) were women. A total of 108 (0.82%; 95% confidence interval (CI) 0.67-0.99) clinically unsuspected AAA of at least 3 cm in diameter (range 3 cm-6.8 cm) were detected. There were 93 (86.1%) men and 15 (13.9%) women with a mean age of 73.8 years (range 59-90). In 7 patients an AAA was suspected by TTE but not verified on subsequent abdominal ultrasound, as the diameter of the abdominal aorta was less than 3 cm. The prevalence of an AAA in patients 50 years and older was 1.34% (95% CI 1.08-1.64) for men and 0.24% (95% CI 0.14-0.40) for women. In patients less than 50 years old no aneurysm was detected. Seventeen patients who were found to have an AAA with a mean diameter of 4.4 cm (range 3-6 cm) underwent successful elective conventional AAA repair after a mean interval of 13.9 months (range 0.2-49 months) following the initial diagnosis. CONCLUSIONS: TTE performed in a highly selected cardiac patient group in a tertiary referral center is not a useful tool to screen for clinically unsuspected abdominal aortic aneurysms due to the low prevalence. The detection of an aneurysm should be confirmed by conventional abdominal ultrasound.

Aged↗

Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.

Whether the higher serum leptin levels in women are due to gender differences in fat mass or to other factors such as sex steroids remains unclear. In addition to sex steroids, serum insulin levels also appear to be related to leptin levels, although whether this effect is independent of the effects of body composition is unclear. The purpose of this study was to identify the major determinants of circulating serum leptin levels. We studied a large, population-based cohort of 345 men (23 to 90 years), 137 premenopausal women (21 to 54 years), and 212 postmenopausal women (34 to 94 years), including 47 women on hormone replacement therapy (HRT). Serum leptin levels were related to body composition as assessed by dual-energy x-ray absorptiometry (DEXA) and to circulating sex steroid and insulin levels. Serum leptin levels remained significantly higher in women versus men even after adjustment for fat mass, and leptin levels were significantly correlated with fat mass independently of age. By univariate analyses, logarithmically transformed serum leptin levels correlated positively with bioavailable estrogen ([E] estradiol plus estrone) in postmenopausal women not on HRT, and negatively with total and bioavailable testosterone (T) levels in men. Serum insulin levels were directly related to leptin levels regardless of gender and age. By multivariate analyses, fat mass, lean mass, and insulin levels were the strongest predictors of leptin levels in all groups. In addition, bioavailable E entered the model in the postmenopausal women not on HRT. These studies indicate that the fat mass, lean mass, and insulin level are the major determinants of the serum leptin level in adults. Moreover, after adjusting for these variables, bioavailable E also explains a significant proportion of the variance in leptin levels among postmenopausal women not on HRT.

Adult↗

Verifying the stroke-free phenotype by structured telephone interview.

BACKGROUND AND PURPOSE: Case-control, cohort, and twin studies support a genetic contribution to ischemic stroke risk. Sibling pair linkage methods require identification of concordant or discordant siblings or both. We designed and tested a structured telephone interview to verify the stroke-free phenotype. METHODS: A coordinator unaware of medical record data used an 8-item questionnaire to conduct a structured telephone interview of 70 outpatients aged >60 years. The questionnaire inquired about the sudden onset of deficits in strength, sensation, vision, and language. A subject was defined as stroke free by interview if responses to all items on the questionnaire were negative. Results of the telephone interview were compared with data obtained from a systematic medical record review (benchmark). RESULTS: Interview time was 5 minutes or less for all subjects. All subjects who began the interview completed it. Records were reviewed in all subjects. Medical record review detected ischemic stroke or transient ischemic attack (TIA), or both, in 5 patients (7%). There were no significant differences in sex distribution or risk factor rates in patients who were designated stroke free or not stroke free by interview. Having 1 or more positive items on the questionnaire was significantly associated with finding stroke (P<0.001), TIA (P<0.001), or either stroke or TIA (P<0.001), on medical record review. The telephone interview had a sensitivity of 1.0 (95% CI 0.48 to 1.0), specificity of 0.86 (95% CI 0.75 to 0.93), positive predictive value of 0.36 (95% CI 0.13 to 0.65), and negative predictive value of 1.0 (95% CI 0.94 to 1.0). CONCLUSIONS: Our instrument can identify the stroke-free individual with a high degree of confidence in a very efficient manner. It may be particularly suited for centralized verification of stroke discordancy in multicentered sib-pair genetic studies.

Aged↗

Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men.

Young adult males who cannot produce or respond to estrogen (E) are osteopenic, suggesting that E may regulate bone turnover in men, as well as in women. Both bioavailable E and testosterone (T) decrease substantially in aging men, but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss. Thus, we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men (mean age 68 years), studying them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E, withdrawing only T, or only E, or continuing both. Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones. By two-factor ANOVA, E played the major role in preventing the increase in the bone resorption markers, whereas T had no significant effect. By contrast, serum osteocalcin, a bone formation marker, decreased in the absence of both hormones, and both E and T maintained osteocalcin levels. We conclude that in aging men, E is the dominant sex steroid regulating bone resorption, whereas both E and T are important in maintaining bone formation.

Aged↗

Determinants of bone loss from the femoral neck in women of different ages.

An age-stratified sample of 304 women from Rochester, Minnesota, aged 30-94 years (median 60 years) at baseline underwent measurement of femoral neck bone mineral density (BMD) over a follow-up period extending to 16 years. The average rate of change in femoral neck BMD was -1.0% per year (range -10.0% to +13.4%) and did not vary significantly with age. Because there was no marked increase in the rate of loss around the time of menopause, nor convincing evidence of there being a subset of fast losers, there was fairly good tracking of individual values over time; the correlation of baseline with femoral neck BMD values 16 years later was 0.83. Although a large number of potential determinants was assessed, the only consistent predictor of femoral neck bone loss in women of different ages was baseline femoral neck BMD (r = -0.15; p = 0.023). Otherwise, different sets of risk factors were identified for premenopausal women, women within 20 years of menopause, and women 20 years or more postmenopausal, but the predictive power of these different multivariate models was modest. Nonetheless, these data indicate that femoral neck BMD is quite predictable for extended periods of time. This is reassuring with respect to the use of statistical models that incorporate such data to estimate future fracture risk.

Absorptiometry, Photon↗

Fracture risk among patients with Paget's disease: a population-based cohort study.

Localized disruption of bone architecture leads to an increased risk of pathological fractures in patients with Paget's disease, but the impact of the disease on overall fracture risk is unknown. We addressed this issue among 236 Olmsted County, Minnesota residents (107 women and 129 men) first diagnosed with Paget's disease from 1950 through 1994. These subjects (mean +/- SD age at diagnosis, 69.6+/-12.2 years) were followed subsequently for 2798 person-years. During this period of observation, 33 pathological fractures were attributed to Paget's disease (1 skull, 11 vertebra, 1 shaft/distal humerus, 1 pelvis, 6 proximal femur, 2 shaft/distal femur, and 11 tibia/fibula). Excluding the fractures through pagetic bone, there was no increase in overall fracture risk in this cohort (standardized incidence ratio [SIR], 1.2; 95% CI, 0.9-1.4). However, there was a statistically significant increase in the risk of subsequent vertebra (SIR, 3.0; 95% CI, 2.2-4.1) and rib fractures (SIR, 1.7; 95% CI, 1.1-2.4) but not fractures of the proximal femur (SIR, 0.6; 95% CI, 0.3-1.1) or distal forearm (SIR, 1.4; 95% CI, 0.7-2.5). Thus, unselected patients with Paget's disease in the community, who mostly have mild disease, have a significantly increased risk of vertebral fractures, although this may relate partly to increased surveillance. Additional work is needed to clarify the relationship between Paget's disease and vertebral fractures and to identify individuals at increased risk for more aggressive therapy.

Adult↗

Hip fractures among infertile women.

A retrospective cohort study was conducted in a population-based inception cohort of 1,157 Olmsted County, Minnesota, women with infertility (failure to conceive after 1 year despite intercourse without contraception) that was first diagnosed at the Mayo Clinic (Rochester, Minnesota) between 1935 and 1964. In this relatively young cohort, 31 hip fractures were observed during 35,849 person-years of follow-up; 36.5 had been expected (standardized incidence ratio = 0.85, 95% confidence interval 0.58-1.20). Standardized incidence ratios did not differ by type or cause of infertility. The data suggested that women with consistently irregular menses may have a greater risk of hip fracture. This finding should be confirmed by additional studies with longer follow-up periods and with assessment of other fracture outcomes.

Adult↗

Contribution of weather to the seasonality of distal forearm fractures: a population-based study in Rochester, Minnesota.

Distal forearm fractures due to falls were more frequent in the winter (p < 0.0001) among Rochester men and women 35 years of age or older in 1952-89. The winter excess was partially explained by a greater relative risk of distal forearm fractures on days with freezing rain (1.65; 95% CI 1.28-2.13) or snow (1.42; 95% CI 1.17-1.74) among women under 65 years of age and on days with freezing rain (1.63; 95% CI 1.23-2.17) among older women. The greater seasonality of forearm compared with hip fractures is explained by the fact that more of them occur out-of-doors. However, residual effects of season after adjusting for daily weather conditions suggest that other factors may play a role.

Accidental Falls↗

Changes in bone density after exposure to oral anticoagulants: a meta-analysis.

Oral anticoagulants are putative risk factors for osteoporosis, but observational cross-sectional studies describing their effects on bone mineral density have reported conflicting results, prospective studies are not available, and randomized trials are not feasible. To determine the association between exposure to oral anticoagulants and changes in bone density, we systematically reviewed nine original cross-sectional studies on the effect of long-term exposure to any oral anticoagulant on bone density in adults. The effect size was assessed by standardized mean difference (SMD, exposed minus unexposed) and pooled by skeletal site; results are reported in standard deviation units. Bone density was significantly decreased among exposed subjects in the ultradistal radius (SMD, -0.39; 95% CI, -0.67 to -0.10) but not in the distal radius (SMD, -0.47; 95% CI, -0.97 to 0.04), lumbar spine (SMD, -0.27; 95% CI, -0.59 to 0.05), femoral neck (SMD, 0.03; 95% CI, -0.22 to 0.29) or femoral trochanter (SMD, -0.18; 95% CI, -0.48 to 0.11). The evidence should be considered with caution, but it is consistent with a negative association of oral anticoagulants with bone density in the ultradistal radius, although not in the spine or hip. This suggests that long-term oral anticoagulation might be associated with no more than a modest increase in osteoporotic fracture risk, but this should be verified in future longitudinal studies.

Administration, Oral↗

Vertebral fractures predict subsequent fractures.

This population-based study documents an increase in most types of fractures following the occurrence of a clinically recognized vertebral fracture among 820 Rochester, Minnesota, residents. During 4349 person-years of follow-up, 896 new fractures were observed. Relative to incidence rates in the community, there was a 2.8-fold increase in the risk of any fracture, which was greater in men (standardized incidence ratio (SIR), 4.2; 95% CI, 3.2-5.3) than women (SIR, 2.7; 95% CI, 2.4-3.0). The estimated cumulative incidence of any fracture after 10 years was 70%. The greatest increase in risk was for subsequent fractures of the axial skeleton, in particular a 12.6-fold increase (95% CI, 11-14) in additional vertebral fractures. There was a lesser increase in most limb fractures, including a 2.3-fold increase (95% CI, 1.8-2.9) in hip fractures and a 1.6-fold increase (95% CI, 1.01-2.4) in distal forearm fractures. There was a slightly greater association with distal forearm fractures among those whose first vertebral fracture occurred before age 70 years but a similar relationship with hip fractures, including cervical and intertrochanteric hip fractures separately, regardless of age at the initial vertebral fracture. There was also an equivalent increase in subsequent fracture risk whether the initial vertebral fracture was attributed to severe or moderate trauma. These data show that vertebral fractures represent an important risk factor for fractures in general, not just those of the spine and hip.

Adult↗

Secondary osteoporosis and the risk of vertebral deformities in women.

Among an age-stratified sample of 942 Rochester, MN women, the overall prevalence of any vertebral deformity, as assessed by radiographic morphometry, was 21.3 per 100. The prevalence increased with age and, after adjusting for age, vertebral deformities were independently associated with height, weight, a history of distal forearm or hip fractures, and anticoagulant use. Altogether, 73% of the women with a vertebral deformity and 66% of controls had one or more of the conditions that have been linked with secondary osteoporosis, which in aggregate were associated with an age-adjusted 1.2-fold (95% CI 0.8-1.7) increase in risk that was not statistically significant. The prevalence of severe vertebral deformities was 11.7 per 100 women and the prevalence of very severe deformities was 5.7 per 100. There was a stronger relationship of age and most other risk factors with severe vertebral deformities than with isolated mild deformities, suggesting that a subset of mild deformities may not represent actual vertebral fractures. The metabolic disorders linked with secondary osteoporosis were associated with little increase in the risk of severe vertebral deformities, taken together, or of mild deformities. However, in aggregate these conditions were associated with a 2.3-fold increase (95% 1.1-4.8) in very severe vertebral deformities, which points to a role for rapid cancellous bone loss among women with the worst spinal osteoporosis.

Case-Control Studies↗

Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups.

An estimate of total body muscle mass with dual-energy X-ray absorptiometry (DXA; appendicular muscle mass divided by 0.75) was compared with 24-h urinary creatinine excretion in 59 healthy men and women [20-30 yr (younger), 45-59 yr (middle age), and 60-79 yr (older)] who stayed in a clinical research center for 5 days. Total body water ((2)H(2)O dilution), fat (underwater weighing), bone mineral (DXA), and total body protein mass (based on a 4-compartment model) were also measured. Muscle mass estimates by DXA and creatinine were highly correlated (r = 0.80). However, stepwise multiple regression indicated that a significant amount of additional between-subject variability in DXA-based muscle mass estimates could be explained by total body water. Creatinine excretion, knee extensor strength, and total body protein mass all decreased with age, suggesting a decline in muscle cell mass with aging. However, DXA-based muscle mass and measures of nonfat body mass (i.e., lean body mass by (2)H(2)O and fat-free body mass by underwater weighing) did not change with age. These results indicate that DXA and urinary creatinine excretion give different results regarding the decline in total body muscle mass with aging. The factor(s) responsible for the apparent underestimate of age-related sarcopenia by DXA remain to be fully defined, but changes in body water may be an important contributor.

Absorptiometry, Photon↗

The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms.

OBJECTIVE: To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. BACKGROUND: Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. METHODS: The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. RESULTS: The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (+/-SD) overall COMPASS score was 9.8 (+/-9) in controls, 25.9 (+/-17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (+/-24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. CONCLUSIONS: We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.

Adult↗

Use of intraoperative duplex ultrasonography and routine patch angioplasty in patients undergoing carotid endarterectomy.

OBJECTIVE: To determine the value of routine patch angioplasty and intraoperative duplex ultrasonography (US) during carotid endarterectomy (CEA) for high-grade internal carotid artery stenosis. PATIENTS AND METHODS: The charts of 102 consecutive patients who underwent CEA with routine patching and intraoperative duplex US for treatment of high-grade carotid stenosis between June 1991 and January 1997 were reviewed retrospectively. Recurrent stenosis was defined as a narrowing in the common or internal carotid artery of more than 40%. RESULTS: Of 102 patients, 65 (63.7%) were men, and 37 (36.3%) were women (mean age, 72.4 years). Thirteen patients (12.7%) had bilateral CEAs. Intraoperative duplex US revealed abnormalities during 29 (25.2%) of 115 CEAs; 14 abnormalities (12.2%) were major and underwent immediate revision. No perioperative neurologic events or deaths occurred. Mean length of follow-up was 21.3 months (range, 1.3-72.6 months). Late neurologic events occurred in 2 patients, and 5 patients died during follow-up. All neurologic events and deaths were unrelated to the patients' carotid surgery. Twelve patients (11.8%) developed moderate restenosis (40%-69%). In 4 of these patients restenosis resolved during further follow-up. No patient developed severe recurrent carotid stenosis. CONCLUSION: Morbidity and mortality following CEA with routine patch angioplasty and intraoperative duplex US appear to be low. Routine intraoperative duplex US detects correctable technical problems that subsequently lead to a low incidence of symptomatic stenosis. The low incidence of recurrent stenosis suggests that routine postoperative follow-up may not be necessary or cost-effective unless the patient has symptoms or a contralateral stenosis.

Aged↗

Assessment of dysequilibrium after acoustic neuroma removal.

OBJECTIVE: Published data evaluating the rate of dysequilibrium after acoustic neuroma removal are inconsistent. The purpose of this investigation was to determine the incidence and severity of dysequilibrium and quality of life in a group of patients after acoustic neuroma surgery. STUDY DESIGN: The study design was a retrospective chart review and survey that included demographic and medical history questions, the Dizziness Handicap Inventory (DHI), the UCLA Dizziness Questionnaire (UCLA-DQ), and the Health Status Questionnaire (HSQ). SETTING: The study was conducted in a multispecialty tertiary care clinic. PATIENTS: Two hundred thirty-seven subjects who underwent initial surgical removal of an acoustic neuroma between January 1990 and June 1997 were studied. MAIN OUTCOME MEASURES: Correlation of dysequilibrium with age, gender, and tumor size was measured. Survey analysis including DHI, UCLA-DQ, and HSQ scores. RESULTS: Sixty-five percent of patients reported persistent dysequilibrium after surgery. A majority of those with dysequilibrium had DHI, UCLA-DQ, and HSQ scores that suggested minimal impact on the quality of life. The HSQ scores were statistically significantly poorer for the patients with dysequilibrium than for those without dysequilibrium. CONCLUSIONS: Sixty-five percent of patients reported dysequilibrium after acoustic neuroma removal. The quality-of-life impact was mild.

Cranial Nerve Neoplasms↗