PubMed Health⌕ Search

Biomedical subjects

K Krueger

Publications and source records attributed to K Krueger.

At least 19 recordsLinked to original sources

Cognitive function in postmenopausal women treated with raloxifene.

BACKGROUND: In postmenopausal women, estrogen may have a beneficial effect on cognition or reduce the risk of decline in cognitive function. Whether raloxifene, a selective estrogen-receptor modulator, might have similar actions is not known. METHODS: As part of the Multiple Outcomes of Raloxifene Evaluation trial, we studied 7478 postmenopausal women with osteoporosis (mean age, 66 years), who were enrolled at 178 sites in 25 countries. The women were randomly assigned to receive raloxifene (60 mg or 120 mg) or placebo daily for three years. We compared the mean scores of the groups on six tests of cognitive function, which were administered at base line and at six months and one, two, and three years. Women were classified as having a decline in cognitive function if the change in their scores at three years was in the worst 10 percent. RESULTS: The mean cognitive scores in the three groups of women were similar at base line. The scores improved slightly in all three groups during the three-year study period, with no significant differences among the groups. The risk of decline in the cognitive function, as measured by four of the six tests, did not differ significantly between the two raloxifene groups combined and the placebo group, but there was a trend toward less decline in the combined raloxifene group on the two tests of verbal memory (relative risk, 0.77) and attention, (relative risk, 0.87). Newly reported or worsening hot flashes did not negatively influence test scores or the effect of treatment on test performance. CONCLUSIONS: Raloxifene treatment for three years does not affect overall cognitive scores in postmenopausal women with osteoporosis.

Aged↗

MRI and CT of adenomatous tumours of the middle ear.

We report three adenomatous middle-ear tumours, an adenoma, an adenocarcinoma and a semimalignant adenomatous tumour, with special attention to CT and MRI findings. In all cases we found small intratympanic masses in which the ossicles were embedded. All showed contrast enhancement and similar signal intensity as brain tissue on T1- and T2-weighted images. The biological nature of the tumours was not reflected by the imaging or operative findings.

Adenocarcinoma↗

Observation of a hybrid spin resonance

A new type of spin depolarization resonance has been observed at the Brookhaven Alternating Gradient Synchrotron (AGS). This spin resonance is identified as a strong closed-orbit sideband around the dominant intrinsic spin resonance. The strength of the resonance was proportional to the 9th harmonic component of the horizontal closed orbit and proportional to the vertical betatron oscillation amplitude. This "hybrid" spin resonance cannot be overcome by the partial snake at the AGS, but it can be corrected by the harmonic orbit correctors.

Journal Article↗

Late resolution of diffusion-weighted MRI changes in a patient with prolonged reversible ischemic neurological deficit after thrombolytic therapy.

BACKGROUND: Reduced apparent diffusion coefficients (ADCs) correlate with cerebral ischemia. The combination of ADC with techniques to measure cerebral perfusion may help to assess the effect of treatment. CASE DESCRIPTION: The authors describe a patient who experienced an acute stroke with hemianopia, consequently treated with intravenous recombinant tissue plasminogen activator. Positron emission tomographic imaging and MRI, including diffusion-weighted MRI, were performed during and shortly after treatment with recombinant tissue plasminogen activator and 34 to 35 hours later. Cerebral perfusion of the left occipital region was reduced to 74%. Diffusion-weighted MRI detected a territory of restricted water movement in the corresponding area. Further magnetic resonance sequences did not show any pathologies. In follow-up, positron emission tomography demonstrated reperfusion. The volume of diffusion and ADC abnormalities detected by MRI decreased markedly. A few hours later, the patient recovered completely. A third MRI examination 10 days later showed normal findings. CONCLUSIONS: In a patient with prolonged reversible ischemic neurological deficit, resolution of early diffusion changes corresponded to cerebral reperfusion and to the recovery of clinical symptoms.

Acute Disease↗

Growth hormone secretory dynamics over the menstrual cycle.

Whether GH secretion in women varies over the menstrual cycle is uncertain. Previous investigations have led to conflicting conclusions; some studies suggested that there is an estrogen mediated rise in GH during the periovulatory (PO) and luteal (L) phases whereas others indicated no change in GH axis over the cycle. Differences in conclusions could relate to heterogeneity of the study populations, GH sampling paradigms or sensitivity of the GH assays used. In order to investigate whether GH secretion varied over the cycle, 24-h GH profiles using every 10-min sampling were obtained in 6 ovulatory women during the early follicular (EF), PO and L phases of the cycle. The TSH response to TRH, GH response to GRH and fasting plasma IGF-I were measured on each occasion. There was a trend toward higher integrated GH concentration (IGHC) during the PO phase, although this difference was not statistically significant (3284+/-721 vs 4542+/-872 vs 4071+/-699 microg/min/L; EF vs PO vs L; p=0.09). Similarly, deconvolution estimated GH secretion did not vary over the cycle (p=0.56). There were no differences in GH pulse amplitude or frequency. There were no correlations between IGHC and sex steroids. Serum IGF-I was constant over the cycle (272+/-38 vs 277+/-31 vs 265+/-38 microg/L; p=0.89). The TSH response to TRH and GH response to GRH did not vary over the cycle. We concluded that the effect of changes in the ovarian steroid milieu on the GH axis during spontaneous menstrual cycles is minimal.

Adult↗

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Adult↗

Development of a novel, N-terminal-proBNP (NT-proBNP) assay with a low detection limit.

A novel, highly sensitive and specific N-Terminal-proBNP (NT-proBNP) assay based on a sandwich format has been developed. The assay time is below 2 hours and no extraction process is needed. The calibration curve covers a NT-proBNP concentration range from 0 pmol/L up to 600 pmol/L. The analytical detection limit of the assay was estimated to be 2.7 pmol/L (3 SD). The intra-assay coefficient of variation is 5.7% (at 50 pmol/L) and 6.1% (at 250 pmol/L), while the inter-assay CVs are 15.8% (15 pmol/L) and 8.2% (250 pmol/L). There is no significant interference by bilirubin (up to 900 mumol/L), haemoglobin (up to 10 g/L), rheumatoid factors (up to 975 IU/mL), triglycerides (up to 20.5 mmol/L), biotin (up to 50 micrograms/L), digoxin (up to 100 micrograms/L) and digitoxin (up to 200 micrograms/L). The analyte NT-proBNP is fully stable in whole blood over 3 days and in EDTA-plasma over 24 hours. This good stability of NT-proBNP compared to other less stable natriuretic peptides is a significant advantage and a main prerequisite for a routine diagnostic marker. Preliminary results of using this new assay in clinical studies for diagnosing and monitoring left ventricular dysfunction demonstrate that there is a significant gain in diagnostic validity.

Antibodies, Monoclonal↗

Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.

Adult↗

Circadian rest-activity disturbances in seasonal affective disorder.

BACKGROUND: Previous studies hypothesized that seasonal affective disorder (SAD) was caused by a circadian rhythm abnormality. The purpose of this study was to ascertain whether rest-activity rhythms were phase delayed, diminished in amplitude, or more poorly entrained to the 24-hour day. METHOD: Twenty healthy adult controls and 25 outpatients meeting Rosenthal-National Institute of Mental Health criteria for SAD and DSM-III-R criteria for major or bipolar depression with seasonal pattern had their levels of activity recorded for 72 hours (weekdays) using wrist-worn actigraphs. RESULTS: Subjects with SAD had activity levels that were 11% lower than controls (P = .03), and their levels of activity were most attenuated during the first 2 hours after arising (P = .004). The relative amplitude of the circadian rhythm did not differ between groups. Patients with SAD were phase delayed by 50 minutes for the entire period (P = .02). Analysis of each individual day indicated that patients were delayed by up to 70 minutes (P = .007). Interdaily stability, an index of coupling between the rhythm and its zeitigeber was reduced in SAD (P = .01). Compared with controls, patients with SAD had best-fit circadian periods that were 92% more deviated from 24 hours (P = .007) and daily acrophase (time of the peak of the fit circadian rhythm) times that were 110% more variable between days (P < .001). CONCLUSIONS: Patients with SAD have circadian rest-activity rhythms that are significantly phase delayed and more poorly entrained to the 24-hour day.

Activity Cycles↗

Temporal processing in cat primary auditory cortex.

In this short review, we discuss several aspects of how temporal coding is reflected in the response of primary auditory cortical neurons. We attempt to establish a link between several different temporal response properties including onset latency, response strength to repetitive stimuli, and the recovery of a response from suppression by a preceding signal. The results suggest a relationship between temporal effects that are expressed at quite different time scales. The results are discussed in relation to spatial representational properties and to coding in other sensory cortices.

Animals↗

Instrumental and perceptual evidence for tracheoesophageal speech.

With 8 men, two methods of alaryngeal speech production, tracheoe-sophageal and electrolaryngeal, were compared on perceptual and acoustic measures of speech intelligibility. Measures consistently identified the tracheoesophageal speech as superior to electrolaryngeal speech.

Aged↗

Dampening of adrenocortical responses during infancy: normative changes and individual differences.

Changes in cortisol and behavioral responses were examined longitudinally in 83 infants (39 girls, 44 boys) tested at their well-baby exams with inoculations at 2, 4, 6, and 15 months (72 infants completed all testing). Another sample of 2-, 4-, and 6-month-olds (n = 18 per age) received mock exams without inoculations to determine early developmental changes to the exam procedures. Behavioral distress was coded every 30 sec during the exam, a 5-min inoculation period, and a 20-min recovery period. Salivary cortisol was obtained upon arrival at the clinic and 25 min after the beginning of the inoculation period. To the exam-inoculation procedures, cortisol responses were high at 2 months, decreased significantly between 2 and 4 months, remained comparable between 4 and 6 months, and then declined again between 6 and 15 months. Between 6 and 15 months there was also a decrease in pretest cortisol. By 15 months, significant increases in cortisol from pre- to posttest were no longer observed for most infants. To the exam-only procedures, cortisol responses decreased between 2 and 4 months, and by 4 months most infants failed to show pre- to posttest increases in cortisol. Behavioral distress decreased between 2 and 6 months, but increased again at 15 months. While crying and cortisol were modestly correlated during the 2- to 6-month exam-inoculation procedures, at 15 months no significant correlations were obtained. Behavioral and hormonal reactions thus followed different ontogenetic paths and may provide different information about infant functioning. There was some evidence that the emergence of the circadian rhythm in cortisol might be related to the early decrease in cortisol response.

Adrenal Cortex↗

The costs and effects of a nutritional education program following work-site cholesterol screening.

OBJECTIVES: The purpose of this study was to assess the costs and impact of a nutrition education program following a cholesterol screening. METHODS: Forty work-sites were randomly assigned to one of two educational interventions: a "usual" intervention of 5 minutes of counseling, or a "special" intervention of 2 hours of behaviorally based education on dietary changes to lower serum cholesterol. Costs were monitored, and cholesterol levels were retested 6 and 12 months later. RESULTS: The total per-person cost for screening and the educational intervention was about $50. Cholesterol levels differed little between the two intervention groups 6 months after screening, but after 12 months those in the special intervention worksites showed a 6.5% drop in cholesterol, whereas those at the usual intervention worksites showed a drop of only 3.0%. Hence a 3.5% cholesterol reduction was attributable to the special intervention. CONCLUSIONS: A behaviorally based nutrition education program following cholesterol screening can have a meaningful impact on long-term cholesterol levels at a low cost. Nutrition education in work-sites may therefore be a useful way to lower the risk of heart disease in communities.

Adult↗

Bopindolol for the treatment of chronic stable angina pectoris--a clinical study of the relationship between dose and effect.

Following a 4-week placebo period, 19 patients (12 male, average age 62.3 years) with chronic stable angina pectoris and a positive exercise test were treated with the beta-adrenoceptor antagonists bopindolol at increasing doses of 0.5, 1 and 2 mg, each being given once daily for 4 weeks. For the final 4 weeks of the study, active treatment was replaced by placebo. Maximum tolerated exercise (bicycle ergometry, performed 24 h after drug administration) increased dose-dependently from 519 +/- 59 s (baseline) to 758 +/- 95 s with 2 mg (p less than 0.001) and fell again to 508 +/- 48 s (placebo). The frequency of anginal attacks also fell dose-dependently from an average of 5.4 per week (baseline) to 0.5 with 2 mg (p less than 0.001) and rose again to 5.1 per week when active treatment was stopped.

Adrenergic beta-Antagonists↗