Search PubMed⌕ Search

Biomedical subjects

M R Klauber

Publications and source records attributed to M R Klauber.

At least 19 recordsLinked to original sources
PubMed1997

A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

BACKGROUND: There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer's disease. METHODS: We conducted a double-blind, placebo-controlled, randomized, multicenter trial in patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia (defined as a Clinical Dementia Rating of 3). RESULTS: Despite random assignment, the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups, and this variable was highly predictive of the primary outcome (P<0.001). In the unadjusted analyses, there was no statistically significant difference in the outcomes among the four groups. In analyses that included the base-line score on the Mini-Mental State Examination as a covariate, there were significant delays in the time to the primary outcome for the patients treated with selegiline (median time, 655 days; P=0.012), alpha-tocopherol (670 days, P=0.001) or combination therapy (585 days, P=0.049), as compared with the placebo group (440 days). CONCLUSIONS: In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.

Activities of Daily Living↗
PubMed1997

Use of wrist activity for monitoring sleep/wake in demented nursing-home patients.

Actigraphy is applicable for studying sleep in populations who are unable to tolerate traditional sleep-recording techniques, such as nursing-home patients who are infirm and demented. This study examined whether actigraphy can accurately reflect sleep/wake activity in this population by testing the reliability of a wrist-activity monitor, the Actillume, against traditional sleep measurements and against observations of nursing-home patients. Data from the Actillume are presented as two variables, the sum (total of all activity movements within the prescribed epoch) and the maximum activity (the largest or maximum movement recorded during the prescribed epoch), and by electroencephalogram (EEG). One difficulty in making comparisons was that the EEG records showed diffuse slowing, making it extremely difficult to score sleep/wake activity and making it difficult to use the EEG as a "gold standard". Nevertheless, the correlation for total sleep time from EEG and Actillume was r = 0.91 (p < 0.001) for sum activity and r = 0.81 for maximum activity (p < 0.005). Correlations for percent sleep were r = 0.78 (p < 0.01) for maximum activity and r = 0.61 for sum activity. The comparison of sleep/wake determined by the Actillume vs. observations resulted in a sensitivity of 87% and specificity of 90%. We conclude that the Actillume is the most feasible technique for studying sleep and wake activity in demented nursing-home patients.

Aged↗
PubMed1997

Prevalence of sleep-disordered breathing in ages 40-64 years: a population-based survey.

Previous research has offered widely varying prevalence estimates for sleep apnea in the population, leaving uncertain which breathing patterns are abnormal. To explore the distribution of sleep apnea in the population and its co-morbidities, random telephone dialing was used between 1990 and 1994 to recruit subjects for a prevalence survey of sleep-disordered breathing in San Diego adults. Events from which blood oxygen desaturations > or = 4% resulted were monitored with home recording instruments, usually for three consecutive nights. Among 190 women ages 40-64 years, a median of 4.3 desaturation events per hour of sleep were observed. A higher median of 6.7 events per hour was observed among 165 men. Frequencies were much higher among members of minority groups, leading to a standard estimate that 16.3% of U.S. Hispanics and racial minorities have > or = 20 events/hour as compared to 4.9% of non-Hispanic Whites ages 40-64. Obesity indicated by body-mass index was the most important demographic predictor of sleep-disordered breathing, followed by age, male gender, and ethnicity. Quality of well-being was not significantly impaired in subjects with more respiratory events; however, there was some increase in blood pressure and wake-within-sleep associated with sleep-disordered breathing. This survey indicates that sleep-disordered breathing is more common, especially among minorities, than had been previously believed, but less co-morbidity may be associated.

Adult↗
PubMed1997

Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects.

The aim of this study was to replicate and extend previous work in which the authors observed lower, shorter, and advanced nocturnal melatonin secretion patterns in premenstrually depressed patients compared to those in healthy control women. The authors also sought to test the hypothesis that the therapeutic effect of bright light in patients was associated with corrective effects on the phase, duration, and amplitude of melatonin rhythms. In 21 subjects with premenstrual dysphoric disorder (PMDD) and 11 normal control (NC) subjects, the authors measured the circadian profile of melatonin during follicular and luteal menstrual cycle phases and after 1 week of light therapy administered daily, in a randomized crossover design. During three separate luteal phases, the treatments were either (1) bright (> 2,500 lux) white morning (AM; 06:30 to 08:30 h), (2) bright white evening (PM; 19:00 to 21:00 h), or (3) dim (< 10 lux) red evening light (RED). In PMDD subjects, during the luteal phase compared to the follicular menstrual cycle phase, melatonin onset time was delayed, duration was compressed, and area under the curve, amplitude, and mean levels were decreased. In NC subjects, melatonin rhythms did not change significantly during the menstrual cycle. After AM light in PMDD subjects, onset and offset times were advanced and both duration and midpoint concentration were decreased as compared to RED light. After PM light in PMDD subjects, onset and offset times were delayed, midpoint concentration was increased, and duration was decreased as compared to RED light. By contrast, after light therapy in NC subjects, duration did not change; onset, offset, and midpoint concentration changed as they did in PMDD subjects. When the magnitude of advance and delay phase shifts in onset versus offset time with AM, PM, or RED light were compared, the authors found that in PMDD subjects light shifted offset time more than onset time and that AM light had a greater effect on shifting melatonin offset time (measured the following night in RED light), whereas PM light had a greater effect in shifting melatonin onset time. These findings replicate the authors' previous observation that nocturnal melatonin concentrations are decreased in women with PMDD and suggest specific effects of light therapy on melatonin circadian rhythms that are associated with mood changes in patient versus control groups. The differential changes in onset and offset times during the menstrual cycle, and in response to AM and PM bright light compared with RED light, support a two-oscillator (complex) model of melatonin regulation in humans.

Adult↗
PubMed1997

Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients.

We measured 24-hour circadian-rhythm patterns of activity and sleep/wake activity in a group of nursing-home patients (58 women and 19 men with a mean age of 85.7 years). Severely demented patients were contrasted with a composite group of moderate y, mild, or not-demented patients. Sleep/wake activity and light exposure were recorded with the Actillume recorder. Cosinor analyses were computed to determine the mesor, amplitude, acrophase, and circadian quotient of the activity rhythms. The diagnosis of dementia was based on the Mini Mental Examination and on examination of medical records. Sleep was extremely fragmented in both groups of nursing-home patients. Severely demented patients slept more both at night and during the day, but there were no significant differences in the number of awakenings during the night or in the number of naps during the day when compared to the composite group of moderate, mild, or no-dementia patients. The severely demented group had lower activity mesor, more blunted amplitude, and were more phase delayed (i.e. had later acrophases) than the other group. In addition, the severely demented patients spent less time exposed to bright light. These results confirm that circadian rhythms in nursing-home patients are disturbed with more disturbance in the severely demented. Much of the disturbance may be related not just to age but to mental status.

Aged↗
PubMed1996

Morbidity, mortality and sleep-disordered breathing in community dwelling elderly.

A population-based probability sample of elderly individuals (n = 426), who were originally studied between 1981 and 1986 (mean age at initial study was 72.5 years), were followed for mortality. Those with > or = 30 respiratory disturbances per hour of sleep had significantly shorter survival (p = 0.0034), but the respiratory disturbance index (RDI) was not an independent predictor of death. When Cox proportional hazards analysis was done, only age (the strongest predictor), cardiovascular disease and pulmonary disease were independent predictors of death. It may be that factors that are secondary to or associated with sleep-disordered breathing (SDB), such as cardiovascular or pulmonary disease, predispose these elderly to death.

Age Factors↗
PubMed1996

Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's Disease Cooperative Study.

This report describes the rationale and design of a clinical trial using selegiline (10 mg/day) and alpha-tocopherol (2,000 IU/day) to slow the progression of dementia in Alzheimer disease (AD). This study was developed by the Alzheimer's Disease Cooperative Study (ADCS), a consortium of clinical research centers actively involved in AD research. The major goal of the consortium is to design and conduct clinical investigations leading to the development of treatments for AD. This study uses a randomized double-blind, placebo-controlled, 2 x 2 factorial, parallel group design to test two drugs for the treatment of AD. The primary outcome of the study is the time to reach any one of the following four endpoints: death, institutionalization, loss of two of three basic activities of daily living, and progression of Clinical Dementia Rating (CDR) stage from 2 to 3. Patients with moderately severe disease (CDR = 2) were enrolled and evaluated 10 times over a period of 2 years to determine if these agents reduce the time to reach any endpoint. A database from the Consortium to Establish a Registry for Alzheimer's Disease indicated adequate power analyses to observe a treatment effect on this clinically meaningful outcome measure. Recruitment and baseline characteristics of the population are provided. The rationale for the choice of a factorial design, the use of a novel, clinically meaningful endpoint, and the selection of a cohort of patients with AD of moderate severity are discussed.

Aged↗
PubMed1995

Clinical validity of the Mattis Dementia Rating Scale in detecting Dementia of the Alzheimer type. A double cross-validation and application to a community-dwelling sample.

OBJECTIVE: To assess the clinical validity of the Dementia Rating Scale (DRS) in detecting patients with dementia of the Alzheimer type (DAT). BACKGROUND: The DRS is widely used to evaluate cognitive functioning in older adults. Adequate normative data are unavailable; studies addressing the clinical validity of the DRS are limited by small sample sizes. DESIGN AND METHODS: Administered the DRS to 254 outpatients with DAT and 105 healthy elderly subjects. Performed (1) multiple regressions of demographic factors on the DRS and its subscales; (2) derivation of optimal DRS cutoff scores using receiver operating characteristic curves; (3) double cross-validation with stepwise logistic regressions; and (4) application of results to a community-dwelling sample. RESULTS: Age- and education-adjusted DRS scores were computed. The optimal DRS cutoff score for DAT of 129 or less revealed a sensitivity of 98% and a specificity of 97%. The logistic regressions resulted in a combination of the Memory and Initiation/Perseveration subscales that correctly classified 98% of all subjects, 92% of a subsample of 76 patients with mild DAT, and 100% of the 51 patients with autopsy-confirmed DAT. The resultant equation was then applied to a community-dwelling sample (238 healthy elderly subjects and 44 patients with DAT): 91% of patients and 93% of normal subjects were correctly classified. Of an additional 77 individuals with questionable DAT, 43 were classified as demented and 34 were classified as nondemented. CONCLUSIONS: The DRS is a clinically valid psychometric test for the detection of DAT. The Memory and Initiation/Perseveration subscales are its best discriminative indexes for an abbreviated version.

Aged↗
PubMed1995

The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease.

Both genetic and environmental factors affect the progression of Alzheimer's disease (AD). The presence of cortical Lewy bodies in AD patients is associated with an altered presentation of AD pathology suggestive of an interaction between the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele is often present in patients with Lewy body diseases (Parkinson's disease and Lewy body variant of AD), we extended these prior observations by studying the neuropathology associated with the presence of the CYP2D6B mutant allele in a pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B mutant allele, in comparison with those without the CYP2D6B allele, were found to have a smaller decline in two synaptic markers, choline acetyltransferase and synaptophysin, in the frontal cortex relative to normal control values. On the other hand, senile plaques and neurofibrillary tangles were not significantly affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD patients. Association of the CYP2D6B mutant allele with Lewy body formation in both Parkinson's disease and the Lewy body variant of AD and with the milder synaptic pathology in pure AD without Lewy bodies suggest that depending on the contribution of other genetic and environmental factors, this mutant allele may be involved with different aspects of neurodegeneration.

Aged↗
PubMed1995

Sleep-disordered breathing in African-American elderly.

Although sleep-disordered breathing (SDB) has been shown to be very prevalent in the elderly, little has been done to examine differences between the elderly of different racial groups. It has been well documented that SDB often results in hypertension and that hypertension is more common in African-Americans than in Caucasians. Therefore, one might suspect that SDB might be more common in African-Americans. Caucasians (n = 346) and African-Americans (n = 54) older than 65 yr of age were studied. African-Americans reported less satisfaction with sleep (p = 0.017), more difficulty falling asleep (p < 0.001), more daytime sleepiness (p = 0.0014), and more frequent morning headaches (p = 0.0043). African-Americans napped 0.8 times more frequently per evening (p = 0.05) and 11 min longer per nap (p = 0.019) than did Caucasians, and they showed a trend toward more total sleep time (428 versus 408 min). Of greater interest was the fact that more African-Americans had severe SDB with a relative risk twofold as great (relative risk = 2.13) as that for Caucasians, which was confirmed in a logistic regression analysis where race was associated with the presence of SDB (RDI > or = 30) independently of age, sex, and body mass index. The mean RDI for those African-Americans with severe SDB was significantly higher than that for Caucasians (72.1 versus 43.3; p = 0.014).

Black or African American↗
PubMed1995

Episodic memory changes are associated with the APOE-epsilon 4 allele in nondemented older adults.

OBJECTIVE: To compare the memory performances of nondemented older adults with and without the epsilon 4 allele of the apolipoprotein E (APOE-epsilon 4). BACKGROUND: Few studies have examined the cognitive status of subjects at high risk for the development of dementia of the Alzheimer type (DAT). A newly reported risk factor for DAT allows for an examination of the cognitive performances of nondemented subjects who are at risk by virtue of being either heterozygous or homozygous for the APOE-epsilon 4 allele. METHODS: The California Verbal Learning Test (CVLT) was administered to 52 nondemented older adults. Subjects were divided into two groups on the basis of the presence (n = 17) or absence (n = 35) of one or two APOE-epsilon 4 alleles. RESULTS: APOE- epsilon 4 and non-epsilon 4 groups did not significantly differ in demographic, mental status, and functional characteristics. APOE-epsilon 4 subjects demonstrated significantly poorer mean performances than non-epsilon 4 subjects on nine CVLT variables. Seven group differences remained significant, and three approached significance (0.05 < p < 0.10), after the effects of age and gender were taken into account. Six of the 14 APOE-epsilon 4 subjects who completed annual follow-up evaluations developed either DAT or questionable DAT, whereas none of the 26 non-epsilon 4 subjects who received follow-up demonstrated any cognitive decline. CONCLUSIONS: Results suggest that episodic memory changes in older adults are associated with APOE-epsilon 4 allele; sensitive cognitive markers such as those of the CVLT may precede the subsequent development of DAT.

Aged↗
PubMed1995

The role of the epidermal growth factor receptor in human gliomas: I. The control of cell growth.

The epidermal growth factor receptor (EGFR) gene is amplified in over 40% of primary human glioblastomas and overexpressed in the majority. The authors' investigations demonstrate that the function of the EGFR in glioblastomas is distinct from that in other human cancers because it does not appear to mediate the primary growth-promoting effect of EGF. Findings show that the level of EGFR expression does not directly predict the growth response to EGF, with growth stimulated in some cells but inhibited in others when cells were cultured in plastic dishes. On the other hand, when human glioblastoma cells were placed in soft agar cultures, the cell line expressing the highest levels of the EGFR demonstrated considerable colony formation in response to EGF treatment. In addition, cell lines with the highest EGFR levels were also more resistant to the growth-suppressive effects of retinoic acid when maintained in soft agar. These observations suggest that even though the overexpression of the EGFR did not confer a distinct growth advantage to glioma cells cultured on flat culture dishes, the ability of these cells to maintain anchorage-independent growth in soft agar especially in response to EGF and retinoic acid is facilitated. Because anchorage-independent growth is the best in vitro correlate to tumorigenicity, amplification and overexpression of the EGFR in human glioblastoma cells may be in part responsible for the tumorigenic potential of these cells.

Animals↗
PubMed1995

The role of the epidermal growth factor receptor in human gliomas: II. The control of glial process extension and the expression of glial fibrillary acidic protein.

Our earlier investigations of the biology of the epidermal growth factor receptor (EGFR) in human gliomas demonstrated that the level of EGFR expression did not directly predict the glioma growth response to EGF, suggesting that the function of the EGFR in glioblastomas might not be limited to mediating the growth effects of EGF. We conducted the current studies to investigate the function(s) of the EGFR not related to growth control in human gliomas. These investigations show that the EGFR mediates the stimulative effects of EGF on glial process extension and glial fibrillary acidic protein (GFAP) expression. In addition, the level of EGFR expression correlates inversely with glioma cell responsiveness to differentiation promoting agents (for example, nerve growth factor and transforming growth factor-beta) that act through transmembrane tyrosine kinase receptors. Thus, glioma lines with a high level of EGFR expression (for example, T-98G cells) responded to fewer differentiation promoting factors than lines with a low level of EGFR expression (such as U-373MG cells). Our results suggest that the EGFR in gliomas may participate in mediating the process extension and GFAP stimulative effects of both EGF and other differentiation promoting agents. These properties represent components of the differentiated state in glia because their expression is stimulated by dibutyryl cyclic adenosine monophosphate in normal astrocytes. The involvement of the EGFR in the expression of these glial specific properties suggests that the EGFR may play an important role in glial differentiation.

Animals↗
PubMed1994

Low illumination experienced by San Diego adults: association with atypical depressive symptoms.

We explored the illumination exposure of middle-aged adults to determine normal values and to explore several correlates of daily light exposures. Subjects aged 40-64 years in San Diego, CA were recruited by random telephone dialing. Subjects completed a demographic interview and the Center for Epidemiologic Studies Depression self-rating scale (the CES-D) supplemented with eight questions related to seasonal affective disorders (SAD). Data were analyzed for 106 volunteers who wore a device that monitors illumination exposures and activity. The median subject was exposed to illumination > or = 1000 lux for only 4% of the time observed, that is, only about 58 min per day were spent in daylight. Subjects scoring higher on the atypical SAD mood symptoms spent less time in bright illumination rs = -0.266, p = 0.003. The CES-D depression score was similarly correlated with illumination but of borderline significance (rs = -0.150, p = 0.063). These results suggest the hypothesis that many Americans may be receiving insufficient light exposure to maintain optimal mood.

Adult↗
PubMed1994

Sex differences in bone mineral density in 1653 men and women in the sixth through tenth decades of life: the Rancho Bernardo Study.

This cross-sectional population-based study examined the effect of age and sex on bone mineral density (BMD) in the elderly. BMD was measured at the spine and hip using dual-energy x-ray absorptiometry and at midshaft and ultradistal radius using single-photon absorptiometry in 672 men and 981 women aged 50-98 years. In both sexes, mean BMD levels decreased significantly with age at all sites except the male spine. In linear regression models, the slope of loss was significantly greater in women than in men at all sites except the ultradistal radius. The slope was steeper at most sites in women aged 50-59 years than in older women, 60-98 years. In both age groups, mean age-adjusted BMD levels were lower at all sites in women who were past or never users of replacement estrogen than in women who were current estrogen users. Current estrogen users generally had lower slopes of loss with age than never or past estrogen users; however, few of these differences were statistically significant. We conclude that BMD levels decrease in old age in both sexes. Continued bone loss in old age raises the possibility that intervention to retard further loss may still be warranted in the elderly.

Absorptiometry, Photon↗
PubMed1994

Sleep in non-institutionalized Alzheimer's disease patients.

The sleep of Alzheimer's disease (AD) patients is often disturbed by medications, depression, circadian rhythm changes and sleep disorders. Institutionalization is often precipitated by the effect of the patient's sleep and wakefulness on the caregiver. We examined reports of sleep disturbance in mild AD patients. The study cohort consisted of 246 AD patients and 94 controls. Self-reports of sleep disturbance in mild AD patients were examined as was the relationship of sleep and medication use. Results were compared to those of normal controls, and the patients' responses to the reports of their caregivers. Dementia was assessed with the Mini Mental Status Exam, the Blessed Dementia Scale, the Mattis Dementia Rating Scale, and the Pfeiffer Outpatient Disability Test. The more demented the patients, the more time they spent in bed, the more fragmented their sleep, and the more naps they took. Caregivers reports of increased wandering at night and more aggressive behavior during the day were associated with increased use of sedative-hypnotics and with going to bed early. Lengthy sleep was associated with disruptive behavior. We conclude that increased sleep may be associated with dementia and with more disruptive behavior.

Aged↗
PubMed1994

Early, routine paralysis for intracranial pressure control in severe head injury: is it necessary?

OBJECTIVE: To investigate the efficacy of early, routine use of neuromuscular blocking agents for intracranial pressure management in patients with severe head injury. DESIGN: Retrospective review of data from the Traumatic Coma Data Bank. The Traumatic Coma Data Bank was a collaborative project of the National Institute of Neurological Disorders and Stroke that involved four Level I trauma centers. The Traumatic Coma Data Bank prospectively collected data on 1,030 severe head-injured patients (Glasgow Coma Score of < or = 8) between 1984 and 1987. SETTING: Four Level I trauma centers coordinated by the National Institute of Neurological Disorders and Stroke. PATIENTS: A total of 514 Traumatic Coma Data Bank patients who met study inclusion criteria were divided into two groups: group 1 consisted of 239 patients who were pharmacologically paralyzed starting within the first intensive care unit (ICU) shift or < or = 6 hrs into the second shift and lasting for at least 12 hrs. Group 2 contained the remaining 275 patients who did not fulfill these criteria. MEASUREMENTS AND MAIN RESULTS: We analyzed the acute care course of these patients from the time of injury through admission, resuscitation, and ICU stay, as well as their rehabilitation follow-up results for < or = 1 yr. These two groups did not differ significantly regarding admission intracranial computed tomography diagnosis, admission Glasgow motor score, percentage of monitored time that intracranial pressure was > or = 20 mm Hg, or frequency of initial intracranial pressure > or = 20 mm Hg. In group 2, more patients were aged > 40 yrs (24% vs. 15% in group 1) or had admission hypotension (33% in group 2 vs. 25% in group 1). Multivariate regression analysis showed that ICU stay was significantly longer in group 1 (mean 7.76 days) than group 2 (mean 4.84 days; p < .001). The occurrence of pneumonia was significantly higher in group 1 (29% vs. 15%, p < .001). There was a tendency toward a higher occurrence of sepsis in group 1, but this difference did not reach statistical significance (11% vs. 7%, p = .08). The final Glasgow Outcome Scale scores for the two groups were not significantly different in those survivors with good and moderate outcomes. Although there were more deaths in group 2 (39% vs. 24%, p < .001), there were more vegetative or severely disabled survivors in group 1 (8% vs. 4% and 21% vs. 13%, respectively). CONCLUSIONS: Our findings suggest that early, routine, long-term use of neuromuscular blocking agents in patients with severe head injuries to manage intracranial pressure does not improve overall outcome and may actually be detrimental because of the prolongation of their ICU stay and the increased frequency of extracranial complications associated with pharmacologic paralysis. We suggest that routine early management of the head-injured patient in the ICU should be accomplished using sedation alone and that neuromuscular blockade should be generally reserved for patients with intracranial hypertension who require escalation of treatment intensity.

Adolescent↗