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Biomedical subjects

C Steele

Publications and source records attributed to C Steele.

At least 19 recordsLinked to original sources

Wandering behaviour in community-residing persons with dementia.

OBJECTIVES: To examine wandering behaviour in elderly demented persons in the community setting with respect to dementia characteristics and other factors that might influence wandering behaviour; to generate a statistical model to assess the relative importance of these various factors in predicting wandering behaviour. DESIGN: Cross-sectional, case-control investigation. SETTING: University-affiliated outpatient neuropsychiatric assessment center. PARTICIPANTS: Six hundred and thirty-eight consecutive community-residing new patients with dementia referred for evaluation. MEASUREMENTS: Comprehensive neuropsychiatric evaluation, including rating with Mini-Mental State Examination; General Medical Health Rating; Comell Scale of Depression in Dementia and caregiver interview. RESULTS: Wandering behaviour occurred in 17.4% of participants. It was significantly more prevalent in patients with Alzheimer Dementia (AD), patients with dementia of longer duration, and patients with more severe dementia. Wandering behaviour was associated with moderate to severe depression, delusions, hallucinations, and sleep disorder. Other significant associations of wandering behaviour included use of neuroleptic medication and male gender. After statistical adjustment for other variables, duration of dementia, severity of dementia and presence of sleep disorder retained significant statistical association with wandering behaviour. CONCLUSIONS: Wandering behaviour among community-residing elderly dementia patients is associated with a number of factors, some of which may be subject to modification. It is possible that management of coexistent psychopathology, particularly of sleep disorder, and of the underlying disease process of AD would help to ameliorate this problematic behavioural disorder. Further investigation is warranted into the relationship between neuroleptic medication and wandering behaviour and into possible alternative measures to control agitation in elderly dementia patients.

Age Distribution

Differential susceptibility of two species of macaques to experimental vaginal candidiasis.

Vulvovaginal candidiasis (VVC) caused by Candida albicans is a significant problem in women of childbearing age. Unfortunately, protective host defense mechanisms against VVC are poorly understood. Although rodent models of experimental vaginal candidiasis have been useful, several differences from humans limit the correlation of experimental data. The purpose of the present study was to examine two species of macaques as an alternative model of experimental vaginitis. Screening of pig-tailed and rhesus macaques demonstrated that each had mucosal Candida colonization and prior immune sensitization to C. albicans. Vaginal-associated immunity (cytokines, antibodies, and innate resistance) was also detected in cervicovaginal lavage fluid from both species. Nevertheless, intravaginal inoculation of C. albicans into both species, either untreated or under estrogen-treated conditions, resulted in vaginal infection in rhesus, but not pig-tailed, macaques. Several estrogen-dependent changes in the rhesus immune status coincided with susceptibility to infection. Taken together, these results suggest that pig-tailed and rhesus macaques may be useful in studying pathogenesis and immunity associated with C. albicans vaginitis.

Animals

The General Medical Health Rating: a bedside global rating of medical comorbidity in patients with dementia.

OBJECTIVE: Dementia is a serious public health problem. General medical comorbidity is common in dementia patients and critical to their care. However, little is known about medical comorbidity in these patients, and there are no straightforward bedside global rating scales for the seriousness of comorbid medical illness. This paper describes the development and measurement properties of the General Medical Health Rating (GHMR), a rapid global rating scale of medical comorbidity in dementia patients. DESIGN: Interrater reliability, concurrent validity, and predictive validity of the GMHR are reported. SETTING: An outpatient dementia clinic, assisted living, and nursing home. PARTICIPANTS: A total of 819 consecutive dementia clinic outpatients and 180 consecutive admissions to Copper Ridge, a long-term care residence for people with dementia, were included in the study. RESULTS: GMHR was found to be highly reliable (weighted kappa = .91). Across all stages and types of dementia, GMHR ratings were correlated with number of comorbid medical conditions, number of medications being taken for comorbid conditions, and with activity of daily living impairment, even after adjustment for severity of dementia. GMHR ratings were also a strong predictor of falls and of mortality in long-term care residents after adjustment for age and severity of dementia. CONCLUSION: GMHR is a reliable, valid, global bedside measure of severity of general medical comorbidity for patients with dementia that can be used for clinical and research purposes.

Accidental Falls

Analysis of vaginal cell populations during experimental vaginal candidiasis.

Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leukocytes (PMN) had no effect on infection in the presence or absence of pseudoestrus. These results indicate a lack of demonstrable effects by systemic CMI or PMN against vaginitis and suggest that if local T cells are important, they are functioning without showing significant increases in numbers within the vaginal mucosa during infection.

Animals

Physical aggression in dementia patients and its relationship to depression.

OBJECTIVE: The goal of this study was to determine the frequency of physically aggressive behavior in community-residing patients with dementia and its relationship to depression. METHOD: A consecutive series of 541 patients with DSM-IV-defined dementia underwent comprehensive neuropsychiatric evaluation and were rated on the Cornell Scale for Depression in Dementia, the Mini-Mental State, the Psychogeriatric Dependency Rating Scale, and the General Medical Health Rating. RESULTS: Physically aggressive behavior was exhibited by 79 patients in the 2 weeks before evaluation. Aggressive behavior was closely associated with moderate to severe depression, male gender, and greater impairment in activities of daily living, even after adjustment for delusions, hallucinations, sleep disturbance, and severity of cognitive impairment. After adjustment for depression, gender, and impairment in activities of daily living, there was no association between physically aggressive behavior and the presence of either delusions or hallucinations. CONCLUSIONS: A substantial minority of patients with dementia exhibit physically aggressive behavior, and this aggression is strongly linked with the presence of depressive symptoms. It is possible that the identification and treatment of depression in dementia may be a means of preventing and managing physically aggressive behavior.

Activities of Daily Living

Lack of association between duration of breast-feeding or introduction of cow's milk and development of islet autoimmunity.

The hypothesis that early exposure to cow's milk or lack of breast-feeding predisposes to type 1 diabetes remains controversial. We aimed to determine prospectively the relationship of, first, duration of exclusive breast-feeding and total duration of breast-feeding, and second, introduction of cow's milk protein as infant formula, cow's milk, or dairy products, to the development of islet antibodies in early life. Some 317 children with a first-degree relative with type 1 diabetes were followed prospectively from birth for 29 months (4-73). Mothers kept a home diary and answered infant feeding questionnaires at 6-month intervals. No systematic feeding advice was given. Insulin autoantibodies (normal range <5.5%), anti-GAD antibodies (<5.0 U), and anti-IA2 antibodies (<3.0 U) were measured at 6-month intervals. Cox proportional hazards model of survival analysis detected no significant difference between children who did not develop islet antibodies (225 of 317 [71%]), children with one islet antibody raised once (52 of 317 [16.4%]), children with one antibody raised repeatedly (18 of 317 [5.7%]), or children with two or more antibodies raised (22 of 317 [6.9%]), in terms of duration of exclusive breast-feeding, total duration of breast-feeding, or introduction of cow's milk-based infant formulas, cow's milk, or dairy products (relative risk: 0.91-1.09). Four of the children with two or more islet antibodies developed type 1 diabetes. We conclude that there is no prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity in high-risk children.

Aging

Growth inhibition of Candida albicans by vaginal cells from naïve mice.

Recurrent vulvovaginal candidiasis (RVVC) is a common idiopathic mucosal infection caused by Candida albicans. Current data suggests that local immunity is more important than that in the peripheral circulation for protection against infection. In the present study, anti-Candida innate resistance at the vaginal mucosa was investigated using a murine model. For this, splenic and vaginal cells were assessed for in vitro growth inhibition (GI) of C. albicans and cytotoxicity of natural killer (NK) cell-sensitive tumour targets (YAC-1). As expected, significant GI of C. albicans by splenic cells was mediated predominantly by polymorphonuclear leucocytes (PMNL) at effector to target (E:T) ratios of 100 and 50:1. From the vaginal mucosa, naïve unfractionated, but not nylon wool non-adherent (NWN), cells extracted from whole vaginal tissue showed significant GI of C. albicans at E:T ratios as low as 1:1, but only modest killing of YAC-1 targets at all E:T ratios. Subsequent experiments showed significant GI of C. albicans by vaginal epithelioid-enriched cells and with several epithelial cell lines, but not in supernatants collected from the co-cultures. In contrast, lymphoid cell lines had no anti-Candida activity. These results suggest that anti-Candida activity is present at the vaginal mucosa, but unlike that from the spleen, the vaginal activity appears to be predominantly mediated by epithelial cells.

Animals

A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care.

BACKGROUND: Agitated behaviors are common in dementia patients residing in chronic care settings. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances. OBJECTIVE: Prior research has suggested that bright light therapy (BLT) may reduce agitated behaviors in dementia patients. The aim of this study was to test the efficacy of BLT in a randomized, controlled, crossover clinical trial. METHOD: Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were randomized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure. Patients were treated in either condition for 4 weeks, followed by 1 week on no treatment, prior to being crossed over to the other condition. RESULTS: Eight out of 15 patients completed the entire study. The rest completed at least 2 weeks of study. Patients randomized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later (p<0.05). The sleep of patients in the control condition did not improve significantly. There were no other significant differences between baseline and follow-up, nor between BLT and control treated patients on the other outcome measures, which included the Behavioral Pathology in Alzheimer Disease scale (Behave-AD) and the Cornell Scale for Depression in Dementia. CONCLUSION: Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT. However, BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles.

Aged

Th1/Th2 cytokine expression in saliva of HIV-positive and HIV-negative individuals: a pilot study in HIV-positive individuals with oropharyngeal candidiasis.

Current data suggest that T-helper (Th)2-type cytokine responses are often associated with progression to AIDS in HIV-positive individuals. Similarly, Th2-type cytokines are associated with susceptibility to mucosal candidiasis, of which oropharyngeal candidiasis (OPC) is one of the most common opportunistic infections in HIV-positive individuals. Although little information is available on host defense mechanisms at the level of the oral mucosa, recent studies suggest that local cell-mediated immunity (CMI) is equally or more important than that in the periphery for host defense against mucosal Candida albicans infections. This study investigated the potential presence of oral-associated CMI through the expression of Th1/Th2-type cytokines in saliva of immunocompetent and immunocompromised individuals with and without OPC. Results showed a constitutive mixed Th1/Th2 cytokine expression (Th0) in whole saliva of healthy HIV-negative individuals. In contrast, HIV-positive individuals had a dominant Th2-type salivary cytokine profile (interleukin-4 [IL-4], IL-10) (IL-2, interferon-y [IFN-gamma], IL-12) that seemingly resulted from a lack of Th1-type cytokines rather than enhanced Th2-type cytokines. Moreover, pilot analyses of those with OPC showed evidence for a more profound salivary Th2-type profile. Both HIV-positive and HIV-negative patients, irrespective of CD4 counts, had some level of positive in vitro systemic lymphocyte proliferative responses to C albicans antigens. These results suggest that the Th1/Th2 cytokine dichotomy in HIV disease is detectable in situ in oral secretions and may be a useful indicator of oral-associated CMI to better understand resistance/susceptibility of HIV-positive individuals to oral opportunistic infections, including OPC.

AIDS-Related Opportunistic Infections

Adjustment to residential placement in Alzheimer disease patients: does premorbid personality matter?

AIM: To evaluate the influence of premorbid personality on adaptation to placement in a long-term care facility. SUBJECTS: Twenty-eight persons with probable Alzheimer disease (AD) residing in an academically affiliated nursing home for 6-9 months. METHODS: Premorbid personality was described retrospectively by two informants for each resident using the revised NEO Personality Inventory (NEO-PI-R). Standardized tests and rating scales were used on admission to the facility to assess cognition, mood state, physical dependency and general health. Nurses rated each AD resident's social behaviour, participation in activities and quality of sleep. RESULTS: Poorer adjustment was associated with more severe dementia but better physical health. None of the NEO-PI-R domain scores predicted adjustment. CONCLUSIONS: Contrary to popular belief, premorbid personality is relatively inconsequential for an AD patient's adaptation to a long-term care facility.

Adaptation, Psychological

Relationship of cognitive and functional impairment to depressive features in Alzheimer's disease and other dementias.

Patients with clinical diagnoses of Alzheimer's disease, vascular dementia, or undifferentiated dementia were rated on standardized measures of depression, cognitive impairment, and functional impairment. Logistic regression was used to evaluate the relationship between functional or cognitive impairment, as well as their interaction, and depressive features in each group. This analysis revealed notable differences by type of dementia. The results imply that the mechanisms underlying depression in Alzheimer's disease may be different from those in vascular and other types of dementia. These results also provide indicators to the clinician for further evaluation of depression in different dementia subtypes.

Aged

Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype.

The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk, and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus. Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28% had major depression, 17% had minor depression, 30% had delusions, and 14% had hallucinations; 69% were carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3). Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes. Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology.

Aged

Major and minor depression in Alzheimer's disease: prevalence and impact.

One hundred nine outpatients with Alzheimer's disease (AD) were neuropsychiatrically evaluated and rated on standardized measures of depression, activities of daily living (ADL), nonmood behavioral disturbance, and burdensome events such as serious wandering, falls, and accidents. Distribution of depression scores revealed three patient groups: very few depressive symptoms (51%), minor depression (27%), and major depression (22%). Major depression was associated with substantially greater impairment in ADL, worse nonmood behavioral disturbance (such as aggression), and more frequent serious wandering, even after adjusting for severity of dementia or comorbid health problems. Minor depression was also associated with nonmood behavioral disturbance and wandering. The authors conclude that both major and minor depression are common in AD and produce considerable mood and nonmood morbidity affecting both patients and caregivers. Efforts are warranted to identify and treat depression in AD.

Aged

The influence of smoking and of oral and transdermal nicotine on blood pressure, and haematology and coagulation indices.

Nicotine is helpful in stopping smoking but its influence on cardiovascular risk factors is incomplete. Our aim was to determine its effect on blood pressure, routine haematology indices, and coagulation indices relevant to thrombosis. Eighteen subjects were seen whilst smoking (cotinine levels 1119 +/- 414 ng/ml), again after stopping smoking but while using nicotine chewing gum and/or skin patches (392 +/- 198 ng/ml), and again when not using nicotine (cotinine undetectable). There were no significant changes in blood pressures, platelet count, mean platelet volume, viscosity or anti-thrombin III. However, white blood cell count (p = 0.003), lymphocyte count (p = 0.016), red blood cell count (p = 0.02), haemoglobin (p <0.001), fibrinogen (p <0.001) and von Willebrand factor (p = 0.001) all fell between the first and second samples (when still using nicotine) but not between the second and third samples (when off nicotine). Oral and/or transdermal nicotine does not influence blood pressure or the haematology and coagulation indices we have measured.

Administration, Cutaneous

Accuracy of clinical diagnosis of Alzheimer disease and clinical features of patients with non-Alzheimer disease neuropathology.

Neuropathological examination confirmed the clinical diagnosis of possible or probable Alzheimer disease (AD) in 90 of the first 100 patients who came to autopsy at the Johns Hopkins Alzheimer's Disease Research Center. In 10 cases, postmortem brain examination did not confirm AD but revealed variable patterns of neuronal loss in neocortex and limbic structures without amyloid deposits. The most common pattern of degeneration was relatively isolated hippocampal sclerosis (HS). Despite the finding that the 10 patients with non-AD neuropathology were ill for less time and were less cognitively impaired at study entry than those patients with definite AD, they had shorter survival times and showed equal behavioral disturbance at study entry (on a standardized measure). The clinical case reports included here suggest early and progressive prominent behavioral disturbance and other indexes of rapid illness progression in three of the four HS patients and two other non-AD patients. We conclude that the criteria of the National Institute of Neurological Disorders and Stroke/Alzheimer Disease and Related Disorders Association for possible or probable AD are highly accurate and that misdiagnosis is most likely to occur early in the course of illness and in patients with prominent behavioral disturbance or other atypical features.

Age of Onset

Hospital-based behavior modification program for adolescents: evaluation and predictors of outcome.

This study is an evaluation of a residential short-term program (10-12 weeks) which utilizes a behavior modification program (BMP) in an inpatient unit for adolescents with mostly conduct problems. Evaluation included predictors of outcome such as age, gender, diagnosis, length of stay, father's presence, other treatments received, and presence of learning problems. The design used was a retrospective analysis of performance of patients on BMP measured by mean point earned in the first four weeks (pre-test) and the last 4 weeks of admission (post-test). Subjects were 60 adolescents aged 12-18 enrolled for at least eight weeks in the BMP. Findings showed that the BMP was generally beneficial especially for females and nonconduct-disordered patients. Factors such as father's presence, and absence of learning problems were associated with better outcome. Age and length of stay were not correlated with significant improvement. It was found that the BMP was effective in reducing frequency of undesirable behaviors for the majority of adolescents with conduct problems. However, males with a diagnosis of conduct disorder might require a longer stay for the program to be effective.

Adolescent

Mania in Alzheimer's disease.

A chart review of 134 patients with Alzheimer's disease (AD) showed a 2.2% prevalence of mania, lower than previously cited. Of 3 patients with mania, 2 had a history of mania before the onset of AD. Prevalence rates and the role of Alzheimer's disease in the development of mania are discussed.

Aged