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Biomedical subjects

K Bell

Publications and source records attributed to K Bell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Discharge disposition from acute care after traumatic brain injury: the effect of insurance type.

OBJECTIVE: To determine if persons with traumatic brain injury (TBI) who are insured by Medicaid or health maintenance organizations (HMOs) are more likely to receive postacute care in skilled nursing facilities (SNFs) than in rehabilitation facilities, compared with persons insured by commercial fee-for-service (FFS) plans. DESIGN: Retrospective cohort study. SETTING: County hospital admitting 30% of all Washington State TBI patients. PATIENTS: Patients with moderate to severe TBI discharged to rehabilitation facilities or SNFs between 1992 and 1997 (n = 1271); 56.3% were insured by Medicaid, 26.1% by FFS plans, and 17.6% by HMOs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Disposition on discharge from acute care (rehabilitation facilities vs SNF); adjusted relative risk (RR) and confidence interval (CI) for different insurance types. RESULTS: After accounting for confounding factors, Medicaid patients were 68% more likely (RR = 1.68, 95% CI = 1.34-2.11) and HMO patients were 23% more likely (RR = 1.23, 95% CI =.90-1.68) to go to a SNF than FFS patients. However, the latter difference was not statistically significant. CONCLUSIONS: An association exists between insurance type and postacute care site. Efforts should be made to determine the effect this relationship has on the cost and outcomes for TBI patients.

Abbreviated Injury Scale↗
PubMed2001

Principles for the use of macrocyclic lactones to minimise selection for resistance.

OBJECTIVE: To provide principles for the appropriate use of avermectin/milbemycin or macrocyclic lactone (ML) anthelmintics in sheep, to ensure effective worm control and to minimise selection for ML resistance. STRATEGY: The principles were based on an assessment of the information currently available. The MLs were categorised into three groups (ivermectin [IVM], abamectin [ABA] and moxidectin [MOX]) based on structural differences, persistence and efficacy against ML resistant strains. The reported order of activity or efficacy against ML resistant worm strains was IVM<ABA<MOX. General treatment schemes were considered for Australian conditions and were divided into the following situations: 1. quarantine treatment, 2. treatment on/to clean pasture, 3. treatment on/to safe pasture, 4. treatment on/to moderate/heavily contaminated pasture. For each of these situations a strategy was considered for farms where ML resistance was present or absent. It was assumed that resistance commonly occurs in some or all other broad spectrum anthelmintics, and even where ML resistance has been detected, the ML group remains the most effective. The guidelines provided are general and it is expected that state agencies and sheep/veterinary advisers would give specific advice to suit their environments and drug resistance/worm problems. CONCLUSIONS: The primary recommendation is to use a mixture of effective drugs when treating sheep. However, unless the combination treatment is highly effective it is unlikely to delay selection for ML resistance if sheep are being treated and moved to a clean or safe pasture. Where possible, reliance on the ML anthelmintics should be reduced by not using them every year, not using them in low risk stock or by using narrow spectrum and low efficacy drugs such as naphthalophos when appropriate. Anthelmintic treatment should be given as part of a strategic worm control program. It is suggested that IVM-oral and IVM-capsules should not be used when ML resistance is present. In this situation MOX or ABA should be used in combination with other drugs, provided that the chosen ML is effective against the resistant parasite. It is essential to monitor the efficacy of ML and drug combinations by post-treatment worm egg counts, particularly when ML resistance has been detected.

Animals↗
PubMed2001

Provision of MRI can significantly reduce CT collective dose.

The purpose of this study was to investigate the proportion of patients currently being investigated by CT that could be investigated by MRI with a potential reduction in exposure to ionizing radiation. The health detriment arising from the radiation dose associated with CT has been quantified in terms of the number of likely cases of serious health effects. The results show that a significant saving in the collective radiation dose is possible, with an associated detriment of between 0.23 and 0.33 cases of cancer or severe hereditary effects averted in one imaging department every year. In selecting the balance of provision of MRI and CT facilities, the health detriment associated with the radiation dose from CT should be considered.

Adolescent↗
PubMed2001

Longitudinal study of quality of life in people with advanced Alzheimer's disease.

The authors examined three indicators of health-related quality of life in people with advanced Alzheimer's disease ([AD]; N=150): confinement to home, null activity, and null positive affect, as reported by patient proxies. Dementia severity predicted time-to-onset for all three disease milestones in models that controlled for sociodemographic indicators, nursing home status, and death in the follow-up period. Patients whose dementia worsened over follow-up were more likely to reach each milestone. These outcomes represent key milestones in the care of patients; they are sensitive to disease progression, and they are likely to be useful for studying treatment in advanced AD.

Activities of Daily Living↗
PubMed2000

Different brain networks mediate task performance in normal aging and AD: defining compensation.

OBJECTIVE: To determine whether the pathologic mechanisms of AD alter the brain networks subserving performance of a verbal recognition task. BACKGROUND: Functional imaging studies comparing task-related activation in AD patients and controls generally have not used network analysis and have not controlled for task difficulty. METHODS: H2 15O PET was used to measure regional cerebral blood flow in 14 patients and 11 healthy elders during the performance of a serial verbal recognition task under two conditions: low demand, with study list size (SLS) equal to one; and titrated demand, with SLS adjusted so that each subject recognized words at 75% accuracy. The Scaled Subprofile Model was used to identify networks of regionally covarying activity across these task conditions. RESULTS: In the elders, higher SLS was associated with the recruitment of a network of brain areas involving left anterior cingulate and anterior insula (R2 = 0.94; p < 0.0001). Three patients also expressed this network. In the remaining patients, higher SLS was associated with the recruitment of an alternate network consisting of left posterior temporal cortex, calcarine cortex, posterior cingulate, and the vermis (R2 = 0.81, p < 0.001). Expression of this network was unrelated to SLS in the elders and more intact AD patients. CONCLUSIONS: The patients' use of the alternate network may indicate compensation for processing deficits. The transition from the normal to the alternate network may indicate a point where brain disease has irreversibly altered brain function and thus may have important implications for therapeutic intervention.

Aged↗
PubMed2000

Endogenous estrogen levels and Alzheimer's disease among postmenopausal women.

BACKGROUND: Although several studies have suggested that hormone replacement therapy lowers the risk of AD among postmenopausal women, few studies have evaluated the relationship of endogenous estrogen levels and AD. The current study investigated whether serum estrone and estradiol levels were related to the presence of AD among postmenopausal women not currently taking hormone replacement therapy. METHODS: Using a case-control design, we examined an ethnically diverse sample of postmenopausal women who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 50) and nondemented controls (n = 93). All women were participants in a study of aging and dementia and were seen consecutively between August 1997 and October 1998. RESULTS: Patients with AD had lower estradiol (F[1,141] = 8.3, p = 0.005) levels than did normal controls. Patients also had lower estrone levels; however, this comparison did not quite meet significance criteria (F[1,141] = 3.6, p = 0.06). Compared to estradiol levels >20 pg/mL, women with AD were four to six times more likely to have levels <20 pg/mL after adjusting for age, years of education, presence of an APOE-epsilon4 allele, ethnicity, and body mass index. There were no significant differences in frequency of AD among women within different quartiles of estrone after adjusting for potential confounds. CONCLUSIONS: The results of this preliminary case-control study suggest that estradiol levels may decline significantly in women in whom AD develops.

Aged↗
PubMed2000

The identification of a potent imidazoline-based vascular K(ATP) channel antagonist.

In this study the activity of a number of novel imidazoline-based compounds (IMID series) was assessed by functional and binding studies to determine their actions at K(ATP) channels. The novel compounds, which we synthesised, were methoxy-, methyl-, butyl- and fluorophenyl derivatives of clonidine. In functional studies we determined the potency (by calculating a pK(B) value) of the IMID compounds to antagonise levcromakalim responses in segments of isolated pig coronary artery. The most potent compounds identified (laboratory codes: IMID-1M, IMID-26F and IMID-4F) had apparent pK(B) values of approximately 7 which is similar to that for the sulphonylurea, glibenclamide and the lipophilic quaternary ion, tetraphenylphosphonium. This inhibitory action was specific for levcromakalim since the imidazoline antagonist IMID-1M failed to effect vasorelaxation response-curves to the non-KATP channel opener, sodium nitroprusside. In the spontaneously beating rat right atrium preparation the majority of the compounds were able to cause slowing of heart rate, but with low EC50 values (approximately 10-30 microM). In binding studies, the compounds were unable to displace binding of [3H]P1075 to bovine aortic smooth muscle preparations nor [3H]glibenclamide binding to rat cerebral cortex membranes. These studies show that some imidazoline-based compounds are potent antagonists of levcromakalim-mediated vasorelaxation responses in the pig coronary artery. The compounds displayed only minimal bradycardic activity. The site of action of the imidazoline compounds does not appear to be the same as that used by K(ATP) channel openers or sulphonylurea-based antagonists. It is likely that these compounds interact with the K(ATP) channel pore itself.

ATP-Binding Cassette Transporters↗
PubMed2000

Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin.

Angiogenesis depends on the cooperation of growth factors and cell adhesion events. Although alphav integrins have been shown to play critical roles in angiogenesis, recent studies in alphav-null mice suggest that other adhesion receptors and their ligands also regulate this process. Evidence is now provided that the integrin alpha5beta1 and its ligand fibronectin are coordinately up-regulated on blood vessels in human tumor biopsies and play critical roles in angiogenesis, resulting in tumor growth in vivo. Angiogenesis induced by multiple growth factors in chick embryos was blocked by monoclonal antibodies to the cell-binding domain of fibronectin. Furthermore, application of fibronectin or a proteolytic fragment of fibronectin containing the central cell-binding domain to the chick chorioallantoic membrane enhanced angiogenesis in an integrin alpha5beta1-dependent manner. Importantly, antibody, peptide, and novel nonpeptide antagonists of integrin alpha5beta1 blocked angiogenesis induced by several growth factors but had little effect on angiogenesis induced by vascular endothelial growth factor (VEGF) in both chick embryo and murine models. In fact, these alpha5beta1 antagonists inhibited tumor angiogenesis, thereby causing regression of human tumors in animal models. Thus, fibronectin and integrin alpha5beta1, like integrin alphavbeta3, contribute to an angiogenesis pathway that is distinct from VEGF-mediated angiogenesis, yet important for the growth of tumors.

Animals↗
PubMed2000

Context-specific enhancement of glutamate transmission by cocaine.

The repeated injection of cocaine causes an increase in the capacity of a subsequent acute injection to elevate extracellular glutamate levels in the nucleus accumbens, and the present study sought to determine if the elevation in extracellular glutamate is regulated by the pairing of environmental stimuli with drug administration. Three treatment groups were injected daily for seven days with saline or cocaine (15 mg/kg, ip); 1) injection of saline in the home cage, 2) injection of cocaine in the home cage (cocaine-unpaired), and 3) injection of cocaine in the test apparatus (cocaine-paired). Three weeks following the last daily injection dialysis probes were placed into the nucleus accumbens and all rats were injected with saline followed by cocaine. Basal levels of extracellular glutamate were significantly reduced in the cocaine-paired treatment group. Moreover, only in the cocaine-paired group did the cocaine injection elevate extracellular glutamate. Repeated administration of cocaine also produces an enduring increase in the motor stimulant response to an acute cocaine injection and it was previously found that administration of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainic acid glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione inhibited the sensitized, but not the acute motor, response to cocaine. In this study it was found that the motor stimulant response elicited by cocaine was blunted by pretreatment of the nucleus accumbens with 6-cyano-7-nitroquinoxaline-2,3-dione only in animals receiving daily cocaine injections in the paired environment. In contrast, the N-methyl-D-aspartate glutamate receptor antagonist R-(-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid did not significantly affect cocaine-induced motor activity in any treatment group. These data support a hypothesis that environmental stimuli previously associated with daily cocaine administration can modulate glutamate transmission in the nucleus accumbens in a manner affecting cocaine-induced behavior.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

The effect of pre-operative topical flurbiprofen or diclofenac on pupil dilatation.

PURPOSE: To assess the clinical benefit and relative efficacy of pre-operative diclofenac and flurbiprofen drops in routine cataract surgery. METHODS: Fifty-two patients undergoing extracapsular cataract extraction with lens implantation were randomised in a double-masked study to compare the efficacy of diclofenac, flurbiprofen and placebo drops in maintaining per-operative mydriasis and reducing post-operative inflammation. Balanced salt solution containing adrenaline was used in all patients. Pupil size was measured prior to the corneal section and after the completion of the operation. The degree of pain, redness, flare and cells in the anterior chamber and intraocular pressure were recorded on the day after surgery. The three groups were analysed with respect to change in pupil size, intraocular pressure and degree of inflammation. RESULTS: The change in pupil size was significantly different among the three groups (p = 0.01), there being a smaller decrease in the treatment groups compared with the placebo group and in the diclofenac treatment group compared with the flurbiprofen treatment group. Significantly less post-operative redness was recorded in the diclofenac treatment group compared with the other groups (p = 0.001). No significant difference was found between the groups as regards anterior chamber cells, flare or intraocular pressure change. CONCLUSIONS: Pre-operative diclofenac and flurbiprofen drops are effective in maintaining intraoperative mydriasis. Diclofenac reduces post-operative redness on day 1. These effects are of debatable clinical benefit.

Adult↗
PubMed2000

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study.

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.

Aged↗
PubMed2000

Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up.

OBJECTIVE: This study evaluated the predictive utility of olfactory identification deficits in patients with mild cognitive impairment for follow-up diagnosis of probable Alzheimer's disease. METHOD: Ninety outpatients with mild cognitive impairment were examined at 6-month intervals. Matched healthy comparison subjects (N=45) were examined annually. The University of Pennsylvania Smell Identification Test was given at baseline. RESULTS: Olfaction scores were lower in patients with mild cognitive impairment than in healthy comparison subjects. Seventy-seven patients were followed up; 19 were diagnosed with Alzheimer's disease by 2 years. Patients with low olfaction scores (< or =34 of 40), and patients with low olfaction scores who reported no subjective problems smelling, were more likely to develop Alzheimer's disease than other patients. In a Cox proportional hazards model adjusted for age, sex, modified Mini-Mental State score, and education, low olfaction scores did not predict time until development of Alzheimer's disease, but low olfaction scores accompanied by lack of awareness of olfactory deficits predicted time to development of Alzheimer's disease. This effect remained when attention or memory measures replaced modified Mini-Mental State score in the model. In patients with high Mini-Mental State scores (> or =27 of 30), low olfaction with lack of awareness remained a significant predictor of Alzheimer's disease. Olfaction scores of 30-35 showed moderate to strong sensitivity and specificity for diagnosis of Alzheimer's disease at follow-up. CONCLUSIONS: In patients with mild cognitive impairment, olfactory identification deficits, particularly with lack of awareness of olfactory deficits, may have clinical utility as an early diagnostic marker for Alzheimer's disease.

Aged↗
PubMed1999

Low-density lipoprotein cholesterol and the risk of dementia with stroke.

CONTEXT: Next to Alzheimer disease, vascular dementia is the second most common form of dementia in the elderly, yet few specific risk factors have been identified. OBJECTIVE: To investigate the relationship of plasma lipids and lipoproteins to dementia with stroke. DESIGN AND SETTING: Prospective longitudinal community-based study over a 7-year period (1991-1998). PARTICIPANTS: A total of 1111 nondemented participants (mean [SD] age, 75.0 [5.9] years) were followed up for an average of 2.1 years (range, 1-7.8 years). MAIN OUTCOME MEASURE: Incident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype. RESULTS: Two hundred eighty-six (25.7%) of the 1111 subjects developed dementia during follow-up; 61 (21.3%) were classified as having dementia with stroke and 225 (78.7%) as having probable Alzheimer disease. Levels of LDL cholesterol were significantly associated with an increased risk of dementia with stroke. Compared with the lowest quartile, the highest quartile of LDL cholesterol was associated with an approximately 3-fold increase in risk of dementia with stroke, adjusting for vascular risk factors and demographic variables (relative risk [RR], 3.1; 95% confidence interval [CI], 1.5-6.1). Levels of LDL corrected for lipoprotein(a) were an even stronger predictor of dementia with stroke in the adjusted multivariate analysis. Compared with the lowest quartile, the RR of dementia with stroke for the highest quartile of lipoprotein(a)-corrected LDL cholesterol was 4.1 (95% CI, 1.8-9.6) after adjusting for vascular factors and demographic variables. Lipid or lipoprotein levels were not associated with the development of Alzheimer disease in our cohort. CONCLUSIONS: Elevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke.

Aged↗
PubMed1999

Assessment of cognition in advanced AD: the test for severe impairment.

The Test for Severe Impairment (TSI) was compared with the Mini-Mental State Examination (MMSE) and a modified MMSE (mMMSE) in a multisite, longitudinal study of AD. The TSI correlated highly with the MMSE (r = 0.83) and the mMMSE (r = 0.82), but was not redundant. There was a wide range of scores on the TSI among those scoring in the severely impaired range on the MMSE and mMMSE. The slope of cognitive change over time detected by the TSI was greater than that revealed by the MMSE or the mMMSE. Performance on the TSI was a significant predictor of survival. The TSI is a valid measure that is sensitive to cognitive change over time in severely demented patients with AD.

Aged↗
PubMed1999

Plasma amyloid beta-peptide 1-42 and incipient Alzheimer's disease.

Mutations in the amyloid precursor protein and presenilin 1 and 2 genes result in elevated plasma levels of the amyloid beta-peptide species terminating at amino acid residue 42 (A beta1-42). In a longitudinal study of unrelated elderly individuals, those who subsequently developed Alzheimer's disease had higher plasma levels of A beta1-42 at entry than did those who remained free of dementia. The results indicate that elevated plasma levels of the released A beta peptide A beta1-42 may be detected several years before the onset of symptoms, supporting that extracellular A beta1-42 plays an important role in the pathogenesis of late-onset Alzheimer's disease.

Age of Onset↗