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Biomedical subjects

D Gustafson

Publications and source records attributed to D Gustafson.

At least 19 recordsLinked to original sources
PubMed2006

A phase I safety, pharmacological and biological study of the farnesyl protein transferase inhibitor, tipifarnib and capecitabine in advanced solid tumors.

BACKGROUND: To evaluate the toxicity and pharmacological and biological properties of the farnesyl protein transferase (FPTase) inhibitor, tipifarnib (R115777, ZARNESTRAtrade mark) and capecitabine administered for 14 days every 3 weeks. PATIENTS AND METHODS: Patients with advanced cancers received twice daily tipifarnib (100-500 mg) and capecitabine (1000-1125 mg/m(2)) for 14 days every 3 weeks. Pharmacokinetics of tipifarnib, capecitabine and 5-fluorouracil (5-FU) were determined. Peripheral blood mononuclear cells were analyzed for farnesylation of the HDJ2 chaperone protein and FPTase activity. RESULTS: Forty-one patients received 185 courses of treatment. Diarrhea and palmar-plantar erythrodysesthesia were dose limiting at 300 mg tipifarnib/1125 mg/m(2) capecitabine b.i.d. When the capecitabine dose was fixed at 1000 mg/m(2) b.i.d., neutropenia was dose limiting at 400 and 500 mg b.i.d. of tipifarnib. Capecitabine did not affect the pharmacology of tipifarnib at 100-300 mg b.i.d., although tipifarnib significantly increased the C(max) of 5-FU at 400 mg b.i.d. HDJ2 farnesylation and FPTase activity decreased between 200 and 400 mg b.i.d. doses of tipifarnib, without a dose-response relationship. Five patients demonstrated partial remissions and 11 patients maintained prolonged stable disease. CONCLUSIONS: Tipifarnib and capecitabine are well tolerated at 300 mg/1000 mg/m(2) b.i.d., respectively, resulting in biologically relevant plasma concentrations and antitumor activity. The recommended dose for further disease-focused studies is 300 mg b.i.d. tipifarnib and 1000 mg/m(2) b.i.d. capecitabine, given for 14 days every 3 weeks.

Adult↗
PubMed2005

Prodromal cognitive signs of dementia in 85-year-olds using four sources of information.

OBJECTIVE: To evaluate the utility of assessing four cognitive domains obtained from four information sources to identify individuals at risk for developing dementia, Alzheimer disease (AD), and vascular dementia (VaD). METHODS: A representative population sample of nondemented 85-year-olds (n = 313) from Gothenburg, Sweden, was examined regarding memory, language, and visuospatial and executive functions, using self- and key informant reports and neuropsychiatric and psychometric examinations. The sample was followed 3 years for incident dementia, AD, or possible VaD. RESULTS: All cases of dementia, AD, and VaD were preceded by low performance in most domains irrespective of information source. Isolated low memory performance or low cognitive performance with unimpaired memory did not predict dementia. Positive predictive values increased with number of domains affected. Self- and key informant reports were less useful for predicting dementia than neuropsychiatric and psychometric examinations. The best positive predictive value (88%) was for low cognitive performance in all domains using neuropsychiatric and psychometric examinations; however, sensitivity was only 18%. CONCLUSIONS: Although memory impairment was necessary to predict dementia, it was not sufficient. Other cognitive domains needed to be affected. Relying on self-reports or key informants for early detection of dementia excluded a large group at risk. In addition, vascular dementia appeared to have a prodromal stage.

Aged, 80 and over↗
PubMed2005

High total cholesterol levels in late life associated with a reduced risk of dementia.

OBJECTIVE: To examine the longitudinal association between plasma total cholesterol and triglyceride levels and incident dementia. METHODS: Neuropsychiatric, anthropometric, laboratory, and other assessments were conducted for 392 participants of a 1901 to 1902 birth cohort first examined at age 70. Follow-up examinations were at ages 75, 79, 81, 83, 85, and 88. Information on those lost to follow-up was collected from case records, hospital linkage system, and death certificates. Cox proportional hazards regression examined lipid levels at ages 70, 75, and 79 and incident dementia between ages 70 and 88. RESULTS: Increasing cholesterol levels (per mmol/L) at ages 70 (hazard ratio [HR] 0.77, 95% CI: 0.61 to 0.96, p = 0.02), 75 (HR 0.70, CI: 0.52 to 0.93, p = 0.01), and 79 (HR 0.73, CI: 0.55 to 0.98, p = 0.04) were associated with a reduced risk of dementia between ages 79 and 88. Examination of cholesterol levels in quartiles showed that the risk reduction was apparent only among the highest quartile at ages 70 (8.03 to 11.44 mmol/L [311 to 442 mg/dL]; HR 0.31, CI: 0.11 to 0.85, p = 0.03), 75 (7.03 to 9.29 mmol/L [272 to 359 mg/dL]; HR 0.20, CI: 0.05 to 0.75, p = 0.02), and 79 (6.82 to 9.10 mmol/L [264 to 352 mg/dL]; HR 0.45, CI: 0.17 to 1.23, p = 0.12). Triglyceride levels were not associated with dementia. CONCLUSIONS: High cholesterol in late life was associated with decreased dementia risk, which is in contrast to previous studies suggesting high cholesterol in mid-life is a risk factor for later dementia. The conflicting results may be explained by the timing of the cholesterol measurements in relationship to age and the clinical onset of dementia.

Age Distribution↗
PubMed2004

A 24-year follow-up of body mass index and cerebral atrophy.

OBJECTIVE: To investigate the longitudinal relationship between body mass index (BMI), a major vascular risk factor, and cerebral atrophy, a marker of neurodegeneration, in a population-based sample of middle-aged women. METHODS: A representative sample of 290 women born in 1908, 1914, 1918, and 1922 was examined in 1968 to 1969, 1974 to 1975, 1980 to 1981, and 1992 to 1993 as part of the Population Study of Women in Göteborg, Sweden. At each examination, women completed a survey on a variety of health and lifestyle factors and underwent anthropometric, clinical, and neuropsychiatric assessments and blood collection. Atrophy of the temporal, frontal, occipital, and parietal lobes was measured on CT in 1992 when participants were age 70 to 84. Univariate and multivariate regression analyses were used to assess the relationship between BMI and brain measures. RESULTS: Women with atrophy of the temporal lobe were, on average, 1.1 to 1.5 kg/m2 higher in BMI at all examinations than women without temporal atrophy (p < 0.05). Multivariate analyses showed that age and BMI were the only significant predictors of temporal atrophy. Risk of temporal atrophy increased 13 to 16% per 1.0-kg/m2 increase in BMI (p < 0.05). There were no associations between BMI and atrophy measured at three other brain locations. CONCLUSION: Overweight and obesity throughout adult life may contribute to the development of temporal atrophy in women.

Adult↗
PubMed2002

Evaluation of quality improvement programmes.

In response to increasing concerns about quality, many countries are carrying out large scale programmes which include national quality strategies, hospital programmes, and quality accreditation, assessment and review processes. Increasing amounts of resources are being devoted to these interventions, but do they ensure or improve quality of care? There is little research evidence as to their effectiveness or the conditions for maximum effectiveness. Reasons for the lack of evaluation research include the methodological challenges of measuring outcomes and attributing causality to these complex, changing, long term social interventions to organisations or health systems, which themselves are complex and changing. However, methods are available which can be used to evaluate these programmes and which can provide decision makers with research based guidance on how to plan and implement them. This paper describes the research challenges, the methods which can be used, and gives examples and guidance for future research. It emphasises the important contribution which such research can make to improving the effectiveness of these programmes and to developing the science of quality improvement.

Evidence-Based Medicine↗
PubMed2002

Quality collaboratives: lessons from research.

Quality improvement collaboratives are increasingly being used in many countries to achieve rapid improvements in health care. However, there is little independent evidence that they are more cost effective than other methods, and little knowledge about how they could be made more effective. A number of systematic evaluations are being performed by researchers in North America, the UK, and Sweden. This paper presents the shared ideas from two meetings of these researchers. The evidence to date is that some collaboratives have stimulated improvements in patient care and organisational performance, but there are significant differences between collaboratives and teams. The researchers agreed on the possible reasons why some were less successful than others, and identified 10 challenges which organisers and teams need to address to achieve improvement. In the absence of more conclusive evidence, these guidelines are likely to be useful for collaborative organisers, teams and their managers and may also contribute to further research into collaboratives and the spread of innovations in health care.

Cooperative Behavior↗
PubMed2001

An aberrant form of CD59 derived from HeLa cells.

We isolated a CD59 cDNA from a HeLa cell library which encoded a mutated form of CD59, having a single base substitution (G to T) that changed Arg55 to Met. Since this mutation occurred in the vicinity of the putative active site of CD59, we expressed the aberrant form of the protein in Chinese hamster ovary cells in order to test for effects upon function. We found that the mutation did not influence complement inhibitory activity of CD59. However, the epitopes recognised by the function-blocking CD59 monoclonal antibodies BRIC229 and YTH 53.1 were significantly affected. The G to T substitution caused loss of an Mnl I restriction site which permitted PCR-RFLP analysis. All of 52 human subjects studied, and our in-house HeLa cells, were homozygous for the normal CD59 sequence, indicating that the altered sequence was not due to normal variation in the general population. Therefore this mutation probably arose spontaneously in the HeLa cell line used to generate the commercially obtained cDNA library.

Amino Acid Sequence↗
PubMed1999

Quinone reductase inhibitors block SAPK/JNK and NFkappaB pathways and potentiate apoptosis.

A variety of environmental stresses stimulate the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEKK) > stress-activated protein kinase (SAPK)-ERK kinase (SEK) > SAPK/c-Jun NH(2)-terminal kinase (JNK) stress-activated protein kinase cascade and coordinately activate the transcription factor NFkappaB. Mechanisms of stress activation upstream of MEKK1 have not been precisely determined. Redox mechanisms involving sulfhydryls are likely because N-acetyl-cysteine at millimolar concentrations blocks stress signals. Because intracellular sulfhydryl concentrations can be regulated through redox cycling involving reactive quinones (1), we tested the ability of quinone reductase inhibitors to alter stress signaling. Several quinone reductases are inhibited by dicoumarol, a coumarin derivative. Dicoumarol prevented SAPK activation in vivo by chemical cell stressors and also prevented SAPK activation induced by expression of the tumor necrosis factor alpha (TNFalpha) receptor-associated protein TRAF2 but not by expression of truncated active MEKK1. Other coumarin derivatives failed to block SAPK activation, but other inhibitors of quinone reductases, particularly menadione, similarly blocked SAPK activation. Cells deficient in a major quinone reductase, NQO1, displayed hypersensitivity to dicoumarol stress inhibition, whereas SAPK in cells reconstituted with the NQO1 gene displayed relative dicoumarol resistance. Consistent with the proposed role of overlapping upstream signaling cascades in activation of NFkappaB, dicoumarol also blocked NFkappaB activation in primary macrophages stimulated with either lipopolysaccharide or TNFalpha. In addition, dicoumarol strongly potentiated TNFalpha-induced apoptosis in HeLa cells, probably by blocking the anti-apoptotic effect of NFkappaB. The ability of dicoumarol to simultaneously inhibit SAPK and NFkappaB activation and to potentiate apoptotic cell death suggests that SAPK is not an obligate participant in apoptosis. Dicoumarol, currently in clinical use as an oral anticoagulant, represents a potential therapeutic inhibitor of the SAPK and NFkappaB response.

Apoptosis↗
PubMed1999

HRT and dementia.

The role of HRT and/or oestrogens in the aetiology, progression and prevention of neurodegenerative disorders is unclear. Various studies have been conducted in cells, animals and humans to better define these relationships. The following is a presentation of data on the role of oestrogens in the two most common dementia syndromes Alzheimer's Disease and vascular dementia. This review examines whether there is support for the hypothesis that the use of oestrogens reduces the risk for dementia and cognitive decline in a variety of experimental models. A literature search was performed using the following key words: oestrogen and dementia, oestrogen and Alzheimer, oestrogen and cognition, oestrogen and learning, and oestrogen and memory. The reference lists for the articles identified using these search strategies were examined. The strongest evidence for a beneficial effect comes from cell and animal studies. These suggest that treatment with oestrogens may influence the pathogenetic processes of AD, mainly by affecting the beta-amyloid metabolism, by promoting the activity of the cholinergic system, by reducing oxidative stress or cardiovascular risk. Observational studies give some support to the hypothesis that HRT may be protective for cognitive decline and dementia in the elderly, but the inherited methodological problems in these studies preclude any conclusions. The treatment trials published thus far have methodological problems that prohibit definite conclusions on the relationship between HRT and cognitive decline and dementia.

Alzheimer Disease↗
PubMed1998

An evidence-based approach to interactive health communication: a challenge to medicine in the information age. Science Panel on Interactive Communication and Health.

OBJECTIVE: To examine the current status of interactive health communication (IHC) and propose evidence-based approaches to improve the quality of such applications. PARTICIPANTS: The Science Panel on Interactive Communication and Health, a 14-member, nonfederal panel with expertise in clinical medicine and nursing, public health, media and instructional design, health systems engineering, decision sciences, computer and communication technologies, and health communication, convened by the Office of Disease Prevention and Health Promotion, US Department of Health and Human Services. EVIDENCE: Published studies, online resources, expert panel opinions, and opinions from outside experts in fields related to IHC. CONSENSUS PROCESS: The panel met 9 times during more than 2 years. Government agencies and private-sector experts provided review and feedback on the panel's work. CONCLUSIONS: Interactive health communication applications have great potential to improve health, but they may also cause harm. To date, few applications have been adequately evaluated. Physicians and other health professionals should promote and participate in an evidence-based approach to the development and diffusion of IHC applications and endorse efforts to rigorously evaluate the safety, quality, and utility of these resources. A standardized reporting template is proposed to help developers and evaluators of IHC applications conduct evaluations and disclose their results and to help clinicians, purchasers, and consumers judge the quality of IHC applications.

Evidence-Based Medicine↗
PubMed1998

Analysis of mutant quantity and quality in human-hamster hybrid AL and AL-179 cells exposed to 137Cs-gamma or HZE-Fe ions.

We measured the number of mutants and the kinds of mutations induced by 137Cs-gamma and by HZE-Fe (56Fe [600 MeV/amu, LET = 190 KeV/micrometer) in standard AL human hamster hybrid cells and in a new variant hybrid, AL-179. We found that HZE-Fe was more mutagenic than 137Cs-gamma per unit dose (about 1.6 fold), but was slightly less mutagenic per mean lethal dose, DO, at both the S1 and hprt- loci of AL cells. On the other hand, HZE-Fe induced about nine fold more complex S1- mutants than 137Cs-gamma rays, 28% vs 3%. 137Cs-gamma rays induced about twice as many S1- mutants and hprt-mutants in AL-179 as in AL cells, and about nine times more of the former were complex, and potentially unstable kinds of mutations.

Animals↗
PubMed1996

The relationship between meeting patients' information needs and their satisfaction with hospital care and general health status outcomes.

OBJECTIVE: The objective of this study was to determine if there is an association between meeting patients' information needs and their overall satisfaction with care and their general health status outcomes. STUDY DESIGN: This non-experimental study used data from hospital medical records as well as patient-completed surveys conducted two and eight weeks post discharge. The setting involved three community hospitals in the southeastern section of the US that provided care to a series of 167 acute myocardial infarction (Acute MI) patients. MEASURES: The independent variable was an index measuring how well patients' information needs were met. The dependent variables were patient satisfaction (ratings of satisfaction with care process, global satisfaction, and health benefit) and general health status outcomes (physical function, psychosocial function and quality of life). Covariates used as control variables to hold patient characteristics constant, included demographics (age, gender) and clinical measures of acute MI severity, comorbidity, angina (at eight weeks), and dyspnea (at eight weeks). ANALYSIS: Univariate analyses were employed to: (1) describe patients' characteristics; (2) determine the relative importance of meeting different types of information needs; and (3) identify information need areas most likely not to be met. Multivariate linear regression and logistic regression was used to evaluate the association between patients' ratings of meeting information needs with satisfaction and health outcomes, respectively, after controlling for covariates. RESULTS: The multivariate regression results show that meeting information needs are positively and significantly associated with both patient satisfaction measures (i.e., Ratings of Care Processes, p < 0.01; Global Satisfaction, p < 0.05, Perceived Health Benefit, p < 0.01) and one general health status measure (i.e. Quality of Life, p < 0.01). CONCLUSION: The results suggest that providers of care should ensure that they meet the information needs of patients with specific conditions because patients' perceptions of both quality of care and quality of life are associated with the clinicians' ability to transfer key information to their patients.

Aged↗
PubMed1995

Belief in pain.

There is a traditional view of pain as a conscious phenomenon which satisfies the following two principles at least: Pain is essentially a belief- or cognition-independent sensation, given for consciousness in an immediate way, and pain's unitary physical base is responsible for both its phenomenal or felt qualities and its functional, causal features. These are "The Raw Feels Principle" (P) and "The Unity of Pain Principle" (Q). Each is shown to be implausible. Evidence comes from recent pain research in a number of dimensions. A further argument against The Unity of Pain Principle is constructed by analogy with facts about blindsight. The consequences of rejecting P or Q are examined in light of (i) the traditional epistemological role of pain as exemplar of sensations thought to be foundational for knowledge, (ii) the prospects of a modularity theory of the pain system, (iii) recent accounts of pain among contemporary philosophers, (iv) a naturalist and realist conception of pain, and (v) views about the status of Folk Psychology.

Attention↗
PubMed1995

Physical control of patients on an inpatient setting: forensic vs. civil populations.

The current study examines the use of physical control (seclusion and restraint) in a sample of patients hospitalized in a public mental hospital during 1989. A total of 243 patient records involving physical control were examined; of these, 124 had been civilly committed and the remaining 119 were forensic (Incompetent to Stand Trial or Not Guilty by Reason of Insanity). Some 870 physical control events occurred in the sample, a rate that is intermediate when compared with other facilities described in the literature. Seclusion was employed most often (46% of events), with the combination of seclusion and restraint used in 32% of events and the remaining 22% of physical control events being restraint. Seclusion tended to be used more often with civilly committed patients, with restraint more frequently employed with forensic patients. Forensic patients differed from civil subjects in their greater frequency of threats, agitation, and verbal hostility. However, civil patients were more frequently aggressive toward others and destructive of property. These findings are discussed in the context of previous evidence also describing forensic patients as being perceived as more dangerous, but behaving in a fashion no more physically aggressive than civil patients.

Adult↗
PubMed1994

Efficacy of nurses suturing pediatric dermal lacerations in an emergency department.

STUDY OBJECTIVE: To assess the efficacy of nurses suturing pediatric dermal lacerations in an emergency department. DESIGN: Prospective study. SETTING: Pediatric ED. PARTICIPANTS: Suturing nurses completed a comprehensive training program provided by physicians at our institution and at a national wound management workshop; both included instruction in wound assessment, preparation, anesthesia, repair, and care after repair. A survey of physician and parent satisfaction with wound repair and for wound healing complications was performed at the time of suture removal in 61 children whose dermal laceration was repaired by suturing nurses. RESULTS: The laceration was located on the face in 40 patients, the scalp in 14, and an extremity in 7. A total of 343 sutures was required (18 lacerations required a layered closure). Pediatricians graded wound repair as "very good" in 32 cases (53%) and "excellent" in 29 cases (47%). Parents rated themselves as "very satisfied" with the wound repair procedure in 60 cases (98%) and with the wound repair outcome in 59 cases (97%). There were no wound-healing complications. Suturing nurses took a total of 72 hours to repair lacerations. In comparison, of 20 lacerations repaired by an ED attending physician, 11 (55%) were graded as "excellent" and 9 (45%) as "very good," with no wound-healing complications (P = NS). CONCLUSION: Nurses who complete a standardized training program in wound management and repair are capable of providing high-quality, definitive care for children with dermal lacerations, thus allowing physicians to use their time more effectively in managing general patient care in the ED.

Anesthesia↗
PubMed1994

Do patients' health status reports predict future hospital stays for patients with an acute myocardial infarction?

OBJECTIVE: Although patients' reports of health status and functioning have been shown to be reliable and valid measures for use in health care research, there is limited information on their practical utility in clinical settings. The purpose of this study was to determine if patients' reports of physical and psychosocial health status have prognostic value by predicting future hospital stays in acute myocardial infarction (AMI) patients. METHODS: Research design was an observational, longitudinal follow-up study involving a sample of 132 AMI patients recently discharged from nine community hospitals. One hundred twelve patients (85%) completed the study. Patient reports of general health status, diagnosis-specific measures of health status, medical history, and demographic characteristics were collected one to two months post AMI; follow-up data were gathered six months later to identify occurrence of new cardiac-related stays. RESULTS: Poor psychosocial functioning and cardiac symptoms were significantly associated with the likelihood of being rehospitalized (odds ratios of 4.62 and 4.00). Multivariate results, however, show that poor psychosocial function and younger age--but not cardiac symptoms--are significant independent predictors of new hospital stays, after controlling for medical history and demographic variables. CONCLUSION: Simple patient reports of health status, which physicians can obtain easily from AMI patients shortly after an infarction, are predictive of rehospitalization.

Acute Disease↗
PubMed1992

The treatment of mentally disordered offenders: a national survey of psychiatrists.

A nationwide (U.S.) survey of major public mental hospitals treating patients who are incompetent for trial, not guilty by reason of insanity, mentally disordered sex offenders, or mentally ill inmates was conducted. Responses were received from 71 percent of the 115 facilities surveyed. Respondents were the directors of psychiatry from the respective facilities. The pattern of treatments delivered generally appeared clinically appropriate. However, behavioral and cognitive-behavioral treatments were reported infrequently, even in areas in which they would be particularly useful.

Antisocial Personality Disorder↗