Depression, one of the most frequent of all medical disorders, is an illness that often concomitantly occurs with many other diseases in hospitalized adult patients. Sadly, overwhelming evidence suggests that comorbid depression is commonly misdiagnosed, undertreated, or not diagnosed at all when present in critically ill patients. While safe, modern, and cost-effective treatments are available for treating this disorder, comorbid depression remains a silent and unseen illness adversely affecting patient outcomes. With an understanding that this pernicious underlying illness frequently exists in hospitalized adults, nurses can identify the symptoms and patterns of comorbid depression, thereby being extremely effective in decreasing the morbidity and mortality that often accompanies this forgotten diagnosis.

Adult↗

PubMed2000

Stress, depression, and psychoneuroimmunology.

Stress is a common phenomenon most people encounter every day, whereas depression represents a vast constellation of mental disorders of multifarious etiology. Both situations have been exhaustively evaluated and scrutinized in the complex field of psychoneuroimmunology (PNI). PNI studies have attempted to ascertain and define the extensive links among and intricate web of neural activity, the endocrine system, and altered immune responses in stressed patients and those with depressive disorders. Although the literature indicates some type of relationship exists between these systems, the associations between and relevance of immune alterations in depression and stress to health and illness remain to be determined. Only by seeking to expand our knowledge of these neurological, endocrine, and immunological alterations in depressed and stressed neurological patients will our understanding of stress, depression, and health be magnified and our ability to provide holistic care be maximized.

Depressive Disorder↗

PubMed2000

Dementia in rural primary care practices in Lake County, Oregon.

Procedures used in assessing patients with dementia in rural settings are little studied. Among all patients aged 65 years and older in the four primary care practices in Lake County, Oregon, dementia cases were identified from computerized office databases using preselected International Classification of Diseases, Ninth Edition, codes. A semi-structured chart review determined (1) a dementia diagnosis, (2) cognitive and functional domains assessed, and (3) diagnostic studies performed. Of 1540 available records, 30 had dementia. Nineteen of them met National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease (AD). Cognitive impairment was documented in 73% of the 51 identified charts and all with AD. Laboratory studies were recorded in 33% overall and in 42% with AD. Neuroimaging was documented in 18% overall and in 16% with AD. The prevalence of documented dementia in these rural practices may be low, possibly because cases of mild dementia may not be labeled as such. Laboratory studies were performed in a minority of cases of dementia.

Aged↗

PubMed2000

Longitudinal analysis of the effects of the aging process on neuropsychological test performance in the healthy young-old and oldest-old.

A sample of 33 young-old (ages 65 to 74) and 20 oldest-old (ages 84 to 93) healthy elderly without dementia were assessed with neuropsychological tests annually over a 4-year period to examine longitudinal changes in cognitive functioning. Significant age-group differences existed at baseline in participants' performances on tests of immediate memory and visuospatial skills. There were no age-group differences in the rate of change over the 4-year interval on any neuropsychological tests. Within each age-group, the amount of change over time was minimal for most tests though some practice effects were apparent, and on some tests mild decline was observed. Results suggest that healthy old adults, including the oldest-old, do not experience measurable declines in cognitive functioning over a 4-year period.

Age Factors↗

PubMed2000

Regulation of T cell development in the thymus.

My colleagues and I are studying the regulation of T cell differentiation and lineage commitment in the thymus. Most recently, we have focused on the role of the mitogen-activated protein kinase (MAPK) signaling pathway in these processes and, in particular, the temporal pattern of activation of this pathway and its effect on downstream gene targets. Our data suggest that thymocyte differentiation to either the CD4 or CD8 lineages requires sustained low-level signaling via MAPK, although the latter requires a weaker signal. We have proposed that both the amplitude and kinetics of MAPK signaling may be one aspect of the link between T cell receptor affinity and cell fate. In addition, we have shown that the Egr family of transcription factors is induced as a consequence of MAPK activation during positive selection in the thymus, and we are taking several approaches to identify other genes that are involved in regulating this developmental process.

Animals↗

PubMed2000

Critical care bug team: a multidisciplinary team approach to reducing ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia rates in the medical-surgical intensive care unit first exceeded the 90th percentile in September 1997 and were significantly (P <.05) higher than National Nosocomial Infections Surveillance System pooled mean data. In January 1998, a multidisciplinary "Critical Care Bug Team" was developed by the Infection Control Committee to review 1997 National Nosocomial Infections Surveillance System data for four adult intensive care units in a 583-bed tertiary care hospital. METHODS: Membership included clinical nurse specialists, a dietitian, a pharmacist, a respiratory therapist, an infection control professional, a research specialist, and a physician adviser. Having the team report directly to the hospital's Infection Control and Adult Critical Care Committees maximized support for recommendations and provided a direct link from patient care to hospital administration. By identifying issues, evaluating patient care processes, performing literature searches, and monitoring compliance, the team implemented numerous interventions, including policy and procedure changes, purchasing of equipment, and implementation of various education tools. RESULTS: Each member of the Critical Care Bug Team contributed to a synergized effort that may have produced the desired outcome of decreasing ventilator-associated pneumonia rates. Except for August 1998, ventilator-associated pneumonia rates have been below the 75th percentile since May 1998. CONCLUSION: This study illustrates the effectiveness of a multidisciplinary team approach devised to reduce and stabilize ventilator-associated pneumonia rates in a medical-surgical intensive care unit.

Adult↗

PubMed1999

Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands.

Recent studies have demonstrated the utility of synthetic combinatorial libraries for the rapid identification of peptide ligands that stimulate clonotypic populations of T cells. Here we screen a decapeptide combinatorial library arranged in a positional scanning format with two different clonotypic populations of CD4+ T cells to identify peptide epitopes that stimulate proliferative responses by these T cells in vitro. An extensive collection of mimic peptide sequences was synthesized and used to explore the fine specificity of TCR/peptide/MHC interactions. We also demonstrate that many of these deduced ligands are not only effective immunogens in vivo, but are capable of inducing T cell responses to the original native ligands used to generate the clones. These results have significant implications for considerations of T cell specificity and the design of peptide vaccines for infectious disease and cancer using clinically relevant T cell clones of unknown specificity.

Amino Acid Sequence↗

PubMed1999

Slow accumulation of active mitogen-activated protein kinase during thymocyte differentiation regulates the temporal pattern of transcription factor gene expression.

Thymocyte-positive selection is believed to result from low affinity/avidity interactions of TCR and MHC proteins, but how these weak interactions translate into downstream biochemical signals and how such signals modulate gene expression is unknown. Using a culture system where isolated immature thymocytes can be induced to differentiate along the CD4 lineage pathway, we show that sustained low level mitogen-activated protein/extracellular regulated kinase activity is required for cell differentiation and survival. Furthermore, induction of mitogen-activated protein/extracellular regulated kinase activity is surprisingly slow under conditions that induce differentiation. This pattern of kinase activity not only selects which genes are expressed but also regulates the temporal pattern of expression of transcription factor genes that are induced during double-positive thymocyte differentiation.

Animals↗

PubMed1999

A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L)

We investigated three separate families (designated D, F and G) with frontotemporal dementia that have the same molecular mutation in exon 10 of the tau gene (P301L). The families share many clinical characteristics, including behavioural aberrations, defective executive functions, language deficits, relatively preserved constructional abilities and frontotemporal atrophy on imaging studies. However, Family D has an earlier mean age of onset and shorter duration of disease than Families F and G (49.0 and 5.1 years versus 61-64 and 7.3-8.0 years, respectively). Two members of Families D and F had neuropathological studies demonstrating lobar atrophy, but the brain from Family D had prominent and diffuse circular, intraneuronal, neurofibrillary tangles not seen in Family F. The brain from Family F had ballooned neurons typical of Pick's disease type B not found in Family D. A second autopsy from Family D showed neurofibrillary tangles in the brainstem with a distribution similar to that found in progressive supranuclear palsy. These three families demonstrate that a missense mutation in the exon 10 microtubule-binding domain of the tau protein gene can produce severe behavioural abnormalities with frontotemporal lobar atrophy and microscopic tau pathology. However, the findings in these families also emphasize that additional unidentified environmental and/or genetic factors must be producing important phenotypic variability on the background of an identical mutation. Apolipoprotein E genotype does not appear to be such a factor influencing age of onset in this disease.

Age of Onset↗

PubMed1999

Sensory organization for balance: specific deficits in Alzheimer's but not in Parkinson's disease.

BACKGROUND: The cause of frequent falling in patients with dementia of the Alzheimer type (AD) is not well understood. Distraction from incongruent visual stimuli may be an important factor as suggested by their poor performance in tests of shifting visual attention in other studies. The purpose of this study was to determine whether AD patients have difficulty maintaining upright balance under absent and/or incongruent visual and other sensory conditions compared to nondemented healthy elderly persons and individuals with Parkinson's disease (PD). METHODS: Seventeen healthy older adults, 15 medicated PD subjects, and 11 AD subjects underwent the Sensory Organization Test protocol. The incidence of loss of balance ("falls"), and the peak-to-peak amplitude of body center of mass sway during stance in the six sensory conditions were used to infer the ability to use visual, somatosensory, and vestibular signals when they provided useful information for balance, and to suppress them when they were incongruent as an orientation reference. Vestibular reflex tests were conducted to ensure normal vestibular function in the subjects. RESULTS: AD subjects had normal vestibular function but had trouble using it in condition 6, where they had to concurrently suppress both incongruent visual and somatosensory inputs. All 11 AD subjects fell in the first trial of this condition. With repeated trials, only three AD subjects were able to stay balanced. AD subjects were able to keep their balance when only somatosensory input was incongruent. In this condition, all AD subjects were able to maintain balance whereas some falls occurred in the other groups. In all conditions, when AD subjects did not fall, they were able to control as large a sway as the healthy controls, except when standing with eyes closed in condition 2: AD subjects did not increase their sway whereas the other groups did. In the PD group, the total fall incidence was similar to the AD group, but the distribution was generalized across more sensory conditions. PD subjects were also able to improve with repeated trials in condition 6. CONCLUSION: Patients with dementia of the Alzheimer type have decreased ability to suppress incongruent visual stimuli when trying to maintain balance. However, they did not seem to be dependent on vision for balance because they did not increase their sway when vision was absent. Parkinsonian patients have a more general balance control problem in the sensory organization test, possibly related to difficulty changing set.

Accidental Falls↗

PubMed1999

A rehabilitation programme for people with Parkinson's disease.

Explore the source record for details and available documents.

Humans↗

PubMed1998

A role for p21ras/MAP kinase in TCR-mediated activation of LFA-1.

LFA-1 is a beta2 integrin that plays well-characterized roles in adhesion of T lymphocytes to APC, T cell-mediated cytolysis, and leukocyte-endothelial cell interactions. Although it is clear that LFA-1 must undergo affinity or avidity changes to bind its cellular ligand ICAM-1, the intracellular signaling pathways involved are not well characterized. Here, we show that the Ras-mitogen-activated protein kinase (MAPK) signaling pathway is also involved in TCR-activated LFA-1 adhesion. Expression of a dominant negative form of p21ras in a thymocyte cell line inhibits, while constitutively active p21ras both enhances and sustains, subsequent TCR-triggered adhesion to isolated ICAM-1. However, the Ras/MAPK pathway alone is not sufficient for activating T cell LFA-1, as inhibition of both downstream MAPK/extracellular regulated kinase kinase (MEK) activity and phosphatidylinositol 3-kinase activity is required for complete inhibition of adhesion.

Animals↗

PubMed1998

Nuclear factor kappaB is required for peptide antigen-induced differentiation of a CD4+CD8+ thymocyte line.

NF-kappaB transcription factors are known to regulate the expression of a number of genes involved in T cell activation and function. Some evidence has suggested that they also play a role in T cell development. However, the role of NF-kappaB in Ag-induced thymocyte differentiation has not been directly addressed to date. Here we critically examine this role by employing DPK, a CD4+CD8+ thymocyte line that undergoes differentiation upon TCR engagement in a process that closely mimics positive selection. Expression of a degradation-resistant form of IkappaBalpha in DPK cells results in constitutive inhibition of NF-kappaB activity. We find that in the absence of NF-kappaB activity, MHC-peptide-induced differentiation of DPK is blocked. Furthermore, differentiation induced by a nonphysiologic stimulus, anti-TCR Ab, is greatly reduced. Altogether, our data indicate a requirement for NF-kappaB in the developmental changes associated with positive selection.

Animals↗

PubMed1998

Analysis of the alpha-synuclein G209A mutation in familial Parkinson's disease.

Explore the source record for details and available documents.

Age of Onset↗