Non-Alzheimer degenerative dementias.
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Atrophy↗
Biomedical subjects
J Lowe
Publications and source records attributed to J Lowe.
Establishing a pathological diagnosis in degenerative dementias.
While clinicopathological studies have confirmed that Alzheimer's disease (AD) is the most common neurodegenerative cause of dementia, these same studies have also revealed that other degenerative pathologies account for a significant proportion of patients with cognitive decline. Because pathological assessment of non-Alzheimer neurodegenerative diseases now demands routine use of a costly panel of immunohistochemical techniques a scheme for staged examination of brain tissue has been developed. This scheme is weighted to initially screen out cases of Alzheimer's disease, dementia with Lewy bodies and vascular dementia using conventional staining methods and established diagnostic protocols, bringing in immunochemical techniques to discriminate between non-Alzheimer degenerative dementias. Diagnosis of pathologies causing the clinical syndrome of frontotemporal dementia can be ascertained using conventional staining supplemented by immunochemical detection of ubiquitin, tau protein and alpha beta crystallin. The diagnosis of prion disease is reliably confirmed by immunohistochemical detection of prion protein. This morphological assessment complements emerging genetic insights into many of these neurodegenerative diseases.
Brain↗
Cultural diversity in Florida nursing programs: a survey of deans and directors.
To determine how nursing programs in the state of Florida promote and integrate cultural diversity, a survey of deans and directors was conducted. Of 90 deans and directors surveyed, 46 (51%) responded. The ethnic composition of students and faculty in the respondents' programs was examined in comparison with that of the Florida population. Hispanics, Blacks, and Asians were found to be underrepresented in nursing faculty as compared with their proportion in the state population. The majority of deans and directors ranked the goal of promoting cultural diversity of moderate importance. The two most critical issues perceived by the respondents were the lack of cultural knowledge, sensitivity, and awareness, and the academic problems and educational deficits of minority students. In 50% of the programs surveyed, culture content was integrated throughout the curriculum. Other programs either integrated culture content in specific classes or offered a course in transcultural nursing. Although numerous approaches are currently being employed to recruit ethnically diverse faculty and students, the data suggest that more extensive and innovative efforts are needed to overcome existing barriers. As nursing faces the challenge of caring for a multicultural society in the 21st century, nursing leaders and organizations must collaborate to resolve the issues and problems revealed in this survey.
Cultural Diversity↗
A 1996 NASN research award winner. Health services provided by school nurses for students with chronic health problems.
Increased numbers of students are entering schools with chronic health problems and in need of nursing and other health services. Some studies have been conducted in recent years describing nursing practice in schools. However, further study of school nursing practice was warranted owing to two major problems. The first was limited financial resources to provide needed nursing services. The second was inadequate documentation of both the health needs of students and current school nursing practice in meeting those needs. The purpose of this descriptive study was to examine the nature and extent of nursing services provided in the schools in the late 1990s and to identify potentially reimbursable nursing services being provided to students with chronic health problems. A survey was mailed to active members of the School Nurse Organization of Minnesota (SNOM). The findings indicated the considerable diversity in the practice setting as well as the large volume of nursing services being delivered in schools. Results will be essential in the acquisition of financial resources, including collaboration with third-party payors for reimbursement of nursing and other health services.
Adolescent↗
Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR141716A.
We evaluated delta-9 tetrahydrocannabinol (Delta9-THC), delta-8 tetrahydrocannabinol (Delta8-THC), CP55,940 (CP55), 1-deoxy-11-hydroxy-Delta8-THC-dimethylheptyl (deoxy-HU210, a CB2-selective cannabinoid that also binds the CB1 receptor) and the endogenous cannabinoid anandamide (ANA) via i.c.v. and/or intrathecal (i.t.) routes of administration, alone and in combination with SR141716A (SR), a CB1 antagonist, using the tail-flick test. Our studies were performed in order better to characterize potential diversity in interactions of the cannabinoids with the cannabinoid (CB1) receptor. When SR was administered i.c.v. or i.p. before Delta9-THC, Delta8-THC or CP55 (i.c.v. or i.t.), SR was a potent antagonist and the blockade was complete (AD50 </= 8.1 microgram/mouse i.c.v. or AD50 </= 1.4 mg/kg i.p.). The AD50 values (dose of antagonist that produced a 50% antagonism of agonist effects) for blockade of Delta9-THC, Delta8-THC, CP55,940 (i.c.v. or i.t.) by SR (i.c.v. or i.p.) differed significantly for only two combinations [Delta8-THC/SR, both i.c.v. and CP55 (i.t.)/SR (i.p.)]. Conversely, SR (i.t.) produced an incomplete block of the antinociceptive effects of i.t. Delta9-THC, Delta8-THC and CP55 (AD50 = 28.6, 50.2 and 20.9 microgram/mouse, respectively). Blockade of the deoxy-HU210 (i.c.v.) by SR (either i.c.v. or i.p.) was incomplete and AD50 values could not be calculated. Although the maximal blockade of deoxy-HU210 (i.t.) by SR (i.t.) was only 50%, SR administered i.p. before deoxy-HU210 (i.t.) produced a potent and complete blockade (AD50 = 0.4 mg/kg). The effects of SR on ANA-induced antinociception were mixed. The maximal attenuation of the ANA (i.t.) by SR (i.t.) was 38%. SR (i.p.) blockade of ANA was complete, but the AD50 was 15.4 mg/kg, greater than 15-fold higher than that required to block Delta9-THC, Delta8-THC, CP55 or deoxy-HU210. In addition, SR (i.p. or i.t.) failed to block the hypothermic effects of ANA (i.t.), while completely reversing the hypothermic effects of Delta9-THC (i.t.). These data indicate that SR has a much greater efficacy at supraspinal than at spinal sites. Alternatively, such data suggest either a differential interaction of the cannabinoids at the CB1 receptor or the existence of subtypes of the CB1 receptor.
Analgesics↗
Wegener's granulomatosis--a review of diagnosis and treatment in 53 subjects.
We reviewed 79 patients with clinically suspected Wegener's granulomatosis (WG) diagnosed in Nottingham between 1990 and 1997. Fifty-three patients were confirmed as having WG. We describe the symptoms and signs, features of diagnostic significance, ANCA results, biopsy sites, histology, treatment and outcome in this group. Nasal symptoms and signs had a positive predictive value of 63%, c-ANCA at presentation 100%, and positive nasal biopsy 100%. The negative predictive values were 41%; 79% and 74% respectively. From this study, we recommend that patients who have a negative ANCA and where there remains a clinical suspicion of WG, an ENT examination should be undertaken. Whilst a suspicious lesion should be biopsied and a positive histological picture has a 100% positive predictive value, a negative nasal biopsy does not exclude WG as 5 patients went on to develop a positive ANCA up to 4 years later. In 11 ANCA negative patients where there were signs of nasal mucosal disease, 6 had a positive biopsy and this highlights the importance of nasal biopsy. The c-ANCA should be repeated in patients with a negative c-ANCA and biopsy results at presentation, in whom there remains a clinical suspicion of WG.
Adult↗
Application of formalin fixation to the purification of amyloid proteins.
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Aged↗
Pathological diagnostic criteria for dementia associated with cortical Lewy bodies: review and proposal for a descriptive approach.
In recent years dementia histologically characterised by the presence of cortical Lewy bodies has been increasingly recognised. There is now need for a scheme for an internationally acceptable scheme for pathological diagnosis and classification so that clinical, pathological and molecular features of disease can be correlated. Recent observations made by different groups in large patient series have used slightly different pathological criteria resulting in at least seven different diagnostic terms. In some patients the only cortical pathology is the presence of Lewy bodies, while in the majority of patients there are coexisting pathological changes which either overlap with those seen in Alzheimer's disease (AD). Cortical Lewy bodies can also be present in patients who do not have any obvious cognitive abnormality. A problem with equating studies from different groups is that different criteria have been used to define AD, so that establishing the relevance of cortical Lewy bodies themselves to cognitive decline and separating this from the contribution which may be related to the AD pathology is problematic. The lesions which appear to be of most relevance to potential cognitive decline in DLB are cortical Lewy bodies, Lewy-related neurites, senile plaques, neurofibrillary tangles, neuronal and synaptic loss, spongiform change, and cortical cholinergic deficits. It is possible to operationally classify patients with cognitive decline and cortical Lewy bodies into three main groups, Cortical Lewy body disease, Cortical Lewy body disease with plaques, and Cortical Lewy body disease with plaques and tangles. There are frequent cases which overlap these groups making operational classification difficult in practice. A descriptive classification, in which the severity of different pathological changes is rated, is easy to use in practice. As new molecular risk factors for AD or DLB are revealed they will need to be related to morphological and clinical features. A descriptive diagnostic assessment for DLB will facilitate such studies and makes no judgements as to what these relationships will be.
Aged↗
Microsatellite polymorphism of the alpha 1-antichymotrypsin gene locus associated with sporadic Alzheimer's disease.
A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic Alzheimer's disease (AD) and a subset of familial AD and this association is stronger with early as opposed to late onset AD. Both APOE*4 and alpha 1-antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and are major constituents of the plaques associated with AD. We now show that a dinucleotide microsatellite allele in the 5'-flanking sequence of the ACT gene, designated A10, in association with APOE*4 significantly increases the risk of developing sporadic AD, which accounts for the majority of AD cases.
Aged↗
Chitosan as a nasal delivery system: the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers.
In these studies, we examined the effect on mucociliary transport rates (MTR) of various 0.25% (w/v) chitosan solutions applied to human nasal tissue both ex vivo and in vivo. In the first study a range of chitosans with different molecular weights were applied to freshly amputated human nasal turbinates, and their effect on MTR was recorded. The transient inhibitory effect on turbinate MTR that was found for most of the chitosan preparations showed a marked dependence on the volume of chitosan solution applied and the molecular weight of the chitosan tested. The higher the molecular weight of the chitosan and the more chitosan applied, the longer the original MTR was depressed. A small scale human trial, investigating the effect of chitosan glutamate, on saccharin clearance times, was also undertaken. The study showed that a once daily application of a 0.25% solution of the chitosan for 7 days had no effect on either saccharin clearance times or nasal histology as examined by light microscopy.
Adult↗
Wernicke's encephalopathy with ballooned neurons in the mamillary bodies: an immunohistochemical study.
Two cases of Wernicke's encephalopathy with the rare phenomenon of ballooned neurons in the mamillary bodies are reported. Both patients suffered from acute Wernicke's symptoms starting approximately two weeks before death. The mamillary bodies contained grossly enlarged, ballooned neurons, in one case associated with focal necrosis. The affected neurons were immunoreactive for phosphorylated neurofilament (160 and 200 kDa), and synaptophysin. Ubiquitin and alpha beta-crystallin expression were not detected. The mamillo-thalamic tract appeared normal in both cases. There was a marked associated microglial reaction, as shown by the antibody Ki-MIP. It is concluded that the ballooning of mamillary neurons reflects an acute retrograde reaction to primarily axonal damage. Rather than being a rare manifestation of the disease, these cases may constitute a typical intermediate early stage (10-15 days) in the development of Wernicke's encephalopathy).
Humans↗
Implementation of guidelines for No-CPR orders by a general medicine unit in a teaching hospital.
BACKGROUND: No-cardiopulmonary resuscitation (CPR) orders are frequently used to limit the use of cardiopulmonary resuscitation in patients who die in hospital. International research has consistently highlighted major deficiencies in the formulation, documentation and communication of such orders. There has been little Australian research into No-CPR orders and the impact of clinical guidelines. AIMS: This audit aimed to examine compliance with published guidelines for No-CPR orders previously developed by the hospital Clinical Ethics Committee. METHODS: The notes of all patients who died while under the care of the General Medicine Unit during June-December 1994 were reviewed to evaluate the use of No-CPR orders. Adherence to hospital No-CPR guidelines was evaluated as well as the principal diagnosis, age, level of care and competence of patients to state their wishes. RESULTS: A No-CPR order was documented in 61% (n = 40) of the 66 patients who died during this period. Of these patients 80% were judged to be incompetent and were unable to be involved in decisions not to resuscitate. There was substantial compliance with the guidelines, with the exception of documenting involvement of nursing staff. CONCLUSIONS: No-CPR orders are frequently implemented as a result of failure to respond to curative therapy and do not represent abandonment of the patient. Although this study demonstrates the value of No-CPR guidelines and the audit process, the findings raise fundamental issues regarding the involvement of nursing staff, and of patients, that need to be further addressed.
Adult↗
Role of P-glycoprotein in chemoresistant superficial bladder tumours.
OBJECTIVE: The drug resistance at cellular level is mediated by P-glycoprotein (P-G), which is variably expressed in bladder tumours. The effect of intravesical chemotherapy on P-G status was studied in chemoresistant and recurrent superficial tumours which progressed to metastasis or needed further treatment. METHODS: Archival histological materials of 14 patients who received intravesical epirubicin for recurrent superficial transitional cell carcinoma of the bladder were studied for the presence of P-G using monoclonal antibody JSB-1. RESULTS: Four patients showed complete absence of P-G following chemotherapy although only 2 patients were recurrence-free. In 4 patients with extravesical metastasis, there was no evidence of increased P-G expression. CONCLUSIONS: The P-glycoprotein expression is not related to histological grading or clinical progression of bladder tumours.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Prion protein immunocytochemistry--UK five centre consensus report.
Creutzfeldt-Jakob disease (CJD) and other prion diseases are associated with the deposition of insoluble prion protein (PrPCJD) in the central nervous system (CNS). Antibodies raised against PrPCJD also react with its precursor protein, a soluble form of PrP (PrPC), which is widely distributed in the normal CNS. This cross-reactivity has in the past raised doubts as to the specificity and diagnostic reliability of PrP immunolocalization, especially in familial cases which are atypical clinically and which lack characteristic pathology findings. Following an MRC-funded workshop which focused on this problem, a multicentre prospective study was set up to identify a reliable protocol for PrPCJD immunocytochemistry. Five UK centres took part in this study and demonstrated consistent staining of plaques, vacuolar deposits in severe spongiform change, and perineuronal deposits using a variety of antibodies and enhancement procedures. A protocol using formic acid, guanidine thiocyanate, and hydrated autoclaving pre-treatment in conjunction with a monoclonal PrPCJD antibody produced the clearest immunochemical results and is presented as the consensus UK recommendation for PrPCJD immunocytochemical procedures.
Brain↗
PET scanning and the human immunodeficiency virus-positive patient.
UNLABELLED: The use of PET scanning in patients with human immunodeficiency virus infection and fever of unknown origin, confusion and/or weight loss was investigated. METHODS: Eighty patients were examined using PET. Fifty-seven patients had half-body scans with [18F]fluorodeoxyglucose (FDG), and 23 patients had brain studies performed with FDG. Fourteen patients also had [11C]methionine studies (2 chest, 1 abdomen and 11 brain) performed. RESULTS: Thirteen patients with lymphoma had the extent of the disease clearly identified in both nodal and extranodal sites. Patients with a variety of infections (Cryptococcus neoformans, Pseudomonas aeruginosa, Mycobacterium tuberculosis and Mycobacterium avium intracellulare) had disease localized for appropriate biopsy or sampling procedures. A half-body FDG-PET scan had a sensitivity of 92% and a specificity of 94% for localization of focal pathology that needed treatment. High uptake of FDG (greater than liver) had a positive predictive value for pathology needing treatment of 95%. FDG brain studies showed that 16 patients with CD4 T-lymphocyte counts less than 200 cells/ml had reduced cortical uptake compared with that in basal ganglia. FDG scans were abnormal in all 19 patients with focal space occupying lesions identified by magnetic resonance scans. The standardized uptake values (SUVs) over cerebral lesions due to toxoplasma were in the range of 0.14-3.7 (13 patients) and due to lymphoma were in the range of 3.9-8.7 (6 patients). Three more patients with progressive multifocal leukoencephalopathy had SUVs in the range of 1.0-1.5 over the lesions. Another patient had a low-grade oligodendroglioma (SUV = 2.9). Carbon-11-methionine uptake also was high in patients with cerebral lymphoma but did not add to the discrimination between toxoplasmosis and lymphoma in these patients obtained with the FDG scan. CONCLUSION: In hospitals with access to PET facilities, FDG scanning allows the rapid evaluation of the whole body, including the brain, of patients with human immunodeficiency virus infection, with a report potentially available within 4 hr of injection. Sites of infection and tumor were identified, and discrimination between cerebral pathologies was possible.
AIDS-Related Opportunistic Infections↗
Pathological lesions of Alzheimer's disease and dementia with Lewy bodies brains exhibit immunoreactivity to an ATPase that is a regulatory subunit of the 26S proteasome.
MS73 is one of a family of ATPases that act as regulatory subunits of the 26S proteasome. Localisation of this ATPase in histological sections of hippocampus from Alzheimer's disease (AD) and in cingulate gyrus sections of dementia with Lewy bodies (DLB) brains was examined immunohistochemically. In all cases of AD (n = 10) neurofibrillary tangles (NFT), plaque neurites and neuropil threads were immunoreactive for MS73. In seven out of the nine cases of DLB, distinctive MS73-positive structures were detected within cortical Lewy bodies. The association of MS73 with these neuronal abnormalities provides further evidence that proteolytic processing involving the 26S proteasome occurs in lesions of AD and DLB.
Adenosine Triphosphatases↗
Neurofibrillary tangles of Alzheimer's disease brains contain 14-3-3 proteins.
The localisation of 14-3-3 proteins compared to that of tau and ubiquitin-protein conjugates in sections of hippocampus from Alzheimer's disease (AD) brains was examined by immunohistochemistry. In all cases (n = 10), anti-14-3-3 stained a proportion of neurofibrillary tangles (NFT). In general, NFT stained by anti-14-3-3 were smaller than those stained by anti-tau or anti-ubiquitin-protein conjugates and were more confined to the neuronal cell body. Occasionally, cortical Lewy bodies in cases of Lewy body dementia were also found to be 14-3-3-positive. Since 14-3-3 proteins are central to MAP kinase signalling, the results support the proposal that this pathway is in part responsible for the hyperphosphorylation of tau, which leads to the formation of the paired helical filaments seen in AD brains.
14-3-3 Proteins↗
Extraction and protein sequencing of immunoglobulin light chain from formalin-fixed cerebrovascular amyloid deposits.
Substantial amounts of a single protein have been extracted into electrophoresis sample buffer from archived formalin-fixed brain blood vessels, taken from a case of cerebral amyloidosis. Cyanogen bromide cleavage and tryptic digestion of the protein on Western blots allowed amino acid sequences from three resultant peptides to be determined. Comparison of these peptides with database sequences identified the extracted protein as being derived from an immunoglobulin light chain. This is the first demonstration of amino acid sequencing of a polypeptide extracted from formalin-fixed tissue. This case also appears to be unique, since primary cerebrovascular amyloidosis involving immunoglobulin light chains has not been previously described. The amyloid protein had clearly resisted formalin fixation; it is possible that this resistance occurred because the protein was deposited in large amounts as insoluble densely packed aggregates, which may exclude infiltration of the formalin. This technique may therefore have applications in the post-mortem diagnosis of amyloidoses and in the purification of other amyloids.
Adult↗