A discussion of cases in the 2001 RCPA-AQAP chemical pathology case report comments program

Aim: We present a descriptive analysis of the 10 case reports distributed in the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program to assess the quality of interpretative commenting in clinical biochemistry in 2001. Method: Participants were asked to comment on a given set of biochemistry results attached with brief clinical details. All responses received were translated into key phrases and graphically presented on a histogram. An expert panel was asked to evaluate the appropriateness of the key phrases and to propose a suggested composite comment. Results: While the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate or misleading. As comments on laboratory reports may affect clinical management of patients, it is important that these comments reflect accepted practice and current guidelines. Conclusion: The Patient Report Comments Program may play an important role in continuing education and possibly in quality assurance of interpretative commenting.

Clinical reporting by occupational therapists and speech pathologists: Therapists' intentions and parental satisfaction

This study employed a qualitative research design to explore therapists' and parents' perspectives of paediatric occupational therapy and speech pathology assessment reports. Aims of the study were to explore the intentions of therapists when writing reports, to expand upon existing literature on parental satisfaction and preferences with respect to paediatric clinical reports, to highlight documentation practices that would serve to maximize parental use of allied health reports, and to develop specific guidelines on how reports can be written to ensure they are useful and beneficial to therapists and parents. Participants were 15 parents of children who had been assessed at 1 of 2 university clinics and subsequently received a written report, and 11 therapists employed at the same university clinics. Questionnaires were used to seek information from therapists concerning the purpose of assessment reports and essential aspects to include when writing reports for parents. In-depth interviews were used to seek information about how understandable and beneficial clinical reports were to parents. The data were subjected to thematic analysis. From comments of therapists' intentions and parents' stated needs, and in accordance with literature reviewed, guidelines were identified for the production of parent-oriented reports. Conclusions drawn from this study can be specifically applied to services producing paediatric occupational therapy or speech pathology assessment reports, but are widely relevant to paediatric allied health services. (author abstract)

Leonard Bell Cox (1894-1976) - pioneer of Australian clinical neurology

The name of Leonard Bell Cox (1894-1976) will long be associated with a number of very significant areas in the intellectual and cultural life of the Australian State of Victoria. A quarter of a century after his death, his cultural achievements, and the enduring products of these achievements, continue to be celebrated in his native city, Melbourne. However his enormous contributions in these cultural fields were matched by his perhaps less widely known achievements in medicine, in particular in the neurosciences. In his time he not only pioneered the foundation and progressive development of the speciality of clinical neurology in Australia, but at the same time became a recognised world expert on the pathology of brain tumours.

Evaluating the role of speech-language pathology with patients with communication disability in the acute hospital setting using the ICF

The practice of speech-language pathology in the acute care hospital setting has changed dramatically over the last 20 years. Speech-language pathologists now routinely assess and manage patients with dysphagia as well as patients with acquired communication disorders. In practice, clinicians have tended to direct their limited resources toward the assessment and management of patients with dysphagia before addressing the needs of patients with acquired communication disorders. This practice has resulted in a decline in speech-language pathology services for patients with communication disorders and has led some clinicians to question the role of the speech-language pathologist in the acute care hospital setting. This article continues this discussion by evaluating the role of the speech-language pathologist in the acute care hospital setting within the context of the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF; WHO, 2001). It argues that by adopting the ICF, speech-language pathologists have a sound rationale for broadening their role to identify the communication needs of all hospital inpatients who experience communication difficulties in the acute care hospital setting.

Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity

Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia is perceived. It has helped to classify difficult cases of carcinoma in situ with indeterminate features and led to the identification of new variants of lobular carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma in situ (PLCIS), recently described variants of invasive and in situ classic lobular carcinoma, are reported to be associated with more aggressive clinical behaviour. Although PLC/PLCIS show morphological features of classic lobular neoplasia and lack E-cadherin expression, it is still unclear whether these lesions evolve through the same genetic pathway as lobular carcinomas or are high-grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative carcinoma in situ with indeterminate features, using immunohistochemistry, chromogenic in situ hybridization, high-resolution comparative genomic hybridization (CGH) and array-based CGH. We observed that all lesions lacked E-cadherin and beta-catenin and showed gain of 1q and loss of 16q, features that are typical of lobular carcinomas but are not seen in high-grade ductal lesions. In addition, amplifications of c-myc and HER2 were detected in the pleomorphic components, which may account for the high-grade features in this case and the reported aggressive clinical behaviour of these lesions. Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Basal-like breast carcinomas: clinical outcome and response to chemotherapy

Background: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival. Material and methods: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups. Results: It was more likely for patients with BLBCs to be found negative for ER (p < 0.0001), PgR (p < 0.0001) and HER2 (p < 0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p < 0.05) and were associated with significantly shorter disease-free and overall survival (both p, 0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p < 0.05). Conclusions: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated.

The roles of exercise-induced immune system disturbances in the pathology of heat stroke - The dual pathway model of heat stroke

Heat stroke is a life-threatening condition that can be fatal if not appropriately managed. Although heat stroke has been recognised as a medical condition for centuries, a universally accepted definition of heat stroke is lacking and the pathology of heat stroke is not fully understood. Information derived from autopsy reports and the clinical presentation of patients with heat stroke indicates that hyperthermia, septicaemia, central nervous system impairment and cardiovascular failure play important roles in the pathology of heat stroke. The current models of heat stroke advocate that heat stroke is triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers the systemic inflammatory response, which can lead to systemic coagulation and haemorrhage, necrosis, cell death and multi-organ failure. However, the current heat stroke models cannot fully explain the discrepancies in high core temperature (Tc) as a trigger of heat stroke within and between individuals. Research on the concept of critical Tc: as a limitation to endurance exercise implies that a high Tc may function as a signal to trigger the protective mechanisms against heat stroke. Athletes undergoing a period of intense training are subjected to a variety of immune and gastrointestinal (GI) disturbances. The immune disturbances include the suppression of immune cells and their functions, suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS), suppression of anti-LPS antibodies, increased macrophage activity due to muscle tissue damage, and increased concentration of circulating inflammatory and pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase gut-related LPS translocation. This article discusses the current evidence that supports the argument that these exercise-induced immune and GI disturbances may contribute to the development of endotoxaemia and heat stroke. When endotoxaemia can be tolerated or prevented, continuing exercise and heat exposure will elevate Tc to a higher level (> 42 degrees C), where heat stroke may occur through the direct thermal effects of heat on organ tissues and cells. We also discuss the evidence suggesting that heat stroke may occur through endotoxaemia (heat sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary pathway of heat stroke. The existence of these two pathways of heat stroke and the contribution of exercise-induced immune and GI disturbances in the primary pathway of heat stroke are illustrated in the dual pathway model of heat stroke. This model of heat stroke suggests that prolonged intense exercise suppresses anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the pathway of heat stroke.

Efficacy of speech pathology management for chronic cough: a randomised placebo controlled trial of treatment efficacy

Background: Chronic cough that persists despite medical treatment may respond to speech pathology intervention, but the efficacy of such treatment has not been investigated in prospective randomised trials. The aim of this study was to determine the efficacy of a speech pathology intervention programme for chronic cough. Methods: A single blind, randomised, placebo controlled trial was conducted in 87 patients with chronic cough that persisted despite medical treatment. Patients were randomly allocated to receive either a specifically designed speech pathology intervention or a placebo intervention. Participants in both groups attended four intervention sessions with a qualified speech pathologist. Results: Participants in the treatment group had a significant reduction in cough (8.9 to 4.6, p, 0.001), breathing (7.9 to 4.7, p < 0.001), voice (7.3 to 4.6, p < 0.001) upper airway (8.9 to 5.9, p < 0.001) symptom scores and limitation (2.3 to 1.6, p < 0.001) ratings following intervention. There was also a significant reduction in breathing (6.8 to 5.6, p=0.047), cough (7.6 to 6.3, p=0.014), and limitation ( 2.3 to 2.0, p=0.038) scores in the placebo group, but the degree of improvement was significantly less than in the treatment group (p < 0.01). Clinical judgement of outcome indicated successful ratings in 88% of participants in the treatment group compared with 14% in the placebo group ( p, 0.001). Conclusion: Speech pathology is an effective management intervention for chronic cough which may be a viable alternative for patients who do not respond to medical treatment.

Hippocampal pathology in progressive supranuclear palsy (PSP): a quantitative study of 8 cases

Objective: To quantify the neuronal and glial cell pathology in the hippocampus and the parahippocampal gyrus (PHG) of 8 cases of progressive supranuclear palsy (PSP). Material: tau-immunolabeled sections of the temporal lobe of 8 diagnosed cases of PSP. Method: The densities of lesions were measured in the PHG, CA sectors of the hippocampus and the dentate gyrus (DG) and studied using spatial pattern analysis. Results: Neurofibrillary tangles (NFT) and abnormally enlarged neurons (EN) were most frequent in the PHG and in sector CA1 of the hippocampus, oligodendroglial inclusions (“coiled bodies”) (GI) in the PHG, subiculum, sectors CA1 and CA2, and neuritic plaques (NP) in sectors CA2 and CA4. The DG was the least affected region. Vacuolation and GI were observed in the alveus. No tufted astrocytes (TA) were observed. Pathological changes exhibited clustering, the lesions often exhibiting a regular distribution of the clusters parallel to the tissue boundary. There was a positive correlation between the degree of vacuolation in the alveus and the densities of NFT in CA1 and GI in CA1 and CA2. Conclusion: The pathology most significantly affected the output pathways of the hippocampus, lesions were topographically distributed, and hippocampal pathology may be one factor contributing to cognitive decline in PSP.

Interhemispheric differences of spectral power in expressive language:a MEG study with clinical applications

In the last decade we have seen an exponential growth of functional imaging studies investigating multiple aspects of language processing. These studies have sparked an interest in applying some of the paradigms to various clinically relevant questions, such as the identification of the cortical regions mediating language function in surgical candidates for refractory epilepsy. Here we present data from a group of adult control participants in order to investigate the potential of using frequency specific spectral power changes in MEG activation patterns to establish lateralisation of language function using expressive language tasks. In addition, we report on a paediatric patient whose language function was assessed before and after a left hemisphere amygdalo-hippocampectomy. Our verb generation task produced left hemisphere decreases in beta-band power accompanied by right hemisphere increases in low beta-band power in the majority of the control group, a previously unreported phenomenon. This pattern of spectral power was also found in the patient's post-surgery data, though not her pre-surgery data. Comparison of pre and post-operative results also provided some evidence of reorganisation in language related cortex both inter- and intra-hemispherically following surgery. The differences were not limited to changes in localisation of language specific cortex but also changes in the spectral and temporal profile of frontal brain regions during verb generation. While further investigation is required to establish concordance with invasive measures, our data suggest that the methods described may serve as a reliable lateralisation marker for clinical assessment. Furthermore, our findings highlight the potential utility of MEG for the investigation of cortical language functioning in both healthy development and pathology.

Progressive supranuclear palsy (PSP): general pathology and visual signs and symptoms

Progressive supranuclear palsy (PSP) is a rare, degenerative disorder of the brain believed to affect between 1.39 and 6.6 individuals per 100,000 of the population. The disorder is likely to be more common than suggested by these data due to difficulties in diagnosis and especially in distinguishing PSP from other conditions with similar symptoms such as multiple system atrophy (MSA), corticobasal degeneration (CBD), and Parkinson’s disease (PD). PSP was first described in 1964 by Steele, Richardson and Olszewski and originally called Steele-Richardson-Olszewski syndrome. The disorder is the second commonest syndrome in which the patient exhibits ‘parkinsonism’, viz., a range of problems involving movement most typically manifest in PD itself but also seen in PSP, MSA and CBD. Although primarily a brain disorder, patients with PSP exhibit a range of visual clinical signs and symptoms that may be useful in differential diagnosis. Hence, the present article describes the general clinical and pathological features of PSP, its specific visual signs and symptoms, discusses the usefulness of these signs in differential diagnosis, and considers the various treatment options.

TDP-43-Immunoreactive pathology in frontotemporal lobar degeneration with TDP proteinopathy (FTLD-TDP) with and without associated motor neuron disease

A proportion of patients with motor neuron disease (MND) exhibit frontotemporal dementia (FTD) and some patients with FTD develop the clinical features of MND. Frontotemporal lobar degeneration (FTLD) is the pathological substrate of FTD and some forms of this disease (referred to as FTLD-U) share with MND the common feature of ubiquitin-immunoreactive, tau-negative cellular inclusions in the cerebral cortex and hippocampus. Recently, the transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) has been found to be a major protein of the inclusions of FTLD-U with or without MND and these cases are referred to as FTLD with TDP-43 proteinopathy (FTLD-TDP). To clarify the relationship between MND and FTLD-TDP, TDP-43 pathology was studied in nine cases of FTLD-MND and compared with cases of familial and sporadic FTLD–TDP without associated MND. A principal components analysis (PCA) of the nine FTLD-MND cases suggested that variations in the density of surviving neurons in the frontal cortex and neuronal cytoplasmic inclusions (NCI) in the dentate gyrus (DG) were the major histological differences between cases. The density of surviving neurons in FTLD-MND was significantly less than in FTLD-TDP cases without MND, and there were greater densities of NCI but fewer neuronal intranuclear inclusions (NII) in some brain regions in FTLD-MND. A PCA of all FTLD-TDP cases, based on TDP-43 pathology alone, suggested that neuropathological heterogeneity was essentially continuously distributed. The FTLD-MND cases exhibited consistently high loadings on PC2 and overlapped with subtypes 2 and 3 of FTLD-TDP. The data suggest: (1) FTLD-MND cases have a consistent pathology, variations in the density of NCI in the DG being the major TDP-43-immunoreactive difference between cases, (2) there are considerable similarities in the neuropathology of FTLD-TDP with and without MND, but with greater neuronal loss in FTLD-MND, and (3) FTLD-MND cases are part of the FTLD-TDP ‘continuum’ overlapping with FTLD-TDP disease subtypes 2 and 3.

Temporal lobe pathology in neurodegenerative disease:a comparative study of eight disorders with special reference to the hippocampus

The temporal lobe is a major site of pathology in a number of neurodegenerative diseases. In this chapter, the densities of the characteristic pathological lesions in various regions of the temporal lobe were compared in eight neurodegenerative disorders, viz., Alzheimer’s disease (AD), Down’s syndrome (DS), dementia with Lewy bodies (DLB), Pick’s disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), sporadic Creutzfeldt-Jakob disease (sCJD), and neuronal intermediate filament inclusion disease (NIFID). Temporal lobe pathology was observed in all of these disorders most notably in AD, DS, PiD, sCJD, and NIFID. The regions of the temporal lobe affected by the pathology, however, varied between disorders. In AD and DS, the greatest densities of ?-amyloid (A?) deposits were recorded in cortical regions adjacent to the hippocampus (HC), DS exhibiting greater densities of A? deposits than AD. Similarly, in sCJD, greatest densities of prion protein (PrPsc) deposits were recorded in cortical areas of the temporal lobe. In AD and PiD, significant densities of neurofibrillary tangles (NFT) and Pick bodies (PB) respectively were present in sector CA1 of the HC while in CBD, the greatest densities of tau-immunoreactive neuronal cytoplasmic inclusions (NCI) were present in the parahippocampal gyrus (PHG). Particularly high densities of PB were present in the DG in PiD, whereas NFT in AD and Lewy bodies (LB) in DLB were usually absent in this region. These data confirm that the temporal lobe is an important site of pathology in the disorders studied regardless of their molecular ‘signature’. However, disorders differ in the extent to which the pathology spreads to affect the HC which may account for some of the observed differences in clinical dementia.