Utilization of fresh human tympanic membranes for structural analysis and cytokeratin immunocytochemistry implementing resin techniques.

Abstract

The results of this study have demonstrated for the first time that tympanic membrane (TM) structure is preserved following removal of fresh, normal tissue from patients undergoing surgery. Greater clarity has been demonstrated using resin sections than in previous studies on paraffin sections. Of particular note, cytokeratin (CK) immunocytochemistry was successfully performed on resin sections, which has not been previously reported. This may have potential applications for future work involving tissues that express CKs.
To analyse the structure of normal, fresh human TM specimens after surgical removal and to evaluate their CK immunocytochemistry using resin techniques, neither of which have been demonstrated previously.
Seven TM specimens were removed during surgery and then preserved in a modified Karnovsky's fixative. Semi-thin and thin sections were examined by means of light and electron microscopy, respectively. For comparison purposes, paraffin block-embedded specimens were also sectioned. CK immunocytochemistry was performed on semi-thin sections using standard immunoperoxidase techniques, with expression being demonstrated using light microscopy.
The three-layer architecture of the TM was preserved. The morphology of the TM was vastly superior in the semi-thin resin sections than in the thicker paraffin sections. The outer, middle and inner layers were clearly demonstrated. The integrity of the outer epithelial layer was maintained, with an outer keratinizing stratum corneum and underlying stratum granulosum, stratum spinosum and stratum basale layers resting on the basal lamina. The thin inner mucosal layer was also viable, consisting of simple squamous or cuboidal cells. Preservation of the middle lamina propria was achieved, with demonstration of the outer radial and inner circular fibres. CK immunocytochemistry utilizing resin techniques provided excellent staining of CK 7 and 8 in the inner layer, with positive staining of CK 5 and 10 in the outer layer.

Full text

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Staff Publications 2005 to 2006


Acta Otolaryngologica. 2006; 126(2): 149-53.
Utilization of fresh human tympanic membranes for structural analysis and cytokeratin
immunocytochemistry implementing resin techniques.
Anandacoomaraswamy KS, Dutton N, et al.
School of Surgery and Pathology, The University of Western Australia, Australia. dockeith@cyllene.uwa.edu.au
CONCLUSIONS: The results of this study have demonstrated for the first time that tympanic membrane (TM)
structure is preserved following removal of fresh, normal tissue from patients undergoing surgery. Greater
clarity has been demonstrated using resin sections than in previous studies on paraffin sections. Of particular
note, cytokeratin (CK) immunocytochemistry was successfully performed on resin sections, which has not been
previously reported. This may have potential applications for future work involving tissues that express CKs.
OBJECTIVES: To analyse the structure of normal, fresh human TM specimens after surgical removal and to
evaluate their CK immunocytochemistry using resin techniques, neither of which have been demonstrated
previously. MATERIAL AND METHODS: Seven TM specimens were removed during surgery and then
preserved in a modified Karnovsky's fixative. Semi-thin and thin sections were examined by means of light and
electron microscopy, respectively. For comparison purposes, paraffin block-embedded specimens were also
sectioned. CK immunocytochemistry was performed on semi-thin sections using standard immunoperoxidase
techniques, with expression being demonstrated using light microscopy. RESULTS: The three-layer
architecture of the TM was preserved. The morphology of the TM was vastly superior in the semi-thin resin
sections than in the thicker paraffin sections. The outer, middle and inner layers were clearly demonstrated.
The integrity of the outer epithelial layer was maintained, with an outer keratinizing stratum corneum and
underlying stratum granulosum, stratum spinosum and stratum basale layers resting on the basal lamina. The
thin inner mucosal layer was also viable, consisting of simple squamous or cuboidal cells. Preservation of the
middle lamina propria was achieved, with demonstration of the outer radial and inner circular fibres. CK
immunocytochemistry utilizing resin techniques provided excellent staining of CK 7 and 8 in the inner layer,
with positive staining of CK 5 and 10 in the outer layer.

AJNR American Journal of Neuroradiology. 2006; 27(2): 430-9.
Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss.
House MJ, St Pierre TG, et al.
School of Physics, University of Western Australia
BACKGROUND AND PURPOSE: In Alzheimer disease (AD), elevated brain iron concentrations in gray matter
suggest a disruption in iron homeostasis, while demyelination processes in white matter increase the water
content. Our aim was to assess whether the transverse proton relaxation rate, or R2, an MR imaging
parameter affected by changes in brain iron concentration and water content, was different in elderly
participants with mild to severe levels of cognitive impairment compared with healthy controls. METHODS:
Twelve elderly participants reporting memory problems and 11 healthy volunteers underwent single-spin-echo
MR imaging in a 1.5T scanner, with subsequent neuropsychological testing. R2 data were collected from 14
brain regions in cortical and subcortical gray and white matter. Those with memory complaints were separated
into 2 further subgroups: MC1 (no objective cognitive impairment) and MC2 (mild to severe objective cognitive
impairment). RESULTS: Mean brain R2 values from the 11 controls correlated strongly (r = 0.94, P < .0001)
with reference brain iron concentrations for healthy adults. R2 values in the MC1 and MC2 subgroups were
significantly higher in the right temporal cortex and significantly lower in the left internal capsule, compared with
healthy controls. R2 values in the MC2 subgroup were significantly lower in the left temporal and frontal white
matter, compared with healthy controls. CONCLUSIONS: R2 differences between both subgroups and the
healthy controls suggest iron has increased in the temporal cortex, and myelin has been lost from several white
matter regions in those with memory complaints, consistent with incipient AD pathogenesis and biochemical
data.

Am J Geriatr Psychiatry. 2005; 13(9): 802-7.
Specificity of symptoms of depression in Alzheimer disease: a longitudinal analysis.
Starkstein SE, Mizrahi R, et al.
Education Building T-7, Fremantle Hospital, Fremantle, 6959 WA, Australia. ses@cyllene.uwa.edu.au
OBJECTIVE: Authors examined the temporal stability of symptoms of major and minor depression and apathy
in dementia. METHODS: A consecutive sample of 65 patients with Alzheimer disease (AD) and depression at
baseline evaluation received a follow-up psychiatric assessment that included the Structured Clinical Interview
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for DSM-IV and the Hamilton Rating Scale for Depression an average of 17 months later. RESULTS: Half of
the sample had no depression at follow-up, and showed a significant improvement in sadness, guilt, suicidal
ideation, disruption in sleep, loss of interest, loss of energy, thoughts of death, social withdrawal, psychomotor
changes, changes in appetite/weight, and symptoms of anxiety. No significant changes were found on scores
of irritability or apathy. CONCLUSIONS: The study demonstrates the specificity of depressive symptoms in AD
and suggests that apathy and depression are different behavioral domains.
PMID:16166410

American Heart Journal. 2006; 151(2): 537-44.
Asymptomatic long-term survivors of coronary artery bypass surgery enjoy a quality of life equal to the
general population.
Bradshaw PJ, Jamrozik KD, et al.
aInstitute for Clinical Evaluative Sciences (ICES) Toronto, Ontario, Canada
bDepartment of Epidemiology, University of Queensland, Brisbane, Queensland, Australia
cDepartment of Cardiothoracic Surgery, Fremantle Hospital, Fremantle, Western Australia, Australia (Gilfillan)
dMedicine and Population Health, University of Western Australia and Cardiologist, Sir Charles Gairdner
Hospital, Nedlands, Western Australia, Australia
BACKGROUND: Health-related quality of life (HRQOL) among long-term survivors of coronary artery bypass
surgery is an important outcome that has been little studied at the population level. METHODS: A postal survey
was conducted in 1999 to 2000 in patients 6 to 20 years after coronary artery bypass graft (CABG) surgery in
Western Australia. A random stratified sample of 2500 was drawn from 8910 patients who had their first CABG
surgery in 1980 to 1993. Health-related quality of life was measured with Short Form 36 and EuroQol visual
analogue scale. RESULTS: Response was 82% (n = 2061). Health-related quality of life declined with age and
was similar for men and women, although scores for women were worse for physical functioning. Compared
with Australian population norms, the age- and sex-standardized scores of survivors of CABG were generally
worse, mainly in the physical domain. Reported angina at the time of follow-up (33%), symptoms of heart
failure equivalent to New York Heart Association (NYHA) classes II to IV (34%), and comorbidities such as
diabetes and hypertension were associated with poorer HRQOL. For both men and women without angina or
heart failure at follow-up, HRQOL was no different from that of the general population. CONCLUSION: Overall,
the quality of life among long-term survivors of CABG is worse than that of the general population, the
difference being mainly attributable to recurrent symptoms and comorbidities. Quality of life for those without
angina or heart failure at follow-up was equivalent to the population norms, providing an incentive to maximize
efforts to abolish angina and ameliorate heart failure symptoms.

American Journal of Geriatric Psychiatry 2006; 14(7): 573-581.
Phenomenology and Clinical Correlates of Delusions in Alzheimer Disease.
Mizrahi R, Starkstein SE, et al.
School of Psychiatry and Clinical Neurosciences, University of Western Australia, and Fremantle Hospital,
Western Australia, Australia (SES), the Department of and Psychiatry, University of Iowa, Iowa City (RJ, RGR),
and the PET Center for Addiction and Mental Health, Clarke Division, Toronto, Canada (RM).
Objectives: The objectives of this study were to determine whether anosognosia, depression, and elevated
mood are associated with delusions in Alzheimer disease (AD), and to examine the validity of standardized
diagnostic criteria for psychosis of dementia. Method: The authors assessed a consecutive series of 771
patients with AD attending a dementia clinic with a comprehensive neuropsychologic and psychiatric evaluation
that included specific measures of delusions, hallucinations, anosognosia, depression, and elevated mood.
Results: Delusions were found in one-third of the patients and hallucinations in 7%. Most patients with
hallucinations also had delusions. A principal component analysis of the Psychosis Dementia Scale, which
rates the presence and severity of delusions, produced the factors of paranoid misidentification and expansive
delusions. Paranoid, but not expansive, delusions increased across the stages of the illness. Anosognosia and
depression were significantly and independently associated with the presence of delusions, whereas elevated
mood was significantly associated with expansive, but not paranoid, delusions. A multiple logistic regression
analysis demonstrated that delusions in AD were significantly associated with depression, anosognosia, overt
aggression, and agitation. Conclusions: Anosognosia, depression, global cognitive deficits, and elevated mood
are the main psychiatric correlates of paranoid misidentification and expansive delusions in AD, whereas overt
aggression and agitation are the most frequent behavioral concomitants of psychosis in AD.

American Journal of Psychiatry. 2005; 162(11): 2086-2093.
The construct of minor and major depression in Alzheimer's disease.
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Starkstein SE, Jorge R, et al.
Dr. S.E. Starkstein, Fremantle Hospital, Education Building T-7, Fremantle, WA 6959; Australia. E-Mail:
ses@cyllene.uwa.edu.au
Objective: This study examined the frequency of major and minor depression in Alzheimer's disease and
determined whether these types of depression have a different functional and psychopathological impact and
whether there is a change in the prevalence of major and minor depression throughout the stages of
Alzheimer's disease. Method: A consecutive series of 670 patients with probable Alzheimer's disease were
assessed with the Structured Clinical Interview for DSM-IV; specific instruments to rate the presence and
severity of depression, anxiety, apathy, irritability, delusions, pathological affective crying, performance of
activities of daily living, and social functioning; and a standardized neuropsychological evaluation. Diagnoses of
major and minor depression were generated from DSM-IV criteria. Results: Twenty-six percent of the patients
had major depression, 26% had minor depression, and 48% were not depressed. Major depression was
significantly associated with sad mood in all three stages of the illness, although this association dropped
significantly for minor depression in severe Alzheimer's disease. Both major and minor depression were
significantly associated with more severe psychopathology, functional impairments, and social dysfunction.
Depressive symptoms that most strongly discriminated between Alzheimer's disease patients with and without
sad mood were guilty ideation, suicidal ideation, loss of energy, insomnia, weight loss, psychomotor
retardation/agitation, poor concentration, and loss of interest. Conclusions: Our study demonstrates that DSM-
IV criteria for major and minor depression identify clinically relevant syndromes of depression in Alzheimer's
disease, mild levels of depression can produce significant functional impairment, and the severity of
psychopathological and neurological impairments increases with increasing severity of depression.
PMID:2005508255

American Journal of Psychiatry. 2005; 162(11): 2086-2093.
The construct of minor and major depression in Alzheimer's disease.
Starkstein SEMDPD, Jorge RMD, et al.
School of Psychiatry and Clinical Neurosciences and Fremantle Hospital, University of Western Australia; the
Department of and Psychiatry, University of Iowa, Iowa City; and the PET Center for Addiction and Mental
Health, Clarke Division, Toronto.
Objective: This study examined the frequency of major and minor depression in Alzheimer's disease and
determined whether these types of depression have a different functional and psychopathological impact and
whether there is a change in the prevalence of major and minor depression throughout the stages of
Alzheimer's disease., Method: A consecutive series of 670 patients with probable Alzheimer's disease were
assessed with the Structured Clinical Interview for DSM-IV; specific instruments to rate the presence and
severity of depression, anxiety, apathy, irritability, delusions, pathological affective crying, performance of
activities of daily living, and social functioning; and a standardized neuropsychological evaluation. Diagnoses of
major and minor depression were generated from DSM-IV criteria., Results: Twenty-six percent of the patients
had major depression, 26% had minor depression, and 48% were not depressed. Major depression was
significantly associated with sad mood in all three stages of the illness, although this association dropped
significantly for minor depression in severe Alzheimer's disease. Both major and minor depression were
significantly associated with more severe psychopathology, functional impairments, and social dysfunction.
Depressive symptoms that most strongly discriminated between Alzheimer's disease patients with and without
sad mood were guilty ideation, suicidal ideation, loss of energy, insomnia, weight loss, psychomotor
retardation/agitation, poor concentration, and loss of interest., Conclusions: Our study demonstrates that DSM-
IV criteria for major and minor depression identify clinically relevant syndromes of depression in Alzheimer's
disease, mild levels of depression can produce significant functional impairment, and the severity of
psychopathological and neurological impairments increases with increasing severity of depression., Copyright
(C) 2005 American Psychiatric Association.

Annals of Clinical Biochemistry. 2005; 42(Pt 4): 304-7.
Alcohol-associated severe hyperhomocysteinaemia.
Gillett MJ, Burnett JR.
Department of Core Clinical Pathology and Biochemistry, Royal Perth Hospital, Wellington Street, GPO Box
X2213, Perth, WA 6847, Australia
Publication Types: Case Reports

Annals of Emergency Medicine 2006; 47(4): 373-380.
Second symposium on the definition and management of anaphylaxis: summary report--second
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National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.
Sampson HA, Munoz-Furlong A, et al.
Fremantle Hospital, Fremantle, WA, Australia (SG Brown)
There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the
National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a
second meeting on anaphylaxis, which included representatives from 16 different organizations or government
bodies, including representatives from North America, Europe, and Australia, to continue working toward a
universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of
anaphylaxis with high precision, further review the evidence on the most appropriate management of
anaphylaxis, and outline the research needs in this area.

Annals of Oncology 9th International Conference on Malignant Lymphoma. 2005; 16 Supplement(5): v155-
v156.
Radioimmunotherapy with iodine-131 anti-CD20 chimeric monoclonal antibody (rituximab) for relapsed
or refractory indolent non-Hodgkin's Lymphoma: results of an Australian phase II trial.
Leahy MF, Seymour JF, et al.
(1)Haematology, Fremantle Hospital, Fremantle, WA, Australia, (2)Peter MacCallum Cancer Centre,
Melbourne, VIC, Australia
Publication Types: Abstract

Antimicrobial Agents & Chemotherapy. 2006; 50(3): 968-74.
Artesunate suppositories versus intramuscular artemether for treatment of severe malaria in children
in Papua New Guinea.
Karunajeewa HA, Reeder J, et al.
Medicine Unit Fremantle, School of Medicine and Pharmacology, University of Western Australia, Crawley
Drug treatment of severe malaria must be rapidly effective. Suppositories may be valuable for childhood
malaria when circumstances prevent oral or parenteral therapy. We compared artesunate suppositories (n =
41; 8 to 16 mg/kg of body weight at 0 and 12 h and then daily) with intramuscular (i.m.) artemether (n = 38; 3.2
mg/kg at 0 h and then 1.6 mg/kg daily) in an open-label, randomized trial with children with severe Plasmodium
falciparum malaria in Papua New Guinea (PNG). Parasite density and temperature were measured every 6 h
for >/=72 h. Primary endpoints included times to 50% and 90% parasite clearance (PCT(50) and PCT(90)) and
the time to per os status. In a subset of 29 patients, plasma levels of artemether, artesunate, and their common
active metabolite dihydroartemisinin were measured during the first 12 h. One suppository-treated patient with
multiple complications died within 2 h of admission, but the remaining 78 recovered uneventfully. Compared to
the artemether-treated children, those receiving artesunate suppositories had a significantly earlier mean
PCT(50) (9.1 versus 13.8 h; P = 0.008) and PCT(90) (15.6 versus 20.4 h; P = 0.011). Mean time to per os
status was similar for each group. Plasma concentrations of primary drug plus active metabolite were
significantly higher in the artesunate suppository group at 2 h postdose. The earlier initial fall in parasitemia
with artesunate is clinically advantageous and mirrors higher initial plasma concentrations of active
drug/metabolite. In severely ill children with malaria in PNG, artesunate suppositories were at least as effective
as i.m. artemether and may, therefore, be useful in settings where parenteral therapy cannot be given.
PMID:16495259

ANZ J Surg. 2005; 75(5): 282-5.
Performing a colonoscopy 12 months after surgery for colorectal neoplasia.
Platell C, Salama P, et al.
The Colorectal Surgical Unit, Fremantle Hospital and the Department of Surgery, University of Western
Australia, Australia. cplatell@cyllene.uwa.edu.au
BACKGROUND: There appears to be acceptance that following up patients after surgery for colorectal
neoplasia is of value. However, specific issues relating to which investigations to perform and how often remain
unresolved. The aim of this project was to evaluate the clinical utility of performing a colonoscopy 12 months
after curative surgery for colorectal neoplasia. METHODS: Patients were selected if they had undergone a
curative resection for colorectal neoplasia, and if they had had a completed colonoscopy prior to surgery. Study
endpoints included: (i) compliance with follow up; (ii) the prevalence, total number, size, and histology of
polyps; and (iii) identification of recurrent or metachronous cancer. RESULTS: The study group included 253
patients of mean age 69.7 years (SD 11.6) and a male : female ratio of 1.4:1.0. Colonoscopies were completed
on 90% of patients at a mean of 1.1 years following surgery. A total of 149 polyps were identified in 30% of
patients. On histology, 42% were tubular adenomas, 6% tubulo-villous adenomas, 7% were villous adenomas,
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and 37% were hyperplastic. Advanced adenomas were identified in 7.9% of patients (95% CI 4.8-12.1%). No
recurrent or metachronous cancers were identified. CONCLUSION: We have observed a high prevalence of
advanced adenomas in patients undergoing a 12-month, follow-up colonoscopy after curative surgery for
colorectal neoplasia. The significance of these observations requires further evaluation.
PMID:15932437

ANZ Journal of Surgery. 2005; 75(11): 929-935.
Colorectal cancer surgical care and survival: do private health insurance, socioeconomic and
locational status make a difference?
Hall SE, Holman CDAJ, et al.
(*)School of Population Health, University of Western Australia, Crawley, Australia, +Department of Surgery,
University of Western Australia, Fremantle Hospital, Fremantle, Australia, ++WA Clinical Oncology Group,
Cancer Council of Western Australia, West Perth, Australia, [S]Western Australian Cancer Registry,
Department of Health, East Perth, Western Australia, Australia
Background: The purpose of the present paper was to examine patterns of surgical care and the likelihood of
death within 5 years after a diagnosis of colorectal cancer, including the effects of demographic, locational and
socioeconomic disadvantage and the possession of private health insurance., Methods: The Western
Australian Data Linkage System was used to extract all hospital morbidity, cancer and death records for people
with a diagnosis of colorectal cancer from 1982 to 2001. Demographic, hospital and private health insurance
information was available for all years and measures of socioeconomic and locational disadvantage from 1991.
A logistic regression model estimated the probability of receiving colorectal surgery. A Cox regression model
estimated the likelihood of death from any cause within 5 years of diagnosis., Results: People were more likely
to undergo colorectal surgery if they were younger, had less comorbidity and were married/defacto or divorced.
People with a first admission to a private hospital (odds ratio (OR) 1.31, 95% confidence interval (CI): 1.16-
1.48) or with private health insurance (OR 1.27, 95% CI: 1.14-1.42) were more likely to undergo surgery. Living
in a rural or remote area made little difference, but a first admission to a rural hospital reduced the likelihood of
surgery (OR 0.76, 95% CI: 0.66-0.87). Residency in lower socioeconomic areas also made no difference to the
likelihood of having surgical treatment. The likelihood of death from any cause was lower in those who were
younger, had less comorbidity, were elective admissions and underwent surgery. Residency in lower
socioeconomic status and rural areas, admission to a rural hospital or a private hospital and possession of
private health insurance had no effect on the likelihood of death., Conclusions: The present study
demonstrates that socioeconomic and locational status and access to private health care had no significant
effects on surgical patterns of care in people with colorectal cancer. However, despite the higher rates of
surgery in the private hospitals and among those with private health insurance, their survival was no better.,
Copyright (C) 2005 Blackwell Publishing Ltd.
Publication Types: Article

Archives of General Psychiatry. 2005; 62(7): 742-9.
Alcohol misuse and mood disorders following traumatic brain injury.
Jorge RE, Starkstein SE, et al.
Department of Psychiatry, The University of Iowa, Iowa City (Drs Jorge, Arndt, Moser, Crespo-Facorro, and
Robinson); and School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth
(Dr Starkstein)
CONTEXT: Alcohol abuse and/or dependence (AA/D) and mood disturbance are co-occurring conditions
among patients who have had a traumatic brain injury (TBI). However, the relationship between these
disorders has not been extensively studied. OBJECTIVE: To examine the relationship of AA/D and post-TBI
mood disorders and the effect of these conditions on psychosocial outcome. DESIGN: Prospective, case-
control surveillance study conducted during the first year following trauma.Settings University hospital level I
trauma centers and specialized rehabilitation units.Patients One hundred fifty-eight TBI patients with closed
head injury with and without a history of AA/D. METHODS: We prospectively compared psychiatric,
neuropsychological, and psychosocial outcomes among the patients, who were evaluated at baseline and at 3,
6, and 12 months after trauma. Psychiatric diagnosis was made using a structured clinical interview and DSM-
IV criteria. Neuropsychological testing results and quantitative magnetic resonance images were obtained at
the 3-month follow-up. RESULTS: A history of AA/D was significantly more frequent among patients who
developed mood disorders during the first year following TBI. There was also a significantly higher frequency of
mood disorders among patients with alcohol abuse relapse. Patients with a history of AA/D had significantly
reduced frontal gray matter volumes than did patients without a history of alcohol abuse. In addition, patients
who resumed alcohol abuse had decreased medial frontal gray matter volumes and impaired performance in
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executive tasks. Both AA/D and mood disorders following TBI were associated with a poor vocational outcome.
CONCLUSIONS: Previous alcohol abuse increases the risk of developing mood disorders after TBI, and
emotional disturbance, in turn, increases the risk of alcohol abuse relapse. Alcohol's neurotoxic effects and TBI
likely interact to produce greater disruption of the neural circuits that modulate reward, mood, and executive
function. Patients with a history of AA/D who also developed mood disorders following TBI had major difficulties
resuming a productive life.

Arterioscler Thromb Vasc Biol. 2005; 25(1): 39-46.
Vitamin D, shedding light on the development of disease in peripheral arteries.
Norman PE, Powell JT.
School of Surgery and Pathology, The University of Western Australia, Fremantle Hospital, Fremantle, Western
Australia.
Vitamin D is generally associated with calcium metabolism, especially in the context of uptake in the intestine
and the formation and maintenance of bone. However, vitamin D influences a wide range of metabolic systems
through both genomic and nongenomic pathways that have an impact on the properties of peripheral arteries.
The genomic effects have wide importance for angiogenesis, elastogenesis, and immunomodulation; the
nongenomic effects have mainly been observed in the presence of hypertension. Although some vitamin D is
essential for cardiovascular health, excess may have detrimental effects, particularly on elastogenesis and
inflammation of the arterial wall. Vitamin D is likely to have a role in the paradoxical association between
arterial calcification and osteoporosis. This review explores the relationship between vitamin D and a range of
physiological and pathological processes relevant to peripheral arteries.
PMID:15499037

Arthritis and Rheumatism. 2005; 52(9): S75-S76.
Primary osteoarthritis in the ankle joint is strongly associated with HFE gene mutations.
Carroll GJ.
Fremantle Hosp, Fremantle, Australia
PMID:ISI:000232207800126

Australas Psychiatry. 2005; 13(1): 80-2.
Severe tachycardia following low-dose clozapine treatment.
Stampfer H, Swanepoel P.
1Senior Lecturer, University Department of Psychiatry and Behavioural Science, QEII Medical Centre,
Nedlands, WA, Australia. hgstamp@cyllene.uwa.edu.au
2Head, Mental Health Service, Alma Street Centre, Fremantle Hospital, WA, Australia.
OBJECTIVE: To report a case of severe and sustained tachycardia that developed asymptomatically on a low
dose of clozapine (150 mg daily). METHOD: Case report. RESULTS: Serially monitored 24 h heart rate after
the introduction of clozapine showed an increase in the 24 h mean from 87 to 126 bpm, a reduction of pulse
variability and anomalies in sleep-wake regulation. Cessation of clozapine was followed by a rapid return to
preclozapine activity. Application of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable
relationship between clozapine and the sustained tachycardia. CONCLUSIONS: Severe and sustained
tachycardia can develop asymptomatically with a relatively low dose of clozapine and a slow titration rate. The
severity of the tachycardia may not be revealed in isolated pulse measurements and may escape clinical
detection without closer monitoring of heart rate.
PMID:15777419

Australian & New Zealand Journal of Public Health. 2006; 30(2): 123-127.
ECHO: The Western Australia emergency care hospitalisation and outcome linked data project.
Sprivulis P, Da Silva JA, et al.
Department of Emergency Medicine, Fremantle Hospital, Western Australia.
Prof. I. Jacobs, School of Primary, Aboriginal and Rural Health Care, Faculty of Medicine and Dentistry,
University of Western Australia (M516), 35 Stirling Highway, Crawley, WA 6009; Australia. E-Mail:
ian.jacobs@uwa.edu.au.
Objective: To describe and assess the quality of the data resources linked for the Western Australian
Emergency Care Hospitalisation and Outcome (ECHO) project. Methods: The ECHO project links electronic
records from the WA Emergency Department Information System to the St John Ambulance Service Pre-
Hospital Care Database, the WA Hospital Morbidity Data System and the WA Mortality Database. Linkages are
created using standard probabilistic matching techniques with extensive clerical review. Commencing with all
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metropolitan Perth public emergency departments from July 2000, these linkages will be updated annually for
at least five successive years. The proportion of actual linkages between emergency department records and
ambulance, admission and death records was assessed in comparison to expected linkage rates. Results: Of
578,200 total emergency department records, there were 144,897 emergency presentations recorded as
arriving by ambulance, of which 135,332 (93.4%) were linked to an ambulance record pertaining to the same
episode. Of the 165,650 presentations recorded as admitted, 162,216 (97.9%) were linked to a hospital
morbidity record relating to the same episode. Furthermore, 96.2% of the 2,084 cases recorded as'dead on
arrival' and 98.9% of the 624 cases recorded as 'died in emergency' were linked to a corresponding death
record. Conclusions: Linkage quality consistent with international standards has been achieved, resulting in an
information infrastructure capable of supporting an extensive research agenda focusing on the interaction and
outcomes of both pre-hospital and within-hospital emergency medical care services.
PMID:2006207147

Australian Family Physician. 2006; 35(1-2): 70-2.
Grey nomads--health and health preparation of older travellers in remote Australia.
Tate J, Mein J, et al.
BACKGROUND: Many older Australians now tour remote Australia (so called 'grey nomads'). Anecdote
suggests they place a burden on limited remote health services, however, this burden is poorly documented.
METHODS: Two groups were approached to participate in the survey: travellers aged 50 years or over and
staying in caravans, motor homes or tents at Fitzroy Crossing, Western Australia; and local primary health care
providers. RESULTS: All 260 travellers approached responded. The prevalence of chronic diseases in those
aged 65 years or over was 68%; 57% had sufficient chronic medications for the entire trip; 19% had a list of
long term medications; and 9% of those with chronic diseases had a health summary from their usual general
practitioner. Sixty-four local health providers responded: 95% rated health summaries highly (particularly if they
included an active problem list, past history, current medications, and allergies). DISCUSSION: Older patients
are poorly prepared for travel in remote Australia. They have a chronic disease rate no less than the national
prevalence and could represent a drain on local health resources. Solutions might include GP review before
travel, bringing sufficient medication for the trip, review of vaccination requirements, and a health summary.
PMID:16489392

Best Practice. 2006; 10(1): 1-4.
Management of asymptomatic hypoglycaemia in healthy term neonates for nurses and midwives.
Hewitt V, Watts R.
Curtin University of Technology and The Western Australian Centre for Evidence-based Nursing and Midwifery
(a collaborating centre of the Joanna Briggs Institute), Perth, Western Australia, Australia
Publication Types: Clinical Guideline

Bioessays. 2005; 27(11): 1192-202.
Jekyll and Hyde: evolving perspectives on the function and potential of the adult liver progenitor (oval)
cell.
Knight B, Matthews VB, et al.
School of Medicine and Pharmacology, University of Western Australia.
The liver progenitor cell (LPC) has enormous potential for use in cell therapy to treat liver disease. Since liver
regenerates readily from pre-existing hepatocytes, a role for LPCs and, indeed, their existence have been
questioned. Research during the last decade has established that LPCs are an important alternative source of
cells for liver regeneration. Their utility for cell therapy lies in their ability to generate both hepatocytes and
cholangiocytes. However, they are observed in liver diseases that often lead to cancer and there is
experimental evidence that implicates LPCs as the source of tumours. This article provides a brief history of the
studies that established the functional importance of LPCs in liver disease. It focuses on mouse models that
have led to the identification of factors that regulate LPC growth and differentiation and discusses LPCs
derived from different sources. Recent promising results from both in vitro and vivo studies suggest that LPCs
could be useful for cell therapy. In the context of liver disease, LPCs may indeed be the cell of the future and
understandably "our favourite cell".
PMID:16237666

Blood Pressure. 2005; 14(6): 337-344.
Swiss Hypertension and Risk Factor Program (SHARP): Cardiovascular risk factors management in
patients with type 2 diabetes in Switzerland.
12th April 2007-04-12 7

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Pechere-Bertschi A, Greminger P, et al.
Ferrari P (reprint author), Univ Western Australia, Sch Med & Pharmacol, Alma St, Perth, WA 6160 Australia
Univ Hosp Geneva, Div Endocrinol, Geneva, Switzerland
Univ Hosp Geneva, Med Policlin, Geneva, Switzerland
Univ Spital Zurich, Med Poliklin, Zurich, Switzerland
Brunner & Hess Software, Zurich, Switzerland
Univ Western Australia, Fremantle Hosp, Dept Nephrol, Perth, WA 6160 Australia
E-mail Addresses: paolo.ferrari@health.wa.gov.au
The prevalence of hypertension in type 2 diabetics is high, though there is no published data for Switzerland.
This prospective cohort survey determined the frequency of type 2 diabetes mellitus associated with
hypertension from medical practitioners in Switzerland, and collected data on the diagnostic and therapeutic
work-up for cardiovascular risk patients. The Swiss Hypertension And Risk Factor Program ( SHARP) is a two-
part survey: The first part, I-SHARP, was a survey among 1040 Swiss physicians to assess what are the target
blood pressure ( BP) values and preferred treatment for their patients. The second part, SHARP, collected data
from 20,956 patients treated on any of 5 consecutive days from 188 participating physicians. In I-SHARP,
target BP <= 135/85 mmHg, as recommended by the Swiss Society of Hypertension, was the goal for 25% of
physicians for hypertensives, and for 60% for hypertensive diabetics; values >140/90 mmHg were targeted by
19% for hypertensives, respectively 9% for hypertensive diabetics. In SHARP, 30% of the 20,956 patients
enrolled were hypertensive ( as defined by the doctors) and 10% were diabetic ( 67% of whom were also
hypertensive). Six per cent of known hypertensive patients and 4% of known hypertensive diabetics did not
receive any antihypertensive treatment. Diabetes was not treated pharmacologically in 20% of diabetics.
Proteinuria was not screened for in 45% of known hypertensives and in 29% of known hypertensive diabetics.
In Switzerland, most physicians set target BP levels higher than recommended in published guidelines. In this
country with easy access to medical care, high medical density and few financial constraints, appropriate
detection and treatment for cardiovascular risk factors remain highly problematic.
PMID:ISI:000234504700003

British Journal of Cancer. 2006; 94(8): 1116-21.
General practice vs surgical-based follow-up for patients with colon cancer: randomised controlled
trial.
Wattchow DA, Weller DP, et al.
Department of Surgery, Fremantle Hospital, Fremantle, 6160 Western Australia (Platell)
This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either
general practitioners or surgeons. In all, 203 consenting patients who had undergone potentially curative
treatment for colon cancer were randomised to follow-up by general practitioners or surgeons. Follow-up
guidance recommended three monthly clinical review and annual faecal occult blood tests (FOBT) and were
identical in both study arms. Primary outcome measures (measured at baseline, 12 and 24 months were (1)
quality of life, SF-12; physical and mental component scores, (2) anxiety and depression: Hospital Anxiety and
Depression Scale and (3) patient satisfaction: Patient Visit-Specific Questionnaire. Secondary outcomes (at 24
months) were: investigations, number and timing of recurrences and deaths. In all, 170 patients were available
for follow-up at 12 months and 157 at 24 months. At 12 and 24 months there were no differences in scores for
quality of life (physical component score, P=0.88 at 12 months; P=0.28 at 24 months: mental component score,
P=0.51, P=0.47; adjusted), anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction
(P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate ratio 2.4, 95% CI 1.4-
4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI 0.5-1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3-
1.0) were undertaken in the surgeon-led group. Results suggest similar recurrence, time to detection and death
rates in each group. Colon cancer patients with follow-up led by surgeons or general practitioners experience
similar outcomes, although patterns of investigation vary.
PMID:16622437

British Journal of Nutrition. 2005; 93(6): 879-884.
Lack of meal intake compensation following nutritional supplements in hospitalised elderly women.
Boudville A, Bruce DG.
(1)Department of Community and Geriatric Medicine, Fremantle Hospital, Fremantle, Western Australia,
(2)School of Medicine & Pharmacology, University of Western Australia, Western Australia
Undernutrition contributes to poor clinical outcomes in hospitalised elderly patients but the potential impact of
oral nutritional supplements may be reduced by suppressing subsequent food intake. We investigated this
possibility in elderly female patients recovering mainly from hip fracture by studying the effect of oral
12th April 2007-04-12 8

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supplements on subsequent food intake during an ad libitum buffet luncheon meal. We tested the effect in
seven women by giving the supplement 90 min before the meal and compared energy and macronutrient
intake with a control water pre-load condition. A similar study was carried out in another seven women with the
supplement or water drink given 30 min beforehand. Both self-rated appetite and energy intake were low in
these women. The nutritional supplement did not alter ratings of hunger, fullness or prospective consumption or
subsequent energy and macronutrient consumption whether given 90 or 30 min before the meal. There were
significant independent correlations between the lack of adequate compensation of energy intake at meals and
chronic undernutrition (as assessed by skinfold thickness) and energy intake during the control meal. We
conclude that elderly women during the recovery phase after major fractures have low appetites and energy
intakes and markedly impaired adjustment of energy intake following liquid oral nutritional supplements. The
reasons for this are unknown but are related to anorexia and undernutrition. The consumption of liquid oral
supplements given up to 30 min before a meal does not suppress subsequent energy intake from meals.,
Copyright(C) 2005 The Nutrition Society

British Journal of Surgery. 2006; 93(4): 427-433.
Randomized clinical trial of bowel preparation with a single phosphate enema or polyethylene glycol
before elective colorectal surgery. [Miscellaneous Article].
Platell C, Barwood N, et al.
(1)Colorectal Surgical Unit, Fremantle Hospital, Fremantle, Western Australia, Australia
(2)Department of Surgery, University of Western Australia, Perth, Western Australia, Australia
Background: A recent meta-analysis has questioned the value of bowel preparation in patients undergoing
colorectal resection. The aim of this clinical trial was to evaluate whether a single phosphate enema was as
effective as oral polyethylene glycol (PEG) solution in preventing anastomotic leakage., Methods: Patients
were randomized to receive either a single phosphate enema or 3 litres of oral PEG solution before surgery.
Patients were followed for a minimum of 6 weeks to detect anastomotic leakage., Results: There were 147
patients in each group and the groups were evenly matched for putative risk factors at baseline. Patients in the
enema group had more anastomotic leaks requiring reoperation than those in the PEG group (4[middle dot]1
versus 0 per cent, P = 0[middle dot]013; relative risk 2[middle dot]04 (95 per cent confidence interval (c.i.)
1[middle dot]82 to 2[middle dot]30)). The mortality rate was higher in the PEG group (2[middle dot]7 versus
0[middle dot]7 per cent, P = 0[middle dot]176; odds ratio 1[middle dot]62 (95 per cent c.i. 0[middle dot]45 to
36[middle dot]98))., Conclusion: Bowel preparation with a phosphate enema was associated with an increased
risk of anastomotic leakage requiring reoperation compared with oral PEG. These results do not support the
routine use of a phosphate enema in patients undergoing elective colorectal surgery. Copyright (C) 2006 British
Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd., (C) 2006 John Wiley & Sons, Inc.

British Journal of Surgery. 2006; 93(7): 866-71.
Population-based study of prognostic factors in stage II colonic cancer.
Morris M, Platell C, et al.
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
BACKGROUND:: Adjuvant chemotherapy in stage II colorectal cancer may be considered for patients whose
tumours have poor prognostic features. The aim of this study was to evaluate the prognostic significance of
commonly reported clinical and pathological features of stage II colonic cancer. METHODS:: A population-
based observational study of all patients with stage II colonic cancer diagnosed in the state of Western
Australia from 1993 to 2003 was performed. A total of 1306 patients treated by surgery alone were identified,
with a median follow-up of 59 (range 0-145) months. RESULTS:: Multivariable analysis revealed that the only
independent prognostic factors for disease-specific survival were stage T4 (hazard ratio (HR) 1.75 (95 per cent
confidence interval (c.i.) 1.32 to 2.32); P < 0.001) and vascular invasion (HR 1.63 (95 per cent c.i. 1.15 to 2.30);
P < 0.001). In younger patients (aged 75 years or less), who are more likely to be considered for
chemotherapy, these two features showed independent prognostic significance but with higher HR values (1.96
for stage T4 and 2.73 for vascular invasion). Stage T4 and/or the presence of vascular invasion identified a
'poor' prognostic group, comprising 26.6 per cent of younger patients and with a 5-year survival rate of 71.2 per
cent. The remaining 'good' prognostic group had a survival rate of 84.3 per cent at 5 years' follow-up.
CONCLUSION:: This study highlights the importance of accurate pathological assessment of tumour stage and
vascular invasion for the prognostic stratification of patients with stage II colonic cancer. The results provide
clarification of guidelines for the management of stage II disease in relation to recommendations for
chemotherapy. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Carcinogenesis. 2005; 26(10): 1782-92.
12th April 2007-04-12 9

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Inhibition of adult liver progenitor (oval) cell growth and viability by an agonist of the peroxisome
proliferator activated receptor (PPAR) family member gamma, but not alpha or delta.
Knight B, Yeap BB, et al.
School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.
belindat@cyllene.uwa.edu.au

Carcinogenesis. 2006; Epub ahead of print.
Hepatic oval cell response to the choline-deficient, ethionine supplemented model of murine liver
injury is attenuated by the administration of a cyclo-oxygenase 2 inhibitor.
Davies RA, Knight B, et al.
University of Western Australia Centre for Medical Research, Western Australian Institute for Medical
Research, Western Australia; School of Medicine & Pharmacology, University of Western Australia, Crawley,
6009, Western Australia; School of Biomedical and Chemical Sciences, University of Western Australia,
Crawley, 6009, Western Australia.
Oval cell proliferation precedes neoplasia in many rodent models of hepatocellular carcinoma and prevention of
this proliferative response can reduce the risk of subsequent carcinoma. This study aimed to determine
whether a selective cyclo-oxygenase-2 (COX-2) inhibitor, SC-236, affects (1) the oval cell response to liver
injury in a mouse model of hepatocarcinogenesis and (2) an oval cell line. Four-week-old mice were fed either
normal chow or a choline deficient, ethionine supplemented (CDE) diet in the presence or absence of SC-236.
Liver histology and oval cell numbers were determined after 2, 4, 12 and 52 weeks of treatment. Oval cells
were scored using morphological criteria and positive immuno-staining for the M2-isozyme of pyruvate kinase
(M2PK) or A6. An immortalised oval cell line (PIL-2) was used to study the in vitro effects of SC-236 on oval
cell proliferation, apoptosis and Akt phosphorylation. The percentage of M2PK-positive oval cells and COX-2
positive cells was reduced by 80% and 45%, respectively, in CDE-fed mice receiving SC-236 compared with
CDE-fed animals not receiving SC-236. Some M2PK positive oval cells were also COX-2 positive. The
percentage of A6-positive cells was not affected by SC-236 administration to CDE fed mice. Administration of
SC-236 increased apoptosis as evidenced by a 73% increase in the number of TUNEL-positive cells at 2
weeks in CDE fed mice. Primary oval cells and PIL-2 cells expressed COX-2. In vitro treatment of PIL-2 cells
with SC-236 resulted in a dose-dependent preferential death of A6-negative cells. Administration of 25 and 50
microM Prostaglandin E2 partially attenuated SC-236 induced cell death by 25%. In vitro oval cell death was
associated with apoptosis and a 70% reduction in Akt phosphorylation. These results suggest that the SC-236
induced reduction of M2PK-positive oval cell numbers may be due to COX-2 dependant inhibition of Akt
phosphorylation and induction of apoptosis.

Circulation. 2005; 111(23): 3119-3125.
Association of osteoprotegerin with human abdominal aortic aneurysm progression.
Moran CSM, McCann MP, et al.
From the Vascular Biology Unit, School of Medicine, James Cook University, Townsville (C.S.M., M.M., M.K.,
N.K., J.G.), and School of Surgery and Pathology, University of Western Australia, Fremantle (P.N.), Australia.
Background-: Abdominal aortic aneurysm (AAA) is characterized by destruction of the arterial media
associated with loss of vascular smooth muscle cells, infiltration of mononuclear cells, and high concentration
of metalloproteinases (MMPs) and cytokines. Osteoprotegerin (OPG) has recently been identified in
atherosclerosis. The presence and functional importance of OPG in human AAA was investigated., Methods
and Results-: In 146 men with small AAA followed up by ultrasound for 3 years, serum OPG was weakly
correlated with aneurysm growth rate. Western analysis showed 3-, 8-, and 12-fold-greater OPG
concentrations in human AAA biopsies compared with biopsies of atherosclerotic narrowed aorta (1.4+/-0.1
versus 0.5+/-0.1 ng/mg tissue; P=0.002), postmortem nondiseased abdominal aorta (1.4+/-0.1 versus 0.2+/-0.1
ng/mg tissue; P<0.001), and nondiseased thoracic aorta (1.4+/-0.1 versus 0.1+/-0.06 ng/mg tissue; P<0.001).
Healthy human aortic vascular smooth muscle cells incubated with recombinant human (rh)OPG (0 to 20 ng
rhOPG/105 cells per 1 mL per 24 hours) developed an aneurysmal phenotype defined by impaired cell
proliferation (P<0.001), increased apoptosis (P<0.01), and increased MMP-9 (92 kDa) expression (P<0.001).
Incubation of monocytic THP-1 cells with 1 ng rhOPG/105 cells per 1 mL per 24 hours induced a 2-fold
increase in MMP-9 expression (P<0.001), a 1.5-fold increase in MMP-2 activity (P=0.005), and a 2-fold
stimulation of IL-6 production in these cells (P=0.02). Finally, secretion of OPG from human AAA explant was
abrogated by treatment with the angiotensin II blocker irbesartan, with the reduction in secreted levels
averaging 63.0+/-0.9 ng/mg tissue per 48-hour period., Conclusions-: These findings support a role for OPG in
the growth of human AAA and suggest a potential benefit for angiotensin II blockade in slowing aneurysm
expansion., (C) 2005 American Heart Association, Inc.
12th April 2007-04-12 10

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Clin Chim Acta. 2005; 358(1-2): 24-36.
Iron overload.
Siah CW, Trinder D, et al.
School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital Campus, P.O. Box
480, Fremantle 6959, Western Australia.
Iron overload disorders represent a heterogenous group of conditions resulting from inherited and acquired
causes. With the discovery of new proteins and genetic defects we have gained greater insight into their
causation at the molecular level and the complex mechanisms of normal and disordered iron homeostasis.
Here we review the normal mechanisms and regulation of gastrointestinal iron absorption and liver iron
transport and their dysregulation in iron overload states. Advances in the understanding of the natural history of
iron overload disorders and new methods for clinical detection and management of hereditary
hemochromatosis are also reviewed.
PMID:15885682

Clinica Chimica Acta. 2005; Sep 30 [Epub ahead of print].
Nurse-based evaluation of point-of-care assays for glycated haemoglobin.
St John A, Davis TM, et al.
ARC Consulting, Perth, W Australia 6050, Australia.

Clinical Chemistry. 2005; 51(10): 1867-1873.
Hepascore: An Accurate Validated Predictor of Liver Fibrosis in Chronic Hepatitis C Infection.
Adams LA, Bulsara M, et al.
1 Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia.
2 School of Population Health and 3 School of Medicine and Pharmacology, The University of Western
Australia, Perth, Australia.
4 PathCentre, Queen Elizabeth II Medical Centre, Perth, Australia.
5 Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia.
6 AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia.
Address correspondence to this author at: Department of Medicine and Pharmacology, The University of
Western Australia, Nedlands, WA 6009, Australia. Fax 618-9346-3098; e-mail gjeffrey@cyllene.uwa.edu.au
Background: Staging hepatic fibrosis by liver biopsy guides prognosis and treatment of hepatitis C, but is
invasive and expensive. We sought to create an algorithm of serum markers that accurately and reliably predict
liver fibrosis stage among hepatitis C patients. Methods: Ten biochemical markers were measured at time of
liver biopsy in 117 untreated hepatitis C patients (training set). Multivariate logistic regression and ROC curve
analyses were used to create a predictive model for significant fibrosis (METAVIR F2, F3, and F4), advanced
fibrosis (F3 and F4), and cirrhosis (F4). The model was validated in 104 patients from other institutions.
Results: A model (Hepascore) of bilirubin, {gamma}-glutamyltransferase, hyaluronic acid, {alpha}2-
macroglobulin, age, and sex produced areas under the ROC curves (AUCs) of 0.85, 0.96, and 0.94 for
significant fibrosis, advanced fibrosis, and cirrhosis, respectively. In the training set, a score [&ge;]0.5 (range,
0.0-1.0) was 92% specific and 67% sensitive for significant fibrosis, a score <0.5 was 81% specific and 95%
sensitive for advanced fibrosis, and a score <0.84 was 84% specific and 71% sensitive for cirrhosis. Among the
validation set, the AUC for significant fibrosis, advanced fibrosis, and cirrhosis were 0.82, 0.90, and 0.89,
respectively. A score [&ge;]0.5 provided a specificity and sensitivity of 89% and 63% for significant fibrosis,
whereas scores <0.5 had 74% specificity and 88% sensitivity for advanced fibrosis. Conclusions: A model of 4
serum markers plus age and sex provides clinically useful information regarding different fibrosis stages among
hepatitis C patients.

Clinical Endocrinology. 2006; 64(4): 476-7.
Subclinical hypothyroidism and mortality in women with type 2 diabetes.
Chubb SA, Davis WA, et al.
*Department of Biochemistry, PathWest Laboratory Medicine WA (Chubb) and †University of Western
Australia, School of Medicine and Pharmacology, Fremantle Hospital, Fremantle, Australia (WA Davis & TME
Davis)
Publication Types: Letter

Clinical Gastroenterology & Hepatology. 2005; 3(12): 1195-1197.
The bulge, booze, and the liver.
12th April 2007-04-12 11

Page 12

Adams LA, Angulo P.
School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Perth, WA
PMID:2005573503

Clinical Rheumatology. 2006; Epub ahead of print.
Cytomegalovirus infection of a cutaneous ulcer in a patient with ANCA-positive vasculitis.
Nolan RC, Sadler GM, et al.
Department of Immunology, Level 4 B Block, Fremantle Hospital, Alma Street, Fremantle, WA, 6160, Australia,
rich@perthnolans.com.
This case describes a patient in whom cytomegalovirus (CMV) infected a preexisting ulcer. The patient was
immune-suppressed because of treatment for Wegener's granulomatosis. Specific antiviral therapy was
delayed because of uncertainty as to the role of CMV, but the infection cleared and the ulcer improved
promptly on institution of valganciclovir.

Colorectal Disease Supplement. 2005; 7 Suppl.(1): 28.
The role of mechanical bowel preparation in patients undergoing elective colorectal surgery.
Platell C, Makin G, et al.
Fremantle Hospital, Perth, Australia

Colorectal Disease Supplement. 2005; 7 Suppl.(1): 82.
Randomised controlled trial of general practitioner compared to surgeon follow-up of patients with
colon cancer.
Wattchow DA, Weller DP, et al.
(*)Flinders University, Adelaide, Australia, (+)Division of Community Health services, University of Edinburgh,
Edinburgh, UK, (++)Fremantle Hospital, Fremantle, Australia

Contemp Nurse. 2005; 20(2): 180-92.
A collaborative model of community health nursing practice.
Downie J, Ogilvie S, et al.
1. Head, School of Nursing and Midwifery, Curtin University of Technology and Research Consultant, South
Metropolitan Population Health Service, Perth, Western Australia.
This paper discusses a strategic collaborative partnership between a Western Australian university and a
community health service based on a Practice-Research Model. The partnership has involved a senior
academic (0.2 FTE) working in the community health setting as a Nurse Research Consultant since 1998. The
first section of the paper draws on the nursing literature on collaborative models and describes the broad
background to the partnership and development of the Model. The second section presents in detail the results
of a recent evaluation that involved a brief survey and follow-up interviews to determine community health
nurses' understanding and perceptions of the partnership Model. Three main themes emerged from the
interviews: (1) Advancement of learning captured the extent to which the Nurse Research Consultant position
helped to educate nurses and promote and develop research and best-practice; (2) Job satisfaction and self-
confidence encompassed the extent to which participants felt nursing management were supportive of their
professional education and pursuit of best-practice solutions, and (3) Situational opportunity, which reflected
the more negative comments expressed by participants and related mostly to the restricted availability of Nurse
Research Consultant and a focus on mainstream research priorities. The results suggest that the partnership
Model provided the nurses with the opportunity to develop an increased understanding of the role of research
in clinical practice and confidence in their own ability to reflect on current nursing practice. This allowed them to
identify clinical problems in order to deliver and evaluate best-practice solutions, as evidenced by a change in
attitude from the previous evaluation. However, it was also noted that the operational performance of the Model
needs continual monitoring to ensure that all nurses have equitable access opportunities.
PMID:16393100

Contemp Nurse. 2006; 21(1): 117-9.
Reflections on mental health nursing education.
Wynaden D.
Research & Development Director and Senior Lecturer (Mental Health), School of Nursing and Midwifery,
Curtin University of Technology and Research and Development Consultant, Directorate of Mental Health,
Fremantle Hospital and Health Services, Perth WA, Australia
Publication Types: Editorial
12th April 2007-04-12 12

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Contemporary Nurse. 2005; 20(2): 267-77.
Establishing best practice guidelines for administration of intra muscular injections in the adult: A
systematic review of the literature.
Wynaden D, Landsborough I, et al.
1. Senior Lecturer, School of Nursing and Midwifery, Curtin University of Technology and Clinical Research
Consultant, Fremantle Mental Health Services, Fremantle Hospital and Health Service, Fremantle, Western
Australia.
This article describes best practice guidelines for the administration of intramuscular injections developed after
the identification of 300 abstracts and a review of 150 articles on the subject area. While the administration of
medication via the intramuscular route is a daily occurrence for nurses working in both hospitals and
community settings, several concerns and complications have been identified with the procedure. Routinely,
nurses are required to make numerous decisions regarding factors such as needle size, length and the site to
be used during the administration of medication into muscle tissue. Therefore, it is important that relevant up-
to-date guidelines are available to assist nurses to make informed decisions about the technique to use.
Techniques delivering medication to the correct site will facilitate efficacious outcomes for the client and ensure
the delivery of quality nursing care in all health care settings.
PMID:16393108

Critical Care & Resuscitation. 2005; 7(2): 111-5.
Supplemental jet ventilation in a case of ARDS complicated by bronchopleural fistulae.
Simes DC.
Intensive Care Unit, Fremantle Hospital, Fremantle, WA, Australia. david.simes@health.wa.gov.au
OBJECTIVE: To present a case of unusual ventilatory strategy in a 17 year old girl with the acute respiratory
distress syndrome (ARDS) complicated by bilateral bronchopleural fistulae. METHODS: The patient was
ventilated with a combination of conventional pressure control ventilation (PCV) and high frequency jet
ventilation (HFJV) for 133 and 110 days, respectively. RESULTS: Despite prolonged hypoxia, extensive
barotrauma and nosocomial infections, she survived without significant impairment of respiratory function. Two
years later she was healthy and independent with only mildly reduced respiratory reserve. CONCLUSIONS:
The combination of PCV and HFJV was beneficial in this case of ARDS complicated by bronchopleural fistulae.
The case also highlights the utility of HFJV in the desperately hypoxic patient with extensive airway disruption.
PMID:16548803

Critical Care & Resuscitation. 2005; 7(1): 62-3.
Critical care research and ethics.
Blythe D.
Intensive Care Unit, Fremantle Hospital, Fremantle, WA, Australia
PMID:16548823

Critical care and resuscitation. 2005; 7(4): 310-21.
Ethical intensive care research: development of an ethics handbook.
Rischbieth A, Blythe D, et al.
Department of Clinical Nursing, University of Adelaide, South Australia. amanda.rischbieth@adelaide.edu.au;
Department of Intensive Care, Fremantle Hospital, Fremantle, Western Australia
Conduct of research involving humans in the intensive care unit (ICU) setting is complex and challenging. The
vulnerable nature of critically ill patients raises issues of patient safety, and informed consent is difficult. With
an increasing global interest in human research ethics, broadened government mandates have targeted
improvements in research participant protection and research governance. A parallel rise in health
consumerism and advocacy for privacy and protection of personal health information requires a clear
understanding of the research participant role and importance of risk disclosure. In addition, the potential for
conflicts of interest in a climate of increasingly competitive research funding, requires caution and transparency
in related financial and contractual arrangements. The Australian and New Zealand Intensive Care Society
Clinical Trials Group (ANZICS CTG) fosters collaborative ICU research activity. We have developed An Ethics
Handbook for Researchers (EH) for the ANZICS CTG for intended use by researchers in Australian and New
Zealand ICUs. The purpose of the EH is to act as a practical advisory guide/supplement; to add clarification
regarding ethical issues specific to intensive care research, to assist in the expedition of ethics committee
research submission and to summarise available useful resources. This article introduces a precis of key
issues from the EH including specific ethical difficulties pertaining to ICU research, a summary of the process
12th April 2007-04-12 13

Page 14

by which ethics committee decisions in Australia and New Zealand are informed, and the use of ethical
checklists to assist researchers.

Curr Opin Allergy Clin Immunol. 2005; 5(4): 359-64.
Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis.
Brown SG.
Discipline of Emergency Medicine, The University of Western Australia at Fremantle Hospital, Fremantle,
Western Australia, Australia. simon.brown@uwa.edu.au
PURPOSE OF REVIEW: Anaphylactic cardiovascular collapse can be resistant to treatment with epinephrine
(adrenaline) and, in some cases, diagnostic uncertainty compromises follow-up care. The purpose of this
review is to examine recent studies relevant to the management and diagnosis of this condition. RECENT
FINDINGS: Nausea, vomiting, incontinence, diaphoresis, dyspnoea, hypoxia, dizziness and collapse are
associated with hypotension. Relative bradycardia (falling heart rate despite hypotension) is a consistent
feature of hypotensive insect sting anaphylaxis and may represent a non-specific physiological response to
severe hypovolaemia in conscious individuals. Upright posture has been found to be associated with death
from anaphylaxis. Animal studies have found the intramuscular route for epinephrine is ineffective, intravenous
boluses temporarily effective, but intravenous infusions of epinephrine are able to reverse anaphylactic shock.
In one animal model, antihistamines were found to be harmful. A prospective human study provides evidence
for the efficacy of treatment with intravenous epinephrine infusion and fluid (volume) resuscitation. Case
reports support the use of the vasoconstrictors metaraminol, methoxamine and vasopressin if adrenaline is
ineffective. Repeated measurements of mast cell tryptase are more sensitive and specific than a single
measurement for the diagnosis of anaphylaxis. SUMMARY: Current evidence supports use of the
supine/Trendelenburg position, epinephrine by intravenous infusion and aggressive volume resuscitation. If
these fail, atropine should be considered for severe bradycardia and potent vasoconstrictors may be useful. To
confirm the diagnosis of anaphylaxis, serial measurements of mast cell tryptase may be preferable to a single
measurement.
PMID:15985820

Current Opinion in Psychiatry. 2006; 19(1): 61-66.
Dissociative and conversion disorders: defining boundaries.
Isaac M, Chand PK.
(a)Primary Care Mental Health Unit, School of Psychiatry and Clinical Neurosciences, University of Western
Australia, Fremantle, Western Australia, (b)Department of Psychiatry, National Institute of Mental Health and
Neurosciences, Bangalore, India
Purpose of review: Although dissociative disorders have been described and diagnosed for some time, their
aetiology, pathogenesis, phenomenology and management continues to arouse debate. It is only in recent
times that researchers have made some progress by integrating trauma related theories with more
contemporary cognitive theories and neurobiology., Recent findings: Dissociation as a phenomenon is reported
to occur in a variety of disorders. This widespread occurrence has contributed to a better understanding of
dissociation. An expansion of this concept may have contributed to the loss of its original significance. Recent
studies in the field of dissociation that pertain to its aetiology, pathophysiology, neurobiology and management
are critically reviewed., Summary: Dissociative disorder is conceptually a difficult disorder to study. Apart from
exposure to trauma, certain primary personality attributes may contribute to the propensity to develop
dissociative disorder. Recent advances in functional neuroimaging facilitated by enhanced knowledge in the
neural representation of body state have helped to improve our understanding of dissociation. There is
confusion over the use of various terms such as sexual abuse and physical abuse in explaining causality.
Current classificatory systems have not been found suitable when applied across cultures. In spite of all of
these limitations, there has been recent progress toward a better understanding of dissociative disorders., (C)
2006 Lippincott Williams & Wilkins, Inc.

Der Anaesthesist. 2006.
Entflammungs- und Brandverhalten von biologischem Gewebe bei In-vitro-Bestrahlung mit dem CO2-
Laser [Ignition and burning of biological tissue under simulated CO2-laser surgery conditions].
Juri O, Frochaux D, et al.
(1) Institut für Anästhesiologie, Universitätsspital, Zürich
(2) Institut für Anästhesiologie, Kantonsspital, Baden
(3) Dept. of Otolaryngology, Head & Neck Surgery, Lions Ear and Hearing Institute, University of Western
Australia, Fremantle, Australia
12th April 2007-04-12 14

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(4) Institut für Anästhesiologie, Universitätsspital, Rämistr. 100, 8091 Zürich, Schweiz
Background Laser surgery in endoscopy has greatly enhanced the surgical armamentarium for treating
various laryngeal and hypopharyngeal disorders, but harbours a risk of tissue ignition and inflammation of
surgical and anaesthetic instrumentation. However, even if non-inflammable material is used, there is still a
residual fire hazard from endogenous tissue that may develop an ignitable aerosol (so-called laser smog) as an
effect of laser irradiation. The aim of this study was to investigate how tissue carbonisation and vaporisation
contributes to the risk of airway fire.
Methods For the simulation of gas accumulation in the hypopharynx and larynx following the European
standard ISO-11990, a cylindrical steel chamber with an open and a closed end has been used to simulate the
operative setting. Pork meat chunks with a tissue composition similar to the larynx and hypopharynx such as
fat, muscle, cartilage and bone were introduced into this chamber. Ventilation was achieved through jet
ventilation with disposable, non-inflammable laser jet catheters. The tissue was then repeatedly exposed to a
laser beam in super-pulse mode (pulse rate 250 Hz) with various intensities and exposure lengths at an impact
angle of 75°. The laser intensity was varied from 2 to 15 W. The type, duration, intensity and incidence of
tissue ignition were recorded and analysed.
Results The degree of tissue ignition correlated with laser intensity. Low laser intensity caused spark formation
whereas high intensity resulted in sustained tissue fire. The type of tissue had an impact on ignition intensity
thereby showing lower ignition thresholds and higher ignition susceptibility in fat-containing tissue compared to
muscle. The most important factor for occurrence of tissue ignition was the chamber oxygen concentration
which displayed an inverse correlation with the time until tissue ignition. Oxygen concentrations of 35% led to
tissue ignition in 42 s, 40% oxygen in 20 s. Oxygen concentrations higher than 60% resulted in immediate
tissue ignition.
Conclusions Despite the use of non-inflammable materials in endoscopic laser surgery of the upper airway
and hypopharynx, the risk of tissue ignition remains due to the inflammable laser smog which is easily ignited
in an oxygen-rich environment. Hence to minimise this risk, we recommend using oxygen concentrations lower
than 40%, low laser intensities (<6 W) and limiting continuous laser activation to periods shorter than 10 s.

Diabet Med. 2005; 22(9): 1129-33.
Recent concepts in non-alcoholic fatty liver disease.
Adams LA, Angulo P.
Department of Medicine and Pharmacology, The University of Western Australia, Perth, Australia.
Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the
majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key
pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn
exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is
established, other factors, including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide
and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease.
Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however, staging the
disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably
because of complications of insulin resistance such as vascular disease, as well as cirrhosis and hepatocellular
carcinoma, which occur in a minority of patients. NAFLD is also now recognized to account for a substantial
proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the
necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver
disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications
appear promising. Further research is needed to identify which patients will achieve the most benefit from
therapy.
PMID:16108837

Diabetes. 2005; 54(Supp 1): A132.
Glycemic determinants of therapeutic progression in type 2 diabetes in a community-based cohort:
The Fremantle Diabetes Study.
Davis TME, Davis WA, et al.

Diabetes Care. 2005; 28(10): 2441-7.
Longitudinal predictors of reduced mobility and physical disability in patients with type 2 diabetes: the
Fremantle Diabetes Study.
Bruce DG, Davis WA, et al.
School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, P.O. Box 480,
12th April 2007-04-12 15