Incorporating indigenous knowledge in health services: a consumer partnership framework.

OBJECTIVES: Healthcare policy and planning should be informed by a partnership between healthcare services and healthcare users. This is critical for people who access care frequently such as indigenous Australians who have a high burden of chronic kidney disease. This study aimed to explore the most appropriate ways of enhancing services by incorporating renal patients' expectations and satisfaction of care in Australia's Northern Territory. STUDY DESIGN: This is a participatory action research. METHODS: Six aboriginal health users with end-stage kidney disease were recruited to form an Indigenous Reference Group. This group met bimonthly between April and November 2017 and meetings took the same structure as a focus group. Findings from these meetings were presented to health policy and planners in a feedback loop implemented by the study. RESULTS: This framework enabled indigenous knowledge to guide the project, indigenous priorities to be identified in this context and timely feedback of information to inform the strengths and priorities of the health service. Changes were recognised and addressed immediately. CONCLUSIONS: This qualitative research framework is a useful mechanism for providing local data to inform patient-centred health system change as expressed by health users. We recommend this consumer partnership framework be embedded into existing operational structures to support the ongoing sustainability of this group.

Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study.

OBJECTIVE: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. METHODS: A cross-sectional analysis of Indigenous participants of the eGFR Study. MEASURES: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. RESULTS: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). CONCLUSION: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

Enhancement of lobster growth.

Selected captive lobsters have been successfully mated at the Massachusetts Lobster Hatchery. Progeny raised in warm seawater grew at least four times as fast as lobsters grown at ambient ocean temperatures. These studies demonstrate that lobsters will reach sexual maturity (a weight of about 454 grams) in less than 2 years, compared to 8 years at ambient temperatures in Canadian waters. A further reduction in this time has been achieved by phenotypic selection for fast-growing lobsters. Our initial success in accelerating growth and in mating selected parents suggests that lobster farming may be possible.

Neuropathology in Germany during World War II: Julius Hallervorden (1882-1965) and the Nazi programme of 'euthanasia'.

In Germany, during World War II, more than 120,000 handicapped children and adults were murdered for the convenience of the State. To gain scientific knowledge, the brains of many of these patients were examined by German neuropathologists. Some 698 of these specimens were examined in the Kaiser-Wilhelm-Institut für Hirnforschung in Berlin-Buch by Julius Hallervorden, whose career is reviewed together with that of his superior, Hugo Spatz. Hallervorden also oversaw the examination of cases of mental handicap by W-J Eiche at a laboratory at the Hospital Brandenburg-Gorden. Also in Berlin was Berthold Ostertag, neuropathologist at the Rudolf-Virchow-Hospital, who examined cases from the Children's Ward at Wiesengrund. Smaller but significant numbers of brains were examined in Munich, Heidelberg, Hamburg and Schleswig. Some brains of similar origin were examined in Vienna and in Lubliniecz. Jürgen Peiffer has estimated that German neuropathologists examined 2097 brains arising from the Nazi Programme of 'Euthanasia'.

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). HYPOTHESIS: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. METHOD: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. RESULTS: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8µmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5µmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). CONCLUSION: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

Associations of serum adiponectin with markers of cardio-metabolic disease risk in Indigenous Australian adults with good health, diabetes and chronic kidney disease.

The higher serum adiponectin concentrations observed in females are often attributed to differences in adiposity or sex hormones. There is little data describing adiponectin in Indigenous Australians, and no studies examining its association with cardio-metabolic disease risk markers and chronic kidney disease (CKD). AIM: To describe the relationship of serum adiponectin with cardio-metabolic disease risk markers and kidney function in a community-based sample of Indigenous Australian adults, with particular reference to sex-specific differences. METHODS: A cross-sectional analysis of a community-based volunteer sample of 548 Indigenous Australian adults (62% female), stratified into five cardio-metabolic risk groups ranging from good health (strata-1) to high cardio-metabolic risk and low measured glomerular filtration rate (mGFR, <60ml/min/1.73m2) (strata-5). We examined serum adiponectin concentrations with cardio-metabolic risk markers, albuminuria and mGFR. RESULTS: Indigenous Australian females had a lower than expected adiponectin concentration (3.5µg/ml), which was higher than males in strata 1-4 (as in other populations), but not in strata-5 (mGFR<60, p=0.19), and higher leptin: adiponectin ratio than other populations (7.8ng/µg - strata-1, healthy females; 12.2ng/µg - strata-3, females with diabetes and mGFR≥90). Female-gender, HDL-cholesterol (positive), mGFR and waist: hip ratio (WHR) (inverse) were independently associated with log-adiponectin when mGFR≥60; when mGFR<60, female-gender was associated with 0.27 units lower log-adiponectin. CONCLUSION: Female-gender was not associated with higher adiponectin concentrations in Indigenous Australians with mGFR<60ml/min/1.73m2. High WHR was frequent in both genders, and inversely associated with adiponectin. Longitudinal studies are needed to examine relationships of serum adiponectin, obesity and cardiovascular disease events in Indigenous Australians.

Development of a single-frequency bioimpedance prediction equation for fat-free mass in an adult Indigenous Australian population.

BACKGROUND/OBJECTIVES: To describe the development of a single-frequency bioimpedance prediction equation for fat-free mass (FFM) suitable for adult Aboriginal and Torres Strait Islander peoples with and without diabetes or indicators of chronic kidney disease (CKD). SUBJECTS/METHODS: FFM was measured by whole-body dual-energy X-ray absorptiometry in 147 adult Indigenous Australians. Height, weight, body circumference and resistance were also measured. Adults with and without diabetes and indicators of CKD were examined. A random split sample with internal cross-validation approach was used to predict and subsequently validate FFM using resistance, height, weight, age and gender against measured FFM. RESULTS: Among 147 adults with a median body mass index of 31 kg/m(2), the final model of FFM was FFM (kg)=0.432 (height, cm(2)/resistance, ohm)-0.086 (age, years)+0.269 (weight, kg)-6.422 (if female)+16.429. Adjusted R(2) was 0.94 and the root mean square error was 3.33 kg. The concordance was high (rc=0.97) between measured and predicted FFM across a wide range of FFM (31-85 kg). CONCLUSIONS: In the context of the high burden of diabetes and CKD among adult Indigenous Australians, this new equation for FFM was both accurate and precise and based on easily acquired variables (height, weight, age, gender and resistance) among a heterogeneous adult cohort.

Some histological and metabolic properties of an isolated perfused rat brain preparation with special reference to monoamine metabolism.

A method is described for perfusing the rat head which results in perfusion of the brain, its covering and the bony skull only. Dye and latex injection studies showed that there was no perfusion of extracranial tissue and thus it was not necessary to remove the lower jaw and facial tissues as described by previous authors. Perfusion with fluorescein demonstrated that the whole brain was perfused. Light microscopy after two hours of perfusion revealed no deterioration in brain-structure. Electron microscopy showed a small increase in the extracellular space and the perivascular space with good preservation of subcellular organelles. Glucose and acetoacetate removal were very similar to those reported for the adult rat in vivo as measured by arterio-venous differences. The concentrations of 5-hydroxytryptamine, dopamine and noradrenaline are maintained at values close to those in vivo during a 2-hr perfusion with a basal medium and the preparation will maintain linear rates of 5-hydroxytryptamine synthesis for 2 h when the medium contains L-tryptophan and tranylcypromine, at rates similar to those measured in vivo. The rate of uptake of L-tryptophan into the brain is similar to that reported after L-tryptophan loading in vivo. The histological and metabolic properties of the preparation are close to those observed in vivo. The method could provide a way in which monoamine metabolism in particular could be studied using an experimental model closer in its properties to the in vivo situation than tissue preparations such as slices or homogenates.

Haemangioblastoma: histological and immunohistological study of an enigmatic cerebellar tumour.

Paraffin-embedded blocks of 36 cerebellar haemangioblastomas were reacted with a panel of antibodies including glial fibrillary acidic protein, vimentin, epithelial membrane antigen, cytokeratin, Factor VIII, a neuroendocrine marker and with Ulex europaeus. agglutinin The main histological features, apart from the characteristic large abnormal vessels, were a prominent reticulin network, a cystic architecture and cellular and nuclear polymorphism. Two cell types were identified: endothelial and stromal. Twenty tumours were positive for glial fibrillary acidic protein because of included or reactive astrocytes as well as positive stromal cells. Vimentin was positive in all tumours with a diffuse distribution and a somatic pattern; blood vessels, stromal cells and reactive astrocytes were strongly positive. Factor VIII and Ulex europaeus agglutinin reactivity were present in a similar pattern of staining in endothelium and in five cases there were stromal cells that were positive with the latter. We were not able to ascertain the histogenesis of the stromal cell, which remains enigmatic.

Immunocytochemical study of the cellular immune response in meningiomas.

Twenty four meningiomas (17 benign and seven "atypical" were reacted with a panel of monoclonal antibodies to macrophages, lymphocytes, and HLA DR antigens. All the tumours contained macrophages but these cells were more numerous in the atypical meningiomas. Lymphocytes, almost exclusively of the CD8 subtype, were also present in 70% of benign meningiomas and in all atypical meningiomas and were more abundant in the latter. B lymphocytes were present in minimal numbers in three atypical meningiomas and in one benign meningioma. CD4 positive T lymphocytes were present in small numbers in one benign meningioma and in moderate numbers in one atypical meningioma. HLA DR antigen expression on tumour cells was present in about 60% of both tumour groups. The numbers of macrophages and T and CD8 lymphocytes in meningiomas seem to be related to atypical histological features, and the presence of these cells raises questions about host immune response and the relation of this to prognosis.

Loss of substance P and enkephalin immunoreactivity in the human substantia nigra after striato-pallidal infarction.

Post-mortem neuropathological material from 3 patients with striato-pallidal infarction provided the first immunohistochemical evidence for substance P- and enkephalin-containing nerve fibre projections from the striato-pallidum to the substantia nigra in the human. The nigra corresponding to the normal side showed abundant substance P and enkephalin immunoreactivity whose patterns of immunostaining were notably similar. In contrast, the substantia nigra ipsilateral to the striato-pallidal infarction showed a decrease in substance P and enkephalin immunoreactivity which was proportional to the extent of the infarction. This suggests that much of the substance P and enkephalin immunoreactivity in the nigra is present in nerve fibres projecting from the striato-pallidum. Furthermore, the similar distribution of remaining substance P and enkephalin immunoreactivity in corresponding areas of the nigra of the infarcted side indicates that the origins and/or projections of nerve fibres containing these two neuropeptides may be closely approximated anatomically. Depletion of substance P immunoreactivity in the pars reticulata of the substantia nigra in a fourth patient with anterior striatal infarction suggests a topographic projection for substance P immunoreactive fibres from the striatum. There is some evidence in one patient with cognitive and behavioural abnormalities to support the suggestion that the basal ganglia may be involved in non-motor functions.

A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus.

The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn. Numerous somatostatin-immunoreactive cell bodies were also present. In the ventral horn, immunoreactive fibres were less abundant. Most motoneurones were closely apposed by fibres immunoreactive for enkephalin, neurokinin, somatostatin and thyrotrophin-releasing hormone (TRH). A subpopulation of motoneurones, most notable in lumbar segments, displayed CGRP immunoreactivity. In common with autonomic nuclei, Onuf's nucleus, which is thought to innervate perineal striated muscle and external urethral and anal sphincters, was densely innervated with CPON-, enkephalin-, and in particular somatostatin-immunoreactive fibres, thus suggesting Onuf's nucleus may have an autonomic component. In the diseased cords, there was a reduction in the area of the ventral horn and numbers of motoneurones as revealed by conventional histological staining and immunostaining of neurofilament triplet proteins. No changes in the distribution of peptides was noted in the dorsal horn or autonomic nuclei. By contrast, in the ventral horn, neurokinin-, enkephalin-, somatostatin- and TRH-immunoreactive fibres, which are normally found associated with motoneurones, were absent. Therefore, not only are motoneurones lost in MND, but also the fibres which innervate them. CGRP-immunoreactive motoneurones were not observed, a finding consistent with the proposed role of this peptide as a muscle-trophic factor. In contrast to the large motoneurone groups in the ventral horn, the neuronal integrity of Onuf's nucleus and the peptides associated with it were spared. These data further imply that Onuf's nucleus is not a typical motor nucleus and it is not purely somatic. The coincident loss of peptide immunoreactivity and motoneurones from the large motor nuclei and sparing of Onuf's nucleus and its peptide-containing constituents in the diseased state suggests that peptides contribute to maintenance of neural integrity.

Loss of substance P immunoreactivity in the nucleus of the spinal trigeminal tract after intradural tumour compression of the trigeminal nerve.

The peptide, substance P (SP), is suspected of being a mediator of nociception. Immunoreactive SP is conspicuously present in areas of the mammalian central nervous system which receive nociceptive input. We have observed that compression of the trigeminal nerve by an intradural tumour deposit results in the ipsilateral depletion of SP immunoreactivity in human spinal trigeminal nucleus. These results expand previous experimental animal studies which associate this peptide with a subpopulation of primary sensory neurones and, in addition, demonstrate a correlation between the levels of SP immunoreactivity and premortem clinical sensory alterations.

Demonstration of substance P immunoreactivity in the nucleus dorsalis of human spinal cord.

Substance P immunoreactivity has been detected in varicosities around cell bodies of the nucleus dorsalis (Clarke's column) of the human spinal cord. This immunostaining probably represents neuropeptide immunoreactivity either in the nerve terminals of spinal interneurone, descending projections or in the primary dorsal root afferents which have been shown previously to synapse with the neurones of Clarke's column. The presence of substance P immunoreactivity in the human nucleus dorsalis suggests a role of substance P in the transmission of proprioceptive and exteroceptive information from the lower trunk and limbs to the cerebellum.

Ultrastructural studies in human polymyositis.

Biopsy of muscle from 13 cases of human polymyositis permitted an ultrastructural study in which attention was directed to the cellular population of the inflammatory reaction. The constant feature was the presence of small and large lymphocytes, and cells of the latter type were frequently in intimate contact with the surface of the muscle fibres. Macrophages were seen both within and outside degenerating muscle fibres. Plasma cells were seen in 2 cases. Filaments bearing some resemblance to virus inclusions were seen in one case. The implications of the cellular reaction in human polymyositis are discussed and the literature of ultrastructural observations on the muscle in this disease is briefly reviewed.

Ponto-bulbar palsy with deafness (Brown-Vialetto-Van Laere syndrome).

The authors describe the clinical and electrophysiological features in 2 cases of ponto-bulbar palsy with deafness, and the clinical course and post-mortem findings in a sibling of one of these, who died in infancy, and who appears to have suffered from the same disease. The cases are compared with 17 previously published cases, and the disease is discussed in relation to other progressive neurological diseases of childhood.