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1.
J Food Prot ; 85(9): 1370-1379, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35653627

ABSTRACT

ABSTRACT: The health and economic burden of foodborne illness is high, with approximately 2.4 million cases occurring annually in the United Kingdom. A survey to understand the baseline microbial quality and prevalence of food-related hazards of fresh beef mince on retail sale could inform risk assessment, management, and communication to ensure the safety of this commodity. In such a survey, a two-stage sampling design was used to reflect variations in population density and the market share of five categories of retail outlets in Scotland. From January to December 2019, 1,009 fresh minced beef samples were collected from 15 geographic areas. The microbial quality of each sample was assessed using aerobic colony count and Escherichia coli count. Samples were cultured for Campylobacter and Salmonella, and PCR was used to detect target genes (stx1 all variants, stx2 a to g, and rfbO157) for Shiga toxin-producing E. coli (STEC). The presence of viable E. coli O157 and STEC in samples with a positive PCR signal was confirmed via culture and isolation. Phenotypic antimicrobial sensitivity patterns of cultured pathogens and 100 E. coli isolates were determined, mostly via disk diffusion. The median aerobic colony count and E. coli counts were 6.4 × 105 (interquartile range, 6.9 × 104 to 9.6 × 106) and <10 CFU/g (interquartile range, <10 to 10) of minced beef, respectively. The prevalence was 0.1% (95% confidence interval [CI], 0 to 0.7%) for Campylobacter, 0.3% (95% CI, 0 to 1%) for Salmonella, 22% (95% CI, 20 to 25%) for PCR-positive STEC, and 4% (95% CI, 2 to 5%) for culture-positive STEC. The evidence for phenotypic antimicrobial resistance detected did not give cause for concern, mainly occurring in a few E. coli isolates as single nonsusceptibilities to first-line active substances. The low prevalence of pathogens and phenotypic antimicrobial resistance is encouraging, but ongoing consumer food safety education is necessary to mitigate the residual public health risk.


Subject(s)
Food Contamination , Food Microbiology , Red Meat , Animals , Anti-Bacterial Agents/pharmacology , Campylobacter/drug effects , Campylobacter/isolation & purification , Cattle , Drug Resistance, Bacterial , Escherichia coli O157/drug effects , Escherichia coli O157/isolation & purification , Hygiene , Red Meat/microbiology , Salmonella/drug effects , Salmonella/isolation & purification , Scotland , Shiga Toxin/genetics
2.
Trials ; 23(1): 433, 2022 May 23.
Article in English | MEDLINE | ID: mdl-35606820

ABSTRACT

BACKGROUND: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. METHODS: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. DISCUSSION: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. TRIAL REGISTRATION: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. CLINICALTRIALS: gov NCT04774224. Registered on 01 March 2021.


Subject(s)
Diabetes Mellitus, Type 1 , Animals , Azetidines , C-Peptide , Clinical Trials, Phase II as Topic , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/drug therapy , Double-Blind Method , Glucose/therapeutic use , Humans , Janus Kinases/therapeutic use , Mice , Multicenter Studies as Topic , Purines , Pyrazoles , Randomized Controlled Trials as Topic , STAT Transcription Factors/therapeutic use , Signal Transduction , Sulfonamides , Treatment Outcome
3.
ANZ J Surg ; 91(12): 2663-2668, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33956377

ABSTRACT

BACKGROUND: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. METHODS: Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. RESULTS: Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. CONCLUSION: The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.


Subject(s)
Pancreatectomy , Pancreatitis, Chronic , Australia/epidemiology , Humans , Pain Management , Pancreatitis, Chronic/surgery , Transplantation, Autologous
4.
Diabet Med ; 37(8): 1340-1343, 2020 08.
Article in English | MEDLINE | ID: mdl-31094026

ABSTRACT

AIMS: To measure pancreatic area and exocrine function in young children with recent-onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes. METHODS: Thirty-two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent-onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase-1 was analysed using an enzyme-linked immunosorbent assay kit in recent-onset Type 1 diabetes and 38 first-degree relative control children. RESULTS: Pancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm2 (1.61) vs. 8.31 cm2 (1.74) in controls, adjusted estimate (95% CI) 1.45 (-2.12, -0.79), P < 0.001; longitudinal area was 1.28 cm2 (0.44) vs. 1.55 cm2 (0.43), adjusted estimate (95% CI) -0.27 (-0.45, -0.09), P = 0.003. Faecal elastase-1 levels in Type 1 diabetes were 455 (323, 833) ug/g, median (IQR) vs. 1408 µg/g (1031, 1989) in controls, P < 0.001. CONCLUSION: Pancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent-onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life.


Subject(s)
Carrier Proteins/metabolism , Diabetes Mellitus, Type 1/metabolism , Pancreas, Exocrine/metabolism , Pancreas/pathology , Pancreatic Elastase/metabolism , Child , Child, Preschool , Diabetes Mellitus, Type 1/pathology , Enzyme-Linked Immunosorbent Assay , Feces/chemistry , Female , Humans , Male , Organ Size , Pancreas/diagnostic imaging , Ultrasonography
5.
Article in English | MEDLINE | ID: mdl-29032859

ABSTRACT

BACKGROUND: Animal studies have suggested that an increased supply of omega-3 long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexaenoic acid (DHA), during the perinatal period can prevent later excess body fat mass. However, previous human studies have produced inconsistent findings, and few have assessed potential effects beyond 6 years of age. OBJECTIVE: To evaluate the effect of supplementing women in the second half of pregnancy with omega-3 LCPUFA, chiefly as DHA, on the percentage body fat of children at 7 years of age, as assessed by two methods: air displacement plethysmography (BOD POD) and bioelectrical impedance spectroscopy (BIS). DESIGN: A time-restricted follow up at 7 years of age of children born to mothers enrolled in DOMInO (DHA to Optimise Maternal Infant Outcome) randomized controlled trial, in which women took either high-DHA tuna oil (800mg/day DHA) or placebo capsules from 20 weeks' gestation to delivery, at Adelaide-based centers. Primary outcomes were the percentage body fat at 7 years of age as assessed by both BOD POD and BIS. Weight, height, waist/hip circumferences and BMI were also recorded. RESULTS: A total of 252 DOMInO children (n=135 males, n=117 females) completed the follow up study. There were no differences between the DHA and placebo groups in percentage body fat as assessed by either BOD POD [adjusted mean difference: -0.35, 95% CI: -1.46, 2.16; P=0.71] or BIS [adjusted mean difference: 0.64, 95% CI: -0.99, 2.27; P=0.44]. BMI z-scores were also similar between groups [adjusted mean difference: 0.18, 95% CI: -0.10, 0.45; P=0.21]. There were also no differences in height, weight or waist and hip circumference between the DHA and placebo groups at 7 years of age. CONCLUSION: DHA supplementation in the second half of pregnancy has no effect on childhood growth or fat mass at 7 years of age, supporting findings from follow ups of the DOMInO children at 3 and 5 years.


Subject(s)
Adiposity/drug effects , Body Mass Index , Dietary Supplements , Docosahexaenoic Acids/administration & dosage , Child , Child, Preschool , Double-Blind Method , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Pregnancy
6.
Article in English | MEDLINE | ID: mdl-26947583

ABSTRACT

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.


Subject(s)
Anxiety/therapy , Carcinoma, Squamous Cell/radiotherapy , Depression/therapy , Head and Neck Neoplasms/radiotherapy , Mindfulness/methods , Stress, Psychological/therapy , Adult , Aged , Anxiety/psychology , Australia , Carcinoma, Squamous Cell/psychology , Depression/psychology , Female , Head and Neck Neoplasms/psychology , Humans , Linear Models , Male , Middle Aged , Pilot Projects , Quality of Life/psychology , Squamous Cell Carcinoma of Head and Neck , Stress, Psychological/psychology , Surveys and Questionnaires , Young Adult
7.
J Diabetes Complications ; 28(6): 904-11, 2014.
Article in English | MEDLINE | ID: mdl-25060530

ABSTRACT

As the average life expectancy of patients with cystic fibrosis (CF) improves, the long term co-morbidities assume increasing importance. CF related diabetes (CFRD) has adverse effects on both nutrition and pulmonary function, and is associated with increased mortality. Abnormalities of glucose metabolism in CF represent a continuum; however the predominant abnormality is postprandial, not pre-prandial, glycemia. Insulin is currently recommended as the treatment of choice for CFRD, but its use is associated with a number of limitations, including hypoglycemia. Both the rate of gastric emptying and the consequent release of the 'incretin' hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1), from the gut are important determinants of overall glycemic control, particularly postprandial glycemia. Both are abnormal in conditions associated with exocrine pancreatic insufficiency. Incretin based therapies that have the capacity to slow gastric emptying and/or modulate the release of 'incretin' hormones, are now used widely in type 2 diabetes (T2D). This paper explores the determinants of glycemic control in CF, with a particular focus on the roles of gastric emptying and 'incretin' hormones, providing a rationale for the use of therapies that delay gastric emptying, including incretin mimetics, to minimize postprandial glycemia and improve nutritional status.


Subject(s)
Cystic Fibrosis/complications , Cystic Fibrosis/therapy , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/therapy , Hyperglycemia/therapy , Blood Glucose/metabolism , Cystic Fibrosis/blood , Cystic Fibrosis/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Gastric Emptying/physiology , Gastric Inhibitory Polypeptide/metabolism , Glucagon-Like Peptide 1/metabolism , Humans , Hyperglycemia/epidemiology , Hyperglycemia/etiology , Incretins/metabolism , Insulin/metabolism , Postprandial Period , Prevalence , Receptors, Gastrointestinal Hormone/metabolism
8.
Eur J Cancer Care (Engl) ; 19(2): 234-42, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19686355

ABSTRACT

The objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer. Semi-structured qualitative interviews were conducted with 50 women at two time points (baseline and 6 months later). The interviews examined emotions, experiences, attitudes to sexual and continence issues and treatment decision making. As part of a larger prospective observational study, demographic data and scores for depression and anxiety were collected. Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months. In contrast, the 39 women in the non-distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves, appraisal of coping strategies and reappraisal of the situation. A surprise finding was the high level of resilience displayed by majority of these women. Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples.


Subject(s)
Adaptation, Psychological , Anxiety/psychology , Prostatic Neoplasms/psychology , Spouses/psychology , Decision Making , Female , Humans , Interviews as Topic , Life Change Events , Male , Prostatic Neoplasms/therapy , Qualitative Research , Quality of Life , Sexual Behavior/psychology , Stress, Psychological , Urinary Incontinence/psychology
9.
Qual Life Res ; 14(2): 395-405, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15892428

ABSTRACT

The aim of this study was to assess prospectively changes in the health-related quality of life (HRQL) of children and adolescents with diabetes, asthma or cystic fibrosis (CF). One hundred and twenty-two parents of children aged 10-16 years with asthma, diabetes, or CF were recruited from specialist paediatric clinics. Parents described their children's HRQL using the Child Health Questionnaire (PF98) at baseline, 6, 12, 18 and 24 months post-baseline. They reported that the general health of children with CF was significantly worse than that of children with asthma and diabetes at baseline. In other domains there were few differences between the HRQL of children in the three groups. In several domains, the HRQL of children with asthma or diabetes improved over the 2 years of the study. This improvement was less evident for children with CF.


Subject(s)
Asthma/physiopathology , Diabetes Mellitus/physiopathology , Quality of Life , Adolescent , Asthma/psychology , Child , Chronic Disease , Diabetes Mellitus/psychology , Family , Humans , Parents/psychology , Peer Group , Schools , Surveys and Questionnaires
10.
J Paediatr Child Health ; 40(9-10): 559-61, 2004.
Article in English | MEDLINE | ID: mdl-15367153

ABSTRACT

The evidence that early intensive behavioural intervention (IBI) is effective for young children with autism has persuaded parents worldwide to finance and advocate for IBI. Intensive behavioural intervention uses applied behavioural analysis to address the deficits of autism with an individualized and systematic approach. Communication, social, cognitive and adaptive gains are seen in the majority of children; a sizeable minority can catch up to near normal functioning, under ideal conditions. However there is not universal acceptance amongst professionals that IBI is the most proven intervention. What level of evidence is required for Australian states to provide adequate public funds for IBI?


Subject(s)
Autistic Disorder/nursing , Critical Care/economics , Adult , Australia , Autistic Disorder/therapy , Child , Family Health , Health Services Accessibility , Humans , Managed Care Programs , Parenting , Parents
11.
Aust N Z J Psychiatry ; 38(9): 753-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15324341

ABSTRACT

OBJECTIVES: To evaluate the use of the World Health Organization Disability Assessment Schedule II (WHODAS II), a patient questionnaire measuring disability, in patients treated for long-term psychotic disorders. METHOD: The study was conducted at St. Vincent's Mental Health Service, Melbourne, Australia. Twenty patients with long-term psychotic disorders under the care of either the residential Community Care Unit or the outpatient Mobile Support and Treatment Service were selected. For all 20 patients a clinician assessment of disability and functional status was recorded using the International Classification of Impairments, Disabilities and Handicaps-2 (ICIDH-2), Life Skills Profile (LSP) and Health of the Nation Outcome Scale (HoNOS). The WHODAS II survey was then administered to each patient. The WHODAS II was re-administered by a second rater within 5 days of the initial assessment for the purpose of test-retest reliability analysis. Each patient also completed the WHO Quality of Life instrument (brief version) (WHQOL-BREF), a self-report questionnaire on quality of life. RESULTS: The WHODAS II was experienced as relatively complex and at times difficult to administer with full co-operation in this clinical context. Overall, test-retest reliability was fair. The information it yielded gave valuable insights into patients' experiences. Most of the participants reported fewer impairments in mental functions and fewer activity limitations than reported by clinicians. However, patients reported significant restrictions in participation in social activities and limitations due to environmental barriers. The WHOQOL-BREF highlighted difficulties experienced by patients in their participation in society, through exploring difficulties and satisfaction with various aspects of life experience and this instrument was well accepted. CONCLUSIONS: The self-reported experience of patients is needed alongside clinician-rated measures to assess outcomes in people with long-term psychotic disorders. The WHODAS II records and measures patients' own experiences of disability. It may be used together with the WHOQOL-BREF, a distinct and complementary self-report assessment of quality of life.


Subject(s)
Disability Evaluation , Psychotic Disorders/diagnosis , World Health Organization , Adult , Feasibility Studies , Female , Humans , Male , Outcome Assessment, Health Care , Psychotic Disorders/therapy , Reproducibility of Results , Residential Treatment , Surveys and Questionnaires , Time Factors
12.
J Paediatr Child Health ; 40(1-2): 44-7, 2004.
Article in English | MEDLINE | ID: mdl-14718004

ABSTRACT

OBJECTIVE: To assess longitudinal changes in folate status in South Australian children and adolescents during fortification of food with folic acid. METHODS: Sixty-nine children and adolescents (age 12.8 +/- 2.3 years), 47 with diabetes and 22 healthy controls, had their folate status assessed at the beginning of 1999 and again after a mean 1.1 +/- 0.23 years. Intake of folate at baseline was assessed with a quantitative food frequency questionnaire. RESULTS: Baseline red cell folate (mean +/- standard deviation (SD)) was 756 +/- 294.5 nmol/L and remained constant at follow up at 736 +/- 299 nmol/L (P = 0.55) in the whole group. Serum folate increased from 24.4 +/- 6.3 nmol/L to 27.2 +/- 8.8 nmol/L (P = 0.002). Children with diabetes showed a significant increase in serum folate (from 26.3 +/- 5.7-30.1 +/- 7.9, P < 0.001) and stable red cell folate (835.8 +/- 278.6 and 808.6 +/- 296.7, P = 0.51) between baseline and the second samples, while controls showed stable serum (20.4 +/- 5.7 and 21.1 +/- 7.7, P = 0.7) and red cell folate (586.6 +/- 255.9 and 579.8 +/- 240.1, P = 0.92). A third sample collected in 17 subjects after a further 9 +/- 1.3 months showed a further increase in serum and red cell folate. Mean folate intake at baseline was 301 +/- 129 micro g/day, below the mean recommended for prevention of neural tube defects. CONCLUSIONS: Voluntary fortification of food with folate is associated with improved folate status in South Australian children and adolescents, but may not be sufficient at current levels to provide maximal protection against neural tube defects at a population level.


Subject(s)
Child Nutritional Physiological Phenomena , Folic Acid/blood , Food, Fortified , Adolescent , Adult , Child , Female , Follow-Up Studies , Homocysteine/blood , Humans , Male , Pregnancy , Prenatal Care , Surveys and Questionnaires
13.
J Paediatr Child Health ; 39(2): 88-92, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12603794

ABSTRACT

Congenital and acquired forms of osteoporosis in childhood and adolescence can result in morbidity from fracture and pain in childhood, and place an individual at significant risk for problems in adult life. A range of therapies exist for the prevention and treatment of osteoporosis, including optimization of daily calcium intake, adequate vitamin D status, weight-bearing exercise, treatment with sex steroids where delayed puberty is a problem and, more recently, use of bisphosphonate therapy. Intravenous pamidronate therapy (a bisphosphonate) has been shown to reduce fractures and improve bone density in children with osteogenesis imperfecta, and might prove to be of benefit in other osteoporotic conditions in childhood. However, a number of issues regarding the optimal use of bisphosphonate therapy in children and adolescents remain to be resolved, including total annual dose and frequency and duration of administration. Bisphosphonate therapy should, therefore, be used only in the context of a well-run clinical programme with specialist knowledge in the management of osteopenic disorders in childhood.


Subject(s)
Diphosphonates/therapeutic use , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Absorptiometry, Photon , Adolescent , Bone Density , Child , Child, Preschool , Diphosphonates/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Risk Assessment , Severity of Illness Index , Treatment Outcome
14.
Cell Tissue Res ; 306(2): 239-50, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11702235

ABSTRACT

Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) are structurally related molecules that stimulate epithelial cell proliferation and migration. MSP also acts directly as a chemoattractant for resident macrophages. These activities are integral to the wound repair processes of inflammation, epithelialization and tissue remodelling. To begin to examine the involvement of HGF and MSP in healing of cutaneous wounds we have mapped the temporal expression of these two molecules and their receptors, MET and RON respectively, in adult rat excisional wounds. Four 2x2-cm full-thickness excisional wounds were created on the dorsum of 18 rats, and biopsies were taken through the wounds at 3, 5, 7, 14, 21, and 28 days postwounding. These biopsies were analyzed using immunofluorescent staining and in situ hybridization (ISH). The number of cells staining positively for HGF and MET significantly increased in response to wounding. HGF staining and mRNA peaked at 7 days postwounding whereas MET was upregulated earlier, peaking after 3 days. Both HGF and MET protein were observed in fibroblasts of the dermis and in the newly forming granulation tissue. ISH studies also revealed that fibroblasts at the wound edges and within the newly forming granulation tissue also expressed HGF and c-met mRNA. Immunofluorescent staining revealed both MSP and RON within the wound, with maximum staining occurring between 7 and 21 days for both the ligand and receptor. In addition, MSP co-localized with a small subset of ED1-positive cells (monocytes). In contrast, ED2-positive cells (macrophages) did not co-localize with MSP. Thus, increased expression of HGF, MSP and their receptors MET and RON respectively was observed in response to wounding. Furthermore, MSP co-localization with a subset of monocytes may confirm a role for MSP in the activation of mature macrophages, which may be important in tissue remodelling.


Subject(s)
Epidermis/metabolism , Growth Substances/metabolism , Hepatocyte Growth Factor/metabolism , Proto-Oncogene Proteins , Wound Healing/physiology , Animals , Biomarkers , Epidermal Cells , Epidermis/injuries , Growth Substances/genetics , Hepatocyte Growth Factor/genetics , In Situ Hybridization , Male , Microscopy, Fluorescence , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/metabolism , Rats , Rats, Sprague-Dawley , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Up-Regulation
15.
J Pediatr Endocrinol Metab ; 14(8): 1093-6, 2001.
Article in English | MEDLINE | ID: mdl-11592565

ABSTRACT

We present a family with X-linked adrenal hypoplasia congenita (AHC) due to a truncation mutation in the DAX1 gene. The three patient reports demonstrate variable clinical and biochemical features at presentation. They presented with adrenal crises at 3 years, 4 weeks, and 3 weeks. Mineralocorticoid deficiency preceded glucocorticoid deficiency in patient 3 and an early ultrasound indicated normal sized adrenal tissue. Genetic analysis showed that potential female carriers were unaffected.


Subject(s)
Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/genetics , Repressor Proteins , X Chromosome , Adrenal Glands/diagnostic imaging , Adrenal Insufficiency/diagnostic imaging , Adrenocorticotropic Hormone/blood , Child, Preschool , DAX-1 Orphan Nuclear Receptor , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Genetic Linkage , Glucocorticoids/deficiency , Heterozygote , Humans , Hydrocortisone/blood , Infant , Infant, Newborn , Male , Mineralocorticoids/deficiency , Mutation , Pedigree , Receptors, Retinoic Acid/genetics , Renin/blood , Transcription Factors/genetics , Ultrasonography
16.
J Paediatr Child Health ; 37(3): 218-20, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11474705

ABSTRACT

High risk HLA class II alleles account for 40% of the genetic susceptibility to type 1 diabetes in Caucasians, but the majority of the genetically predisposed do not develop the disease. This supports some environmental modification of the autoimmune destruction of beta cells that precedes type 1 diabetes. Identical twin studies and geographical variation in incidence also argue for a critical role of environmental factors. Attention has been directed to the possible harmful effect of cow's milk protein (or protective effect of breast-feeding) and enteric infections in early life. Natural history studies that follow children at increased risk of type 1 diabetes provide the best opportunity to study environmental triggers. The Australian Baby Diab Study has followed approximately 500 babies from birth who have a first-degree relative with type 1 diabetes. No prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity was found. The same Australian cohort demonstrated a relationship between rotavirus infection and the first appearance or increase in islet antibodies. Enteroviral infection is seen more frequently in prediabetic children and prior to the onset of islet autoimmunity in Finnish cohorts. Environmental factors may interact. Breast milk protects against enteric infections; enteric infections in turn could increase immunity to dietary antigens by increasing intestinal permeability. It is also possible that an alteration in gut mucosal immune function in genetically susceptible individuals underlies any effect of dietary or viral proteins on the development of islet autoimmunity in early life.


Subject(s)
Diabetes Mellitus, Type 1/virology , Environmental Exposure/adverse effects , Animals , Breast Feeding , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Enterovirus Infections/virology , Gene Frequency , Genetic Predisposition to Disease , HLA Antigens/genetics , Humans , Infant , Infant, Newborn , Milk/immunology , Rotavirus Infections/virology , Viral Proteins/immunology
17.
J Pediatr ; 138(6): 888-93, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11391334

ABSTRACT

OBJECTIVES: The objective was to investigate total plasma homocyst(e)ine (tHcy), methylenetetrahydrofolate reductase (MTHFR) genotype, and the contribution of diet to homocysteine values in children and adolescents with type 1 diabetes and a control group. STUDY DESIGN: A total of 78 children with type 1 diabetes and 59 members of an age- and sex-matched control group were recruited. Fasting samples were collected for tHcy, MTHFR genotype, serum vitamin B(12), serum folate, red cell folate, and plasma creatinine. Food frequency questionnaires targeted intake of folate, vitamin B(6), and vitamin B(12). RESULTS: Fasting tHcy was reduced in patients compared with the control group (4.7 vs 5.9 micromol/L, P <.001). Serum folate (P =.002), red cell folate(P <.001), and serum vitamin B(12) (P =.005) were higher, and plasma creatinine was lower. A significant difference in tHcy values between patients and the control group persisted after correction was done for these factors (r = 0.1, P =.02). No difference was seen in the frequency of MTHFR polymorphisms. tHcy was not elevated in those patients with the 677TT or 677T/1298C genotypes, although red cell folate was significantly higher in members of the case (P =.01) and control groups (P =.05) with a 677 TT genotype. Dietary intake of folate correlated with serum folate (r = 0.4,P =.005). CONCLUSION: tHcy values are lower in children and adolescents with type 1 diabetes. Higher serum levels of folic acid and vitamin B(12), reflecting differences in dietary intake between children with diabetes and members of a control group, partially account for this difference.


Subject(s)
Diabetes Mellitus, Type 1/blood , Homocysteine/blood , Homocystine/blood , Adolescent , Child , Creatinine/blood , Erythrocytes/chemistry , Female , Folic Acid/blood , Genotype , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Oxidoreductases Acting on CH-NH Group Donors/blood , Vitamin B 12/blood
18.
Aust N Z J Psychiatry ; 34(5): 762-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11037362

ABSTRACT

OBJECTIVE: The aim of this paper is to outline the opportunities and dangers the chronic fatigue syndrome (CFS) issue presents to Australian psychiatry. METHOD: The scientific literature of the last 50 years on CFS in adults was reviewed and samples of recent media portrayals of CFS in the UK and Australia were collected. The author has worked in both the UK and Australia managing adult CFS patients in specialist outpatient consultation-liaison (C-L) psychiatry settings. RESULTS: Chronic fatigue syndrome has been at the heart of an acrimonious debate in the UK, both within the medical profession and in the wider community. UK psychiatry has been drawn into the debate, at times being the target of strong and potentially damaging criticism, yet UK psychiatry, especially the C-L subspecialty, has played a crucial role in clarifying appropriate research questions and in devising management strategies. The issue has served to enhance and broaden psychiatry's perceived research and clinical role at the important medicine-psychiatry interface in that country. CONCLUSIONS: Handled properly, the CFS issue offers Australian psychiatry, especially C-L psychiatry, an opportunity to make a useful contribution to patient care in a clinically difficult and contentious area, while at the same time serving to help broaden psychiatry's scope in the Australian medical landscape.


Subject(s)
Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/etiology , Psychiatry/trends , Public Opinion , Social Perception , Australia , Cognitive Behavioral Therapy , Diagnosis, Differential , Fatigue Syndrome, Chronic/psychology , Fatigue Syndrome, Chronic/therapy , Humans , Neurasthenia/etiology , Practice Guidelines as Topic , Psychiatry/organization & administration , Randomized Controlled Trials as Topic , United Kingdom
20.
Diabetes ; 49(8): 1319-24, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10923632

ABSTRACT

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children.


Subject(s)
Autoantibodies/blood , Diabetes Mellitus, Type 1/epidemiology , Islets of Langerhans/immunology , Rotavirus Infections/epidemiology , Antigens, Viral/immunology , Australia/epidemiology , Autoantigens , Autoimmunity , Diabetes Mellitus, Type 1/immunology , Gastroenteritis/complications , Gastroenteritis/epidemiology , Gastroenteritis/virology , Glutamate Decarboxylase/immunology , Humans , Infant, Newborn , Insulin Antibodies/blood , Longitudinal Studies , Membrane Proteins/immunology , Molecular Mimicry , Odds Ratio , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatases/immunology , Receptor-Like Protein Tyrosine Phosphatases, Class 8 , Risk Factors , Rotavirus/immunology , Rotavirus Infections/complications
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