ORCID Profile
0000-0002-4153-934X
Current Organisations
Mater Research
,
University of Queensland
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Publisher: Elsevier BV
Date: 1991
DOI: 10.3109/00313029109061431
Abstract: We describe 2 patients presenting with severe chronic hyponatremia in whom clinical and biochemical features strongly suggested the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both, however, were proven to have a primary pituitary deficiency of corticotropin. Their short synacthen tests were only mildly abnormal but associated with low basal ACTH levels. The diagnosis of ACTH deficiency was made more convincingly by their dramatic response to glucocorticoid replacement therapy. In patients in whom no cause for SIADH can be found, a trial of maintenance cortisol therapy is warranted to exclude this eminently treatable condition.
Publisher: Elsevier BV
Date: 12-2004
Publisher: American Academy of Pediatrics (AAP)
Date: 08-2009
Abstract: OBJECTIVE: Tandem mass spectrometry is widely applied to routine newborn screening but there are no long-term studies of outcome. We studied the clinical outcome at six years of age in Australia. METHODS: In a cohort study, we analyzed the outcome at 6 years for patients detected by screening or by clinical diagnosis among & million infants born from 1994 to 1998 (1 017 800, all unscreened) and 1998 to 2002 (461 500 screened, 533 400 unscreened) recording intellectual and physical condition, school placement, other medical problems, growth, treatment, diet, and hospital admissions. Results were analyzed separately for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and other disorders, and grouped patients as those who presented clinically or died in the first 5 days of life patients presented later or diagnosed by screening, and those with substantially benign disorders. RESULTS: Inborn errors, excluding phenylketonuria, were diagnosed in 116 of 1 551 200 unscreened infants (7.5/100 000 births) and 70 of 461 500 screened infants (15.2/100 000 births). Excluding MCADD, 21 unscreened patients with metabolic disorders diagnosed after 5 days of life died or had a significant intellectual or physical handicap (1.35/100 000 population) compared with 2 of the screened cohort (0.43/100 000 odds ratio: 3.1 [95% CI: 0.73–13.32]). Considering the likely morbidity or mortality among the expected number of never-diagnosed unscreened patients, there would be a significant difference. Growth distribution was normal in all cohorts. CONCLUSION: Screening by tandem mass spectrometry provides a better outcome for patients at 6 years of age, with fewer deaths and fewer clinically significant disabilities.
Publisher: Elsevier BV
Date: 1995
DOI: 10.1080/00313029500169103
Abstract: We describe a case of 2 siblings aged 2 1/2 and 3 1/2 yrs accidentally poisoned by ethylene glycol ingestion. We found estimating the level of ethylene glycol in plasma by calculation of osmolar gap too insensitive to be of value and advocate the availability of a specific method. In our study only one of the 2 children had a toxic level of ethylene glycol but assay by conventional assay and by proton magnetic resonance spectroscopy (1HMRS) of toxic metabolites viz glycolate, glyoxylate and oxalate showed both to be excreting grossly elevated levels. This indicates the desirability of assaying the toxic metabolites of the glycol as well as the parent compound in assessing ingestions.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/541710
Abstract: Kidney stones are a global health problem, incurring massive health costs annually. Why stones recur in many patients remains unknown but likely involves environmental, physiological, and genetic factors. The solute linked carrier (SLC) 26A1 gene has previously been linked to kidney stones in mice. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) protein, and its loss in mice leads to hyperoxaluria and calcium oxalate renal stones. To investigate the possible involvement of SAT1 in human urolithiasis, we screened the SLC26A1 gene in a cohort of 13 in iduals with recurrent calcium oxalate urolithiasis, which is the commonest type. DNA sequence analyses showed missense mutations in seven patients: one in idual was heterozygous R372H 4 in iduals were heterozygous Q556R one patient was homozygous Q556R and one patient with severe nephrocalcinosis (requiring nephrectomy) was homozygous Q556R and heterozygous M132T. The M132 amino acid in human SAT1 is conserved with 15 other species and is located within the third transmembrane domain of the predicted SAT1 protein structure, suggesting that this amino acid may be important for SAT1 function. These initial findings demonstrate genetic variants in SLC26A1 of recurrent stone formers and warrant wider independent studies of SLC26A1 in humans with recurrent calcium oxalate stones.
Publisher: Japanese Society for Pediatric Endocrinology
Date: 2009
DOI: 10.1297/CPE.18.73
Publisher: Wiley
Date: 02-1996
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1998
Publisher: Walter de Gruyter GmbH
Date: 2007
DOI: 10.1515/JPEM.2007.20.8.893
Abstract: We genotyped the androgen receptor (AR) gene in 31 Australasian patients with androgen insensitivity syndrome (AIS). The entire coding region of AR was examined including analysis of polymorphic CAG and GGN repeats in all patients. AR defects were found in 66.7% (6/9) of patients with complete AIS (CAIS) and 13.6% (3/22) of patients with partial AIS (PAIS). A novel deletion (N858delG) leading to a premature stop codon was found in CAIS patient P1. CAIS patient P2 has a novel deletion (N2676delGAGT) resulting in a stop at codon 787. These mutations would result in inactivation of AR protein. A novel insertion of a cysteine residue in the first zinc finger of the AR DNA-binding domain (N2045_2047dupCTG) was found in CAIS patient P3. PAIS patient P4 has a novel amino acid substitution (Arg760Ser) in the AR ligand binding domain, which may impair ligand binding. Five patients were found to have previously reported AR mutations and no mutations were identified in the remaining patients.
Publisher: Wiley
Date: 04-1993
DOI: 10.1111/J.1440-1754.1993.TB00462.X
Abstract: The role of bioelectrical impedance (BI) in estimating the pharmacokinetics and, therefore, in idualized doses, of aminophylline in preterm infants (gestational age 26-35 weeks) was assessed in a two-phase study. Multiple regression analysis in the first group of neonates (phase I, n = 19) identified resistance, reactance, weight and length as optimal predictors of distribution volume (adjusted R2 = 0.84, coefficient of variation (CV) = 10.17%), and length2/impedance and postconceptual age as predictors of clearance (adjusted R2 = 0.74, CV = 26.73%). Application of these models to an independent group (phase II, n = 20) generated doses which satisfactorily achieved target theophylline loading and steady-state (SS) 'peaks' of 10 micrograms/mL and SS 'troughs' of 7.7 +/- 0.6 micrograms/mL. A better understanding of specific criteria and limitations of the impedance technique in neonates is necessary in order to refine BI measurements.
Publisher: SAGE Publications
Date: 05-2005
DOI: 10.1007/S10024-005-0004-0
Abstract: A 5-month-old boy with no history of vomiting, early sexual development, or noticeable significant illness was found dead in bed. Autopsy demonstrated bilateral adrenal hyperplasia unequivocally shown on biochemical testing of blood and urine to be due to 21-hydroxylase deficiency. Genetic analysis of the CYP21 gene showed compound heterozygosity 1 allele contained a pseudogene sequence (gene conversion) and the other contained a previously described I172N point mutation. On theoretical grounds, the genotype would have been expected to cause simple virilizing congenital adrenal hyperplasia but, because no other cause of death could be found, it is possible that it caused a fatally severe loss of enzyme activity in this child. If this assumption is valid, newborn screening would have prevented this death, had it been available.
Publisher: American Society for Clinical Investigation
Date: 03-2010
DOI: 10.1172/JCI31474
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
DOI: 10.1097/FTD.0000000000000532
Abstract: Chemotherapy for colorectal, head and neck, and breast cancer continues to rely heavily on 5-fluorouracil and its oral prodrug capecitabine. Associations of serious fluoropyrimidine adverse effects have focused on inherited deficiency of the catabolic enzyme, dihydropyrimidine dehydrogenase. However, abnormal dihydropyrimidine dehydrogenase activity accounts for only about one-third of observed toxicity cases. Thus, the cause of most fluorouracil toxicity cases remains unexplained. For this small cohort study, thymine (THY) 250 mg was administered orally to 6 patients who had experienced severe toxicity during treatment with 5FU or capecitabine. Plasma and urine were analyzed for THY and its catabolites dihydrothymine (DHT) and β-ureidoisobutyrate. Of the 6 patients, 2 had decreased THY elimination and raised urinary THY recovery consistent with inherited partial dihydropyrimidine dehydrogenase deficiency, confirmed by DPYD sequencing. Unexpectedly, 3 patients displayed grossly raised plasma THY concentrations but normal elimination profiles (compared with a normal range for healthy volunteers previously published by the authors). DPYD and DPYS sequencing of these 3 patients did not reveal any significant loss-of-activity allelic variants. The authors labeled the phenotype in these 3 patients as “enhanced thymine absorption”. Only 1 of the 6 cases of toxicity had a normal postdose plasma profile for THY and its catabolites. Postdose urine collections from all 6 patients had THY/DHT urinary ratios above 4.0, clearly separated from the ratios in healthy subjects that were all below 3.0. This small cohort provided evidence for a hypothesis that fluorouracil toxicity cases may include a previously undescribed pyrimidine absorption variant, “enhanced thymine absorption,” and elevated THY/DHT ratios in urine may predict fluorouracil toxicity. A prospective study is currently being conducted.
Publisher: Wiley
Date: 02-2003
DOI: 10.1046/J.1440-0960.2003.00637.X
Abstract: Two cases of scurvy diagnosed following presentation with a purpuric rash are presented. A 44-year-old man developed scurvy as a result of poor dietary intake of vitamin C. This occurred because of a number of factors. including poor dentition, diarrhoea, depression and benzodiazepine/narcotic dependence. A 69-year-old man with acute myeloid leukaemic transformation of myelodysplastic syndrome developed mucositis, nausea, vomiting and diarrhoea as complications of chemotherapy. This led to poor dietary intake and consequently scurvy. Both cases demonstrated specific and diagnostic cutaneous manifestations of scurvy, particularly perifollicular purpura, ecchymoses and coiled corkscrew hairs. The diagnosis was supported by specific diet history. Ascorbic acid tolerance test was used as a simple laboratory method to confirm the clinical diagnosis.
Publisher: Massachusetts Medical Society
Date: 09-10-1986
DOI: 10.1056/NEJM198610093151516
Abstract: We constructed and simulated a "minimal proteome" model using Langevin dynamics. It contains 206 essential protein types that were compiled from the literature. For comparison, we generated six proteomes with randomized concentrations. We found that the net charges and molecular weights of the proteins in the minimal genome are not random. The net charge of a protein decreases linearly with molecular weight, with small proteins being mostly positively charged and large proteins negatively charged. The protein copy numbers in the minimal genome have the tendency to maximize the number of protein-protein interactions in the network. Negatively charged proteins that tend to have larger sizes can provide a large collision cross-section allowing them to interact with other proteins on the other hand, the smaller positively charged proteins could have higher diffusion speed and are more likely to collide with other proteins. Proteomes with random charge/mass populations form less stable clusters than those with experimental protein copy numbers. Our study suggests that "proper" populations of negatively and positively charged proteins are important for maintaining a protein-protein interaction network in a proteome. It is interesting to note that the minimal genome model based on the charge and mass of Escherichia coli may have a larger protein-protein interaction network than that based on the lower organism Mycoplasma pneumoniae.
Publisher: Wiley
Date: 02-1986
DOI: 10.1111/J.1445-5994.1986.TB01114.X
Abstract: A calcium loading test performed on seven of eight children with idiopathic hypercalciuria identified the hyperabsorptive form of hypercalciuria in five and renal hypercalciuria in one. The type of hypercalciuria was not identified in the other patient. Three children presented with hematuria without calculus formation. Chlorothiazide reduced the urinary calcium excretion level in two of six patients to the normal range. The addition of cellulose phosphate to chlorothiazide reduced the urinary calcium excretion level to the normal range in those four patients who showed an incomplete response to chlorothiazide alone. There was clinical improvement with cellulose phosphate in another child whose symptoms did not disappear after chlorothiazide had reduced urinary calcium level to the normal range. Cellulose phosphate is effective in children with recurrent stone formation who have shown inadequate response to chlorothiazide.
Publisher: Elsevier BV
Date: 1986
Publisher: Elsevier BV
Date: 03-2000
Publisher: Wiley
Date: 06-2003
DOI: 10.1046/J.1365-2265.2003.01781.X
Abstract: Mutations in the gene for the POU domain transcription factor POU1F1 (human Pit-1) have been reported in patients with GH, TSH and PRL deficiencies. PROP1 (Prophet of Pit-1) gene mutations also cause gonadotrophin deficiencies and in some cases partial ACTH deficiency. This study analyses the POU1F1 and PROP1 genes in a cohort of Australian children with combined pituitary hormone deficiency (CPHD) and correlates results with patient phenotype. Genomic analysis was carried out on 33 patients with CPHD referred from centres around Australia. Clinical data were collected from medical records and referring physicans. POU1F1 mutations were identified in two of four patients with a suggestive phenotype. In a female patient, novel compound heterozygous POU1F1 mutations were identified: Arg143Leu in exon 3 and Leu194Gln in exon 4. This patient presented with failure to thrive at 6 weeks of age and has deficiencies of TSH and GH. A previously described heterozygous Arg271Trp mutation in exon 6 of the POU1F1 gene was identified in a female infant who presented with growth failure and was diagnosed with TSH then GH deficiencies. No PROP1 mutations were identified however, we describe a number of previously unreported PROP1 polymorphisms. No patients presenting with deficiencies of all anterior pituitary hormones early in life had POU1F1 or PROP1 gene mutations. In 33 Australian children with CPHD we have identified POU1F1 mutations in two patients and no PROP1 mutations. We speculate that in the majority of children other genes must be responsible for the CPHD phenotype.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JCHROMB.2013.05.001
Abstract: Saliva contains a number of biochemical components which may be useful for diagnosis/monitoring of metabolic disorders, and as markers of cancer or heart disease. Saliva collection is attractive as a non-invasive s ling method for infants and elderly patients. We present a method suitable for saliva collection from neonates. We have applied this technique for the determination of salivary nucleotide metabolites. Saliva was collected from 10 healthy neonates using washed cotton swabs, and directly from 10 adults. Two methods for saliva extraction from oral swabs were evaluated. The analytes were then separated using high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS). The limits of detection for 14 purine yrimidine metabolites were variable, ranging from 0.01 to 1.0μM. Recovery of hydrophobic purine yrimidine metabolites from cotton tips was consistently high using water/acetonitrile extraction (92.7-111%) compared with water extraction alone. The concentrations of these metabolites were significantly higher in neonatal saliva than in adults. Preliminary ranges for nucleotide metabolites in neonatal and adult saliva are reported. Hypoxanthine and xanthine were grossly raised in neonates (49.3±25.4 30.9±19.5μM respectively) compared to adults (4.3±3.3 4.6±4.5μM) nucleosides were also markedly raised in neonates. This study focuses on three essential details: contamination of oral swabs during manufacturing and how to overcome this weighing swabs to accurately measure small saliva volumes and methods for extracting saliva metabolites of interest from cotton swabs. A method is described for determining nucleotide metabolites using HPLC with photodiode array or MS/MS. The advantages of utilising saliva are highlighted. Nucleotide metabolites were not simply in equilibrium with plasma, but may be actively secreted into saliva, and this process is more active in neonates than adults.
Publisher: Oxford University Press (OUP)
Date: 1983
DOI: 10.1093/JAC/11.5.455
Abstract: We studied the urinary excretion of the proximal tubular enzyme alanine aminopeptidase (AAP) by 38 patients who received gentamicin and by 45 similar control patients. AAP excretion by the control patients was highly variable. The pattern of AAP excretion distinguished patients with pre-renal and renal causes for increases in serum creatinine (SCr) but this can be done more simply with the urine to serum creatinine ratio. Peak AAP excretion did not reflect renal damage in oliguric patients and di not identify gentamicin patients with a renal cause for increases in SCr. The level of AAP excretion in the first three days of gentamicin treatment did identify the three patients with renal causes for an increase in SCr and was highest in a patient with symptomatic hypomagnesaemia due to impairment of proximal tubular function. We concluded that study of AAP excretion in normal volunteers receiving three-day courses of aminoglycosides is a valid screening test for nephrotoxicity but that AAP excretion is too non-specific to use in clinical practice.
Publisher: Wiley
Date: 05-1992
Publisher: Wiley
Date: 06-1988
DOI: 10.1111/J.1445-2197.1988.TB06240.X
Abstract: Eight paediatric patients undergoing major surgery for correction of scoliosis who were treated postoperatively with hypotonic saline and 5% dextrose have been studied. Plasma sodium, renin and aldosterone, and urine volume, sodium and osmolality were measured. These patients had an impaired ability to excrete a sodium-free water load. In the first 60 h urine volume remained reduced, while in the first 36 h urine sodium remained concurrently high. If the first 36 h postoperation are considered, the sodium-free water given was quantitatively retained and the serum sodium at 36 h was significantly correlated with the amount of free water given (P less than 0.01). To minimize postoperative hyponatraemia and the associated shift of water into the brain causing cerebral oedema, it is recommended that no more than 50 ml/kg sodium-free water be given until urine sodium falls and volume increases.
Publisher: Walter de Gruyter GmbH
Date: 2009
DOI: 10.1515/JPEM.2009.22.2.127
Abstract: Mutations in CYP21 (21-hydroxylase) lead to congenital adrenal hyperplasia (CAH). We genotyped 26 probands with CAH by PCR-sequencing the entire CYP21 gene. 25/26 had homozygous or compound heterozygous mutations. The frequencies of mutations were similar to other populations with deletion/hybrid, I2 G splice and I172N the most common. Five patients with a I172N allele predicting simple-virilising CAH had a salt-wasting phenotype. Two other probands also had a more severe phenotype than predicted by genotype. Two families had both non-classic and salt-wasting phenotypes arising from combinations of three deleterious alleles. Two novel CYP21 alleles were detected: D106N and a large deletion encompassing CYP21 and adjacent pseudogene. Two rare CYP21 alleles were also found. Three of these four novel/rare alleles were only detected as a result of sequencing the entire CYP21 gene. Entire CYP21 sequencing will increase the number of mutations detected in CAH, and in combination with functional studies should contribute a greater understanding of phenotype-genotype correlations.
Publisher: Public Library of Science (PLoS)
Date: 09-2015
Publisher: Elsevier BV
Date: 02-1999
DOI: 10.1016/S0022-3476(99)70413-0
Abstract: The purpose of this study was to evaluate the usefulness of 17 hydroxyprogesterone (17OHP) determination in dried filter paper blood s les from patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. It was hypothesized that these home s les would enhance patient treatment. Results of 17OHP determination in simultaneously collected venous and dried filter paper blood s les were compared to establish assay reliability. Thereafter, parents mailed dried filter paper blood s les collected before each hydrocortisone dose. The 17OHP levels in wet and dried blood s les correlated well (r = 0.98). Results did not change when stored for 2 weeks under various conditions. Blood s ling at different times of the day provided insights into the patterns of 17OHP secretion and identified times of inadequate adrenal suppression. Dose adjustments were then made considering the time of day when adrenal suppression was inadequate. Home monitoring of 17OHP is a reliable and practical approach for assessing adrenal steroid activity in patients with congenital adrenal hyperplasia. Considering the time of day of 17OHP elevations also facilitates hydrocortisone dosing adjustment.
Publisher: BMJ
Date: 12-1995
Abstract: Inhaled glucocorticoid therapy has systemic effects including hypothalamic-pituitary-adrenal (HPA) suppression. The optimal test for detecting these effects has not been defined. Timed urine collections and 09.00 hour plasma cortisol levels were obtained from 12 normal volunteers receiving inhaled placebo, beclomethasone (BDP) 800 or 2000 micrograms/day. The 24 hour urine s les were collected as follows: first hour after waking (hour 1), the next two hours after waking (hours 2 and 3), remainder of day, and overnight, with results expressed as urine cortisol/creatinine (UCC) ratios and as hourly cortisol output in the timed collections. Twenty four hour urinary cortisol excretion was also calculated. Medication was blinded and given in random order with a washout period of at least 11 days between each treatment arm. None of the UCC ratios changed with BDP 800 micrograms/day. UCC ratios at hour 1, hour 2 and 3, and overnight, and 24 hour urinary free cortisol excretion were reduced after BDP 2000 micrograms/day, whilst remainder of day UCC ratio and the plasma cortisol level did not change significantly. Cortisol output showed similar changes. In a follow up study BDP 1400 micrograms/day also reduced UCC ratios for the first two hours after waking. UCC ratios are as sensitive as the more cumbersome 24 hour urinary free cortisol excretion, and more sensitive than single morning plasma cortisol measurements, in detecting the effects of inhaled beclomethasone on the HPA axis.
Publisher: Wiley
Date: 02-1984
DOI: 10.1038/ICB.1984.7
Abstract: The cytotoxic effects of hyperthermia on tumours are readily measured. Parameters of injury to normal tissues are needed to evaluate therapeutic potential. Fifty-five isolated rat livers were perfused in vitro for 180 min in order to determine parameters of hyperthermic injury. During this period they were heated for 1 h at temperatures ranging from 37 degrees to 45 degrees and then assessed for evidence of hyperthermic injury. The most critical indicator of hyperthermic injury was sustained depression of bile production. Bile secretion decreased by 80% after heating at temperatures above 42 degrees. Aspartate amino transferase (AST) release increased significantly at temperatures of 42 degrees and above. Potassium and variable amounts of glucose were released into the medium during heating, reflecting temporary changes in metabolism at high temperatures.
Publisher: Elsevier BV
Date: 10-1983
DOI: 10.1016/0009-8981(83)90185-7
Abstract: Prealbumin (PA) was purified 35-fold from human serum and antibodies raised against it in rabbits. A 2-hour radioimmunoassay (RIA) using polyethyleneglycol (PEG) to separate bound and free PA was used to determine levels in body fluids. Using patient serum specimens the new method was compared with an electroimmunoassay (EIA) method and the regression equation obtained was: y = 1.13x - 9.91. The RIA and EIA methods compared favourably with respect to precision to practicability and economy. The RIA method seems especially suitable for large scale assays of PA and is 100 times more sensitive than EIA. Preliminary estimations of PA with the RIA method in plasma, cerebrospinal fluids, amniotic fluids, duodenal juices and urines were carried out. The results indicate that this method can be conveniently used to assay PA in body fluids where the protein is present in low concentration.
Publisher: Wiley
Date: 05-1997
DOI: 10.1111/J.1445-2197.1997.TB01958.X
Abstract: To compare already used serum markers in advanced breast cancer, namely erythrocyte sedimentation rate (ESR), carcino-embryonic antigen (CEA), and polymorphic epithelial mucins (e.g. CA15-3) with a newer potential marker: parathyroid hormone related protein (PTHrP). A study group of 33 patients of proven advanced breast cancer was compared with 11 patients with benign breast lumps who were undergoing surgery, and eight patients with humoral hypercalcaemia of malignancy of non-breast origin. ESR, CA15-3, CEA, PTHrP, parathormone (PTH), liver and renal function were measured using commercially available kits. Using given reference ranges, results were classified into normal versus abnormal, and univariate statistical comparisons were made using Fisher's exact test. For multivariate analysis, absolute serum levels were used, and multivariate logistic regression models were employed. By univariate analysis, only CA15-3 (P = 0.007), and CEA (P = 0.004), were significant markers of metastatic disease. By multivariate analysis the only independently significant serum marker was CA15-3 (P = 0.043). PTHrP was neither a sensitive (22%) nor specific (90.1%) serum marker when compared to CEA or CA15-3. ESR was the most sensitive single serum marker (93%). An incidental finding of elevations of serum parathormone was found in as many patients as in the study group as there were elevations of PTHrP. PTHrP would not have revealed any patients with metastatic disease that would not have been predicted by any existing tumour markers including CA15-3, CEA and ESR. The finding of elevated PTH in as many patients as PTHrP indicates the possible need for a study inclusive of other polypeptide hormones as markers in advanced breast cancer.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.CLIM.2007.03.002
Abstract: In this study DC numbers, phenotype and DC responses to the Toll-like receptor (TLR)-3 ligand, poly I:C, were examined in new-onset Type 1 diabetes (T1D) patients (ND) and in established T1D patients (ED). Absolute blood myeloid DC (MDC) and plasmacytoid DC (PDC) numbers were decreased in ND and ED patients compared to age-matched controls. The decrease in MDC and PDC counts was less evident in patients with a combination of T1D and coeliac disease (CD) or CD alone. The age-dependent decline in blood DC numbers, found in control children, was not evident in ND patients, such that 2-10 years old ND children had similar MDC and PDC numbers to 15-17 years old controls. In ED patients the t-score of MDC and PDC numbers related to the age of diagnosis but not to disease duration. Blood DC in T1D patients were not distinguished from those of controls by the levels of HLA-DR, CD40 and CD86 expression or the percentage of DC expressing cytokines, IL-12, IL-10, IL-6 and TNF-alpha, in responses to poly I:C. If low DC numbers are shown to contribute to the autoimmunity in T1D, interventions aimed to increase DC numbers may mitigate against beta-cell loss.
Publisher: Public Library of Science (PLoS)
Date: 04-03-2016
Publisher: Hindawi Limited
Date: 02-2009
DOI: 10.1111/J.1399-5448.2008.00439.X
Abstract: There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D(3) and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM. To determine the relationship between measured 25(OH)-vitamin D(3) levels and the degree of acidosis in children at diagnosis with T1DM. Children presenting with new-onset T1DM at a tertiary children's hospital. 25(OH)-vitamin D(3) and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D(3) levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation. Fourteen of the 64 children had low 25(OH)-vitamin D(3) levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r(2) = 0.20, p < 0.001) and ethnic background a further 10% (partial r(2) = 0.10, p = 0.002). The levels of 25(OH)-vitamin D(3) increased in 10 of the 11 children with resolution of the acidosis. Acid-base status should be considered when interpreting 25(OH)-vitamin D(3) levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.
Publisher: Georg Thieme Verlag KG
Date: 05-2002
DOI: 10.1055/S-2002-32138
Abstract: Placental growth hormone (PGH) progressively replaces pituitary growth hormone in the maternal circulation from mid-gestation onwards in human pregnancy. Our previous investigations have shown that placental growth hormone concentrations correlate well with foetal growth. Despite the apparent correlation between PGH and birthweight, the physiology of its secretion during pregnancy has not been well defined. We investigated the response of maternal serum PGH to oral glucose loading in pregnant women (n = 24) who demonstrated normal glucose tolerance at a mean gestation of 29 weeks. Mean (SEM) fasting PGH concentrations were high (36.9 [6.4] ng/ml). No suppression of PGH was noted at one, two or three hours after a 75 g oral glucose load. Similarly, no changes were noted in growth hormone binding protein or in calculated free PGH over the course of the glucose tolerance test. As expected, insulin concentrations rose sixfold and insulin like growth factor binding protein 1 concentrations fell by 20 % with glucose loading. Correlation analysis showed maternal weight, BMI, fasting serum glucose serum insulin to be significantly correlated with the babies' birthweight. Our results support the proposition that PGH concentrations in maternal serum are not suppressed by oral glucose loading in non-diabetic mothers.
Publisher: Elsevier BV
Date: 12-2002
DOI: 10.1016/S0378-3782(02)00072-5
Abstract: The aims of this study were to determine, in a cohort of extremely premature infants, the prevalence of iron deficiency identified by zinc protoporphyrin/heme ratio (ZPP) testing, and its association with neurodevelopmental problems and dietary risk factors for iron deficiency. Infants of less than 29 weeks' gestation or less than 1000 g birth weight were studied prospectively at a multidisciplinary follow-up clinic. Assessments were made at a corrected age of either 12 months (n=72) or 2 years (n=69). Physical examination, Griffiths Developmental Scale, and neurosensory-motor assessment were administered, information on diet and behaviour was obtained by questionnaire, and a fingerprick ZPP ratio was performed to identify iron deficiency. 18.4% of infants had positive ZPP tests. There was no significant association between a positive ZPP test result and dietary risk factors, or symptoms of lethargy, irritability or poor attention. In children without cerebral palsy, there was no difference on Griffiths scores or neurosensory-motor assessment between ZPP-positive and ZPP-negative groups. The diagnosis of cerebral palsy (n=12) was significantly associated with both a positive ZPP test and a lower Griffiths general quotient (GQ) score. Iron deficiency occurs commonly in extremely low birth weight (ELBW) children in early childhood, and is not predicted by dietary risk factors. The prevalence of iron deficiency is increased in ELBW children with cerebral palsy. Non-anaemic iron deficiency (NAID) does not impair development or significantly affect behaviour of ELBW subjects who do not have cerebral palsy.
Publisher: Wiley
Date: 12-11-2008
DOI: 10.1111/J.1365-2265.2008.03303.X
Abstract: Familial neurohypophyseal diabetes insipidus (FNDI) is a rare disorder resulting from arginine vasopressin (AVP) gene mutations. A partial defect in AVP secretion occurs early in the course of FNDI and may not be detected by a water deprivation test (WDT). Testing for AVP gene mutations may confirm a diagnosis of FNDI when a WDT is inconclusive and may also predict in iduals who will later develop FNDI. To test the utility of AVP gene analysis in confirming the diagnosis of FNDI. Five families (20 subjects, 14 symptomatic and six asymptomatic) with FNDI and nine children with idiopathic neurohypophyseal diabetes insipidus (INDI). Genomic DNA was analysed for AVP gene mutations using polymerase chain reaction (PCR) lification and sequencing. Heterozygous AVP gene mutations were found in all subjects with FNDI but none of the ICDI patients. Each family had their own distinct mutation. We identified two novel mutations (C44W and C105S). One asymptomatic subject developed diabetes insipidus (DI) 4 months after detection of an AVP gene mutation. The WDT suggested partial DI in 4/6 but was normal in 2/6 children with FNDI. AVP gene testing allowed diagnostic confirmation of FNDI when the WDT was inconclusive in symptomatic children, therefore obviating the need for a repeat WDT and enabling earlier initiation of appropriate treatment. AVP gene testing also has the potential to identify which asymptomatic children will later develop FNDI.
Publisher: Oxford University Press
Date: 07-2011
DOI: 10.1093/MED/9780199235292.003.7033
Abstract: Hypoglycaemia is defined as a blood glucose level less than 2.6 mmol/l. This is based on the consistent impairment of central nervous system function observed in subjects when blood glucose levels are below this (1). Glucose homeostatic mechanisms should maintain blood glucose level to preserve cognitive function. Hypoglycaemia triggers protective glucose homeostatic mechanisms and persistent hypoglycaemia is the result of a failure of homeostasis. This is a medical emergency with serious short- and long-term consequences, which result from a reduced supply of glucose to the brain. Recurrent and persistent hypoglycaemia does cause significant morbidity and death due to brain damage. In an adult, after recovery of glucose levels, neurological impairment usually recovers over minutes to hours. In children, the duration of hypoglycaemia leading to permanent damage is not known, but is presumed to depend on the age of the child, the frequency of hypoglycaemia, the degree and the rapidity of the fall in glucose, concurrent circumstances such as infection, trauma and hypoxia, the degree of resilience of the brain tissue at the current stage of development. and the energy demands of the particular parts of the brain. The reasons for the increased sensitivity in children appear to relate to the higher energy requirements and immaturity of the homeostatic mechanisms of the brain. In congenital hyperinsulinism of infancy (CHI) the rates of severe neurological impairment remain high at 20–50%, permanent neurological impairment with damage occurring mainly in the cerebral cortex, hippoc us, and caudate putamen. Appropriate long term management of hypoglycaemia requires the correct diagnosis, and this depends on obtaining ‘critical blood and urine s les’ during a hypoglycaemic episode. In the first 48 h of life 20% of normal full–term infants have a blood glucose level .6 mmol/l (2), after this it is relatively uncommon in infancy and childhood with the incidence of various underlying diagnoses varying with age. The causes of hypoglycaemia can be classified into five groups: ◆ excess insulin (or insulin-like factors) for the given circumstances ◆ lack of one or more of the counter regulatory hormones (cortisol, growth hormone) ◆ disturbance of intermediate metabolism causing impairment of gluconeogenesis and/or glycogenolysis ◆ disturbance of fat breakdown or ketone body formation or utilization ◆ lack of nutrient sufficient for current energy demands
Publisher: Wiley
Date: 03-2002
DOI: 10.1046/J.1365-2265.2002.01484.X
Abstract: Cystic fibrosis-related diabetes mellitus (CFRD) is an increasingly common complication of cystic fibrosis. CFRD is preceded by a progressive decline in insulin secretion but there is no accepted definition of the prediabetic state in CFRD. This prediabetic state appears to have adverse effects on clinical status, nutrition and lung function, but there is no direct evidence that the impaired glucose homeostasis is the cause of these deteriorations. This study examined the prevalence of glucose intolerance and impaired insulin secretion in a population of children with CF without CFRD. Severe CF lung disease is often associated with poor weight gain and slower growth but the mechanism for this is still unclear. The relationships between the current state of glucose homeostasis, insulin secretion and the insulin-like growth factor axis, height velocity, nutrition status and lung function were therefore studied. Eighteen children with cystic fibrosis aged 9.5-15 years had oral glucose tolerance tests and 14 of these also had intravenous glucose tolerance tests (four refused). Blood s les were collected for insulin, C-peptide, glucose, HbA1c, insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-1 and IGFBP-3. Data on height, weight, puberty status, clinical score (Shwachman score) and lung function were recorded. Height velocity, height and weight standard deviation scores (SDS) were calculated using WHO/CDC data. The mean height SDS (-0.52 +/- 0.17) was less than the normal population (P = 0.007) and the mean height velocity was 4.6 +/- 0.5 cm/year, 39% with a height velocity less than the third percentile for age. The weight SDS and body mass index (BMI) were similar to the normal population. Four children had impaired glucose tolerance. The first-phase insulin response (FPIR) was below the first percentile of normal population values in nine (65%). Impaired FPIR or impaired glucose tolerance did not correlate with the Shwachman score, nutritional status or pulmonary function. There was a significant positive correlation between insulin secretion (area under the curve) and height velocity (P = 0.001) and serum IGFBP-3 levels (P = 0.001). Impaired glucose tolerance was present in 20% of children with cystic fibrosis. Impaired insulin secretion was common (65%) even in children with normal glucose tolerance. The mean height SDS for the group was low and the height velocity was abnormally slow in 39%, yet nutritional status as measured by BMI was appropriate for age. Relative insulin deficiency rather than nutritional deprivation or poor clinical status thus appears to be implicated in the poor linear growth of these children with relatively stable lung disease. This was a small study and firm conclusions on this chronic suppurative disease as to the cause of poor growth are not possible. The causes of poor growth are likely to be complex nevertheless, the apparent decrease in insulin secretion combined with the expected increased demands on insulin production during pubertal growth raises the question as to whether insulin therapy should be considered in children with cystic fibrosis before the onset of cystic fibrosis-related diabetes mellitus.
Publisher: Springer Science and Business Media LLC
Date: 28-09-2016
DOI: 10.1007/S10877-016-9938-1
Abstract: An estimated 25 % of indirect ion selective electrode (ISE) ICU plasma sodium measurements differ from corresponding direct ISE values by at least 4 mmol/L, the dominant factor being indirect ISE over-estimation driven by hypoproteinemia. Since direct measurements are considered unaffected by protein concentrations, we investigated whether direct ISE plasma sodium measurements in the laboratory and at point of care in ICU show sufficient agreement to be clinically interchangeable. From a 5 year clinical chemistry database, 9910 ICU plasma s les were assessed for agreement between direct ISE sodium measurements in ICU (ABL 700) and in the central laboratory (Vitros Fusion). The relationship between differences in paired plasma sodium measurements (Vitros-ABL) and total plasma protein concentrations was evaluated by generalized estimating equation linear regression. Patients were hypo-proteinemic [mean (SD) total protein concentration 56.9 (9.04) g/L]. Mean (SD) paired Vitros-ABL sodium measurements was -0.087 (1.74) mmol/L, range -14 to +10 mmol/L. Disagreement at ≥|4|mmol/L, ≥|3|mmol/L and ≥|2|mmol/L was present in 409 (4.1 %), 1333 (13.4 %) and 3591 (36.2 %) pairs respectively. Test-retest disagreement estimates within either source alone were substantially lower. Small negative Vitros-ABL differences associated with low plasma protein concentrations were reversed at high protein concentrations. Disagreement between plasma sodium concentrations monitored by two common direct ISE analyzers was substantially less than reported between direct and indirect ISE devices, although a protein influence of low clinical importance persisted. Disagreement was sufficient to jeopardize safe interchangeable interpretation in situations with a low tolerance for imprecision, such as hyponatremia correction.
Publisher: American Medical Association (AMA)
Date: 11-1981
DOI: 10.1001/ARCHPEDI.1981.02130350075030
Abstract: The personal traits of expatriates influence their work performance in a subsidiary. Nevertheless, organizations tend to hire candidates who are suitable from the technological dimension but ignore personal and family factors. Expatriates might not be familiar with a foreign place, and most organizations do not provide the so-called cultural adjustment training. The selected expatriates often accept the job without knowing the future prospects of their career, which can result in in idual and family turmoil initially. Moreover, the unknown future career prospects and concern over when they will return to the parent company can affect expatriates' work. Cross-cultural competence refers to the ability of in iduals to work effectively and live normally in different cultural contexts, and this ability requires expatriate employees to adopt adaptive thinking patterns and behaviors in the host country. To explore the effect of expatriates' cross-culture adjustment on their work stress and job involvement, this study therefore uses an empirical approach in which data are collected with a questionnaire survey and proposes specific suggestions, according to the results, to aid expatriates in their personal psychological adjustment. The results show that the challenges faced by expatriate employees are derived from assigned tasks, unknown environments, language barriers, and cultural differences. Excessive pressure will impose ideological and psychological burdens upon the expatriates and even lead to physical symptoms, however, the appropriate amount of pressure can play a driving role and promote the smooth progress of the work. High-tech industry employees who can adapt to the customs and cultures of foreign countries have higher work participation and are more likely to find ways to alleviate work stress. It has also been found that the stronger the cross-cultural competence of employees, the better their adjustment to the host country and the higher their corresponding job performance.
Publisher: Wiley
Date: 15-07-2012
DOI: 10.1111/J.1464-5491.2011.03551.X
Abstract: To assess associations between maternal serum vitamin D concentration and glucose metabolism in a cohort of pregnant women living in an Australian subtropical environment. Cross-sectional assessment of 25-hydroxy vitamin D concentrations in 399 Hyperglycemia and Adverse Pregnancy Outcome ancillary study participants, treated at an obstetric teaching hospital in Brisbane, Australia. All patients underwent a blinded 75-g oral glucose tolerance test at 24-32 (target 28) weeks' gestation. The mean (± standard deviation) fasting plasma glucose was 4.5 ± 0.4 mmol/l. Mean (± standard deviation) serum 25-hydroxy vitamin D was 132.5 ± 44.0 nmol/l. A difference of one standard deviation in maternal 25-hydroxy vitamin D was inversely related to fasting glucose (fasting glucose lower by 0.047 mmol/l, P=0.012) when assessed with multiple linear regression after adjusting for confounders. Maternal 25-hydroxy vitamin D correlated with β-cell function as estimated by the log-transformed homeostasis model assessment-β-cell function equation (r=0.131, P=0.009), but not with the homeostasis model assessment of insulin resistance. An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and β-cell function suggests that vitamin D may influence glucose metabolism through this mechanism. Intervention studies are required to determine causality and the role of vitamin D replacement in deficient in iduals.
Publisher: Wiley
Date: 24-07-2009
Publisher: Wiley
Date: 08-1998
Publisher: AMPCo
Date: 09-2011
DOI: 10.5694/MJA11.10284
Abstract: 21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia, with an incidence of 1:14000 live births and equal prevalence among males and females. Newborns with the most severe "salt-wasting" form of 21-OHD are susceptible to salt-wasting crises in the first few weeks of life. This is associated with morbidity and mortality. 21-OHD newborn screening (NBS) is currently performed in many countries. Despite several prominent medical societies recommending 21-OHD NBS, no state in Australia currently screens for this condition. We report a case that illustrates the need to reconsider including 21-OHD in NBS. 21-OHD NBS can be reliable, sensitive and effective in reducing morbidity and mortality.
Publisher: Wiley
Date: 05-1999
Publisher: SAGE Publications
Date: 2007
DOI: 10.2350/06-04-0083.1
Abstract: In hyperinsulinism of infancy (HI), unregulated insulin secretion causes hypoglycemia. Pancreatectomy may be required in severe cases, most of which result from a defect in the β-cell K ATP channel, encoded by ABCC8 and KCNJ11. Pancreatic histology may be classified as diffuse or focal disease (the latter associated with single paternal ABCC8 mutations), indicated by the presence of islet cell nuclear enlargement in areas of diffuse abnormality. We investigated genotype-phenotype associations in a heterogeneous Australian cohort. ABCC8 and KCNJ11 genes were sequenced and case histology was reviewed in 21 infants who had pancreatectomy. Ninety-eight control DNA s les were tested by single nucleotide polymorphism analysis. Eighteen ABCC8 mutations were identified, 10 novel. Eleven patients (4 compound heterozygote, 4 single mutation, 3 no mutation detected) had diffuse hyperinsulinism. Nine patients had focal hyperinsulinism (6 single paternal mutation, 2 single mutation of undetermined parental origin, 1 none found) with absence of islet cell nuclear enlargement outside the focal area, although centroacinar cell proliferation and/or nesidiodysplasia was present in 7 cases. Regeneration after near-total pancreatectomy was documented in 4 patients, with aggregates of endocrine tissue observed at subsequent operations in 3. Although the absence of enlarged islet cell nuclei is a useful discriminant of focal hyperinsulinism associated with a paternal ABCC8 mutation, further research is needed to understand the pathophysiology of other histological abnormalities in patients with HI, which may have implications for mechanisms of ductal and islet cell proliferation. Previous surgery should be taken into account when interpreting pancreatic histology.
Publisher: American Diabetes Association
Date: 30-10-2010
DOI: 10.2337/DC09-1196
Abstract: The objective of this study was to determine maternal hormonal and metabolic factors associated with insulin sensitivity in human pregnancy. This was a prospective observational cross-sectional study of 180 normal pregnant women, using s les collected at the time of a blinded oral glucose tolerance test (OGTT) between 24 and 32 weeks' gestation as an ancillary to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The study was conducted at two public university teaching hospitals, Cleveland, Ohio, and Brisbane, Australia. Fasting maternal serum cholesterol, triglycerides, free fatty acids, insulin, leptin, tumor necrosis factor-α, placental growth hormone (PGH), insulin-like growth factors (IGFs) 1 and 2, and insulin-like growth factor binding proteins (IGFBPs) 1 and 3 were assayed. Correlation and multiple regression analyses were used to determine factors associated with maternal insulin sensitivity (IS) estimated using both OGTT-derived (ISOGTT) and fasting (using the homeostasis model assessment [HOMA] ISHOMA) insulin and glucose concentrations. Insulin sensitivity correlated (r = x and y for ISOGTT and ISHOMA, respectively) with fasting maternal serum leptin (−0.44 and −0.52), IGFBP1 (0.42 and 0.39), and triglycerides (−0.31 and −0.27). These factors were significantly associated with insulin sensitivity in multiple regression analyses (adjusted R2 0.44 for ISOGTT and ISHOMA). These variables explained more than 40% of the variance in estimates of insulin sensitivity. Maternal hormonal and metabolic factors related to the placenta, adipose tissue, and the growth hormone axis are associated with the variation in insulin sensitivity seen during normal human pregnancy.
Publisher: Wiley
Date: 28-02-2003
DOI: 10.1046/J.1365-2265.2003.01725.X
Abstract: Hyperinsulinism of infancy (HI) is characterized by unregulated insulin secretion in the presence of hypoglycaemia, often resulting in brain damage. Pancreatic resection for control of hypoglycaemia is frequently resisted because of the risk of diabetes mellitus (DM). We investigated retrospectively 62 children with HI from nine Australian treatment centres born between 1972 and 1998, comparing endocrine and neurological outcome in 28 patients receiving medical therapy alone with 34 who required pancreatic resection to control their hypoglycaemia. History, treatment and clinical course were ascertained from file audit and interview. Risk of DM (hazard ratio) attributable to age at surgery ( or = 100 days at last pancreatectomy) and extent of resection ( or = 95%) were calculated using Cox proportional hazards regression and categorical variables compared by the chi2-test. Neurological outcome (normal, mild deficit or severe deficit) was derived from the most authoritative source. Surgically treated patients had a greater birthweight, earlier presentation and higher plasma insulin levels. Of 18 infants or = 100 days of age at surgery, four (all > or = 100 days) became diabetic as an immediate consequence of surgery and five (two or = 100 days) became diabetic 7-18 years later. Surgery > or = 100 days and pancreatectomy > or = 95% were associated with development of diabetes (HR = 12.61, CI 1.53-104.07 and HR = 7.03, CI 1.43-34.58, respectively). Neurodevelopmental outcome was no different between the surgical and medical groups with 44% overall with neurological deficits. Patients euglycaemic within 35 days of the first symptom of hypoglycaemia (Group A) had a better neurodevelopmental outcome than those still hypoglycaemic > 35 days from first presentation (Group B) (P = 0.007). Prolonged hypoglycaemia in Group B was due either to delayed diagnosis or to need for repeat surgery because of continued hypoglycaemia. Within Group A, medically treated patients (who presented later with apparently milder disease) had a higher incidence of neurodevelopmental deficit (n = 15, four mild, three severe deficit) compared with surgically treated patients (n = 18, two mild, none severe deficit) (P < 0.025). Poor neurodevelopmental outcome remains a major problem in hyperinsulinism of infancy. Risk of diabetes mellitus with pancreatectomy varies according to age at surgery and extent of resection. Patients presenting early with severe disease have a better neurodevelopmental outcome and lower risk of diabetes if they are treated with early extensive surgery.
Publisher: Wiley
Date: 12-03-2013
DOI: 10.1111/CEN.12012
Publisher: Elsevier BV
Date: 1986
DOI: 10.3109/00313028609059482
Abstract: We have devised a simple, sensitive quantitative method for the determination of serum methemalbumin. The method uses a modified Allen correction to correct the alpha band of methemalbumin at 623 nm for background turbidity. The technique is robust and is more sensitive than Schumm's test.
Publisher: Elsevier BV
Date: 1986
DOI: 10.3109/00313028609087566
Abstract: The need exists for a fast and accurate method of estimating glomerular filtration rate (GFR). A number of nomograms and formulae which estimate GFR on the basis of a plasma creatinine level have appeared in the literature. We examined some of these nomograms and formulae and showed that when the formula published by Cockcroft and Gault was compared with the GFR as estimated by 51Cr EDTA clearance, the coefficient of correlation was better than 0.94. We also compared creatinine clearance with the Cockcroft and Gault formula, and the Siersbaek-Nielsen nomogram. In each case, the correlation coefficient was less than that for the Cockcroft and Gault-51Cr EDTA comparison. Because of the inherent difficulties in making accurate 24 h urine collections, and problems associated with 51Cr EDTA studies, it is suggested that the formula prediction of GFR is more reliable than a GFR estimate using a 24 h collection.
Publisher: SAGE Publications
Date: 07-1987
DOI: 10.1177/000456328702400407
Abstract: Twenty-two recurrent calcium stone formers had 24-h urinary oxalate excretions on their home diets which were significantly greater than those of 30 normal subjects (0·48±0·23 mmol/d mean±SD compared with 0·31±0·11 P ·01). The stone formers also demonstrated marked day to day variability in oxalate excretion indicating that a single normal urinary oxalate measurement did not exclude significant hyperoxaluria at other times. On a hospital diet containing 1000 mg calcium per day, urinary oxalate excretion fell significantly from 0·48±0·23 mmol/d to 0·32±0·12 P ·01. As the urinary calcium excretion in and out of hospital was similar, it seems unlikely that low calcium intake at home was responsible for the hyperoxaluria. All patients had recurrent symptomatic stone disease and had been advised to avoid foods rich in oxalate. Whilst poor compliance is a possible explanation for the variability in oxalate excretion, we believe it is more likely that there is an inadvertent intake of oxalogenic precursors in their diet. As normal subjects do not demonstrate hyperoxaluria on similar home diets, stone formers may have a metabolic defect in the handling of these precursors.
Publisher: American Diabetes Association
Date: 05-04-2016
DOI: 10.2337/DB15-1748
Abstract: Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of in idual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for in idual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity.
Publisher: The Endocrine Society
Date: 03-2000
DOI: 10.1210/JC.85.3.1143
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Cowley.