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Biomedical subjects

J R Allen

Publications and source records attributed to J R Allen.

At least 19 recordsLinked to original sources

Growth and feeding practices of Vietnamese infants in Australia.

OBJECTIVE: To investigate the growth and feeding practices in first-generation Vietnamese infants living in Australia. DESIGN: Cohort study. SETTING: The study was conducted between 1999 and 2002 in Sydney. SUBJECTS: A total of 239 Vietnamese women were recruited randomly from antenatal clinics, and of these 210 were initially seen. During the first year, 20 cases (9.5%) were lost to follow-up. Data were collected at 0.5, 2, 4, 6, 9 and 12 months. RESULTS: Vietnamese infants were significantly longer and heavier than reference data (both P<0.0001). The Vietnamese infants had a significant decline in weight growth with age compared with reference data (P<0.001). The Vietnamese infants had marginally higher s.d. score for ideal weight for length than reference data (P=0.044). There was a significant decline in ideal weight for length with age compared with reference data (P=0.0065). Both parents were significantly shorter (mean s.d. height scores: -1.5+/-0.8 (mother) and -1.8+/-0.8 (father)) than reference data (P<0.001). The incidence of breast feeding was 79%, but half of the breast feeding women had stopped breast feeding by 3 months. A total of 162 (79.8%) infants were given infant formula within the first week, of whom 131 (80.1%) were fed infant formula within the first 24 h after birth. CONCLUSIONS: Vietnamese infants in this study had growth comparable with reference data despite their parents being shorter than reference data. Breast feeding duration was short with infant formula being introduced early.

Anthropometry↗

Iron status of young Vietnamese children in Australia.

OBJECTIVE: The aim of this study was to estimate the prevalence of iron deficiency in Vietnamese children living in Australia and to identify risk factors associated with iron deficiency. METHODS: A cohort of healthy term Vietnamese infants, were followed from birth (n = 210) to 18 months (n = 174) with anthropometry, dietary intake and feeding practices measured at seven time points. Socio-demographic data were collected from the parents at the first home visit. At 18 months iron status was examined by full blood count and plasma ferritin concentration in 129/152 (85%) of the eligible children. Iron depletion was defined as a plasma ferritin level < 10 microg/L. Iron deficiency without anaemia was defined as iron depletion plus MCV < 70fl and iron deficiency anaemia was defined as iron deficiency anaemia plus Hb < 110 g/L. RESULTS: The prevalence of iron deficiency was iron depletion 19.4% (95% CI: 13.0%, 27.3%), iron deficiency without anaemia 3.1% (95% CI: 0.9%, 7.8%) and iron deficiency anaemia 3.9% (95% CI: 1.3%, 8.8%). Multiple regression analysis showed three significant predictors of iron deficiency: cows milk intake (negative effect), meat, fish or poultry intake (positive effect) and weight gain (negative effect). A cows milk intake > or = 650 mL/day was a risk factor for iron deficiency. CONCLUSION: Prevalence of iron deficiency at 18 months was high despite appropriate infant feeding practices during the first year. Modification of the diet in the second year of life may decrease the risk of iron deficiency in Vietnamese children.

Animals↗

Isolation of the components of a complex mixture by means of column switching for their enhanced detection by mass spectrometry.

Mass spectral characterization of low-level impurities in drug substances and formulations may be challenging when using a validated HPLC method developed for optimal chromatographic performance. In many cases, either the mobile phase contains non-volatile additives that are deleterious to the operation of the mass spectrometer, or some of the related substances fail to ionize effectively under electrospray ionization or atmospheric pressure chemical ionization conditions. This paper describes a way to capture these low-level compounds from an analytical HPLC column using a small trapping column. Mixture components are retained on the trapping column by means of reducing the solvent strength of the eluent. Subsequent elution of trapped compounds using mobile phases more amenable to mass spectral analysis yields improved detection and characterization of low-level compounds of interest. Possible applications of peak trapping and elution include: (1) analysis of compounds separated using a mobile phase containing high concentrations of non-volatile additives, (2) analysis of organic acids separated using a low-pH mobile phase (containing trifluoroacetic acid), and (3) improving the detection limit of a low-level compound of interest through multiple collections. The peak trapping apparatus and optimization experiments are described.

Chromatography, High Pressure Liquid↗

Pursuit of optimal carbohydrate-based anticancer vaccines: preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewis(y) antigens.

A novel preparation of nonnatural glycoamino acids starting from n-pentenyl glycosides is described. The approach involves a Horner-Emmons olefination with a suitably protected glycine-derived phosphonate, followed by catalytic asymmetric hydrogenation, which proceeds with excellent diastereomeric selectivity. The synthetic methodology was useful for the preparation of glycoamino acids containing the Tn antigen, the MBr1 antigen (Globo-H), the Le(y) antigen, and lactose. These glycoamino acids can also serve as units for peptide synthesis. The synthesis of polyvalent glycopeptides containing three different antitumor antigens is described (28 and 29), and these have been prepared for conjugation to carrier protein in order to access the immunogenicity for tumor immunotherapy applications.

Amino Sugars↗

Variations in the measurement of resting energy expenditure in children with cystic fibrosis.

OBJECTIVE: To investigate in children with cystic fibrosis (CF) and children without CF: (1) the test-retest reproducibility of a 20 min resting energy expenditure (REE) measurement; and (2) the long-term reproducibility of REE measurements in children with CF using longitudinal data. DESIGN: Cross-sectional study and longitudinal cohort. SETTING: A tertiary referral paediatric hospital. SUBJECTS: A total of 31 (11 male, 20 female) children (aged 12.8+/-3.6 y) with CF and 32 (14 male, 18 female) healthy children without CF (aged 12.2+/-2.3 y) were enrolled in the short-term reproducibility study. Long-term REE measurement reproducibility was assessed in another 14 children (5 male, 9 female) with CF, comparing their initial REE measurement with a subsequent measurement 1-2 y later. METHODS: All children had measurements of height, weight, skinfold thickness and indirect calorimetry. RESULTS: There was no statistically significant difference in REE between repeated measurements in children with CF (mean+/-s.d., 6240+/-1280 and 6220+/-1315 kJ/24 h) and in the children without CF (6040+/-956 and 6015+/-943 kJ/24 h). For the children with CF, the intraclass correlation coefficient was 0.99 and for children without CF the intraclass correlation coefficient was 0.97. The measurement errors were 119 and 177 kJ, respectively. Approximately 80% of the variation in REE in the CF group and 70% in the group without CF was explained by fat-free mass (FFM). Analysis of the longitudinal CF data show there was no difference in REE between a child's first measurement (5140+/-1140 kJ) and their subsequent measurement (5460+/-1190 kJ), after adjustment for changes in body size between the measurements. CONCLUSION: This study has demonstrated that a short-term 20 min REE measurement is reproducible and therefore valid in children with CF and children without CF. These results also indicate that in children with CF, long-term REE measurements are reproducible.

Adolescent↗

The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision.

OBJECTIVE: To follow the clinical and biochemical course of a cohort of women who had postpartum thyroid dysfunction (PPTD) at 6 months postpartum and to examine the treatment practices of general practitioners and endocrinologists in the setting of PPTD. DESIGN: Prospective longitudinal study. SETTING: Metropolitan, Perth, Australia. PARTICIPANTS: Eighty-six Caucasian women who were identified to have PPTD at 6 months postpartum in a cross-sectional study of 748 women. MAIN OUTCOME MEASURES: Characteristics of the clinical and biochemical course of PPTD and documentation of the treatment practices and factors influencing treatment of PPTD by general practitioners and endocrinologists. RESULTS: Sixteen of 86 women (19%) were receiving treatment at 9 months postpartum and by 30 months postpartum 27% of women had received treatment for PPTD. Fifty-one percent of those not treated were biochemically euthyroid at 9 months, although, for those with hypothyroid biochemistry at 6 months, the median TSH at 18 months was at the upper limit of the reference range. Thyroid peroxidase antibody titre fell over the 2 years of follow-up. There was no significant change in clinical parameters over the study. Forty-nine percent of endocrinologists and 73% of general practitioners reported that they required clinical signs or symptoms before initiating treatment for hypothyroid PPTD. CONCLUSIONS: In a cohort of women with postpartum thyroid dysfunction, a quarter received treatment. Elevated TSH in untreated women does not completely return to the normal median. The role of clinical assessment in treatment decision-making differs between primary care physicians and endocrinologists. A case is made for the early Institution of permanent thyroxine replacement in women with postpartum thyroid dysfunction, elevated TSH and positive thyroid antibodies.

Chi-Square Distribution↗

In vivo proton (H1) magnetic resonance spectroscopy for cervical carcinoma.

Proton magnetic resonance spectroscopy (MRS) may be a useful tool in both the initial diagnosis of cervical carcinoma and the subsequent surveillance after radiation therapy, particularly when other standard diagnostic methods are inconclusive. Single voxel magnetic resonance (MR) spectral data were acquired from 8 normal volunteers, 16 patients with cervical cancer before radiation therapy, and 18 patients with cervical cancer after radiation therapy using an external pelvic coil at a 1.5-T on a Signa system. The presence or absence of various resonances within each spectrum was evaluated for similarities within each patient group and for spectral differences between groups. Resonances corresponding to lipid and creatine dominated the spectrum for the eight normal volunteers without detection of a choline resonance. Spectra from 16 pretreatment patients with biopsy-proven cervical cancer revealed strong resonances at a chemical shift of 3.25 ppm corresponding to choline. Data acquired from the 18 posttreatment setting studies was variable, but often correlated well with the clinical findings. Biopsy confirmation was obtained in seven patients. H1 MRS of the cervix using a noninvasive pelvic coil consistently demonstrates reproducible spectral differences between normal and neoplastic cervical tissue in vivo. However, signal is still poor for minimal disease recurrence. Further study is needed at intervals before, during, and after definitive irradiation with biopsy confirmation to validate the accuracy of MRS in distinguishing persistence or recurrence of disease from necrosis and fibrosis.

Adult↗

A second generation synthesis of the MBr1 (globo-H) breast tumor antigen: new application of the n-pentenyl glycoside method for achieving complex carbohydrate protein linkages.

A new synthesis of the hexasaccharide MBr1 antigen (globo-H) is reported. A revised construction with improved efficiency was necessary because an anti-cancer vaccine containing this antigen is entering phase II and phase III clinical trials for prostate cancer. The key feature of this second generation synthesis is the preparation of globo-H as its n-pentenyl glycoside. This group serves as an anomeric protecting group and as a linker for bioconjugation to carrier protein. The resultant synthesis allows for the production of suitable quantities of globo-H for clinical trials.

Antigens, Neoplasm↗

Characterization of five catalytic activities associated with the NADPH:2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate] oxidoreductase/carboxylase of the Xanthobacter strain Py2 epoxide carboxylase system.

The bacterial metabolism of propylene proceeds by epoxidation to epoxypropane followed by carboxylation to acetoacetate. Epoxypropane carboxylation is a minimetabolic pathway that requires four enzymes, NADPH, NAD(+), and coenzyme M (CoM; 2-mercaptoethanesulfonate) and occurs with the overall reaction stoichiometry: epoxypropane + CO(2) + NADPH + NAD(+) + CoM --> acetoacetate + H(+) + NADP(+) + NADH + CoM. The terminal enzyme of the pathway is NADPH:2-ketopropyl-CoM [2-(2-ketopropylthio)ethanesulfonate] oxidoreductase/carboxylase (2-KPCC), an FAD-containing enzyme that is a member of the NADPH:disulfide oxidoreductase family of enzymes and that catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-CoM to form acetoacetate and CoM according to the reaction: 2-ketopropyl-CoM + NADPH + CO(2) --> acetoacetate + NADP(+) + CoM. In the present work, 2-KPCC has been characterized with respect to the above reaction and four newly discovered partial reactions of relevance to the catalytic mechanism, and each of which requires the formation of a stabilized enolacetone intermediate. These four reactions are (1) NADPH-dependent cleavage and protonation of 2-ketopropyl-CoM to form NADP(+), CoM, and acetone, a reaction analogous to the physiological reaction but in which H(+) is the electrophile; (2) NADP(+)-dependent synthesis of 2-ketopropyl-CoM from CoM and acetoacetate, the reverse of the physiologically important forward reaction; (3) acetoacetate decarboxylation to form acetone and CO(2); and (4) acetoacetate/(14)CO(2) exchange to form (14)C(1)-acetoacetate and CO(2). Acetoacetate decarboxylation and (14)CO(2) exchange occurred independent of NADP(H) and CoM, demonstrating that these substrates are not central to the mechanism of enolate generation and stabilization. 2-KPCC did not uncouple NADPH oxidation or NADP(+) reduction from the reactions involving cleavage or formation of 2-ketopropyl-CoM. N-Ethylmaleimide inactivated the reactions forming/using 2-ketopropyl-CoM but did not inactivate acetoacetate decarboxylation or (14)CO(2) exchange reactions. The biochemical characterization of 2-KPCC and the associated five catalytic activities has allowed the formulation of an unprecedented mechanism of substrate activation and carboxylation that involves NADPH oxidation, a redox active disulfide, thiol-mediated reductive cleavage of a C-S thioether bond, the formation of a CoM:cysteine mixed disulfide, and enolacetone stabilization.

Acetoacetates↗

A disturbed child's use of a public event: Cotard's syndrome in a ten-year-old.

Public events can be incorporated into the mental life and life narratives of children with psychiatric illnesses. A 10-year-old boy who was not in Oklahoma City at the time of the 1995 bombing of the Murrah Federal Building and who knew no one directly impacted, claimed that he himself was dead, then that his grandfather, and finally that a peer and the peer's family had been killed in the blast. This is the first known reported case of Cotard's syndrome, the delusion of being dead, in a prepubescent child. The article also explores the relationships between this boy's symptoms, transference phenomena, real life events, themes of loss, abandonment, neglect, and death, and his fabricated stories.

Child↗

A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial pathway of aliphatic epoxide carboxylation.

The bacterial metabolism of short-chain aliphatic alkenes occurs via oxidation to epoxyalkanes followed by carboxylation to beta-ketoacids. Epoxyalkane carboxylation requires four enzymes (components I-IV), NADPH, NAD(+), and a previously unidentified nucleophilic thiol. In the present work, coenzyme M (2-mercaptoethanesulfonic acid), a compound previously found only in the methanogenic Archaea where it serves as a methyl group carrier and activator, has been identified as the thiol and central cofactor of aliphatic epoxide carboxylation in the Gram-negative bacterium Xanthobacter strain Py2. Component I catalyzed the addition of coenzyme M to epoxypropane to form a beta-hydroxythioether, 2-(2-hydroxypropylthio)ethanesulfonate. Components III and IV catalyzed the NAD(+)-dependent stereoselective dehydrogenation of R- and S-enantiomers of 2-(2-hydroxypropylthio)ethanesulfonate to form 2-(2-ketopropylthio)ethanesulfonate. Component II catalyzed the NADPH-dependent cleavage and carboxylation of the beta-ketothioether to form acetoacetate and coenzyme M. These findings evince a newfound versatility for coenzyme M as a carrier and activator of alkyl groups longer in chain-length than methane, a function for coenzyme M in a catabolic pathway of hydrocarbon oxidation, and the presence of coenzyme M in the bacterial domain of the phylogenetic tree. These results serve to unify bacterial and Archaeal metabolism further and showcase diverse biological functions for an elegantly simple organic molecule.

Alkenes↗

Two short-chain dehydrogenases confer stereoselectivity for enantiomers of epoxypropane in the multiprotein epoxide carboxylating systems of Xanthobacter strain Py2 and Nocardia corallina B276.

Epoxide carboxylase from the bacterium Xanthobacter strain Py2 is a multicomponent enzyme system which catalyzes the pyridine nucleotide-dependent carboxylation of aliphatic epoxides to beta-ketoacids as illustrated by the reaction epoxypropane + CO2 + NADPH + NAD+ --> acetoacetate + H+ + NADP+ + NADH. The combination of four distinct proteins, designated components I-IV, are required for the reconstitution of epoxide carboxylase activity with racemic mixtures of short-chain (C3-C5) terminal epoxyalkanes. In this work, components III and IV of the epoxide carboxylase system are shown to confer specificity for epoxyalkane enantiomers. Components I-III supported the carboxylation of (R)-epoxypropane, while components I, II, and IV supported the carboxylation of (S)-epoxypropane. At fixed concentrations of components I and II, the rates of (R)- and (S)-epoxypropane carboxylation saturated with increasing concentrations of component III or IV to give identical maximal rates for the two epoxide substrates. (S)-Epoxypropane was an inactivator of (R)-epoxypropane carboxylation by components I- III, while (R)-epoxypropane was an inactivator of (S)-epoxypropane carboxylation by components I, II, and IV. These inactivating effects were fully reversed upon the addition of the correct complementing dehydrogenase component. Amino acid sequence analysis of components III and IV demonstrates that they belong to the short-chain dehydrogenase/reductase (SDR) family of enzymes. Both components contain highly conserved residues within the coenzyme binding fold and catalytic regions found in SDR enzymes. Components III and IV are proposed to catalyze the NAD+-dependent abstraction of a hydride from a chiral secondary alcohol-like intermediate bound to the active site component of the enzyme system to form the corresponding beta-ketone intermediate. A multicomponent epoxide carboxylase system was purified to homogeneity from Nocardia corallina B276, a bacterium phylogenetically unrelated to Xanthobacter Py2, and found to consist of four proteins with functions identical to those of the Xanthobacter Py2 system. The stereoselective dehydrogenases of the Xanthobacter epoxide carboxylase system were able to substitute for the corresponding components of the N. corallina system when using (R)- and (S)-epoxypropane as substrates, and vice versa. These results provide the first demonstration of the involvement of stereospecific dehydrogenases in aliphatic epoxide metabolism and provide new insights into microbial strategies for the utilization of chiral organic molecules.

Carboxy-Lyases↗

Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity.

OBJECTIVE: Postpartum thyroid dysfunction (PPTD), diagnosed using biochemical criteria, is usually transient with a wide range of reported prevalence rates. The specific clinical and psychiatric morbidity associated with PPTD is still uncertain. The aims of the study were to determine the point prevalence of PPTD in Australian women at 6 months postpartum and to assess the specific clinical and psychiatric morbidity in these women. DESIGN: Women who were Caucasian, aged 20-45 years and 4.5-5.5 months postpartum, were randomly selected and invited into the study. The respondents were assessed for biochemical and psychiatric morbidity. PPTD for this study was defined as TSH or free T4 outside the adult reference range. A double blind clinical assessment of PPTD women and their matched controls used standardized clinical hypo- and hyperthyroid clinical indices. PATIENTS: From the total randomly selected sample size of 1816 women, 748 participated. MEASUREMENTS: Biochemical measurements were serum TSH, free T4, microsomal antibody (MsAb) and thyroid peroxidase antibody (TPOAb), and thyroid receptor antibodies (only in women with low TSH). Psychiatric assessment involved screening all participants using the General Health Questionnaire 28, followed by classifying and quantifying severity of cases using DSM-III-R categories for depression and anxiety. Clinical signs and symptoms of hypo- and hyper-thyroidism were measured using weighted standardized indices. Thyroid size was assessed by palpation. Achilles tendon reflex time was measured by photomotograph. RESULTS: The prevalence of PPTD in the participants was 11.5% (95% CI 9.2-13. 8%), giving a minimum prevalence for the randomly selected sample of 4.7% (95% CI 3.7-5.7%). In the PPTD women, 54% had an elevated TSH, 30% had a suppressed TSH and the remainder had a low fT4 and normal TSH. Positive thyroid autoantibody titres in the PPTD group were 46. 5% for microsomal antibody (MsAb) and 63.9% for thyroid peroxidase antibody (TPOAb), and in the non-PPTD group were 1.7% and 4.9%, respectively. The 6 month point prevalence rates of depression, generalized anxiety disorder and panic disorder and/or agoraphobia were 9.4%, 1.4% and 3.1%, respectively. No relationship was found between PPTD status and the diagnosis of current depression or between thyroid antibody status and current depression. In women who were diagnosed as anxious at the time of assessment, the number of anxiety symptoms was higher in the PPTD group (P < 0.05). There was no difference in signs and symptom scores for the hypo- and hyper-thyroid clinical indices between PPTD women and their controls. CONCLUSION: This study has shown a high prevalence of postpartum thyroid dysfunction but there was no difference in the clinical and psychiatric signs and symptoms between cases and controls. In the social, psychological, physical and endocrine setting of the postpartum period, women with postpartum thyroid dysfunction are identifiable by the attending physician only by their abnormal thyroid function tests.

Adult↗

Fabricated trauma exposure: an analysis of cognitive, behavioral, and emotional factors.

The 1995 Oklahoma City bombing was a disaster of unparalleled dimension in the United States. The professional response included the development of systematic clinical and research programs. This article describes the case of a child who, as a participant in a research study, appeared to fabricate a story of bomb-related loss. The research and clinical records of this child were examined and analyzed according to the factors and conditions that might underlie this fabrication. These include issues related to memory and suggestibility, symptom contagion, and mass hysteria. The report describes the role of psychological vulnerability in trauma and this child's coping and adaptation.

Adaptation, Psychological↗

Avoidance in trauma: conscious and unconscious defense, pathology, and health.

Drawing from our work with children seen following the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City, Oklahoma, this article describes clinical aspects of avoidance in traumatized children and their families. Avoidance in traumatized children and their families seems a final common pathway arising from a number of diverse factors. The importance of particular factors for assessment and treatment is emphasized.

Avoidance Learning↗