Pressure enhancement of ion mobilities in liquid silicates from computer simulation studies to 800 kilobars.

Ion dynamics computer simulation methods show that for many liquid silicates, like silica itself, the component diffusion coefficients show anomalous pressure dependences. This implies that their viscosities have negative pressure dependences. Overall, there is an interesting degree of analogy between the fundamental binary solutions of geochemistry and the aqueous solutions of common experience; however, due to the stronger bonding in silicate systems, the anomalies are much more persistent. Diffusivity maxima occur at pressures of 200 to 300 kilobars and are correlated with a prevalence of fivefold coordination of silicon ions. The relevance of these findings to planetary dynamics and thermophysical modeling problems is briefly considered.

Detection of liver kidney microsomal type 1 antibody using molecularly based immunoassays.

AIMS: To assess the diagnostic value of two commercial molecularly based immunoassays detecting liver kidney microsomal type 1 antibody (LKM1). METHODS: The performance of Varelisa and LKM1 enzyme linked immunosorbent assay (ELISA) was compared with immunofluorescence, and two validated research techniques-an in house ELISA and a radioligand assay measuring antibodies to P4502D6. Thirty serum samples from three patients with autoimmune hepatitis type 2 covering immunofluorescence titres of 1/10 to 1/10 240 and 55 LKM1 negative controls were tested. RESULTS: All 30 sera that were LKM1 positive by immunofluorescence were positive by the in house ELISA, the radioligand assay, and LKM1-ELISA, and 29 were also positive by Varelisa. None of the 55 sera negative for LKM1 by immunofluorescence was positive by the in house ELISA and radioligand assay, but one was positive by Varelisa and 14 were positive using the LKM1-ELISA. Agreement between immunofluorescence, the in house ELISA, the radioligand assay, and Varelisa was high (kappa > 0.8), and agreement between immunofluorescence and LKM1-ELISA was moderate (kappa = 0.63). CONCLUSION: The assay kit marketed as Varelisa allows accurate detection of LKM1.

Serum hyaluronic acid in healthy infants and children and its value as a marker of progressive hepatobiliary disease starting in infancy.

We have established reference ranges for the concentrations of hyaluronic acid in serum from 397 infants and children and measured serum hyaluronic acid at presentation and 1 year follow-up in 37 infants who presented with hepatobiliary disease in the first 6 months of life. In health, hyaluronic acid concentrations fell progressively from median (10-90 percentile) values of 93 micrograms/l (49-153) at 1-3 months of age to 20 micrograms/l (9-40) at 2-3 years and 16 micrograms/l (6-32) at 4-18 years. In patients at presentation, the hyaluronic acid concentration was raised in 11 of 15 with biliary atresia, 6 of 11 with alpha-1 antitrypsin deficiency and 6 of 11 with cryptogenic hepatitis of infancy. One year later, the 9 patients who developed progressive liver disease showed 2-6-fold increases in hyaluronic acid concentration while no increase was observed in the 28 with undetectable or mild disease. Increases in serum hyaluronic acid concentration appeared to be a better indicator of progressive liver disease in infancy than standard laboratory tests.

Serum type III procollagen peptide as a non-invasive marker of liver damage during infancy and childhood in extrahepatic biliary atresia, idiopathic hepatitis of infancy and alpha 1 antitrypsin deficiency.

To evaluate the role of serum procollagen III peptide as a non-invasive marker of liver damage and prognosis in hepatobiliary disorders of infancy, we have measured its concentration at presentation and serially in 30 infants with extrahepatic biliary atresia, 22 with idiopathic hepatitis of infancy, 10 with alpha 1 antitrypsin deficiency and 105 age-matched controls. Raised procollagen III peptide concentrations occurred in 51% of patients at presentation and 59% at follow up but were not related to the type of liver disease or the severity of liver damage, as assessed either by standard biochemical tests of liver function, serum glycocholic acid, semiquantitative assessment of 11 histopathological features or hepatic prolyl hydroxylase activity. Serum procollagen III peptide concentrations also gave no guide to prognosis. Although the factors determining serum procollagen III peptide concentrations in hepatobiliary disorders of infancy are unknown at the present time, we suggest that changes in growth rate may be of major importance in determining the significance of serum procollagen III peptide concentrations in infants and children.

First trimester invasive procedures: effects on symptom status and lung volume in very young children.

First trimester procedures have been associated with perinatal lung function abnormalities that may suggest subsequent respiratory problems. Our aim was, therefore, to assess the impact of first trimester invasive procedures [early amniocentesis (EA) and chorion villus sampling (CVS)] on respiratory morbidity in very young children. A questionnaire was issued to parents of 439 EA and 453 CVS (subjects), and 435 controls (their mothers had undergone no invasive procedures) when their children were one year old. Data were also obtained from diary cards issued to a subset of 278 of the EA, 262 of the CVS, and 264 of the control infants followed prospectively. Functional residual capacity (FRC) was measured at a median age of 5 months (range: 0.25-24) in 159 children whose mothers had undergone EA, 168 following CVS and in 165 controls. Analysis of the one-year questionnaire demonstrated an excess of symptomatic infants in the EA group (31%) compared to the CVS (22%; P < 0.01) and control groups (17%; P < 0.01). Findings from the prospective follow-up study confirmed those results and also demonstrated an increase in chest-related hospital admissions in the EA group (3%) compared to the controls (0.4%; P < 0.05). Logistic regression analysis revealed that positive symptom status related significantly to EA and CVS interventions (P < 0.0001), bottle feeding (P < 0.001), parental smoking (P < 0.01), a family history of atopy (P < 0.01), and immaturity (P < 0.01). In the control group, FRC correlated best with weight (r = 0.92). The mean FRC of the EA and CVS groups was higher than that of the controls (P < 0.01). A higher proportion of children had an FRC two standard deviations above the controls' mean in the EA group (n = 14) compared to the CVS group (n = 3; P < 0.01). The symptomatic infants tended to have higher FRCs than the asymptomatic children. We conclude that first trimester procedures are associated with increased respiratory morbidity in very young children.

Exhaled nitric oxide in chronically ventilated preterm infants.

Exhaled nitric oxide (eNO) levels were measured in eight ventilated infants, mean gestational age 25.8 (SD 1.7) weeks and postnatal age 55 (SD 39) days, before and after three days of dexamethasone treatment. The eNO levels fell from a mean of 6.5 (SD 3.4) to 4.2 (SD 2.6) parts per billion (p = 0.031) and the mean supplementary oxygen levels from 62% to 45% (p = 0.0078).

Growth effects of systemic versus inhaled steroids in chronic lung disease.

AIM: To compare the effects of inhaled and systemic steroids on growth in very low birthweight (VLBW) infants with chronic lung disease (CLD). METHODS: Sixteen babies with CLD randomly received inhaled budesonide (100 microg four times daily for 10 days via Aerochamber) or systemic steroids (dexamethasone 0.5 mg/kg/day, reducing over nine days). Linear growth (lower leg length, LLL) was measured by knemometry twice weekly. RESULTS: The gestational age, birth weight, postnatal age, and LLL velocity (LLLvel) were similar between the two groups at the start of treatment. At the end of the treatment period, LLLvel was reduced in the dexamethasone group (mean -0.01 mm/day) but had increased in the budesonide group (mean 0.48 mm/day). Mean weight gain was non-significantly lower in the dexamethasone group (5.8 g/kg/day) compared to the budesonide group (mean 12.7 g/kg/day). CONCLUSION: Inhaled budesonide has less short term effects on growth than systemically administered dexamethasone.

Serum hyaluronic acid as an early prognostic marker in biliary atresia.

PURPOSE: The aim of this study was to assess whether serum concentrations of hyaluronic acid (HA), measured at diagnosis is an early biochemical marker of prognosis in biliary atresia. METHODS: Serum HA was measured at diagnosis using a radiometric assay in 84 infants with biliary atresia (BA), and related to outcome by 5 years of age. RESULTS: Serum HA was higher in the 29 patients who died or required liver transplant by 5 years of age compared with the 56 who survived to 5 years without transplant (490 +/- 216 microg/L v 262 +/- 163 microg/L; P <.001, 95% confidence intervals of the difference 145 to 311 microg/L). CONCLUSION: High serum concentrations of HA at diagnosis may help to identify at an early stage those patients with BA who have a poor prognosis and will require liver transplant by 5 years of age.

Perinatal lung function measurements and prediction of respiratory problems in infancy.

The aim of this study was to determine which lung function test employed in the perinatal period gave the results most significantly associated with respiratory problems in infancy. The ratio of the proportion of time to reach peak tidal expiratory flow to total expiratory time (tPTEF:tE), thoracic gas volume (TGV) and airway resistance (R(aw)) (from which specific conductance (SG(aw)) was calculated) measurements were examined from 85 infants born at or near term. The infants were followed until at least one year of age and described as symptomatic if they wheezed for at least 24 hours. Twenty-three infants were symptomatic in the first year. The symptomatic group, compared to the asymptomatic, had a higher median FRC (p < 0.01) and R(aw) (p < 0.001); their median SG(aw) was lower (p < 0.001). It was possible to obtain tPTEF:tE results from only 61 infants; the median tPTEF:tE did not differ significantly between symptomatic and asymptomatic infants. Logistic regression analysis demonstrated a high R(aw) and FRC, but not a low tPTEF:tE, independently related to positive symptom status. A high R(aw) (>26 cm H2O (1 s(-1))(-1)) was the most sensitive (83%) predictor of subsequent respiratory problems, but all the tests examined had low positive predictive values.

Monosulfidic black ooze accumulations in sediments of the Geographe Bay area, Western Australia.

Mobilisation of sedimentary monosulfidic black ooze (MBO) may result in rapid deoxygenation and acidification of surface waters, and release of potentially toxic metals. This study examines the extent and nature of MBO accumulation in the Geographe Bay area, Western Australia. MBO accumulations were found to be widespread in benthic sediments of the Geographe Bay area with acid-volatile sulfide (AVS) contents as high as 320 µmol g(-1). The MBO materials often had unusually high dissolved sulfide (S(-II)) concentrations in their pore-waters (up to 610 mg L(-1)) and elevated elemental sulfur (S(0)) contents (up to 51 µmol g(-1)). Dissolved S(-II) is able to accumulate due to limited iron availability and S(0) is largely its partial oxidation product. The availability of organic carbon and Fe limited MBO accumulation at many sites. A comparison of AVS and simultaneously extracted metal (SEM) concentrations has shown that metals are likely to be bound in sulfide complexes.

Variable degree of liver involvement in siblings with PiZZ alpha-1-antitrypsin deficiency-related liver disease.

PiZZ alpha-1-antitrypsin deficiency is the commonest genetic cause of chronic liver disease, but only 10-15% of PiZZ individuals develop liver disease in childhood. Studies have demonstrated varying patterns of disease progression within siblings with the PiZZ phenotype. We retrospectively analysed the case-notes of all patients diagnosed with PiZZ A1ATD between 1978-2002 and compared the pattern of liver disease between affected siblings. We identified 29 families with more than 1 child with the PiZZ phenotype. Twenty-one (72%) PiZZ siblings of the 29 probands had liver disease, which was concordant for severity in 6 (29%), while 8 (28%) had no liver involvement. Five of 7 children requiring liver transplantation had siblings with no persistent liver dysfunction. This study suggests that there is a variable degree of liver involvement in siblings with PiZZ A1ATD-related liver disease and environmental and/or other genetic factors must be involved in determining disease severity.

Effect of in utero growth retardation on lung function at follow-up of prematurely born infants.

The aim of the study was to determine if prematurely born children who had suffered intra-uterine growth retardation (IUGR) had more severe lung function abnormalities than those born an appropriate weight for gestational age (AGA). Analysis of the lung function results of 119 infants (median (range) gestational age of 30 (23-35) weeks) was undertaken. In total, 31 of the infants had suffered IUGR and were born small for gestational age (SGA). Functional residual capacity and airways resistance (Raw) were measured at a median post-natal age of 10 (6-24) months. Specific airway conductance (sGaw) was calculated from thoracic gas volume and Raw. The SGA children were born at a greater gestational age and had a lower body weight at testing than the AGA children. Raw and sGaw differed between the SGA and AGA children. Regression analysis demonstrated that lung volumes were significantly related to body weight at testing, Raw was related to IUGR, maternal smoking and bronchopulmonary dysplasia, and sGaw to maternal smoking. In conclusion, these results suggest that prematurely born infants who have suffered intra-uterine growth retardation may be at increased risk of impaired lung function at follow-up.

Lung volume and the response to high volume strategy, high frequency oscillation.

BACKGROUND: Infants with severe respiratory failure are frequently transferred to high volume strategy, high frequency oscillation (HFO). Mean airway pressure (MAP) is then elevated, the aim being to open up atelectatic lungs and hence improve gas exchange. AIM: To test the hypothesis that lung volume prior to transfer would predict the response to high volume strategy HFO and identify which factors related to poor outcome (death). METHODS: Lung volume was assessed by measurement of functional residual capacity (FRC) and the response to HFO determined by the change in the alveolar arterial gradient (AaDO2) on transfer from conventional mechanical ventilation (CMV) to the optimal MAP on high volume strategy HFO. PATIENTS: Forty-two infants with a median gestational age of 28 (range 23 to 40) wk were studied. RESULTS: FRC prior to transfer correlated significantly with the change in MAP necessary to optimize oxygenation (p = 0.012), but not the change in AaDO2 in response to HFO. There were no significant differences in the lung volumes of survivors and non-survivors, but those who died were more immature (p = 0.0009) and had a smaller response to HFO (p = 0.035). CONCLUSION: Lung volume prior to transfer to high volume strategy HFO might be helpful to guide oscillatory settings, but is a poor predictor of the response to high volume strategy HFO.

Partial purification and properties of D-desthiobiotin synthetase from Escherichia coli.

d-Desthiobiotin synthetase, an enzyme that catalyzes the synthesis of d-desthiobiotin from dl-7,8-diaminopelargonic acid and HCO(3) (-), was purified 100-fold from cells of a biotin mutant strain of Escherichia coli. Adenosine triphosphate and Mg(2+) were shown, especially in purified extracts, to be obligatory for enzyme activity, although concentrations higher than 5 mm caused severe inhibition of the reaction with unpurified cell-free extracts. Adenosine diphosphate and adenosine monophosphate were shown to inhibit the reaction, but fluoride (up to 50 mm) had no detectable effect. The product of the enzyme reaction was identical to d-desthiobiotin on the basis of biological activity and chromatography. Furthermore, when H(14)CO(3) (-) was used as a substrate, the radioactive product was shown to be (14)C-desthiobiotin labeled exclusively in the ureido carbon.

Vitamin A status in preterm and term infants at birth.

Vitamin A status was determined in infants born at term or prematurely to assess if vitamin A levels at birth were related to gestational age. Vitamin A levels were measured in cord blood samples from 13 infants born at term and in blood samples obtained within two hours of birth in 26 preterm infants (median gestational age 31 weeks, range 27-35). None of the preterm infants developed chronic lung disease. The vitamin A levels of the term infants (median 0.71 mumol/l, range 0.34 to 1.27) were significantly higher than those of infants born preterm (median 0.35 mumol/l, range 0.12 to 1.22), p < 0.01. Vitamin A levels correlated significantly with gestational age (vitamin A level = 0.024 gestational age (weeks) -0.23, r = 0.39, p < 0.02. We thus conclude that gestational age must be taken into account when interpreting vitamin A levels.

Vitamin A levels at birth of high risk preterm infants.

Vitamin A levels were measured shortly after birth in preterm infants at high risk of developing chronic lung disease (CLD). Eleven infants, median gestational age 24 weeks, developed CLD. Their results were compared to 11 infants who, although they required mechanical ventilation for at least 48 hours, did not develop CLD. The median gestational age of this latter group was 30 weeks (range 27-35). The median vitamin A level of the infants who developed CLD was 0.62 umol/l (range 0.41-0.95), which was significantly higher than the median level of the infants who did not develop CLD, which was 0.36 umol/l (range 0.13-0.89). We conclude preterm infants who develop CLD are not predisposed to develop that complication by low vitamin A levels at birth.

Vitamin A levels and feeding practice in neonates with and without chronic lung disease.

Infants with chronic lung disease (CLD) have been demonstrated to have low vitamin A levels. The aim of this study was to assess factors which influenced this association. Vitamin A levels of infants born at less than 32 weeks gestational age with and without CLD were determined and related to feeding practice. The infants with CLD had statistically significantly lower vitamin A levels on days 21 to 30 and days 31 to 40. From day 11 onwards, the median Vitamin A levels were less than 60% of the minimum acceptable level for a healthy child or adult. Infants with CLD required significantly longer mechanical ventilation and parenteral nutrition than controls and there was a significant positive correlation between duration of mechanical ventilation and parenteral nutrition (r = 0.83). Infants with CLD received significantly less vitamin A supplementation than the infants without CLD. Our results thus suggest that feeding practice explains the association of CLD and vitamin A deficiency in preterm infants.

Isolation and properties of a fluorescent compound, factor 420 , from Methanobacterium strain M.o.H.

A new fluorescent compound, factor(420) (F(420)), which is involved in the hydrogen metabolism of hydrogen-grown Methanobacterium strain M.o.H. has been isolated and purified. Acid hydrolysis of this compound with 6 m HCl for 24 hr releases a ninhydrin-positive compound (glutamic acid), an acid-stable chromophore, phosphate, and an ether-soluble phenolic component. Factor(420) may be reduced by either sodium dithionite or sodium borohydride at pH 7.3 with concomitant loss of its fluorescence and its major absorption peak at 420 nm. Crude cell-free extracts of strain M.o.H. reduce F(420) only under a hydrogen atmosphere. F(420) is photolabile aerobically in neutral and basic solutions, whereas the acid-stable chromophore is not photolabile under these conditions. An approximate molecular weight of 630 +/- 8% for F(420) was determined by Sephadex G-25 chromatography. At the present time, F(420) is proposed as a trivial name for the unknown fluorescent compound because of its strong absorption maximum of 420 nm at pH 7.