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.

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).

The spectrum of surgical jaundice in infancy.

BACKGROUND: Conjugated jaundice arising during infancy may be caused by a number of different surgical conditions. The aim of this study was to compare clinical features, management, and outcome of all types of surgical jaundice presenting in the first year of life. METHODS: A retrospective review was conducted of all infants born in the United Kingdom with jaundice caused by a surgical cause referred to the authors' institution from January 1992 to December 1999. RESULTS: There were 171 infants who could be separated into 3 specific groups: biliary atresia (BA, n = 137), inspissated bile syndrome (IBS; n = 14), and choledochal malformation (CM; n = 12) together with a group containing various miscellaneous conditions (n = 8). Infants with BA had higher bilirubin (P <.01) and aspartate aminotransferase levels (P <.001) and came to surgery earlier (P <.01) than infants with either IBS or CM. Infants with IBS and CM were more likely to be premature and have other malformations, respectively. Ultrasound scan was the principal investigation in the differentiation of BA from other causes of jaundice. Accurate prelaparotomy diagnosis was made by percutaneous liver biopsy in 87% of cases later shown to be BA. Currently, 88 (64%) of children with BA are alive with their native liver postportoenterostomy, 4 have died, and 45 have undergone liver transplantation (with 1 death postoperatively). A policy of primary portoenterostomy for BA followed by transplantation, if necessary, resulted in a survival rate of over 95%. All children in the other diagnostic groups are alive and anicteric after appropriate surgical intervention. CONCLUSIONS: Approximately 80% of infants presenting with surgical jaundice have biliary atresia, whereas those with inspissated bile syndrome and choledochal malformations make up most of the remainder. Mortality in this age-group is confined to infants with BA, but even on these infants an overall survival rate of greater than 95% is currently expected.

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.

Intestinal permeability and absorptive capacity in children with portal hypertension.

BACKGROUND: Portal hypertension may affect intestinal function leading to malnutrition in children with liver disease. The aim was to determine whether children with portal hypertension with or without liver disease had impaired absorptive capacity and intestinal barrier function (intestinal permeability) and to ascertain whether these abnormalities related to changes in body composition. METHODS: Twenty-six children with portal hypertension were divided according to aetiology into: Group 1 intrahepatic (n = 15) and Group 2 prehepatic (n = 11). Thirty-five children acted as controls. Carbohydrate absorption and intestinal permeability were assessed using a sugar absorption/permeability test and a variety of anthropometric measurements were obtained. RESULTS: 3-O-methyl-D-glucose, D-xylose and L-rhamnose excretion were significantly reduced in both patient groups compared to controls (P < or = 0.008) and the differential urinary excretion of melibiose/rhamnose (intestinal permeability) was significantly increased in Group 1 only (P < 0.05). Anthropometric measurements showed low Z scores in both groups, but there was no significant (P > 0.05) difference between them. There was no significant correlation between urinary excretion of sugars. anthropometric measurements and energy intake. CONCLUSIONS: Increased portal pressure reduces the absorptive capacity of the small intestine, while liver disease itself leads to increased intestinal permeability.

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 concentrations are increased in cystic fibrosis patients with liver disease.

AIM: To determine whether serum hyaluronic acid (HA) concentrations are abnormal in patients with cystic fibrosis (CF) liver disease, and if so, whether the abnormality is associated with disease severity. METHODS: A total of 74 patients with CF were assessed for evidence of liver involvement as indicated by clinical, ultrasound, and biochemical findings. Serum hyaluronic acid concentrations were measured and compared with concentrations in 293 normal controls. Lung function in the CF patients was also recorded. RESULTS: Thirty four CF patients had no evidence of liver disease; in these, serum HA concentrations were similar to those in healthy controls (median (range): 16.1 (9.4-75.1) v 15 (1-77) microg/l). Nineteen CF patients had established liver disease detected by clinical and ultrasound examination, with significantly increased HA concentrations (56.1 (26-355) microg/l). Serum HA concentrations were also significantly increased, although to a lesser extent, in 21 CF patients with an abnormal liver ultrasound scan alone (22.4 (9.5-43.4) microg/l). There was no correlation between serum HA concentration and lung function. CONCLUSION: Serum HA concentrations were significantly increased in children with clinical or ultrasound evidence of liver disease, being higher in those with more advanced hepatic damage. Despite the inflammation and fibrosis present in CF lungs there was no correlation between HA concentration and lung function, suggesting that high concentrations were a failure of hepatic clearance rather than overproduction in the lung. Longitudinal measurement of HA concentrations may prove a useful marker for the development of significant liver damage in CF patients.

Autoantibodies to human cytosol: a marker of sporadic porphyria cutanea tarda.

The enzymes potentially involved in the pathogenesis of sporadic porphyria cutanea tarda (PCT) reside in liver cytosoles and microsomes. PCT is frequently associated with hepatitis C virus (HCV) infection, which is in turn associated with autoimmune manifestations. To investigate whether autoimmune reactions, possibly triggered by HCV, are involved in the pathogenesis of PCT, we measured by immunoblot autoantibodies to human cytosolic and microsomal liver fractions in 82 patients with PCT (77% with HCV infection), 105 with other liver disorders and 40 healthy subjects. Anti-liver cytosolic antibodies were more frequent in PCT patients (38/82, 46%) than in pathological controls (P < 0.05-P < 0.001) or in healthy subjects (3/40, 8%, P < 0.001). Among PCT patients, anticytosolic antibodies were more frequent in HCV positive (36/63, 57%) than in HCV negative (2/19, 11%, P < 0.05) cases. Reactivity to a 40-kDa cytosolic polypeptide was present in 20 PCT patients (19 HCV positive), being more frequent than in all pathological controls (P < 0.01-P < 0.0001). Histological activity index (P = 0.04) and antibodies to HCV (P = 0.027) - but not HCV RNA - were associated independently with anticytosolic antibodies as assessed by multivariate analysis. In contrast, frequency of antiliver microsomal antibodies was similar in PCT patients (24/82, 29%) and pathological controls (8-26%), being higher in the autoimmune hepatitis control group (23/23, 100%, P < 0.0001). In conclusion, anticytosolic antibodies, particularly to a 40-kDa polypeptide, are frequent in PCT and associated with HCV infection and severity of liver damage.

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.

Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation.

BACKGROUND/AIM: Alpha-1-antitrypsin deficiency (alpha1ATD) is the commonest metabolic disease leading to liver transplantation (LT) in children. Approximately 10-15% of the PiZZ population develops liver disease. Five percent of them will require LT within the first 4 years of life. This study aimed to investigate the prognosis of the liver disease associated with PiZZ alpha1ATD in the era of liver transplantation and to determine predictors of outcome. METHODS: We reviewed retrospectively the clinical notes of 97 consecutive patients referred from January 1989, when LT became routinely available in our Unit, to July 1998. RESULTS: Of 26 (27%) patients who developed end-stage liver disease, 24 have been transplanted and two are waiting for LT. Twenty-one (81%) of these patients presented with neonatal hepatitis at a median age of 2.1 months. Of 71 (73%) children who have not required LT, 61 (86%) presented with neonatal hepatitis at a median age of 1.6 months. Among infants with neonatal hepatitis who required LT, 18 out of 21 (86%) had jaundice for more than 6 weeks compared with 34 of 61 (56%) who survived without LT (p<0.01). Children requiring LT had higher aspartate aminotransferase (AST) at presentation (p<0.0001) and both higher AST and gamma-glutamyl transferase (GGT) at 6 months (p<0.001), 1-year (p<0.0003) and 5-year (p<0.01) follow up when compared to those who are well without LT. Furthermore, children who developed end-stage liver disease more frequently had severe bile duct reduplication (p<0.01), severe fibrosis (p<0.03) with bridging septa (p<0.02) and established cirrhosis (p<0.04) in the initial liver biopsy. Ninety-five of the 97 children (98%) are currently alive; two died after LT. CONCLUSIONS: The advent of liver transplantation has significantly improved the prognosis of liver disease associated with PiZZ alpha1ATD. Duration of jaundice, severity of histological features and biochemical abnormalities predict outcome at an early stage of the disease.

The role of HBV DNA quantitative PCR in monitoring the response to interferon treatment in chronic hepatitis B virus infection.

BACKGROUND/AIMS: To investigate whether the measurement of HBV DNA by quantitative polymerase chain reaction (PCR) is helpful in monitoring response to interferon treatment in chronic hepatitis B virus infection, we have determined sequentially serum levels of HBV DNA during and up to 18 months after treatment, in 10 patients with a sustained response (all anti-HBe positive, five also HBsAg negative and anti-HBs positive) and, as controls, in 12 non-responders. METHODS: Serum HBV DNA was measured by standard hybrisation assay (Genostics, Abbott) and by quantitative PCR (Amplicor HBV Monitor test, Roche Diagnostic Systems). RESULTS: A clear difference in HBV viral load between responders and non-responders was observed from the fourth week of treatment and was maintained throughout the study period. At the last follow up 16-26 (median 21) months after starting treatment, all the 10 responders were HBV DNA negative by hybridisation. By PCR, however, five (one anti-HBs and four anti-HBe positive) were still HBV DNA positive. In addition, one anti-HBs positive patient HBV DNA negative by PCR at last follow up, had fluctuating levels of HBV DNA by PCR during the observation period, only intermittently falling below the threshold of the assay. CONCLUSIONS: The measurement of HBV DNA by quantitative PCR provides early prediction of response to interferon, allowing prompt modification of treatment. With this technique, HBV DNA is detected in a high proportion of sustained responders, suggesting that HBV may never be completely eliminated by interferon treatment, even after anti-HBs seroconversion.

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.

Hepatitis GB virus-C/hepatitis G virus infection in liver disease.

Hepatitis GB virus-C (HGBV-C)/hepatitis G virus (HGV) infection was investigated in 106 children with liver disease (54 boys and 52 girls, mean age 7.3 years); 12 with chronic hepatitis C virus infection, 29 with positive hepatitis B surface antigen, nine with idiopathic fulminant hepatic failure, seven with graft dysfunction after liver transplantation associated with autoimmune features, 20 with cryptogenic liver disease, and 29 with autoimmune liver disease. HGV RNA detected by reverse transcription polymerase chain reaction was found to be positive in 4/106 patients (3.8%). Risk factors were identified in three patients, including blood transfusion and/or medical treatment in Eastern Europe. The prevalence was higher than that of blood donors but lower than that of 2 adult patients with liver disease. HGV is not associated with any specific disease group and does not seem to be a major aetiological agent of liver disease in childhood in the UK.

Invasive antenatal procedures and requirement for neonatal intensive care unit admission.

Neonatal respiratory difficulties are increased following second trimester amniocentesis. In preterm, prolonged rupture of the membranes, respiratory outcome is particularly poor when rupture occurs in the first trimester. It therefore seems likely that first trimester/ early amniocentesis (EA) would be associated with severe respiratory problems necessitating a high neonatal intensive care unit (NICU) admission rate. To test that hypothesis, the requirement for admission to the NICU of 278 infants whose mothers had undergone EA, 262 whose mothers had undergone chorion villus sampling (CVS group) and 264 controls whose mothers had undergone no invasive procedures were reviewed as were their diagnoses if they needed admission. There was no significant difference in the mode of delivery, gestational age or gender distribution of the three groups and the median maternal age of the EA and CVS groups was similar. Nineteen EA, eight CVS and five control infants required admission to the NICU (EA versus controls, P < 0.01; EA versus CVS plus controls, P < 0.005). Nine EA, one CVS and four control infants had suffered respiratory problems (EA versus CVS P < 0.05). Logistic regression analysis demonstrated that immaturity and EA were significantly associated with a requirement for NICU admission. We conclude infants whose mothers have undergone EA may be at increased risk for NICU admission, this is partly due to respiratory problems but the association is uncommon.

Perinatal lung function and invasive antenatal procedures.

BACKGROUND: Second trimester amniocentesis has been associated with an excess of perinatal lung function abnormalities. Early amniocentesis might have a similar adverse effect, as could other invasive investigations carried out in the first trimester. METHODS: Plethysmographic measurements of thoracic gas volume (TGV) and airway resistance (Raw), from which specific conductance (sGaw) was calculated, were made in the perinatal period in non-sedated infants. In addition, functional residual capacity (FRC) was measured using a helium gas dilution technique. Measurements were made in 47 infants whose mothers had undergone early amniocentesis, 19 whose mothers had undergone chorion villus sampling, and 25 controls whose mothers had undergone no invasive antenatal procedures. RESULTS: The infants of mothers who had undergone early amniocentesis had higher TGV (95% CI -6.3 to 1.1 ml/kg) and Raw values (95% CI -10.68 to -5.23 cm H2O/l/s) and lower sGaw (0.11 to 0.84 l/cm H2O.s) and FRC (-5.17 to - 0.87 ml/kg) values than the controls. Infants whose mothers had undergone chorion villus sampling also differed significantly from the controls with higher Raw (-7.59 to -1.99 cm H2O/l/s) and lower sGaw values (0.11 to 0.24 l/cm H2O.s), and had lower Raw values than those in the early amniocentesis group (not significant). Logistic regression analysis, taking into account possible risk factors for abnormal lung function, showed that the procedures performed in the first trimester were independently associated with a high airways resistance. CONCLUSION: These results suggest that invasive procedures performed in the first trimester of pregnancy have an adverse effect on perinatal lung function.

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.