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Biomedical subjects

P Cheeseman

Publications and source records attributed to P Cheeseman.

At least 37 records · Page 2Linked to original sources

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.

Adult↗

Prognostic value of serum hyaluronic acid and type I and III procollagen propeptides in extrahepatic biliary atresia.

Although portoenterostomy has greatly improved the prognosis of extrahepatic biliary atresia (EHBA), 10-20% of patients still die before 5 y of age, and the only treatment option is liver transplantation (LT). To investigate whether these patients may be identified at an early stage, when the changes of successful LT are optimal, we have measured serum concentrations of hyaluronic acid (HA), the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP, PINP) in 24 selected patients with EHBA, both before portoenterostomy and then every 6 mo until death (n = 10, age at death = 7-20 mo), LT (n = 6, age at LT = 1.1-4.8 y) or 5 y of age (n = 8). Raised serum HA above 200 micrograms/L before portoenterostomy identified those patients who would die or require LT in the first 5 y of life with a positive predictive value of 88%; after portoenterostomy, longitudinal changes in HA reflected clinical status in each patient. None of the other three markers was of prognostic value, and only PIIINP showed any relationship with clinical status, and then only up to 1.5 y. Interestingly, PINP (but not PICP) tended to be low in all patients before portoenterostomy and may reflect impaired bone collagen metabolism during early skeletal changes in EHBA. This study therefore suggests that measurement of serum HA may be a useful complementary test in EHBA, particularly in identifying, at an early stage, those patients who should be considered for LT.

Age Factors↗

Monitoring of veno-occlusive disease after bone marrow transplantation by serum aminopropeptide of type III procollagen.

Differential diagnosis of hepatic complications after bone marrow transplantation (BMT) is often difficult. To assess whether serum concentrations of the aminopropeptide of type III procollagen (PIIINP) could facilitate diagnosis, we measured serum PIIINP, corrected for age by conversion to standard deviation scores (SDS), serially after BMT in 27 children. A preliminary study of 11 patients showed that a PNIIINP-SDS cutoff of 8.0 was an optimum for diagnosis of veno-occlusive disease (VOD). PIIINP-SDS was increased above cut-off 1-25 days before the onset of clinical signs in the 12 patients (4 from the preliminary group, the others from a group of 16 studied prospectively) who developed VOD, with subsequent changes in PIIINP-SDS mirroring the course of VOD. By contrast, PIIINP-SDS remained below cut-off in all other patients, including 7 with liver graft-versus-host disease and 3 with drug hepatotoxicity. PIIINP-SDS values greater than 8.0 predict, diagnose, and monitor VOD after BMT.

Bone Marrow Transplantation↗

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.

Adolescent↗

Antineutrophil antibody: a test for autoimmune primary sclerosing cholangitis in childhood?

The detection of an antineutrophil antibody which is highly sensitive and specific for adult primary sclerosing cholangitis using indirect immunoalkaline phosphatase has been previously described. In this study, the diagnostic potential of this method in childhood primary sclerosing cholangitis is described. A range of 72 blinded children's sera (36 boys), aged six months to 21 years (10 primary sclerosing cholangitis, eight autoimmune chronic active hepatitis, 10 alpha-1 antitrypsin deficiency, 12 extrahepatic bile duct atresia, 11 ulcerative colitis and 21 normal subjects) was assayed. Eight of the 10 primary sclerosing cholangitis patients were correctly identified. Three patients with chronic active hepatitis also showed the characteristic primary sclerosing cholangitis pattern of staining. No ulcerative colitis patients or any other patients showed this pattern of staining. All normal subjects were negative. As in adult primary sclerosing cholangitis, there is a specific antineutrophil antibody in childhood primary sclerosing cholangitis and this provides further evidence towards an autoimmune aetiology of this condition. The test may have diagnostic potential.

Adolescent↗

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.

Chronic Disease↗

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.

Chronic Disease↗

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.

Chronic Disease↗

The application of quantitative cytochemistry to study the acinar distribution of enzymatic activities in human liver biopsy sections.

The zonal distribution of enzyme activities was measured by quantitative cytochemistry in cryosections of liver from three normal children and five infants with idiopathic hepatitis of infancy. Optimal conditions for cytochemical reactions were first validated in rat liver and subsequently used in human livers to quantify zonal activities of acid phosphatase (AP), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), glucose-6-phosphatase (G6P) and NADPH-dehydrogenase (ND). In normal rat and human livers, activities were greater for SDH and G6P in periportal and for GDH and ND in perivenular hepatocytes, while AP was evenly distributed along the sinusoids. In five infants with idiopathic hepatitis of infancy (IHI), a similar trend of distribution was observed for the two mitochondrial (SDH and GDH) and the two microsomal (G6P and ND) enzymes, although the distribution gradient was less pronounced than, in normal livers. AP showed a mildly greater periportal than perivenular activity. This preliminary study shows that a similar metabolic zonation exists for these enzymes in human livers as is observed in rats.

Acid Phosphatase↗

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.

Biliary Atresia↗

Variation in serum type III procollagen peptide with age in healthy subjects and its comparative value in the assessment of disease activity in children and adults with chronic active hepatitis.

To determine the comparative value of serum Type III procollagen peptide (PIIIP) in paediatric and adult liver disease we have measured PIIIP in 201 healthy subjects (aged 1 day-77 years) and twenty-one children and five adults with chronic active hepatitis (CAH). Healthy children had significantly higher PIIIP levels than adults (P less than 0.001), with highest values of 298 +/- 88 ng ml-1 (s.d.) in the neonatal period. PIIIP fell to 30.9 +/- 7.0 by 1 year, 19.1 +/- 4.5 by 3 years and rose significantly (P less than 0.01) at puberty. Adult levels (8.3 +/- 3.2) occurred by 16 years of age. Serum PIIIP levels were significantly elevated (P less than 0.001) in adults when they had biochemical and histological evidence of active liver disease but were consistently within the normal range for age in 70% of children with similar hepatic pathology. The minor elevations in PIIIP in the other children were unrelated to clinical, biochemical or histological evidence of active liver disease. While raised PIIIP may be a non-invasive marker of liver disease activity in adults, its value in childrens' disorders appears to be limited by the high levels of PIIIP which occur during growth.

Adolescent↗

Partial purification and characterization of the ovulation hormone of the freshwater pulmonate snail Lymnaea stagnalis.

The neurosecretory caudodorsal cells in the cerebral ganglia of the basommatophoran snail Lymnaea stagnalis produce an ovulation hormone (CDCH), which is released from the periphery of the intercerebral commissure. In the present study CDCH has been partially purified, starting with a hydrochloride acid extract of commissures, by gel permeation chromatography on Bio-Gel P-6 followed by cation exchange on SP-Sephadex C-25. This two-step procedure resulted in a ca. 22-fold purification of CDCH. The low purification factor is caused by poor resolution of both purification steps and low recovery on the Bio-Gel P-6 column. With stability tests, proteolytic enzymes, SDS/urea polyacrylamide electrophoresis and isoelectric focussing, purified CDCH was characterized as a stable peptide with a molecular weight of ca. 4700 d and a pI of ca. 9.3. The properties of CDCH are similar to those of the ovulation hormones of opisthobranch snails. Studies on species specificity indicate, however, that it is unlikely that CDCH will cause ovulation when injected in opisthobranchs, or vice versa.

Animals↗

Changes in organ weights and blood parameters in ageing Brattleboro rats with hereditary diabetes insipidus.

Organ weights and blood parameters were measured in male and female Brattleboro rats with hereditary diabetes insipidus (DI) and in normal rats of the same strain, between 37 and 138 weeks old. Although differences in body weight between the homozygous DI and heterozygous normal rats accounted for differences in the weights of the heart and gonads, the weights of the spleen, liver and kidney were not solely body-weight dependent; there were significant sex and genotype differences in the mean weights of these organs. The liver, heart and gonads were the only organs showing age-dependent changes. No genotype-dependent differences were observed in the haematocrit and haemoglobin concentration, although there was a sex difference; the mean values of these parameters were higher in males. Plasma glucose concentrations were significantly lower in homozygous than in heterozygous rats; in the latter, plasma glucose concentration decreased with age. No significant changes occurred in the mean plasma concentrations of sodium or potassium with age or genotype. Total plasma lipids of heterozygous female rats showed both age- and genotype-dependent changes; this parameter reached a plateau at 90-100 weeks old, and was significantly higher in heterozygous females than in all other groups. Plasma proteins showed no age-dependent changes, but were of higher mean value in heterozygous than in homozygous rats and were greater in females than in males. Differences in blood parameters of homozygous and heterozygous Brattleboro rats are discussed in terms of differences in hormone concentrations.

Age Factors↗