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Biomedical subjects

A F Heeley

Publications and source records attributed to A F Heeley.

At least 19 recordsLinked to original sources
PubMed2000

Indirect measurements of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis.

AIM: To investigate whether analytical methods based on the colligative physical chemical properties of ions or solutes in sweat are less effective than the specific measurement of electrolytes in the diagnosis of cystic fibrosis (CF). METHODS: A single sweat sample was collected (Macroduct) from each of 211 infants and children, of whom 57 had CF, for the measurement of sodium, chloride, osmolality, and conductivity. RESULTS: The ranges within which CF and non-CF individual values overlapped (equivocal ranges), were wider for sodium and osmolality measurement than for chloride or conductivity. Neither of the latter two measurements provided a discriminatory advantage over the other. The utilisation of broadly based age related ranges for non-CF control subjects served to improve the discriminatory power of all four measurements to an extent that, in this cohort, both chloride and conductivity provided complete discrimination. CONCLUSION: Sweat conductivity is as effective as chloride measurement in the laboratory diagnosis of CF.

Adolescent↗
PubMed1996

Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population.

Hereditary fructose intolerance (HFI) causes severe and sometimes fatal metabolic disturbances in infants and children but responds to dietary treatment. To determine the practicability of screening newborn infants for HFI, we have investigated the frequency of the most common and widespread mutant allele of aldolase B, A149P, in the neonatal population. The polymerase chain reaction was used to amplify aldolase B exon 5 genomic sequences in DNA present in dried blood specimens preserved on Guthrie cards. The A149P mutation was identified by discriminatory hybridisation to allele specific oligonucleotides and confirmed independently by digestion with the restriction endonuclease BsaHI. Twenty-seven A149P heterozygotes were identified by the molecular analysis of aldolase B genes in blood samples obtained from a random cohort of 2050 subjects born in 1994 and 1995, 1.32 +/- 0.49% (95% confidence level). Although no A149P homozygotes were identified, the data allow the frequency of 1 in 23,000 homozygotes for this allele to be predicted. Our findings have implications for establishing an interventional mass screening programme to identify newborn infants with HFI in the UK.

Alleles↗
PubMed1993

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.

Cystic Fibrosis↗
PubMed1989

Immunoreactive trypsin in Shwachman's syndrome.

We studied two infants with Shwachman's syndrome in whom the immunoreactive trypsin concentration was found to be abnormally low. Experience with several hundred assays for immunoreactive trypsin has not shown this low concentration. This finding is probably specific for pancreatic acinar deficiency at this age and strongly suggests Shwachman's syndrome.

Agranulocytosis↗
PubMed1987

Immunoreactive trypsin in acute pancreatitis: elevated levels do not correlate with hyperamylasaemia.

Immunoreactive trypsin (IRT) was measured in the serum of patients presenting with acute pancreatitis (AP) and compared to serum amylase levels. Both were elevated beyond the normal range at presentation (mean IRT 557 +/- 252 micrograms/l, range 181-1000 micrograms/l, mean control IRT 42 +/- 14 micrograms/l, range 15-82 micrograms/l; mean amylase 4500 +/- 3200 IU/l, range 600-10,500 IU/l, control amylase mean 175 +/- 43 IU/l, range 48-320 IU/l). There was minimal correlation between IRT and amylase elevation but both returned to normal at the same rate in patients who recovered. In 2 patients with persistently elevated IRT levels, one was found to have a pancreatic pseudocyst and the other subsequently died from alcoholic haemorrhagic pancreatitis. IRT is no better than amylase as a single diagnostic assay in AP but may be greatly elevated when amylase elevation is minimal. The combination of the two may improve diagnostic accuracy and persistent elevation of IRT may be of prognostic importance.

Acute Disease↗
PubMed1986

Diagnosis of cystic fibrosis in premature infants.

Meconium ileus and pancreatic changes, as described in cystic fibrosis, were found, at autopsy, in a series of six infants who received prolonged neonatal intensive care for prematurity. Cystic fibrosis had not been suspected clinically. These pathological findings are so frequent in sick premature infants, amounting to 12% of all neonatal autopsies conducted over a period of 2 yr in our unit, that we question their specificity for cystic fibrosis and suggest they may be a manifestation of disordered physiology in the severely ill neonate.

Autopsy↗
PubMed1984

Improved sweat test method for the diagnosis of cystic fibrosis.

We describe a new technique of collecting sweat for measurement of osmolality and sodium concentrations. Eighty two subjects were studied--39 controls and 43 patients with cystic fibrosis. Adequate amounts of sweat were obtained in 81 subjects and sweat was analysed for both osmolality and sodium concentrations in 73 subjects. The 34 controls gave sweat osmolality and sodium values ranging from 62 to 196 mmol/kg and 9 to 72 mmol/l respectively. The 39 cystic fibrosis patients gave osmolality values ranging from 220 to 416 mmol/kg and sodium concentrations ranging from 60 to 150 mmol/l. Sweat osmolality alone was determined in eight infants under 50 days of age--four later developed the clinical features of cystic fibrosis and four, in whom cystic fibrosis was suspected, were later excluded. Sweat osmolality values in these two groups ranged from 255 to 345 mmol/kg and 87 to 123 mmol/kg respectively. The simplicity of collecting sweat and the measurement of osmolality offer distinct advantages over techniques previously described.

Adolescent↗
PubMed1983

Cystic fibrosis--its biochemical detection.

We examine critically the biochemical methods capable of detecting and monitoring the end-organ disease processes in patients with cystic fibrosis. Although the diagnosis of cystic fibrosis is never justified on the basis of the sweat salt test alone, the original filter-paper technic (Gibson-Cooke, Pediatrics 23:545-549, 1959) for determining Na+ and Cl- concentrations in sweat remains the most discriminating method. We discuss the contributions for neonatal screening of the so-called cystic fibrosis protein, associated decreased enzymic activities in the homo- and heterozygous state, and immunoreactive trypsin. Because evidence of either intestinal malabsorption or a pancreatic lesion must be sought, we review the use and interpretation of some tests of pancreatic dysfunction (meconium albumin, duodenal juice components, serum pancreatic isoamylase, and trypsinogen), both in establishing and in confirming the diagnosis of cystic fibrosis.

Age Factors↗
PubMed1983

Low plasma 25-hydroxyvitamin D and serum calcium levels in institutionalized epileptic subjects: associated risk factors, consequences and response to treatment with vitamin D.

In a survey of 108 subjects with a history of epilepsy in a hospital for the mentally handicapped, administration of both phenobarbitone and phenytoin was associated with low serum calcium and plasma 25-hydroxyvitamin D (25-(OH)D) levels in female subjects only. Intake of phenytoin (as mg/kg body weight) in female subjects exceeded that in males by 22 per cent, whilst the intake of phenobarbitone was 37 per cent higher. The doses of phenobarbitone and phenytoin were each inversely related to plasma 25-(OH)D concentration, but anticonvulsant drug dosage did not correlate with the magnitude of the decline of plasma 25-(OH)D concentration in winter (November-February). No influence of sodium valproate was detected on serum calcium or on plasma 25-(OH)D levels. Limited exposure to ultraviolet irradiation (UVR) or oral administration of vitamin D restored plasma 25-(OH)D to normal levels and healed osteomalacia in a subject with tuberous sclerosis. In this subject, fit frequency declined in response to UVR and to a lesser extent in response to oral vitamin D, despite the attainment of similar levels of serum calcium and of plasma 25-(OH)D. Serum calcium levels in the other 108 subjects were lower in those experiencing the most frequent fits, but serum calcium could not be restored to levels found in subjects not receiving anticonvulsant drugs unless supraphysiological doses of vitamin D were given. Vitamin D deficiency in the epileptic population receiving drugs was assessed by the response of alkaline phosphatase to vitamin D administration. A consistent fall of serum alkaline phosphatase was found only if the initial level exceeded 175 per cent of the normal value established by reference to a population not receiving phenobarbitone or phenytoin. By this criterion five out of 45 subjects (11 per cent), aged nine to 36 years were vitamin D deficient.

25-Hydroxyvitamin D 2↗
PubMed1982

Screening for cystic fibrosis by died blood spot trypsin assay.

Immunoreactive trypsin was measured in dried blood specimens from 14,000 infants. A second test was performed in 0 . 2% of the population in whom blood trypsin levels were greater than 80 ng/ml. Five infants with cystic fibrosis were then detected, with only one case of persistent hypertrypsinaemia in whom this diagnosis could not be established. No false-negative test results have yet been identified. Seventeen infants with cystic fibrosis were tested inthe first 2 weeks of life, only one of whom had a blood trypsin concentration less than 80 ng/ml.

Cystic Fibrosis↗
PubMed1979

Sensitive trypsin assay for dried-blood specimens as a screening procedure for early detection of cystic fibrosis.

An immunoreactive-trypsin assay uses small dried-blood spots (diameter 1.25 mm) and is therefore suitable for incorporation in established neonatal screening schemes. Blood specimens from neonates with cystic fibrosis had trypsin levels greater than those in control subjects, thus confirming earlier findings. Trypsin levels were below normal in several older patients with cystic fibrosis.

Adolescent↗