History of Newborn Screening for Cystic Fibrosis-The Early Years.

This review summarises the trajectory of neonatal screening strategies for the detection of cystic fibrosis (CF) using the measurement of Immunoreactive Trypsin (IRT) in dried blood spots (DBS) from 1979 until the beginning of the 21st century when newborn screening (NBS) programmes started to spread throughout many countries, using IRT measurement combined with a CF genotype analysis of DBS.

Miniature Uncooled and Unchopped Fiber Optic Infrared Thermometer for Application to Cutting Tool Temperature Measurement.

A new infrared thermometer, sensitive to wavelengths between 3 μm and 3.5 μm, has been developed. It is based on an Indium Arsenide Antimony (InAsSb) photodiode, a transimpedance amplifier, and a sapphire fiber optic cable.

Thirty-years of screening for cystic fibrosis in East Anglia.

Background: Newborn screening for cystic fibrosis (CF) relies on the measurement of immunoreactive trypsinogen (IRT) originating from the pancreas. The Norfolk, Suffolk and Cambridgeshire screening programme initially exploited the persistent increase in IRT seen in CF (IRT-IRT protocol) and later changed to include mutation analysis as a second tier test (IRT-DNA-IRT protocol).

Results: During a 30 year period 582 966 babies have been screened by IRT-IRT and 147 764 by IRT-DNA-IRT (total 730730), resulting in 296 screen positive cases of CF and 29 false negatives (including 10 false negatives with meconium ileus).

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

Clinical response and tricyclic plasma levels during treatment with clomipramine.

Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear.

Half life of theophylline in the preterm baby with apnoeic attacks.

Plasma theophylline levels were measured by an enzyme immunoassay method in 6 preterm babies. The method gave accurate and rapid results. The study showed a considerably prolonged half life of an oral preparation.