Laboratory medicine in the United Kingdom: 1948-1998 and beyond.

The National Health Service in the United Kingdom was created in 1948, effectively becoming the main provider of healthcare and funded by the government from taxation. By the late 1970's, and despite many achievements, it was seen to be approaching a financial crisis. Radical reforms were introduced in the early 1990's bringing in general management, a split between purchaser and provider, and competition. Whilst there has been a change of government more recently several of these initiatives have been retained, with the exception of competition (the internal market) which has been abandoned. There is now a much greater focus on the quality of care with increased clinical and financial accountability. Laboratory medicine (generally termed pathology in the United Kingdom) has evolved to meet the demands of more patients, reducing turnaround times, a greater repertoire of investigations and a continuing improvement in productivity. There is an increasing focus on improved dialogue between the laboratory and the clinician covering interpretation of results, audit of services and outcomes, research and development and continuous education in the pursuit of a high quality service. The major challenges for the future focus on alternative modes of delivery, on issues relating to staffing and on quality of service, in the face of an ever increasing demand.

Synovial fluid concentration of five different cytokines in rheumatic diseases.

Interleukin-1 beta, interleukin-2, tumour necrosis factor alpha, and the interferons, alfa and gamma, were measured concurrently in synovial fluid samples from 68 patients with rheumatic diseases. Mean interleukin-1 beta concentrations (130.3 (SD 22) pg/ml) were higher in synovial fluids from patients with rheumatoid arthritis (RA) than in those from patients with osteoarthritis (27.8(4.5)pg/ml), while measurements in synovial fluids from patients with seronegative spondarthritis were intermediate (72.7 (32) pg/ml). Interleukin-2 and tumour necrosis factor alpha concentrations were lower in the inflammatory arthropathies (RA: 4.5 (0.6) U/ml, 0.39 (0.04) ng/ml; seronegative spondarthritis: 3.1 (0.3) U/ml, 0.33 (0.03) ng/ml respectively) than those in patients with osteoarthritis (5.2 (0.6) U/ml; 0.05 (0.04) ng/ml). Interleukin-2 and tumour necrosis factor alpha concentrations correlated in all groups (r = 0.7), as did the interferons alfa and gamma (r = 0.7). There was no relation between interleukin-1 beta and either interleukin-2 or tumour necrosis factor alpha, or between the interferons and any other cytokine. Several distinct cytokine patterns were noted. Synovial fluids from two non-arthritic subjects were also examined: interleukin-1 beta concentrations were low, but concentrations of the other cytokines were higher than those seen in most arthritic fluids.

The oxidation of octanoic acid by cultured amniotic fluid cells: the effect of cell type and passage number.

We have measured the rate of oxidation of [1(-14)C]octanoate in cultured amniotic fluid (AF) cells at various passages and in AF cell lines with different clonal morphology. It is possible that both the passage number and the cell type may influence the outcome of prenatal diagnosis of fatty acid oxidation defects using this technique. We found that there was no significant difference between the three major AF cell types (epithelial, large epithelial, and fibroblast) when analysed at identical passage number but there was a significant reduction in octanoate oxidation in all cell types with increasing passage. For reliable prenatal diagnosis, cell lines of similar low passage number should be used.

A duplication/deficient X chromosome in a girl with mental retardation and dysmorphic features.

A structurally abnormal X chromosome was found in a nine year old girl with mild mental retardation and dysmorphic features. Subsequent clinical examination at 18 years of age showed tall stature and gonadal dysgenesis. Re-examination of her karyotype using a variety of banding techniques on prometaphase chromosomes allowed the identification of the abnormal chromosome as a duplication/deficient X chromosome, 46,Xder X(pter----q28::p11.2----pter). The clinical features are discussed in terms of karyotype/phenotype correlation.

An isodicentric X chromosome with short arm fusion in a woman without somatic features of Turner's syndrome.

A 25 year old woman with gonadal dysgenesis but no other somatic features of Turner's syndrome was found to have a 45,X/46,XidicX(p22.3) karyotype. It is postulated that because her stature is within the normal range there has been no loss of genetic material in the fusion of the two Xs. Her mother, who also had a history of menstrual problems, was found to be a 46,XX/47,XXX mosaic.

Oral administration of active vitamin D metabolites to low birthweight infants.

The active vitamin D metabolites 1 alpha, 25-dihydroxycholecalciferol (Rocaltrol) and the analogue 1 alpha-hydroxycholecalciferol (One-Alpha) are adequately absorbed after oral administration in the preterm infant. The absorption pattern is similar to that seen in adults.

Prometaphase chromosome analysis as a routine diagnostic technique.

The use of techniques for the production of prometaphase chromosomes leading to increased resolution of banding patterns has resulted in problems as well as advantages in their routine use. A simple technique utilising the folate antagonist methotrexate has been in use in this regional diagnostic cytogenetics centre for three years, and a number of chromosome abnormalities have been detected in cases previously reported as normal following G banding studies. With reference to this, the routine analysis of prometaphase-type chromosomes is discussed and assessed.

Growth velocity and plasma alkaline phosphatase activity in the preterm infant.

The relationship between growth and plasma alkaline phosphatase activity differs in the preterm infant when compared with older children and adolescents. 18 preterm infants were studied over the first 12 postnatal weeks; growth velocity and plasma alkaline phosphatase activity were measured serially. Plasma calcium, inorganic phosphate, the vitamin D metabolites and parathyroid hormone were assayed at a median age of 3 and 6 weeks. There was an overall significant negative correlation between growth and plasma alkaline phosphatase activity (r = -0.37; P less than 0.005); this was more marked in a group where the plasma alkaline phosphatase activity exceeded the preterm reference range. Plasma 1,25-dihydroxycholecalciferol and inorganic phosphate were lower in this group at 3 weeks but not at 6 weeks when compared with infants where plasma alkaline phosphatase activity did not exceed the reference range. There was no difference in caloric intake between the groups. In the preterm infant biochemical rickets is common and unlike older children and adolescents an increase in plasma alkaline phosphatase activity correlates with decreased rather than increased growth.

A child with a recombinant of chromosome 8 inherited from her carrier mother.

A female child with mental retardation and dysmorphic features was found to have a duplication deficiency of chromosome 8: rec(8)dup q,inv(8)(p23q24), a recombinant product derived from a familial pericentric inversion, inv(8)(p23q24)mat. Clinical features of this previously undescribed inversion product are compared with other reported cases of partial trisomy for the distal long arm of chromosome 8, since this segment is thought to be primarily responsible for the phenotypic features of the trisomy 8 syndrome.

Plasma ionised calcium in preterm infants: comparison with adults.

Plasma calcium (ionised and total) and albumin concentrations and pH were measured in preterm infants and in healthy adults and patients dependent on respirators. Plasma ionised calcium and total calcium values fell during the first week after birth and subsequently rose. Plasma ionised calcium concentrations in preterm infants were higher than those found in both healthy and sick adults. This difference was only partially explained by the lower blood pH in the infant population. There was no correlation between plasma ionised calcium or the ratio of ionised calcium to total calcium and total bilirubin concentrations. These results suggest that the metabolic control of plasma ionised calcium in preterm infants is different from that in adults.

Mannosidosis in two brothers: prolonged survival in the severe phenotype.

Two cases of mannosidosis are reported in brothers, one aged 41 years at death, the other aged 40 years and still alive. These patients are the oldest reported in the literature. Prolonged survival has previously been associated with the milder Type II phenotype. In addition to the characteristic clinical and radiological features of mannosidosis, both had severe joint destruction, which may be related to abnormal lysosomal enzymes in cartilage. The activity of acidic alpha-mannosidase was markedly reduced in plasma, leucocytes and fibroblasts, and the altered kinetic and physical properties are described.

Hepatic beta galactosidase and feline GMI gangliosidosis.

This paper describes the clinical, morphological and biochemical features of three cats with a progressive neurological disorder. Clinical features were ataxia and progressive tremor. The morphological characteristics were those of lysosomal storage disease affecting neurones of the central nervous system and autonomic ganglia; membranous cytoplasmic bodies were demonstrated by electron microscopy in cerebral neurones. Chemical analysis of brain from two of the cats revealed an increased content of total gangliosides, sialic acid and a specific increase in GMI ganglioside. Enzyme analysis of homogenates of leucocytes, spleen and brain showed less than 5% or normal 4-methylumbelliferyl-beta galactosidase (4MU-beta gal) activity. In liver, activity was markedly reduced at pH values below 4.2, but there was considerable activity above this value. The properties of 4MU-beta gal in normal and diseased feline livers were investigated. Sephadex gel filtration of diseased liver homogenates showed an absence of two thermolabile "acid' components, and reduced activity of a third thermostable "neutral' component. The biochemical abnormalities found in the diseased cats are similar to those found in human juvenile GMI gangliosidosis (type 2).