Fetal lung maturity tests on the 10,000 X g pellet.

Centrifugation has a profound effect on tests of fetal lung maturity performed on amniotic fluid. We have investigated the effect of a 700 X g centrifugal force for 10 min and a 10,000 X g force for 20 min on a battery of tests. While 91% of the OD650 was removed by the 10,000 X g centrifugal force, the supernatant fraction retained 34% and 38% of the L/S ratio and enzymatic lecithin respectively, when compared to the sample before centrifugation. Phosphatidylglycerol, when present in an amniotic fluid, was always absent from the 10,000 X g supernatant but present in the pellet formed by this centrifugal force. The pellet after 10,000 X g was unsuitable for OD650 and L/S ratio determinations but contained 63% of the enzymatic lecithin. When the pellet tests were subjected to a clinical trial, respiratory immaturity did not occur when phosphatidylglycerol was present or when the 10,000 X g pellet may be a useful means of detecting amniotic fluid surfactant and thus determining fetal lung maturity.

Retinal cotton-wool spots: an early finding in diabetic retinopathy?

Five insulin dependent diabetic patients are reported on who had a few small retinal cotton-wool spots or 'soft exudates' either totally isolated or associated with fewer than 10 microaneurysms. These observations suggest that cotton-wool spots may be an early finding in diabetic retinopathy. Significant biological abnormalities in these patients were high levels of glycosylated haemoglobin and mild increases in thrombin generation, indicating slight activation of the coagulation system. The possible significance of these clinical and biological findings is discussed.

An evaluation of factors associated with proliferative diabetic retinopathy.

Many individual factors have been related to development of proliferative diabetic retinopathy. To evaluate possible interactions among these, a constellation of variables were studied in 22 patients with long duration of insulin-dependent diabetes mellitus for greater than 25 years, with minimal background diabetic retinopathy, and compared to 27 patients with insulin-dependent diabetes mellitus for a variable duration, but with bilateral proliferative retinopathy. The patients were compatible in age at onset of diabetes (12 +/- 2 in proliferative retinopathy group vs 12 +/- 1 yr in the background retinopathy group). Following initial standard statistical analyses, data were further analysed using Logistic Regression Analysis. In the proliferative retinopathy group males were more prevalent (2.9:1), and patients were treated with larger insulin doses (0.86 +/- 0.07 vs 0.59 +/- 0.04 U/Kg B.W., p less than 0.001). Systemic hypertension and neuropathy were more prevalent (p less than 0.02 and less than 0.004 respectively), and diastolic blood pressure was higher (87 +/- 3 vs 75 +/- 2, p less than 0.01). In the same group diet was higher in carbohydrate and the ratio of polyunsaturated to saturated fats was lower (p less than 0.03, less than 0.05 respectively). HbA1 was higher (0.127 +/- 0.004 vs 0.110 +/- 0.004%, p less than 0.004), but the mean of all available plasma glucose values was not different. Impaired renal function expressed by higher BUN, serum creatinine, and urinary protein and lower creatinine clearance was observed. Nerve conduction parameters were more significantly impaired and plasma triglycerides were higher (1.74 +/- 0.2 vs 0.85 +/- 0.1 mmol/l, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acids in retinitis pigmentosa.

A survey of fasting whole blood amino acids in 65 patients with various subtypes of retinitis pigmentosa performed. Eight X-linked recessive patients showed decreased taurine and aspartate. Nineteen autosomal recessive patients, and to lesser extent 10 autosomal dominant patients, showed reduced levels of whole blood threonine and histidine. Branched-chain amino acids and arginine were present in increased amounts in 2 patients with Laurence-Moon-Bardet-Biedl syndrome. These findings in LMBB patients are probably related in part to their obesity and emphasise that appropriate controls are required, and other factors (including age) known to affect amino acid levels must be accounted for. The biochemical implications of our findings are not yet apparent.

Hyperornithinaemia and gyrate atrophy of the retina: improvement of vision during treatment with a low-arginine diet.

A 15-year-old patient with hyperornithinaemia (0.6--1.2 mmol/l) and gyrate atrophy of the retina was given a low-arginine diet to reduce plasma ornithine to a concentration (0.15--0.25 mmol/l) near the normal range. After five weeks of treatment, there was improvement in the visual function of one eye which had been severely impaired without improvement for 3 years. This improved visual function was maintained until compliance with the diet deteriorated at eight months, after which visual function regressed towards pretreatment status. Overrestriction of dietary arginine produced hyperammonaemia, indicating that arginine is an essential aminoacid in ornithine transaminase deficiency. These results suggest that reduction of plasma ornithine may reverse a metabolic neuroretinopathy in this disease, and offer hope that progression of the retinal atrophy can be arrested as well.

Pathological findings from two cases of choroideremia.

Light and electron microscopic study of material from two cases of old, quiescent choroideremia led to three conclusions: there was nearly total loss of the outer segments of the visual receptors, there was reduplication of the basement membrane of the pigment epithelium and thickening of Bruch's membrane, and there was gliosis of the inner part of the retina and a preretinal membrane.

Amino-acid metabolism and liver ultrastructure in hyperornithinemia with gyrate atrophy of the choroid and retina.

Three patients with the rare hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) syndrome were studied to elucidate the metabolic derangement and its pathologic concomitants. Tenfold elevations of blood ornithine levels, decreases in lysine levels, and hitherto unreported decreases in blood glutamate and glutamine concentration were observed. The output of ornithine from muscle kidney and splanchnic beds was curtailed or reversed after intravenous glucose. Levels of ornithine in venous blood declined after oral glucose, and rose after intravenous arginine. Increased amounts of 3-amino-2-piperidone were found in the urine, but these did not increase after the arginine-induced increase in ornithine levels. Liver biopsies in two patients revealed a marked alteration in mitochondrial ultrastructure. These studies extend the knowledge of the metabolic and pathologic derangements in HOGA. These findings are consistent with a disorder of ornithine-ketoacid transaminase, but such a disorder might not account for all the observations.

Diagnosis of red cell G-6-PD deficiency in a Chinese neonate.

In a neonatal period, a red cell deficiency of glucose-6-phosphate dehydrogenase (G-6-PD) may result in jaundice, the severity of which will vary between patients. Diagnosis of this inborn error of metabolism presents a problem if there is a large number of young enzyme-rich red cells in circulation, and this paper details the technique used to confirm a red cell deficiency of G-6-PD in a neonate.

Hyperornithinemia and gyrate atrophy of the choroid and retina.

The diagnosis of hyperornithinemia and gyrate atrophy (HOGA) depends upon the presence of five characteristic features: (1) typical chorioretinal lesions, (2) high myopia, (3) cataracts, (4) hyperornithinemia, and (5) autosomal recessive inheritance. We have seen three patients and described four new findings: (1) decreased whole blood glutamic acid, (2) low normal intelligence, (3) hepatic mitochondrial changes, and (4) urinary excretion of ornithine methyl ester. Investigations of amino acid metabolism in vivo are consistent with the presence of a defect in ornithine keto-acid transaminase.

A solubility problem in the preparation of uric acid standards.

Consistently high (13-16%) uric acid values for quality control sera were found when using freshly-prepared working uric acid standards on the Autoanalyser II system. After investigation several conclusions are made, with the recommendation that working uric acid standards are best diluted with pH 9.5 glycine buffer (0.007 M).

Uveitis in children.

Endogenous uveitis in 117 children aged 15 years or under was investigated at The Hospital for Sick Children, Toronto, in a 12-year period from 1953 to 1964. This group included 55 children with anterior uveitis, 59 with posterior uveitis, and three with diffuse uveitis. An etiologic diagnosis could be made or the uveitis recognized as part of a definite clinical syndrome in approximately 47% of the 117 children. The commonest cause of posterior uveitis was toxoplasmosis and the commonest associated finding in anterior uveitis was juvenile rheumatoid arthritis. Chronic cyclitis of unknown etiology was a relatively common disease.