Performance of a computerised visual acuity measurement device in subjects with age-related macular degeneration: comparison with gold standard ETDRS chart measurements.

PURPOSE: The aim of the study was to compare the performance of two different COMPlog computerised, single letter scoring, visual acuity (VA) measurements against gold standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart measurements in patients with age-related macular degeneration (AMD). One computerised algorithm presented five and the other presented three letters per line; both computerised algorithms utilised half, rather than the full-letter width spacing standard on ETDRS charts that might induce crowding, fixation problems, increased test-retest variability (TRV), and bias. METHODS: Fifty patients with AMD (mean age 83 years) underwent timed test and retest VA measurements using ETDRS charts and COMPlog five (C5) and three (C3) letters per line computerised VA measurement algorithms. All tests utilised single-letter scoring methodology. Bland and Altman methods were employed. Performance was measured in terms of bias, TRV, and test time. RESULTS: The C5 and C3 scores showed no bias compared with the ETDRS chart measurements. C5 measurements had equal TRV to the ETDRS chart (±0.13 logMAR) with similar median test times (105 and 96 s, respectively). C3 measurements were slightly more variable (TRV ±0.17 logMAR), but 30 s quicker than ETDRS chart measurements. CONCLUSIONS: The closer letter spacing employed in COMPlog testing algorithms appears to have no adverse effect on VA measurements compared with the gold standard ETDRS chart in patients with AMD. The three letter per line testing algorithm facilitates faster testing but with a two letter increase in TRV.

The effect of plasmapheresis on the concentration of certain plasma proteins: a case identified by an inaccurate LDL-cholesterol estimation.

A 35-year-old man was found to have a negative LDL-cholesterol concentration (-0.05 mmol/L) when estimated on a fasting plasma sample using the Friedewald equation. Plasma urea, electrolytes and liver function tests (LFTs) were normal except for a raised total bilirubin of 74 micromol/L. Haematological results showed both a low haemoglobin and fibrinogen concentration. It transpired that the patient had undergone daily plasmapheresis treatments on the previous four days; plasma had been exchanged with a 5% albumin solution. He had been diagnosed with Evan's syndrome previously (characterized by autoimmune haemolytic anaemia) and had been admitted with severe anaemia, which had proved unresponsive to conventional treatments. The concentration of most plasma substances is reduced by 50-60% after one standard plasmapheresis treatment, with the rate of return to steady state concentrations varying among analytes. The finding of a negative LDL-cholesterol concentration (arising primarily as a result of normal triglyceride concentrations) may reflect the more efficient removal of LDL and HDL lipoproteins during the plasmapheresis procedure (PP) than lipoproteins containing proportionally more triglycerides. Plasma lipids, total protein, immunoglobulins and transferrin had recovered to steady state concentrations by eight days post-plasmapheresis, whereas caeruloplasmin concentrations had not. This case report illustrates the difficulties of obtaining accurate information on the steady state concentrations of plasma analytes, in particular protein bound substances, when analysis is carried out on a sample from a patient that has recently undergone plasmapheresis. The normal plasma albumin in this situation did not flag the possibility of the sample being artefactually diluted.

In vitro cold activation of complement shown by an overestimation of total complement 4: a study in patients with hepatitis C virus infection.

Total complement 4 (C4) levels, when analysed on the Beckman Array nephelometer, were found to increase number of serum specimens [predominantly from patients with hepatitis C virus (HCV) infection] after overnight storage at 4 degrees C. In order to investigate whether the phenomenon of in vitro cold-dependent activation of complement (CDAC) was the explanation for this increase, paired specimens were collected from 63 patients with HCV infection in tubes with no anticoagulant (serum) and in tubes containing EDTA (which inhibits complement activation). C4 levels increased after overnight storage at 4 degrees C in 33 serum specimens (52%). In contrast, no increase in C4 levels was observed in any of the 63 EDTA specimens. Immunofixation of intact and activated C4 products confirmed that complement activation had taken place in the serum specimens in which C4 levels had increased after storage. There was a higher frequency of hepatitis C viraemia (P<0.0001), HCV antibody positivity (P<0.05) and the presence of rheumatoid factor (P<0.05) in the group of patients in whose serum samples CDAC had occurred (n = 33) than in the other group (n = 30). As a result of our findings on C4 analysis in stored serum specimens, we would recommend potassium EDTA plasma as the specimen of choice for complement analysis on the Beckman Array.

Serum bile acids and ursodeoxycholic acid treatment in cystic fibrosis-related liver disease.

Increased circulating levels of hepatotoxic bile acids may contribute to the cholestasis characteristic of cystic fibrosis-related liver disease. The aims of this study were to compare serum bile acid profiles in patients with cystic fibrosis with and without liver disease, and to evaluate the effect of treatment with ursodeoxycholic acid, a non-hepatotoxic bile acid, on liver biochemistry and serum bile acids in patients with cystic fibrosis-related liver disease. Fasting and postprandial serum bile acid levels were analysed in 15 patients (nine males; median age 18 years) with cystic fibrosis-related liver disease and compared with serum bile acid levels in 18 cystic fibrosis patients (12 males; median age 22 years) without liver disease and 10 control subjects. Fasting and postprandial serum levels of primary and secondary serum bile acids were analysed using high-performance liquid chromatography. Liver biochemistry and serum bile acids were measured in six cystic fibrosis patients with liver disease before and 6 months after treatment with ursodeoxycholic acid 20 mg/kg/day and compared with six control patients with cystic fibrosis-related liver disease. Total fasting and postprandial serum bile acid levels were significantly (P < 0.01) elevated in patients with liver disease compared to those without liver disease and controls. The fasting glycine conjugates of cholic acid, chenodeoxycholic acid and deoxycholic acid, and the fasting and postprandial taurine conjugates of cholic acid and chenodeoxycholic acid were significantly (P < 0.05) elevated in liver disease patients compared to patients without liver disease and controls. After 6 months' treatment with ursodeoxycholic acid, although the serum was significantly saturated with ursodeoxycholic acid and significant improvements in liver biochemistry were observed in the treatment group, there was no significant reduction in the levels of individual serum bile acids. Although circulating levels of potentially hepatotoxic serum bile acids are elevated in patients with cystic fibrosis-related liver disease, improvements in liver biochemistry associated with ursodeoxycholic acid treatment cannot be attributed solely to alterations in levels of endogenous bile acids.

Atopy and cystic fibrosis. A study of CF sibling pairs and their families.

We have investigated the prevalence of atopy within families of cystic fibrosis (CF) patients and compared its frequence in CF patients, their parents and their non-CF siblings. By studying families with two CF patients it was also possible to evaluate the factors influencing the development of atopy in one CF patient relative to the other patient within the same family. A significant correlation with age (P less than 0.001) for skin test positivity to common allergens within CF sibling pairs was observed. In 14/18 families studied, only the older CF patient was atopic. The presence of atopy in CF patients was independent of the atopic status of their parents.

Atopy and bronchial reactivity in older patients with cystic fibrosis.

We studied 25 adolescent and adult patients with cystic fibrosis (CF) and 25 control subjects to determine if the prevalence of atopy and bronchial hyperreactivity was increased in this disease. Results showed that atopic symptoms, as defined by history, were more frequently present in the CF patients. Prick testing of the skin produced positive reactions in 88% of the CF group and 36% of the control subjects (p less than 0.001), and the mean number of reactions per subject was significantly higher in the former group (p less than 0.001); reactions to fungal antigens were strikingly positive in the CF group. The CF patients had a significantly higher mean serum IgG4 (p less than 0.001), IgE (p less than 0.01), and higher mean eosinophil count (p less than 0.05). Clear-cut bronchial hyperreactivity was demonstrated in the CF group compared with control subjects. Bronchial provocation with 400 micrograms of histamine led to a greater than 15% fall in the preinhalation FEV1 in 35% of the CF subjects compared with 4% of the control group, with a mean percentage fall of 15% and 3% respectively (p less than 0.001). In the CF group a greater than 15% rise in PEFR occurred in 32% after inhalation of the parasympatholytic, ipratropium bromide (54 micrograms), and in 27% after inhalation of the sympathomimetic, fenoterol (400 micrograms). No correlation was found between bronchial reactivity and atopic status, HLA phenotype pattern, or disease severity. The cause of the increased prevalence of atopy and bronchial reactivity in CF patients remains unknown. However, it is clear that a trial of bronchodilator therapy is warranted in adolescents and young adults with CF.

Insulin immunology: humoral and cellular aspects in mono-component insulin treated patients.

A study on humoral and cellular immune response to monocomponent (MC) insulin is reported. Humoral insulin antibody did not reach detectable levels in 80% of patients studied. Two out of six patients in whom a detectable antibody response was found had bovine species specific antibody suggesting some contamination of the insulin preparation used. No evidence for lymphocyte transformation with MC insulin was observed in the patients treated. B component resulted in transformation in patients treated with non-MC insulins. Zinc acted as a stimulant to lymphocyte transformation in the control group. The significance of the observations is discussed.