The Tayside insulin management course: an effective education programme in type 1 diabetes.

AIMS: The Tayside insulin management (TIM) course is an intensive insulin management programme for adults with type 1 diabetes. The aim was to assess its effectiveness. METHODS: Haemoglobin A1c (HbA1c) and body mass index (BMI) from individuals with type 1 diabetes were collected 3 months before, and 6 and 24 months after the programme. The programme involved a full day of education per week for 4 weeks in a row. Quality of life was assessed using the standardised Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire completed both before and 3 months after the course. Subjects were also asked to complete a pre- and postcourse questionnaire gathering information about aspects of their diabetes management. In addition, individual satisfaction with course content and delivery was recorded. RESULTS: Participants had a median reduction in haemoglobin A1c (HbA1c) of 4 mmol/mol (0.4%) after 6 months and 5 mmol/mol (0.5%) 2 years after the course (p < 0.001). Mean daily dose of short-acting insulin decreased from 31.5 (1.9) units to 27.3 (1.9, p < 0.001). There was no significant change in BMI. There was an improvement in all 18 domains of the ADDQoL questionnaire. There was a decrease in hypoglycaemia unawareness from 34.3 ± 47.8% of patients to 8.6 ± 28% (p < 0.001), and a decrease in self-reported lipohypertrophy from 27.8% to 11.1% (p = 0.001). There was a significant reduction in the mean number of diabetic ketoacidosis and severe hypoglycaemic episodes. The number of blood glucose checks changed from 2.8 ± 2.1 to 3.2 ± 1.1 (p = 0.058) per day. Participant satisfaction with all aspects of course content and delivery was high. CONCLUSIONS: TIM is an effective intensive education programme for patients with type 1 diabetes.

Temporal changes in biotypes of Haemophilus influenzae isolated from patients with cystic fibrosis.

Isolates of Haemophilus influenzae obtained sequentially over a period of 2 years from 62 patients with cystic fibrosis were biotyped. Rapid changes were seen from month to month in biotypes isolated from the respiratory tract and only a few of the patients harboured the same biotype for several months. Up to four biotypes were present simultaneously, whereas even two different biotypes were found in only one of a series of 148 patients with respiratory infections but not cystic fibrosis. Colony morphology was no guide to biotype, since the same biotype may show different colony appearances on the same plate and different biotypes may show identical colony forms.

Distribution of biotypes of Haemophilus influenzae and H parainfluenzae in patients with cystic fibrosis.

One hundred and eighty eight isolates of Haemophilus influenzae and 187 isolates of H parainfluenzae from patients with cystic fibrosis, patients with respiratory infections but without cystic fibrosis, and patients with neither cystic fibrosis nor respiratory infections were biotyped. Biotype I of H influenzae were found significantly more often in patients with cystic fibrosis compared with those with normal respiratory tracts. On the other hand, biotype II strains of H influenzae were found less often in the cystic fibrosis group. Half of the biotype V strains produced beta-lactamase.

Specificity of antibodies for T sites and F sites of streptolysin O.

Antistreptolysin antibody (ASO) inhibits haemolysis of erythrocytes coated with streptolysin O (SLO), but antistreptolysin activity may also be due to the presence in sera of peptide fragments of altered beta lipoproteins. SLO-mediated haemolysis results from activity of a molecular site (the t site) distinct from that at which the SLO becomes attached to the cell (the f site), and both sites might be expected to function antigenically. Absorption studies with SLO-coated latex particles, and with SLO-coated erythrocytes in the cold, provide evidence for the existence of both classes of antibody. Results also suggest explanations for the frequent observation of false-negative and false-positive latex tests.

Comparison of agglutination, complement fixation and immunofluorescence tests in Campylobacter jejuni infections.

Good antibody responses usually follow infection with Campylobacter jejuni. A comparison of agglutination, complement fixation and immunofluorescence tests was done on 55 sera from 40 sporadic patients with diarrhoeal disease and positive cultures for C. jejuni. Results showed 82% positive with immunofluorescence, 62% by complement fixation but only 38% by agglutination, using two reference strains COP and MEL as antigens. Overall 90% of the 40 patients were positive by one or more serological tests. Paired sera from 15 patients showed a fourfold or greater rise in only five, confirming previous observations that antibody formation occurs early in the course of infection. Results also suggest that different test systems may be detecting antibodies of different specificities. Results confirm the value of serological tests, but further information on serotypes is required for selection of suitable reference strains.

Polyene antibiotics in assessing significance of antistreptolysin O activity.

Antistreptolysin O activity in serum is due either to antibody or to altered lipoprotein molecules. The latter can be inhibited by performing antistreptolysin tests using a polyene antibiotic such as amphotericin B as diluent.

A specific direct radioimmunoassay for oestriol-16alpha-glucuronide in pregnancy plasma.

A specific radioimmunoassay has been developed for measuring oestriol-16alpha glucuronide in pregnancy plasma using a highly specific antiserum. The specificity of this antiserum has been assessed by the 50% displacement method and by measuring oestriol-16alpha-glucuronide concentrations in pregnancy plasma samples, both with and without chromatography. The antiserum was found to have Ka of 1.3 X 10(10) M-1. The assay had a sensitivity of 5 pg (least quantity of oestriol-16alpha-glucuronide distinguishable from the zero point, p less than 0.05), an intra-assay variation of 6.07% and an inter-assay variation of 3.36%. The assay was used to measure plasma oestriol-16alpha-glucuronide concentrations throughout eight pregnancies, five of which were normal and three had some defined abnormality.

Cholesterol esterase activity in body fluids.

Antistreptolysin O activity (greater than or equal to 200 Todd units/ml) was found in 20% of 25 ascitic fluids, 20% of 55 pleural fluids and 37-5% of 56 joint fluids. These levels are not due to antibody but to the cholesterol moiety of altered beta-lipoproteins. The activity is precipitable with 10% dextran sulphate. Incubation of mixtures of fluids with titres less than 200 and normal human serum generated eight-fold or greater rises in antistreptolysin titres. This results from the activity of cholesterol esterase in the fluid acting on the beta-lipoprotein of the serum and activity was noted in 90% of ascitic fluids, 59% of pleural fluids and 54% of joint fluids. However, mixtures showing no such rise probably also contain esterase, the failure to demonstrate antistreptolysin activity being due to equilibration of ester derived cholesterol with sub-fractions of high density and very low density lipoproteins.

Studies on antistreptolysin O activity generated in serum by microorganisms.

An antistreptolysin factor (ASF) was generated in normal human serum by the growth of Staph, aureus and Pseud, aeruginosa. Alpha toxin producing strains of the former were usually positive but activity was not restricted to such strains. Positive strains produce cholesterol esterase which was obtained from DEAE-cellulose column fractions of 18 h broth cultures. Antistreptolysin factor develops slowly in serum, being maximal between the 5th and 10th days and is associated with alterations and disappearance of beta lipoproteins on gel electrophoresis. Activity also appeared in beta lipoproteins precipitated from normal serum with dextran sulphate and redissolved in nutrient broth before inoculation with Staph, aureus. The slow appearance of antistreptolysin activity in serum appears to be due to an esterase inhibitor which is present in high concentrations in some sera. Activity is also modified by the production of a staphylococcal fraction capable of binding to the antistreptolysin factor and reducing its activity. It is suggested that antistreptolysin factor which can be demonstrated in small amounts in normal human serum represents a readily available non-specific defence mechanism capable of binding to certain bacterial products and possible to other foreign protein molecules.

Partial characterisation of an inhibitor of streptolysin O produced by bacterial growth in serum.

An inhibitor of streptolysin O is generated in human and animal sera by the growth of certain organisms. The ability to do this occurs most often in Pseudomonas aeruginosa and Staphylococcus aureus (in 90% and 86% of strains respectively), but in only 32% of Staph. epidermidis strains. The inhibitor is not formed in broth. The effect appears slowly on incubation, with maximum activity after 4-7 days. Evidence suggests that two enzymes are involved, an esterase which splits ester-bound cholesterol and a proteolytic enzyme which partially hydrolyses lipoprotein, resulting in cholesterol remaining attached to protein or polypeptide fractions but with some alteration of its spatial configuration such that it is now capable of attaching to streptolysin O. The inhibitory factor appears to prevent streptolysin becoming attached to cholesterol receptor sites on the erythrocyte membrane. Removal of the precursor from serum with magnesium carbonate suggests that low-density lipoproteins may be the precursor of the inhibitor.

Functional role of cholesterol in infection and autoimmunity.

Cholesterol binds to streptolysin O and related bacterial toxins. In normal serum, only a fraction of the cholesterol attached to lipoprotein is available for binding, probably as a cholesterol-peptide complex formed during catabolic breakdown of the lipoprotein. Cholesterol esterase produced by certain organisms--e.g., Staphylococcus pyogenes and Pseudomonas oeruginosa--augments this fraction both in vitro and in vivo. Endogenous esterase similarly increases the amount of cholesterol-peptide complex, a mechanism which may be activated as a feedback process following binding of toxin to the cholesterol component of the complex. These complexes will thus supply a readily available means of binding bacterial toxins before antibody formation begins; Cholesterol-peptide complexes, either alone or modified by binding to toxin, may function as autoantigens. It is postulated that immune complexes so formed may be involved in atherosclerosis either by directly damaging vessels walls or by cross-reaction of antibody with cell-membrane-bound lipoproteins which equilibrate with plasma-lipoproteins.

Clinical evaluation of the macrophage electrophoretic mobility test for cancer.

Experience with the macrophage electrophoretic mobility (MEM) test of Field and Caspary in subjects with malignant and non-malignant disease is reported. There was some discrimination between groups of patients with benign and malignant lesions but there was no clear separation between the groups. A trial of the Cardiff modification of the test failed to discriminate between groups of patients with benign and malignant chest disease. In the view of the authors the MEM test in its present form is not sufficiently reproducible to warrant more general clinical application as an in vitro test for cancer.

Sterol structural requirements for inhibition of streptolysin O activity.

Reduced streptolysin O, a toxin produced by certain beta-haemolytic streptococci, lyses human erythrocytes. The reaction is inhibited by cholesterol at concentrations of about 1.0mug/ml. Other sterols inhibit the lysin and there is a specific requirement for a 3beta-hydroxyl group. Inhibition was obtained with 3beta-hydroxychol-5-en-24-oic acid, containing a hydrophilic group at C-24. The mode of inhibition is likely to involve attachment to the fixation site of the lysin which attaches the molecule to cell membranes, probably to membrane cholesterol. A second streptolysin site, concerned in the final haemolytic event, may also be involved. Inhibitors of the latter site have not been characterized, other than antibody with specificity for the site.