Biomedical subjects
D F Child
Publications and source records attributed to D F Child.
Pseudohypercalcaemia in two patients with IgM paraproteinaemia.
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Inappropriate phosphate excretion in idiopathic hypercalciuria: the key to a common cause and future treatment?
AIMS: To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management. METHODS: An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months. RESULTS: In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups. CONCLUSIONS: It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism.
Heat shock protein studies in type 1 and type 2 diabetes and human islet cell culture.
Heat shock proteins (HSP) play an important role in auto-immunity and infection. Glutamic acid decarboxylase (GAD) the prime antigen in Type 1 diabetes has similar amino acid sequences to HSP65. An ELISA was developed using a plant-derived HSP65 antibody. HSP65 antibody was present in the serum of all normal subjects (median 1.64 AU, IQ range 1.49-1.74). Lower levels were found in established Type 1 diabetes (1.41 AU, 1.32-1.61, p < 0.001) and Type 2 diabetes (1.45 AU, 1.35-1.59, p < 0.006). In Type 1 HSP antibody levels fell with age (p = 0.007) and with duration (p = 0.008) and women with Type 1 had lower levels than men (p = 0.009). Human islet cell culture subjected to heat shock revealed an approximate four fold increase in heat shock protein antigen in the surrounding medium. The release of HSP antigen from stressed islet cells together with the finding of HSP antibody in the serum of all subjects suggest that HSP65 should not be completely discarded as having a possible role in the development of Type 1 diabetes. Low levels of HSP antibody in patients with established diabetes is probably a manifestation of impaired immunity induced by the diabetic state.
Hyperthyroidism and radio-iodine therapy in a district general hospital.
A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine.
Heat shock protein and the double insult theory for the development of insulin dependent diabetes.
Heat shock proteins (HSP) are the most widely conserved group of proteins in phylogeny and play an important role in infection and autoimmunity. HSP65 has been suggested as the primary antigen in insulin dependent diabetes while an alternative antigen glutamic acid decarboxylase (GAD), has similar amino acid sequences. A 'double insult theory' for the development of insulin dependent diabetes is suggested whereby a bacterial infection leads to the production of HSP antibody. If during a 'window of opportunity' this is followed by a viral infection of the islet cells this could, in certain histocompatibility locus antigen (HLA) groups only, lead to the production of HSPs on the cell surface and a destructive autoimmune reaction.
Dysthyroid eye disease with radiological features of orbital tumour.
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Value of emergency cardiac enzymes: audit in a coronary care unit.
Medical audit in a district general hospital coronary care unit led to the introduction of an emergency cardiac enzyme service. 91.2% of patients eligible for thrombolysis therapy received treatment following this introduction compared to 73.7% before (P = .05). No patient was treated inappropriately on the basis of a raised cardiac enzyme.
Persistent hypersecretion of ACTH in treated Addison's disease.
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Lack of relation between glycosylated haemoglobin concentrations and number of daily insulin injections.
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Multivariate analysis of glycosylated haemoglobin in insulin-treated diabetics.
Glycosylated haemoglobin (HbA1), as an assessment of overall control, was estimated in 858 insulin-treated diabetics attending for changeover to U100 insulin in North East Wales. Details of age, sex, duration of diabetes, insulin regimen and monitoring method were recorded. Multivariate analysis revealed lower HbA1 in patients receiving twice-daily (mean 11.01) as compared with once-daily insulin (11.42, P = 0.011), but no difference was found between urine and blood glucose testers when other variables were taken into consideration. HbA1 was lower in men (mean 10.94) compared with women (mean 11.39, P = 0.004) and there was a positive correlation of HbA1 in men with age (P = 0.046) and in women with duration of disease (P = 0.005).
IgE antibody studies in a case of generalized allergic reaction to human insulin.
A patient developed a generalized reaction to purified bovine, purified porcine and human insulin. High levels of IgE antibody to bovine, porcine, human emp and human crb insulin were demonstrated. These fell dramatically following desensitization with human crb insulin. All four types of insulin gave superimposable RAST inhibition curves indicating a common allergen determinant.
Generalised allergic reaction with synthetic human insulin.
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Audit in a diabetic clinic.
Diabetic control was assessed in 82 established insulin-dependent diabetics using a microcapillary system for home preprandial blood glucose sampling. At initial assessment control in the majority (62%) was found to be unsatisfactory (at least 1 preprandial blood glucose greater than 13.0 mmol/l or frequent and severe hypoglycaemia). Sixty-three of these patients were assessed on more than one occasion. Only 24% were satisfactorily controlled at their first assessment, but this proportion had risen to 60% after 12 months. The ability of patients to perform unsupervised blood glucose levels using Ames Glucometers or BM-Glycemie 20-800 test strips was also assessed: 86% of the meter results were within one-third of the laboratory-based results, but there was evidence of bias towards the under-reading of higher glucose values using BM-Glycemie 20-800 test strips. Random blood glucose estimations performed in the diabetic clinic were of little value.
The acromegaly syndrome. Relation between clinical features, growth hormone values and radiological characteristics of the pituitary tumours.
One hundred and fifty-five acromegalics, 76 males (mean age 44 +/- 1.3 years) and 79 females (45 +/- 1.4 years) were studied. The frequency of clinical features were: acral enlargement 100 per cent, hyperhidrosis 65 per cent, headache 55 per cent, paraesthesiae 49 per cent, cardiac problems 34 per cent, hypertension 32 per cent, diabetes mellitus (clinical and chemical) 27 per cent, and visual field defects 6 per cent. Signs and symptoms, and particularly headache, did not show any relation with the size or shape of pituitary tumours, nor with growth hormone (GH) values, age, sex or weight. Mean of GH values at 60, 90 and 120 minutes during a GTT averaged 135 mIU/l, range 8-1833. Diabetes mellitus was more frequent and severe in patients with higher GH values, occurring in 32 per cent of patients with mean GH values greater than or equal to 50 mIU/l and only in 16 per cent of the rest (p less than 0.05). GH values correlated positively with size of tumours. Forty-nine per cent of patients presented with entirely intrasellar tumours, 27 per cent with suprasellar extensions and 23 per cent with partially empty sellae. The mean GH (238 mIU/l) of patients with suprasellar extensions was significantly higher (p less than 0.004) than those of the others. Younger acromegalics showed a tendency to larger tumours. Early treatment of acromegaly, particularly in young patients and those presenting with high GH values, is recommended.
A novel five-microlitre capillary system for home glucose monitoring.
Improvement in the control of diabetic patients is aided by a knowledge of blood glucose levels during a 'normal' (non-hospitalised) day. We have devised a 5 microliter capillary tube collection system as a 'kit' for home use by diabetics. Blood collected into 5 microliter capillary tubes is washed into a protein precipitant by the patient. The completed kit is posted to the laboratory for analysis. The technique has achieved a high degree of patient acceptability. Subsequent analysis involves the addition of a single reagent. Reagents, patient samples, and standards are stable, and the precision of the technique compares favourably with our routine glucose procedure.
Adrenal steroidogenesis in hirsute women.
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Heterogeneity in adrenal steroidogenesis in normal men and women.
Adrenal steroidogenesis has been studied in vivo in normal men and women. Serum levels of nine steroids on the biosynthetic pathway (the delta 5 3-beta-hydroxysteroids, pregnenolone (Pe), 17 alpha-hydroxypregnenolone (17Pe), dehydroepiandrosterone (DHEA), androstenediol (Adiol), and their delta 4 3-keto counterparts, progesterone (Po), 17 alpha-hydroxyprogesterone (17Po), androstenedione (Adione), and testosterone (T)) as well as cortisol were measured during adrenal suppression and stimulation. This study demonstrates a marked heterogeneity in adrenal steroid responses between different subjects in the normal population. Thus, in three subjects ACTH stimulation from a dexamethasone-suppressed state resulted in a far greater increment of 17Po than in the other nineteen normal subjects. These three individuals (designated Type 2 responders) may have a partial deficiency of 21-hydroxylase activity. In the remaining nineteen subjects (designated as Type 1 responders) the women had a greater increment of Adiol (P less than 0.05) and a lower increment of Po (P less than 0.01) than the men, suggesting that adrenal 3-beta-hydroxysteroid dehydrogenase/isomerase activity may be slightly lower in women than men.