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Biomedical subjects

J J Milles

Publications and source records attributed to J J Milles.

11 recordsLinked to original sources

Lipoprotein subfraction composition in non-insulin-dependent diabetes treated by diet, sulphonylurea, and insulin.

Lipoprotein abnormalities may predispose to an increased risk of coronary heart disease in type II (non-insulin-dependent) diabetes mellitus. To investigate the effects of different treatment modalities, the composition and concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of patients with type II diabetes at diagnosis, treated by diet alone, treated by diet + glibenclamide (2.5 to 15 mg/d for 6 to 48 months), and treated by diet + insulin (25 to 65 U/d for 8 to 144 months). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, type II patients at diagnosis showed increased concentrations of nonesterified and esterified cholesterol, triglyceride, phospholipid, and protein in the very low density lipoprotein (VLDL) fraction. However, the only alteration in VLDL composition was a small decrease in the relative proportion of phospholipid. Apolipoprotein-B and low density lipoprotein (LDL) cholesterol concentrations were also raised in type II patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) nonesterified and esterified cholesterol, phospholipid, and apo-AI were lower in type II patients at diagnosis. This was largely accounted for by reduced concentrations of these components in the HDL2 subfraction, which retained a normal composition. Type II patients treated by diet alone and diet + glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations, which are associated with premature coronary disease, to the type II patients at diagnosis. However, in type II patients treated with insulin, plasma lipoprotein concentrations and composition were normal, except LDL cholesterol, which was lower than normal in insulin-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B

Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin.

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.

Adult

Lipoprotein subfraction composition in non-obese newly diagnosed non-insulin dependent diabetes after treatment with diet and glibenclamide.

The composition and concentrations of fasting plasma lipoproteins were determined in a prospective study of 11 +/- 2 (mean +/- 1 SD) months in 16 non-obese (body mass index less than or equal to 30) patients with Type 2 (non-insulin dependent) diabetes mellitus at diagnosis, treated by diet alone or diet plus glibenclamide (2.5-7.5 mg/day). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, Type 2 patients at diagnosis showed increased concentrations of non-esterified and esterified cholesterol, triglyceride, phospholipid and protein in the very low density lipoprotein (VLDL) fraction. The apolipoprotein (apo) B concentrations was also raised, but low density lipoprotein (LDL) cholesterol concentrations were not significantly altered in Type 2 patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) non-esterified and esterified cholesterol, HDL phospholipid and apo AI were lower in Type 2 patients at diagnosis. This was largely accounted for by a reduced number of HDL2 molecules of normal composition. After treatment of Type 2 patients with diet alone, there was a marginal increase in plasma HDL cholesterol and phospholipid, and in plasma HDL2 cholesterol, phospholipid, protein and apo AI concentrations, in association with reductions of VLDL component concentrations, body mass index and glycaemia. Type 2 patients treated with diet plus glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations before and after treatment, except for a small reduction in VLDL component concentrations and a slight increase in the apo AI:B ratio. Institution of diet alone and diet plus glibenclamide generally failed to restore VLDL, HDL and HDL2 component concentrations and the apo AI:B ratio to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking

Effect of acetazolamide on blood gases and 2,3 DPG during ascent and acclimatization to high altitude.

Blood gases and red cell 2,3 DPG concentrations were measured during ascent and a stay for 6 days at 4846 m in 20 subjects. Acetazolamide improved Pa,O2 and reduced pH and Pa,CO2. 2,3 DPG concentrations were lower in the acetazolamide group during ascent and at high altitude. However, 2,3 DPG concentrations were significantly greater at high altitude in both the acetazolamide and placebo groups compared with low altitude. The acetazolamide group remained different from the placebo group during the stay at high altitude with higher Pa,O2, lower PaCO2, lower pH and lower 2,3 DPG concentrations.

2,3-Diphosphoglycerate

Effect of acetazolamide on exercise performance and muscle mass at high altitude.

The effect of acetazolamide (Az) on exercise performance and muscle mass in acclimatised subjects at an altitude of 4846 m was assessed in 11 subjects and compared with the effect of placebo on 10 other subjects. Exercise performance at 85% maximum heart rate fell by 37% in the Az group and by 45% in controls (p less than 0.05). Weight loss was greater in the placebo group at high altitude (p less than 0.01) and this correlated with the fall in exercise performance (p less than 0.001). During the expedition anterior quadriceps muscle thickness fell by 12.9% in the control group and 8.5% in the Az group (p less than 0.001), while biceps muscle thickness fell by 8.6% in controls and 2.3% in the Az group (p less than 0.001). Measurements of skin-fold thickness indicated a loss of 18% of total body fat in the placebo group and 5% in the Az group by the end of the expedition (p less than 0.001). Calorie intakes at altitudes above 3000 m were low and similar for the two groups. The Az group had fewer symptoms of acute mountain sickness but differences between the two groups were not statistically significant. Acetazolamide is therefore useful for climbers and trekkers who are acclimatised to high altitudes. It could be most useful at extreme altitudes, where maintenance of exercise performance and muscle mass are important.

Acetazolamide

Conflict between classifications based on free thyroxine and thyroid stimulating hormone concentrations in thyroxine-treated patients.

The use of free thyroxine assay as the basis for monitoring patients on thyroxine replacement therapy was assessed. Patients with normal free thyroxine levels were divided into sub-groups on the basis of serum TSH levels. Of these, patients with normal TSH levels had higher serum free thyroxine and free 3,5,3'-triiodothyronine concentrations than patients with elevated TSH levels. No significant differences were seen in the level of duration of replacement therapy. Patients were almost equally divided between the high and normal TSH sub-groups. It was concluded that free thyroxine assay had little role to play in the monitoring of these patients.

Humans

A comparison of diagnostic methods to differentiate diabetes insipidus from primary polyuria: a review of 21 patients.

Direct measurement of plasma AVP and indirect assessment of antidiuretic activity during standard dehydration tests were made in 21 polyuric and polydipsic patients to establish the efficacy of each method in determining the cause of polyuria. Patients with acquired nephrogenic diabetes insipidus (e.g. diabetes mellitus, renal failure, hypercalcaemia) were excluded from the study. Cranial diabetes insipidus was diagnosed by plasma AVP responses to osmotic stimulation during infusion of hypertonic 5% saline which were subnormal in 13 patients, 4 of whom had undetectable plasma AVP and 3 who had reduced but osmoregulated AVP release. Standard water deprivation tests confirmed cranial diabetes insipidus in all but 2 patients who were diagnosed as partial nephrogenic diabetes insipidus. The remaining 8 patients had normal, osmoregulated AVP secretion; the cause of their polyuria was determined by their renal response to desmopressin. Two patients had nephrogenic diabetes insipidus and 6 had primary polydipsia. The majority of polyuric patients could be accurately diagnosed by carefully performed dehydration tests. We suggest that direct measurements of plasma AVP during osmotic stimulation are only necessary to distinguish mild forms of cranial from nephrogenic diabetes, or to define precisely the characteristics of AVP secretion.

Adolescent

Plasma vasopressin during insulin withdrawal in insulin-dependent diabetes.

Plasma vasopressin was measured in seven insulin-treated diabetics during 24 h of insulin withdrawal to determine: 1) if abnormalities of the neurohypophysial-renal axis contribute to the dehydration of uncontrolled diabetes mellitus; and 2) the factors causing elevated levels of vasopressin in diabetic ketoacidosis. During the 24 h period of insulin withdrawal, blood glucose rose from 6.7 +/- 1.0 to 20.7 +/- 2.4 mmol/l, whereas plasma vasopressin was 3.6 +/- 0.5 pg/ml initially and in four patients showed little change. Markedly elevated levels of plasma vasopressin (17.8, 19.8 and 26.6 pg/ml) were observed in three patients following the onset of hypovolaemia, nausea and/or vomiting which are known to stimulate vasopressin release. Free water clearance was negative throughout the study in all patients. Thirst was not noted despite marked hyperglycaemia (16.9 +/- 2.5 mmol/l) until a significant fall in body weight of 0.9 +/- 0.2 kg had occurred (p less than 0.005). We concluded that marked elevation of vasopressin results from non-osmotic stimulation and that the mechanisms of body water conservation are overridden by the glycosuric diuresis.

Adult

Vasopressin function in hypercalcaemia.

Vasopressin function and thirst were studied in fourteen hypercalcaemic patients (ten hyperparathyroid and four disseminated malignant disease). Ten patients had decreased renal concentrating ability which reversed within a few days in the majority of patients whose hypercalcaemia was corrected by parathyroidectomy. Although eight patients complained of thirst, none showed a lowered threshold of thirst appreciation during hypertonic saline infusion. Osmoregulation of vasopressin secretion was not reduced in any patient, but the hyperparathyroid group had an exaggerated vasopressin response to osmotic stimulation. We conclude that a partial, reversible nephrogenic diabetes insipidus occurs in at least 70% of hypercalcaemic patients irrespective of cause, which accounts for the polyuria induced by hypercalcaemia.

Adult

Inhibition of vasopressin release in man by an opiate peptide.

The opiate control of vasopressin secretion in man was investigated with a long-acting analogue of met-enkephalin, DAMME (FK33-824, Sandoz). Infusion of 1 mg DAMME into water-deprived volunteers produced a diuresis which was attenuated by naloxone; there was no change in water excretion when subjects were hydrated. Plasma-immunoreactive-vasopressin failed to rise after DAMME administration, despite osmotic stimulation with hypertonic saline infusion. Opiates appear to be involved in mechanisms which suppress the osmotically mediated release of vasopressin, while opiate involvement in baroceptor-mediated release may be quite different.

Adolescent