Calibration of a wearable glucose sensor.

Calibration of glucose sensors proved difficult for electrodes with immobilized glucose-oxidase. The correlation between the sensitivity of the electrodes in vitro and in vivo appeared to be poor. We developed a new type of glucose sensor, based on a microdialysis system, in which an oxygen electrode is used as detector outside the body and the enzyme glucose-oxidase dissolved in water is used as a dynamic selector. The enzyme solution is pumped through a hollow fiber placed subcutaneously, before the fluid passes the detector. The glucose sensor was tested in the subcutaneous abdominal tissue of 12 healthy volunteers and 12 type I diabetic patients. Blood glucose was clamped at two levels to permit a two-point calibration of the sensor in vivo. These values correlated well with the in vitro calibration factors (r = 0.949). In subcutaneous tissue the sensor measures 43 +/- 9% of the blood glucose value, using the in vitro calibration factor. No differences were detected between healthy volunteers and diabetic patients.

Elevated cholesteryl ester transfer protein activity in IDDM men who smoke. Possible factor for unfavorable lipoprotein profile.

OBJECTIVES: To determine the effect of cigarette smoking on the activity of cholesteryl ester transfer protein (CETP) and high-density (HDL), low-density (LDL), and very-low-density (VLDL) lipoproteins in insulin-dependent diabetic (IDDM) men with microvascular complications. RESEARCH DESIGN AND METHODS: We performed a case-control study in a referral-based diabetes clinic on a sequential sample of 9 cigarette-smoking and 12 nonsmoking IDDM men with microvascular complications and 12 nonsmoking control men. CETP activity was determined in each serum with an isotope assay with exogenous cholesteryl ester-labeled LDL and HDL. The method is independent of the endogenous lipoprotein present in serum. RESULTS: The HDL-cholesterol (VLDL and LDL) ratio was lower in the smoking diabetic men than in the other groups (P less than 0.05 vs. the nonsmoking diabetic men and P less than 0.01 vs. the control subjects). CETP activity was 70% higher in the smoking diabetic men than in the control subjects (P less than 0.01) and 30% higher than in the nonsmoking diabetic men (P less than 0.05). The HDL-cholesterol (VLDL and LDL) ratio and the apolipoprotein A-I-B ratio were inversely correlated to CETP activity in the diabetic patients (r = -0.52, P less than 0.02 and r = -0.45, P less than 0.05, respectively). CONCLUSIONS: CETP activity is increased in cigarette-smoking IDDM men with microvascular complications. High CETP activity may contribute to the unfavorable lipoprotein profile in these patients.

Development of a wearable glucose sensor; studies in healthy volunteers and in diabetic patients.

A glucose sensor with a subcutaneous dialysis system was tested in six healthy volunteers during an oral glucose tolerance test and in ten diabetic patients with hyperglycemia during rapid decline of blood glucose levels. There was a good correlation between sensor and blood glucose values. During oral glucose tolerance tests in the volunteers, there was a mean delay of 4.4 minutes in the rise of the value registered subcutaneously and of 8.2 minutes in the fall of the curves. In the diabetic patients the maximum delay was 22 minutes. Nine days after insertion of the dialysis system it was still functioning well.

PET studies with L-[1-11C]tyrosine, L-[methyl-11C]methionine and 18F-fluorodeoxyglucose in prolactinomas in relation to bromocryptine treatment.

Aspects of metabolism in prolactinomas were investigated by positron emission tomography using L-[1-11C]tyrosine, L-[methyl-11C]methionine and 18F-fluorodeoxyglucose (18FDG). Using L-[1-11C]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocriptine. At 18 h after bromocriptine intervention, L-[1-11C]tyrosine uptake into tumour was reduced with 28% (P less than 0.07). A correlation analysis of the bromocriptine-induced decrease in L-[1-11C]tyrosine uptake and the reduction of serum prolactin levels indicated that the action of bromocriptine on prolactin synthesis and prolactin release is not coupled. In the untreated situation, the four patients were investigated with 18FDG as well, but the prolactinomas could not be visualized. Three untreated patients were studied with L-[methyl-11C]methionine. The tumour-imaging potential of L-[methyl-11C]methionine and L-[1-11C]tyrosine appeared to be nearly equivalent for prolactinomas. Unlike prolactinoma tissue, the salivary glands showed a pronounced preference for L-[1-11C]tyrosine as compared to L-[methyl-11C]methionine. L-[1-11C]tyrosine is a valuable tool to obtain information on the metabolism and treatment of prolactinomas.

The activity of cholesteryl ester transfer protein is decreased in hypothyroidism: a possible contribution to alterations in high-density lipoproteins.

The activity of cholesteryl ester transfer protein is instrumental in the distribution of cholesteryl ester between lipoproteins in plasma. We measured the activity of cholesteryl ester transfer protein in plasma, designated cholesteryl ester transfer activity, as the rate of cholesteryl ester transfer between exogenous radiolabelled low-density and high-density lipoproteins. The effect of hypothyroidism on cholesteryl ester transfer activity was investigated in 13 athyreotic patients who were studied in the hypothyroid condition and in the euthyroid state, after they had received triiodothyronine supplementation for 33 to 67 days. During hypothyroidism plasma total cholesterol, very-low- plus low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, plasma triacylglycerol, apolipoprotein A1 and B were significantly higher than in the euthyroid state. Cholesteryl ester transfer activity was 15% lower during hypothyroidism (P less than 0.02), and an effect of treatment duration was observed. The changes in high-density lipoprotein total cholesterol (P less than 0.02), free cholesterol (P less than 0.001), triacylglycerol (P less than 0.05) and the free cholesterol/cholesteryl ester molar ratio in high-density lipoproteins (P less than 0.01) were inversely-related to the changes in cholesteryl ester transfer activity. We concluded that thyroid hormone is involved in the regulation of cholesteryl ester transfer protein activity, and that cholesteryl ester transfer protein activity may play a role in the alterations in high-density lipoprotein lipids observed in hypothyroidism.

Paternity in idiopathic hypothalamic hypogonadism during testosterone therapy in two unrelated patients.

When fertility is desired, idiopathic hypothalamic hypogonadism is amenable to treatment with pulsatile low dosage GnRH administration or injections of gonadotrophins. Patients with this disorder are hypogonadal and require therapy with androgens or oestrogens/progestagens. This would presumably lower pituitary gonadotrophin production even further. However, fertility occurring spontaneously during testosterone substitution, as proven by paternity testing, has been described twice. The present report adds two more cases. It is unwise to make a definite statement about infertility in male patients with this condition.

Renal haemodynamic changes in response to moderate hyperglycaemia in type 1 (insulin-dependent) diabetes mellitus.

The prevailing blood-glucose level has been found to influence renal haemodynamics in type 1 (insulin-dependent) diabetes mellitus. In a group of 48 type 1 diabetic patients with normal serum creatinine (less than 120 mumol l-1) and without persistent proteinuria, no relationship was present between blood glucose, corrected to near normoglycaemia (6.8 [6.2 to 7.3] mmol l-1 (median [95% confidence interval]), and glomerular filtration rate (GFR), effective renal plasma flow (ERPF) determined with 125I-iothalamate and 131I-hippuran respectively. GFR tended to increase (2 [-1 to +4] ml min-1 1.73 m-2, 0.05 less than P less than 0.10) and ERPF did not change after a blood glucose rise of 7.9 (7.0 to 8.9) mmol l-1, achieved by an intravenous glucose load in 31 patients. The individual changes in GFR and ERPF were correlated (r = 0.60, P less than 0.005). The changes in GFR were inversely related to baseline blood glucose (r = -0.45, P less than 0.02), but not to baseline GFR. GFR increased (3.5 [0 to +12] ml min-1 1.73 m-2, P less than 0.01) if baseline blood glucose was less than or equal to 6.8 mmol l-1 (n = 16) but ERPF did not. Achievement of near normoglycaemia before measurement of kidney function in type 1 diabetes appears to reduce the influence of variation in glycaemia on renal haemodynamics and thus would improve comparison between and within individuals. Moderate hyperglycaemia can cause a small rise in the glomerular filtration rate.

Hypogonadism in untreated male normoprolactinaemic acromegalics.

Hypogonadism is a distinct feature of acromegaly, even in the absence of hyperprolactinaemia. In 10 untreated male acromegalics, aged 24 to 46 yr, without evidence of any other disturbance of anterior pituitary function, low testosterone values were found in the presence of a normal reaction of pituitary gonadotrophins following GnRH administration. In three patients, one injection of 5000 IU hCG resulted in a sharp rise in testosterone. Although we were unable to elicit a similar reaction pattern of the GnRH-gonadotrophins-testosterone axis following administration of biosynthetic methionyl-hGH, it is suggested that suppression of testicular function in untreated acromegaly without other endocrine disturbances may be partly caused by increased somatostatin production.

Incomplete virilization and subclinical mineralocorticoid excess in a boy with partial 17,20-desmolase/17 alpha-hydroxylase deficiency.

A 17-year-old boy is described with impaired virilization and subclinical mineralocorticoid excess owing to combined 17,20-desmolase/17 alpha-hydroxylase deficiency. His basal plasma progesterone was 20.9 nmol/l (reference value 0.50-1.88), 17-hydroxyprogesterone 21.3 nmol/l (reference value 3.05-4.84), testosterone 6.85 nmol/l (reference value 14.1-22.0), and his excretion of tetrahydro-11-deoxycorticosterone 11.8 mumol/24 h (reference value 1.0-1.5). The differential effects of this combined enzyme deficiency on adrenal and testicular function were studied by ACTH stimulation, dexamethasone suppression, hCG stimulation, and suppression treatment with testosterone.

Alpha- and gamma-tocopherol in plasma, red blood cells, and platelets during plasma exchange.

The effect of a rapid reduction of plasma lipoproteins on the alpha- and gamma-tocopherol levels in plasma, erythrocytes, and platelets was studied. Sixteen successive plasma exchange procedures performed weekly in an adult with heterozygous familial hypercholesterolemia were evaluated. Plasma exchange was done by intermittent flow centrifugation, exchanging one plasma volume against a 4% human albumin solution. Plasma exchange reduced in plasma alpha-tocopherol from 41.5 +/- 8.9 to 23.6 +/- 4.8 mumol/L and gamma-tocopherol from 4.9 +/- 4.1 to 2.4 +/- 2.1 mumol/L, without changing their ratios to total lipids. It diminished alpha-tocopherol in platelets from 12.97 +/- 4.37 to 10.03 +/- 1.78 mumol/10(13) cells and gamma-tocopherol from 1.43 +/- 0.55 to 1.06 +/- 0.41 mumol/10(13) cells, but did not affect erythrocyte tocopherols. The total amount removed per procedure was 47.57 +/- 13.65 mumol for alpha-tocopherol and 4.70 +/- 3.59 mumol for gamma-tocopherol. Plasma exchange increased the number of erythrocytes from 3.67 +/- 0.10.10(12) to 4.05 +/- 0.13.10(12) cells/L, without affecting their volume. Platelet count did not change, but mean platelet volume decreased from 7.7 +/- 0.5 to 6.9 +/- 0.5 fl and platelet distribution width from 15.1 +/- 0.4 to 14.9 +/- 0.5. Thus, plasma exchange reduces plasma alpha- and gamma-tocopherol to the same extent as total lipids, and decreases these tocopherols in circulating platelets, along with a reduction in platelet size and, compared to the change in erythrocyte count, a fall of platelet number.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in serum lipids and apolipoproteins in male type 1 (insulin-dependent) diabetic patients with microalbuminuria.

The relationships between serum lipid, apolipoprotein levels and urinary albumin excretion were investigated in 20 male Type 1 (insulin-dependent) diabetic patients with microalbuminuria (overnight urinary albumin excretion between 10 and 200 micrograms/min), in 18 male Type 1 diabetic patients without microalbuminuria and in 18 male control subjects. In the microalbuminuric patients low density lipoprotein cholesterol was higher than in the control subjects (p less than 0.05); the high density lipoprotein/low density lipoprotein cholesterol ratio was lower than in the normalbuminuric diabetic patients (p less than 0.05), and in the control subjects (p less than 0.01); apolipo-protein B was higher than in the normalbuminuric patients (p less than 0.05); the apolipoprotein A1/B ratio was lower than in the normoalbuminuric diabetic patients (p less than 0.05). Serum triglyceride was higher in the microalbuminuric diabetic patients and in the control subjects than in the normalbuminuric diabetic patients (p less than 0.05, for both), but was not different between the microalbuminuric diabetic patients and the control subjects. No significant differnces between the 3 groups were present with respect to serum cholesterol, high density lipo-protein cholesterol and apolipoprotein A1. In the 2 combined Type 1 diabetic groups there were significant correlations between urinary albumin excretion and the high density lipoprotein/low density lipoprotein cholesterol ratio (R -0.40, p less than 0.02), apolipoprotein B (R 0.35, p less than 0.05) and the apolipoprotein A1/B ratio (R -0.44, p les than 0.01). These results indicate microalbuminuria related differences in lipid and apolipoprotein levels in male Type 1 diabetic patients, which may contribute to an increased risk of cardiovascular disease.

Invasive fibrous thyroiditis (Riedel's struma): a manifestation of multifocal fibrosclerosis? A case report with review of the literature.

A patient is described with Riedel's thyroiditis and invasive fibrous growth in parathyroid, lacrimal glands, and retroperitoneally. It is proposed that Riedel's thyroiditis is not a disease in its own right but a manifestation of a generalized disease of fibrous tissues.

The usefulness of a sensitive thyrotrophin assay in the fine adjustment of thyroxine therapy following ablation for carcinoma.

The usefulness of FT4 and FT3 measurements as an index of adequate thyroxine treatment in differentiated thyroid cancer was evaluated in 25 athyreotic patients on two occasions with an interval of at least 6 months. The determinations were combined with a TRH test. The TSH measurements were performed using a sensitive immunoassay. The great interindividual differences in absorption and metabolism of thyroxine made the measurements of FT4 and FT3 unsuitable for fine adjustment of thyroxine substitution therapy. When all patients are divided into 4 categories according to their TRH test (1: delta TSH less than or equal to 1 mU/l; 2: greater than or equal to 1 less than or equal to 4 mU/l; 3: greater than 4 mU/l and 4: basal TSH greater than or equal to 6 mU/l), there is a considerable overlap between these categories in relation to FT4 and FT3. In the second TRH test all patients were found to belong to the same category when their thyroxine dose had not been changed. A basal TSH level below 0.30 mU/l suggests nearly complete suppression of TSH secretion. However, a TRH test is necessary to allow a definite conclusion to be drawn. It is argued that complete suppression of TSH is not necessarily desirable in patients with treated thyroid carcinoma. From the results of our study it would seem advisable to use the TRH test once to adjust the thyroxine dose in such a manner that subnormal basal TSH is achieved as in the second category. Once the dosage has been established, a determination of basal TSH suffices in follow-up.

Variability of albumin excretion in diabetes.

The variability of urinary albumin excretion was determined in 3 consecutive overnight urine collections from 152 adult type I diabetic patients (study A) and in two 1-h urine collections from 57 adult type I and type II diabetic patients, obtained at a 10-wk interval (= median, range = 2-30 wk) (study B). In both studies the coefficient of variation (CV) of urinary albumin excretion recorded as urinary albumin concentration (mg/l) was highest (study A: CV 51.1%; study B: CV 61.8%), whereas the CV of the urinary albumin/urinary creatinine ratio (mg/mmol) was lowest (study A: CV 41.9%; study B: CV 50.8%). In study A the CV of urinary albumin excretion rate (microgram/min) (CV 43.5%) did not differ from that of urinary albumin/urinary creatinine ratio. In study B, however, the CV of urinary albumin excretion rate (CV 57.2%) was higher than that of the urinary albumin/urinary creatinine ratio and of fractional albumin clearance (CV 51.0%). The variability of urinary albumin excretion was not related to its magnitude and could not be attributed to variations in plasma glucose, glycosylated haemoglobin or renal tubular glucose reabsorption. This high variability stresses the need to obtain several urine samples before the amount of albumin excreted can be reliably estimated. It is recommended that one does not use urinary albumin concentration but urinary albumin/urinary creatinine ratio or fractional albumin clearance in the assessment of urinary albumin excretion in diabetes management.

Abdominal applications of fast MR imaging: a comparison of fast field echo (FFE) and spin echo (SE) pulse sequences.

Fast gradient echo (GE) MR imaging during breathhold was performed in 73 abdominal MR examinations in order to determine the value of GE technique in the reduction of movement artefacts and improvement of image quality. The results were compared with conventional spin-echo (SE) technique. T1-weighted SE images consistently demonstrated normal anatomy and pathology. T2*-weighted and intermediate GE technique proved to be superior to T2-weighted SE technique in a considerable number of cases providing not only better delineation of normal structures but also better lesion detection. At this stage GE technique should be considered as an adjunct to T1-weighted SE technique. If the artefacts presently inherent to GE imaging could be reduced or compensated for, this technique of rapid MR imaging during suspended respiration could become an important tool being one of the fastest techniques for abdominal MR imaging.

Hydroxycholesterols in serum from hypercholesterolaemic patients with and without bile acid sequestrant therapy.

To assess the effect of bile acid sequestrant therapy on bile acid precursors in plasma, we determined hydroxycholesterols in serum from patients with primary hypercholesterolaemia. Compared with a group of 5 male and 12 female patients without any lipid-lowering drug therapy, which has normal to slightly elevated 7 alpha-hydroxycholesterol, normal 7 beta-hydroxycholesterol and high normal to elevated 26-hydroxycholesterol levels, a group of 5 male and 9 female patients, using colestipol had higher 7 alpha-hydroxycholesterol without overlap, and higher 7 beta-hydroxycholesterol levels, but similar levels of 26-hydroxycholesterol. In the latter group, the ratio between 7 alpha-hydroxycholesterol and total cholesterol in serum was also higher without overlap. Both groups did not differ for age, body weight, body mass index and serum lipid levels. In the group of patients without lipid-lowering drug therapy, 7 alpha-hydroxycholesterol correlated positively with total and low-densitylipoprotein cholesterol, 7 beta-hydroxycholesterol negatively with body weight and body mass index, and 26-hydroxycholesterol positively with body weight. In both groups, 7 alpha-hydroxycholesterol correlated positively with 7 beta-hydroxycholesterol. These results suggest that (1) bile acid sequestrants enhance bile acid synthesis via the 7 alpha-hydroxylation but not via the 26-hydroxylation pathway, (2) serum 7 alpha-hydroxycholesterol level and the ratio between this hydroxycholesterol and total cholesterol in serum might be suitable parameters to check intake of bile acid sequestrants irrespective of dose, and (3) 7 beta-hydroxycholesterol is unlikely to be the result of cholesterol auto-oxidation in vitro.

Increased cholesterylester transfer activity in complicated type 1 (insulin-dependent) diabetes mellitus--its relationship with serum lipids.

In Type 1 (insulin-dependent) diabetes mellitus, macrovascular complications and the increased risk for cardiovascular disease in patients with microvascular complications may be related to alterations in plasma cholesterylester transfer. The activity of cholesterylester transfer protein, which mediates cholesterylester transfer between lipoproteins and lipoprotein lipid levels, was assessed in 7 normolipidaemic control subjects, 7 Type 1 diabetic control subjects without complications, 11 Type 1 diabetic patients with microvascular complications (retinopathy, incipient nephropathy) and in 7 Type 1 diabetic patients with macrovascular atherosclerotic lesions. The cholesterylester transfer activity was 30% higher in the diabetic groups with macrovascular and microvascular lesions than in the 2 control groups. Very low + low density lipoprotein cholesterol was higher in the 3 diabetic groups than in the non-diabetic control group. High density lipoprotein cholesterol was not different. The cholesterylester transfer activity was correlated positively with HbA1, urinary albumin excretion rate, serum cholesterol, very low + low density lipoprotein cholesterol and apolipoprotein B. The high density lipoprotein over very low + low density lipoprotein cholesterylester molar ratio was lower in the diabetic groups with micro- and macrovascular complications. A role for cholesterylester transfer activity in the lipoprotein abnormalities found in complicated Type 1 diabetes is suggested. A high cholesterylester transfer activity might be indicative of mechanisms which promote atherogenesis.