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Oral magnesium (Mg) supplementation can improve insulin sensitivity and secretion in patients with Type 2 diabetes mellitus (DM). We studied the effect of Mg supplementation on glycaemic control, blood pressure, and plasma lipids in insulin-requiring patients with Type 2 DM. Fifty moderately controlled patients were randomized to 15 mmol Mg or placebo daily for 3 months. Plasma Mg, glucose, HbA1c, lipids, erythrocyte Mg, Mg and glucose concentrations in 24-h urine, and systolic and diastolic pressure were measured before and after 3 months treatment. Plasma Mg concentration was higher after supplementation than after placebo (0.82 +/- 0.07 vs 0.78 +/- 0.08 mmol l(-1), p < 0.05), as was Mg excretion (5.5 +/- 1.9 vs 3.7 +/- 1.4 mmol 24 h(-1), p = 0.004) but erythrocyte Mg concentrations were similar. No significant differences were found in glycaemic control (glucose: 10.7 +/- 3.8 vs 11.6 +/- 6.2 mmol l(-1), p = 0.8; HbA1c: 8.9 +/- 1.6 vs 9.1 +/- 1.2%, p = 0.8), lipids or blood pressure. On-treatment analysis (34 patients: 18 on Mg, 16 on placebo) yielded similar results. An increase in plasma Mg concentration irrespective of medication was associated with a tendency to a decrease in diastolic pressure (increased plasma Mg vs no increase: -4.0 +/- 10.1 vs +2.5 +/- 12.0 mmHg, p = 0.059). Three months' oral Mg supplementation of insulin-requiring patients with Type 2 DM increased plasma Mg concentration and urinary Mg excretion but had no effect on glycaemic control or plasma lipid concentrations.

To investigate whether sodium fluoride (NaF) is able to prevent bone loss in patients treated with corticosteroids (Cs), we performed a randomized double-masked, placebo-controlled trial with 44 Cs-treated patients without established osteoporosis, defined as the absence of previous peripheral fractures and vertebral deformities on radiographs. The effects of NaF (25 mg twice daily) and placebo on the bone mineral density (BMD) of the lumbar spine and hips were compared at baseline and at 6, 12, 18 and 24 months. After 2 years, the BMD of the lumbar spine had decreased in the placebo group by 3.0% (95% CI: -4.9% to -1.0%; p < 0.01); in the NaF group there was a statistically insignificant increase in BMD of 2.2% (95% CI: -0.8% to +5.3%). The difference in the changes in BMD between the two groups was +5.2% (95% CI: +1.8% to +8.6%; p < 0.01). In the hips, BMD had decreased after 2 years in both groups: in the placebo group by -3.0% (95% CI: -5.0% to -1.0%; p < 0.05) and in the NaF group by 3.8% (95% CI: -6.1% to -1.5%; p < 0.01). The difference in the changes in BMD between the two groups was not significant: +0.8% (95% CI: -2.1% to +3.8%). Three vertebral deformities were observed in the placebo group and one in the NaF group (insignificant difference), while no peripheral fractures occurred during the study period. It is concluded that in Cs-treated patients without established osteoporosis NaF prevents bone loss in the lumbar spine but does not have a positive effect on the BMD of the hips

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

We studied the effects of a single dose (100 mg orally) and repeated administration (100 mg o.d. for 7 days) of FK453, a novel adenosine-1 receptor antagonist, on renal sodium handling and blood pressure in eight patients with essential hypertension. Within 60 minutes after administration of FK453, sodium excretion increased threefold. This occurred in the absence of a change in renal hemodynamics, assessed from inulin and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by increased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery term and a decrease in the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not occur until about 3 hours after ingestion, that is, when the natriuresis was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied by some net sodium retention. Blood pressure on the seventh day before FK453 treatment was not different from blood pressure before administration of the first dose of FK453. Again an acute natriuretic response followed, although less than after the first dose. Changes in intrarenal sodium handling parameters, blood pressure, and heart rate were similar to those seen after the first dose. The natriuretic and hypotensive effects of FK453 indicate that adenosine-1 receptor activity plays a role in the regulation of blood pressure and renal sodium handling in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Background. Dyslipidemia is found in the majority of renal and cardiac transplant recipients. Although 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors significantly lower low-density lipoprotein cholesterol (LDL-C) levels, such treatment has been associated with muscle toxicity, especially when used in combination with cyclosporine (CsA). We investigated the efficacy and muscle safety of fluvastatin, a new 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, in CsA-treated transplant recipients. Methods. The efficacy was determined by measuring the lipid profile before and after 8 weeks of fluvastatin therapy. As parameter for possible muscle damage, the rise in serum levels of the muscle proteins creatine kinase and myoglobin was measured after an exercise provocation test (30 min on a bicycle ergometer at 60% of their maximal work load) before and during fluvastatin therapy. Nineteen CsA-treated renal and cardiac transplant recipients with hypercholesterolemia were selected. Results. After 8 weeks of treatment with a dose of fluvastatin necessary to reduce LDL-C below 3.5 mmol/L (20 mg for 3 and 40 mg for 16 patients), total cholesterol was lowered by 20% and LDL-C by 30%, and HDL 2 -C was increased by 35% (all P

OBJECTIVE—To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids. PATIENTS AND METHODS—47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months. RESULTS—After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p

Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.OBJECTIVE: Patients with familial combined hyperlipidemia (FCH) have an increased cardiovascular mortality despite only moderate elevations of LDL-cholesterol. Since endothelial NO release is intimately involved in the anti-atherosclerotic effects of the endothelium, we studied the effect of short-term lipid-lowering therapy on NO-mediated vasodilatation in patients with FCH. In view of only moderate LDL elevations, we evaluated whether alterations in other lipid fractions upon therapy correlated to changes in NO-mediated vasodilatation. METHODS: NO activity was assessed by serotonin-induced, nitric oxide-mediated increase in forearm blood flow (FBF). Measurements were performed 2 weeks off and 4 weeks on lipid-lowering therapy in 12 FCH patients using forearm venous occlusion plethysmography. Control experiments were performed in 12 healthy subjects. RESULTS: Serotonin-induced vasodilatation was impaired in FCH patients (FBF (unit ml/100 ml forearm tissue/min) from 3.0 (0.3) to 4.8 (0.4)) compared to controls (FBF from 2.9 (0.3) to 6.5 (0.6); p < 0.05 vs. FCH). FBF response to serotonin improved significantly upon lipid-lowering therapy (from 3.0 (0.3) to 5.7 (0.5); p < 0.05 treated vs. untreated). The level of improvement in endothelial function was significantly correlated to the absolute reduction of intermediate density lipoproteins upon lipid-lowering therapy (r = -0.64; p < 0.05), whereas it did not correlate to changes in VLDL- or LDL-cholesterol, nor to Lp(a). CONCLUSION: Patients with familial combined hyperlipidemia have impaired NO-mediated vasodilatation, that responds rapidly to lipid lowering medication, and may be related to changes in intermediate density lipoproteins.Publication Types: Clinical Trial

The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption.

Hyperglycaemia in diabetes mellitus is responsible for the process of non-enzymatic glycosylation of different proteins. Since we did not find elevated glycated apolipoprotein B levels in diabetic patients, an altered glycated apolipoprotein B metabolism was suspected in diabetic patients. Experiments in normal rabbits showed that non-reductive (in vitro) glycated low density lipoprotein (gly-LDL) was cleared at a slower rate than control LDL and thus stayed longer in the circulation (vascular mean residence time: 10 vs 8 h, p less than 0.001). The body mean residence time for gly-LDL was 22 h vs 17 h for control LDL. In diabetic animals the catabolic parameters of both LDL preparations changed towards a faster clearance, the effect being greatest for gly-LDL (total mean residence times of gly-LDL pre-diabetic: 19 h, diabetic: 16 h; control LDL pre-diabetic and diabetic: 14 h). The difference in clearance between glycated and control LDL was thus strongly reduced. Virtually no antibody complexed to gly-LDL could be measured. The results suggest an increased activity of the non-receptor mediated pathway in diabetes mellitus, possibly co-responsible for an increased atherosclerotic risk.

We present the oxalate excretion in two studies before and after intravenous infusion of diuretics in healthy subjects. One study was performed in 7 male subjects. An intravenous injection of 1 mg bumetanide was given, followed by intravenous infusion at a rate of 0.5 mg/h. A similar study was performed in 5 male subjects, who received an intravenous injection of 500 mg acetazolamide, followed by intravenous infusion at a rate of 250 mg/h. Urinary oxalate was measured by an enzymatic method

The C-peptide increase after an oral glucose tolerance test (OGTT) and intravenous glucagon test (GT) was assessed to establish actual insulin dependency in 16 obese diabetic patients treated with insulin for years. The results, compared to five reference groups, showed two types of reaction: first, a negative response in 3 patients with a minimal C-peptide increase after either stimulation (range 0–0.1 ng/ml during GT, 0–0.5 during OGTT), not different from that in the insulin-dependent reference group (GT: 0.1 ± 0.2, OGTT: 0.1 ± 0.3. x¯ ± SD). Second, a positive response in 13 patients with a C-peptide increase, different from that in the insulin-dependent group after glucagon (range 0.7–5.6), and in 6 patients after OGTT (range 0.8–1.8). When insulin treatment was discontinued in two nonresponders, the B-hydroxybutyrate levels and ketobutyrate levels increased to over 2.1 and 0.60 mmol/L within 10 days, proving insulin dependency, and thus type I diabetes. B-hydroxybutyrate and ketobutyrate levels increased to maximal 0.4 and 0.17 after stopping insulin therapy in nine positive responders. No ketoacidosis developed during a 4-wk follow-up, indicating non-insulin dependency (type II diabetes). Measuring C-peptide after glucagon is a simple test that may be a discriminative method to establish insulin dependency in obese diabetic patients treated with insulin.

BACKGROUND Control of renal hemodynamics by the arterial baroreflex has never been proved in humans. Apart from the physiological viewpoint, this issue is relevant because altered baroreflex function has been implicated in the pathogenesis of human hypertension. METHODS AND RESULTS Renal function studies were performed in seated healthy volunteers (n = 12; age range, 20 to 34 years) during sustained neck suction at -60 mm Hg, aiming to selectively activate the carotid sinus arterial baroreceptors. Two protocols were followed. One group of 6 volunteers taking a 20 mmol/d sodium diet underwent 90 minutes of neck suction. Compared with a time-control study, neck suction decreased arterial pressure and heart rate; increased glomerular filtration rate (inulin clearance) from 104 +/- 6 to 114 +/- 8 mL/min (P < .01), renal plasma flow (para-aminohippurate clearance) from 616 +/- 52 to 665 +/- 42 mL/min (P < .01), and renal blood flow (from 1120 +/- 95 to 1209 +/- 77 mL/min, P < .01); and decreased renal vascular resistance (from 86 +/- 8 to 76 +/- 6 mm Hg.min.L-1, P < .01). Neck suction had no effect on plasma renin activity, aldosterone, atrial natriuretic peptide, catecholamines, and renal sodium excretion. The other 6 volunteers took a normal sodium diet and underwent sustained neck suction for 60 minutes. In this group, no effects on renal hemodynamics could be discerned, despite a modest decrease in blood pressure and heart rate. CONCLUSIONS These data show, for the first time, that the arterial baroreflex is involved in the control of renal hemodynamics in humans. However, basal arterial baroreflex control of renal hemodynamics is probably low, and arterial baroreflex activation with subsequent renal vasorelaxation may be found only in conditions in which basal arterial baroreflex control of kidney function is significant, as is presumably the case in seated sodium-restricted subjects.

Unexpected uptake of 99mTc-phosphate by a neuroblastoma in a 36-year-old woman is described. Awareness of this phenomenon can be helpful in establishing the diagnosis.