Magnesium deficiency and diabetes mellitus.
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Biomedical subjects
Publications and source records attributed to K Kisters.
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A decrease in total magnesium content is not a direct proof of a decreased magnesium ion concentration. It could reflect a phosphate alteration or an ATP metabolism disorder. Plasma phosphate levels are lower in spontaneously hypertensive rats (SHRs) than in Wistar-Kyoto rats (WKYs), and defects in membrane regulation or mitochondrial ATP synthase occur. Only sparse data exist concerning cellular magnesium and phosphate concentrations in hypertensive cells. In aortic smooth muscle cells from 10 SHRs of the Münster strain and 10 age-matched normotensive WKY rats, the intracellular phosphate and magnesium content was measured by electron probe X-ray microanalysis (Camscan CS 24 apparatus, Cambridge, U.K.). The Mg++ content was 0.09 +/- 0.15 g/kg dry weight in SHRs versus 1.15 +/- 0.10 g/kg dry weight in WKY rats (p < 0.01). Vascular smooth muscle phosphate content was 23.6 +/- 0.79 g/kg dry weight in WKY rats versus 15.81 +/- 1.22 g/kg dry weight in SHRs (p < 0.01). In aortic smooth muscle cells of one month old SHRs intracellular magnesium was measured as 1.05 +/- 0.08 versus 1.09 +/- 0.09 g/kg dry weight in WKYs. Intracellular phosphate concentration in one month old SHRs was 18.71 +/- 2.41 versus 21.36 +/- 1.25 g/kg dry weight in WKYs (eight animals in each group). Aortic smooth muscle cells of SHRs are caracterized by markedly lowered intracellular phosphate and magnesium concentrations, resulting in an altered ATP-metabolism, as described earlier. Possibly a membrane defect or a magnesium deficiency or disturbed magnesium channels are responsible for the early onset in the pathogenesis of primary hypertension.
Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives, our group showed increased calcium and decreased magnesium and an increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4+/-9.8 mmHg) and 13 normotensive rats (NT, systolic blood pressure 118.5+/-7.2 mmHg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron-probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick. The calcium content was 124.7+/-4.5* mmol/kg dry weight in SHR versus 110.3+/-4.1 mmol/kg dry weight in NT (Means+/-SD, p < 0.01), the magnesium content was 35.5+/-3.9* in SHR versus 50.1+/-4.9 mmol/kg dry weight in NT /p < 0.01). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56+/-0.39* versus 2.23+/-0.27, p < 0.01). In hypertensive one month old animals the increase in the calcium/magnesium ratio was not as pronounced as in 9 month old animals. The calcium/magnesium ratio was measured 3.3+/-0.42 in SHR (n = 8) as compared to 2.51+/-0.39 in normotensive animals (n = 8, p < 0.01). Aortic smooth muscle cells from SHR are characterized by markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. The increased calcium/magnesium ratio in hypertensive cells may be a pathogenetic factor for the development of arteriosclerosis and hypertension.
BACKGROUND: Complementary/alternative medicine (CAM) is gaining increasing importance especially in the treatment of patients with breast carcinoma. The purpose of this analysis was to investigate the prevalence of CAM in patients with breast carcinoma, to statistically describe the preparations and therapies used, and to determine the reasons for their use, the source of information and the individual perception. PATIENTS AND METHODS: The statements of 203 patients with breast carcinoma who underwent radiotherapy were analyzed. The median age was 54 years (range 38-77 years). All patients underwent surgery as first therapy. 36 patients received a second-line radiotherapy because of metastases (27 patients) or local recurrence (9 patients). RESULTS: 159 patients (78%) stated to carry out an additional treatment. 31 out of the 36 patients with metastases or local recurrence used CAM. Vitamin preparations (67%), mistletoe therapy (59%), and mineral preparations (33%) were used most frequently. 70% of the patients used a combination of two or more preparations/therapies. The most cited reason for using CAM was the aim of increasing quality of life (28%) and improving the immune system (27%). 72% stated an improvement of their individual perception. The main source of information was the general practitioner or the gynecologist. CONCLUSION: The radiotherapist has to take these complementary/alternative therapies into consideration; their importance should be evaluated in further studies.
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The purpose of this study was to use high-resolution magnetic resonance (HR-MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after renal transplantation and to compare this technique with bone mineral density (BMD) in predicting therapy-induced bone loss and osteoporotic fracture status. HR-MR imaging (voxel size: 0.195 x 0.195 x 1 mm) was performed at 1.5 T with an axial and sagittal orientation in 48 patients after transplantation, 12 patients before renal transplantation and 20 healthy controls. Structure measures analogous to standard histomorphometry and fractal dimension were determined in these images. BMD measurements of the lumbar spine and the proximal femur were obtained in the healthy female controls and the patients. Vertebral and peripheral fracture status were determined in all patients. The structural measures app.BV/TV, Tb.Sp, Tb.Th and Tb.N showed significant differences between controls and patients (p<0.05) while fractal dimension showed no significant differences. Neither the structural measures nor BMD showed significant differences between patients before and after transplantation. Correlations between time after transplantation versus structural measures and BMD were not significant. Differences between fracture and nonfracture patients were significant for the structural measures app.BV/TV, Tb.Sp and Tb.N (axial images) as well as for app.Tb.Th (sagittal images) and spine BMD (p<0.05) but not for hip BMD. Using odds ratios the strongest discriminators between patients with and without fractures were app. BV/TV, app.Tb.Sp (axial images) and app.Tb.Th (sagittal images), even after adjustment for age and BMD. Using receiver operating characteristic analysis the highest diagnostic performance was found for a combination of BMD and structural measures. In conclusion, our results indicate that structural measures obtained from HR-MR images may be used to characterize fracture incidence in kidney transplant patients; the best results, however, are obtained using a combination of BMD and structural measures.
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BACKGROUND: Necrobiotic xanthogranuloma is a largely unknown disease. Both the frequency of this disease and the involvement of internal organs have clearly been underestimated until now. CASE REPORT: A patient was admitted because of ulcerating, xanthomatous, subcutaneous nodules, scleritis and conjunctivitis. Laboratory studies revealed an elevated erythrocyte sedimentation rate, a monoclonal IgG-lambda protein, a pancytopenia and later a hypocomplementemia. Furthermore, a hepatosplenomegaly and esophageal varices were found. A skin biopsy specimen showed a granulomatous infiltrate consisting of lymphocytes, histiocytes, plasma cells, foam cells as well as Touton and bizarre-appearing foreign-body giant cells and cholesterol clefts typical of necrobiotic xanthogranuloma besides a deposit of amyloid. A liver biopsy sample disclosed an amyloidosis of the parenchyma, too. Neither a therapy with chlorambucil and prednisolone nor with interferon alpha-2a resulted in improvement. CONCLUSION: Apart from treatment of skin lesions and ophthalmic manifestations further investigations are necessary because necrobiotic xanthogranuloma can be associated with malignancy and can involve internal viscera like lungs, heart and liver.
We report the case of a 42-year-old male who was admitted to our hospital after an acute hypertensive crisis despite four-way anti-hypertensive therapy. The renal scintigraphy, the excretory urogram and the biochemical profile performed two years before were unremarkable, except for slightly elevated serum creatinine and plasma aldosterone, in presence of normal aldosterone/renin ratio. The renal arterial angiography that was performed despite a second unremarkable scintigraphy revealed high-grade bilateral arterial stenosis in the presence of multiple renal arteries. Following dilatation of the left stenosis, the aldosterone/renin ratio was pathologic. Recumbent and orthostatic aldosterone values were 830 pg/ml and 1824 pg/ml, respectively, and recumbent and orthostatic renin values were 0.82 and 1.21 ng angiotensin I/ml/h, respectively. The abdominal computed tomography performed to investigate a possible concomitant Conn's syndrome resulted in the detection of a left adrenal tumor. After resection of the lesion, plasma-aldosterone levels normalized and a pronounced rise in serum potassium levels was observed. Following angioplasty of the right renal artery stenosis, blood pressure could easily be managed with combined beta and calcium channel blocker therapy. Particularly in cases of bilateral (but also in the presence of unilateral) renal artery stenosis in association with Conn's syndrome, all the available screening methods for these disorders can fail. In cases of poor response to combination hypertensive therapies, renal arteriography and a fludrocortisone-suppression test should be performed in order to rule out both renal arterial stenosis and Conn's syndrome, even in the absence of clinical and biochemical findings suspicious for either disorder.
A cellular calcium-magnesium antagonism seems to be involved in the pathogenesis of primary hypertension. Total plasma, intracellular, and membranous calcium (Ca) and magnesium (Mg) contents were determined in 39 untreated patients with essential hypertension (EH) and 40 normotensive healthy subjects (NT). Membranous and intracellular measurements were performed in erythrocytes. Ca and Mg contents were measured by atomic absorption spectroscopy and membrane protein was determined according to Bradford's method as a membranous reference. There was no significant difference in plasma Ca (NT: 2.60 +/- 0.15 v EH: 2.64 +/- 0.17 mmol/L) and Mg concentrations (NT: 0.83 +/- 0.12 v EH: 0.87 +/- 0.14 mmol/L) in the studied groups. Intracellular Mg (NT: 1.72 +/- 0.15 mmol/L v EH: 1.64 +/- 0.19 mmol/L) and Ca (NT: 2.06 +/- 0.20 mmol/L v EH: 2.10 +/- 0.24 mmol/L) contents were also not significantly different between groups. Membrane Ca content was significantly increased in the EH group (2.23 +/- 0.32 micromol/g membranous protein) compared to controls (1.05 +/- 0.30 micromol/g membranous protein, P < .01). On the contrary, membranous Mg content was significantly decreased compared to controls (0.31 +/- 0.09 v 0.50 +/- 0.10 mmol/g membranous protein content, P < .01). The Ca/Mg ratio in membranes was significantly increased in EH as compared to healthy subjects (P < .01) and correlated to mean arterial blood pressure values (r = 0.47, P < .01). We conclude that the membranous alterations of Ca and Mg metabolism, shown by increased Ca/Mg ratio in red cell membranes of hypertensive subjects, may play a role in the pathogenesis of primary hypertension.
BACKGROUND: Disturbance in calcium metabolism has been suggested in the pathogenesis of hypertension, however, membrane calcium content in humans has not been studied in detail yet in primary hypertension. We compared plasma, intracellular and membrane calcium concentrations in erythrocytes of patients with essential hypertension and in healthy, normotensive control subjects to determine a possible alteration of membrane calcium in primary hypertension. SUBJECTS AND METHODS: Thirty-four never treated patients with essential hypertension were included and 34 healthy, age- and sex-matched volunteers served as controls. Atomic absorption spectroscopy was used for measurement of intracellular and membrane calcium content in erythrocytes and plasmalemmal preparations. RESULTS: Plasma and intracellular Ca(++) concentrations were not significantly different between hypertensives and controls (plasma: 2.59 +/- 0.18 vs2.50 +/- 0.16 mmol/l, intracellular: 1.89 +/- 0.20 mmol/l vs 1.97 +/- 0.24 mmol/l, NS resp., mean +/- s.e.m.). However, membrane calcium content was significantly higher in hypertensive patients compared to control subjects (2.38 +/- 0.28 micromol/g membraneous protein vs0.86 +/- 0.32 micromol/g membrane protein, P < 0.01). Membrane calcium content was correlated to mean arterial blood pressure (r = 0.59, P < 0.01). CONCLUSION: Membrane calcium content is significantly increased in patients with untreated primary hypertension and correlates to blood pressure levels. This data suggest, that an membrane mechanism may contribute to alterations in calcium metabolism and to the pathogenesis of primary hypertension.
BACKGROUND: Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on brachial artery flow-mediated vasodilation (FMD) and DC in hypercholesterolemic NTX. METHODS: Eighteen NTX received FLU 40 mg/day and 18 NTX placebo (PLA). Before and after six months of treatment, the brachial artery diameter and DC at rest were measured by a Doppler frequency analysis in the M mode, and then changes in diameter during reactive hyperemia (to assess endothelial-dependent FMD) and after 400 microg sublingual nitroglycerin (to assess endothelium-independent vasodilation-NMD). RESULTS: FLU, but not PLA, treatment resulted in significant decreases in total (from 288 +/- 10 to 239 +/- 8 mg/dL, P < 0.05) and low-density lipoprotein cholesterol (from 182 +/- 779 to 138 +/- 8 mg/dL, P < 0.05). Blood pressure did not differ between FLU- and PLA-treated patients and was not affected by either treatment. Also, the brachial artery baseline diameter was not different between groups and was not affected by FLU or PLA. Brachial artery flow at rest and during reactive hyperemia as measured by pulsed Doppler did not differ between groups. Brachial artery FMD increased with FLU from 0.23 +/- 0.08 to 0.54 +/- 0.08 mm (P < 0.05), whereas PLA did not alter FMD (0.22 +/- 0.07 vs. 0.14 +/- 0.05 mm at baseline and after six months of PLA treatment, respectively, P = NS). In contrast, NMD did not change significantly with either treatment (0.76 +/- 0.13 vs. 0.83 +/- 0.15 mm at baseline and after 6 months of FLU treatment, respectively, P = NS, and 0.64 +/- 0.09 vs. 0.66 +/- 0.10 mm at baseline and after 6 months of PLA treatment, respectively, P = NS). Also, brachial artery DC was not altered by FLU (6.4 +/- 1.0 vs. 5.8 +/- 0.6 x 10-3/kPa, P = NS) or PLA treatment (5.8 +/- 0.6 vs. 6.8 +/- 0.8 x 10-3/kPa, P = NS). CONCLUSIONS: In hypercholesterolemic NTX, the HMG-CoA reductase inhibitor FLU significantly improves brachial artery FMD as a measure of endothelial function after six months of treatment. In contrast, FLU does not have a beneficial effect on brachial artery DC.
BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.
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PURPOSE: To assess the renal tolerance of 1.0 mol/L gadobutrol as an electrically neutral contrast agent at magnetic resonance (MR) imaging in patients with impaired renal function. MATERIALS AND METHODS: Twenty-one patients with impaired renal function were enrolled in this prospective randomized study and classified into two subgroups according to their creatinine clearance: group 1 (n = 12), less than 80 mL/min (<1.33 mL/sec) and greater than 30 mL/min (>0.50 mL/sec); group 2 (n = 9), less than 30 mL/min (<0.50 mL/sec) and not requiring dialysis. Gadobutrol (1.0 mol/L) was injected intravenously at randomly assigned doses of either 0.1 or 0.3 mmol per kilogram of body weight. Changes in vital signs, clinical chemistry, and urinalysis results, including creatinine clearance, were monitored before, at 6 hours, and then every 24 hours until 72 hours (group 1) or 120 hours (group 2) after intravenous injection of gadobutrol. Hematologic results were checked every other day. RESULTS: No serious adverse event occurred, and no clinically relevant changes in vital signs, hematologic results, clinical chemistry, or urinalysis results were detected in the observation period. Markers for glomerular filtration (creatinine, cystatin C, beta2-microglobulin, creatinine clearance) and tubular function (N-acetyl-beta-D-glucosaminidase, alpha1-microglobulin) were unaffected by gadobutrol in both groups. CONCLUSION: Gadobutrol did not affect renal function and, therefore, proved to be a safe MR contrast agent in patients with impaired renal function. Even in patients with marginal excretory function (creatinine clearance, <30 mL/min [<0.50 mL/sec]), prehydration or treatment with diuretics or hemodialysis are not required after the administration of gadobutrol.
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AIMS: There is evidence that secondary hyperparathyroidism alters arterial vessel wall properties. However, it is unclear whether effects of parathyroid hormone (PTH) on the vascular wall are direct or permissive and related to hypertension and renal failure. To assess early direct effects of PTH on large artery wall properties isobaric distensibility (DC), pulse wave velocity (PWV) and intima-media thickness (IMT) were studied before and after parathyroidectomy (Ptx) in patients with primary hyperparathyroidism (pHPT). METHODS: DC and IMT of the brachial and carotid artery were measured by echo-tracking and tonometry, PWV by the automatic Complior-device at baseline and 6 months after Ptx in 20 patients with pHPT (data mean +/- SEM, age 45+/-5 years, PTH 240+/-61 ng/l). Cardiovascular risk factors like diabetes, hypertension, renal insufficiency and hypercholesterolemia were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. RESULTS: Six months after Ptx, PTH decreased to normal; however, blood pressure levels and vessel wall parameter remained unchanged. At baseline, there were no significant differences in brachial and carotid IMT (0.48+/-0.04 and 0.62+/-0.04 mm vs. 0.47+/-0.06 and 0.61+/-0.06 mm), radial and aortic PWV (9.1+/-0.4 and 9.9+/-0.7 m/s vs. 9.2+/-0.5 and 10.0+/-0.6 m/s), brachial and isobaric carotid DC (10.1+/-1.4 and 19.5+/-3.4 10(-3)/kPa vs. 9.1+/-0.9 and 20.4+/-3.2 10(-3)/kPa) or artery diameter between patients and controls. CONCLUSIONS: Structural and viscoelastic properties of large arteries are not disturbed and not influenced by parathyroidectomy in patients with early pHPT devoid of hypertension and renal disease. We conclude that increased PTH levels per se are not associated with alterations of mechanical arteriall wall properties; permissive factors like renal insufficiency may be necessary to mediate vessel wall alterations in patients with hyperparathyroidism.
Familial hypomagnesemia-hypercalciuria with nephrocalcinosis and renal insufficiency in childhood is a rarely described disease. Two siblings of consanguineous Tunesian parents (first cousins), a 2-year-old boy and a 4-year-old girl presented with renal insufficiency and severe bilateral nephrocalcinosis. Both were found to have decreased serum and intracellular magnesium concentrations, increased urinary excretion of magnesium and calcium, mild glomerular and severe tubular proteinuria and low citrate excretion in urine. Pathological biochemical findings and the severity of nephrocalcinosis of the boy compared to findings of the sister were strongly marked, Histology of the boy's kidney showed severe medullary nephrocalcinosis, tubular atrophy, focal lymphoplasmacellulary infiltration, focal cortical fibrosis, immature glomerula, segmental and global glomerulosclerosis. Subsequent mutation analysis revealed a homozygous frameshift mutation in the gene paracellin-1 in both affected individuals. Therapy consisted of sodium bicarbonate, cholecalciferol, calcitriol, hydrochlorothiazide, citrate salts and oral magnesium administration. Hypercalciuria decreased in both children by therapy with thiazide diuretics, but hypomagnesemia was unresponsive to magnesium administration. After a 32-month follow-up the boy commenced hemodialysis at the age of 5 years, whereas his sister showed no decline in renal function.