Biomedical subjects
Publications and source records attributed to E Mayer.
129 children and adolescents had 111 bronchial histamine and 85 allergen challenges. Airways resistance measured by the occlusion technique was found to be inferior to the body plethysmography in discriminating children with hyperreactive or allergic airways from healthy children.
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A comparative study of the effects of captopril, an angiotensin converting enzyme inhibitor and endralazine, a new vasodilator drug, were performed in a group of 20 homogeneous patients with moderate hypertension (WHO: phase I and II). Both drugs produced a marked (p less than 0.001) decrease in mean arterial pressure, but the drop in blood pressure levels and the percentage of patients free of side-effects (p less than 0.001) were greater in patients treated with endralazine. Neither drug affected the lipid profile, nor pulmonary function tests and both increased significantly (p less than 0.001) plasma renin activity levels. The results of this study suggest that both drugs may be recommended for the treatment of hypertensive asthmatic patients, but endralazine should be preferred as first-choice drug, due to its lower incidence of side-effects and higher hypotensive effect obtained with the administration of a lower daily dosage.
These 48-h homologous equilibrium radioimmunoassays for human parathyrin (hPTH) are based on the use of two antisera, MS 6 and MS 7, raised in guinea pigs against human parathyroid adenoma extract. For the assay with MS 6, Tyr43-hPTH(44-68) and hPTH(44-68) were radioiodinated for use as the assay tracer. Labeled peptides were separated from free iodine by passage through Sep-Pak C18 cartridges. This RIA appears to be mid-region specific: hPTH(28-48) and hPTH(64-84) were not recognized, whereas hPTH(53-84) was 100% cross reactive with hPTH(44-68). Thus, the PTH recognition site of antiserum MS 6 must be between amino-acid residues 53 and 63. With antiserum MS 7, which recognized the PTH molecule between amino-acid residues 69 and 84, we used hPTH(53-84) for preparing the standard curve and 125I-labeled Tyr52-hPTH(53-84) as the assay tracer. Because this RIA recognized PTH fragments containing residues 69-84 of hPTH, we termed it a C-terminal assay. Both assays were useful for diagnosis of primary and secondary hyperparathyroidism.
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Phenylobacterium immobile, a bacterium which is able to degrade the herbicide chloridazon, utilizes for L-tyrosine synthesis arogenate as an obligatory intermediate which is converted in the final biosynthetic step by a dehydrogenase to tyrosine. This enzyme, the arogenate dehydrogenase, has been purified for the first time in a 5-step procedure to homogeneity as confirmed by electrophoresis. The Mr of the enzyme that consists of two identical subunits amounts to 69000 as established by gel electrophoresis after cross-linking the enzyme with dimethylsuberimidate. The Km values were 0.09 mM for arogenate and 0.02 mM for NAD+. The enzyme has a high specificity with respect to its substrate arogenate.
The diagnostic accuracy of sonographic screening is demonstrated by the results obtained in 171 pregnant women referred to the Department of Gynaecology of the University of Munich during 1984 for on-target sonography of foetal developmental disturbances. The accuracy was found to be 80%. Examination of pregnant women at risk shows a very low rate of developmental disturbances. The consequences arising from the observed disturbances of development are discussed.
The accumulation of endogenous noradrenaline within the extracellular space of the ischemic myocardium was studied in the isolated perfused (Langendorff) rat heart. The hearts were subjected to various periods of ischemia, and the noradrenaline overflow that occurred during the ensuing period of reperfusion was estimated radioenzymatically. Ischemic periods of less than 10 min are not associated with an increased overflow of noradrenaline during reperfusion. Longer periods are accompanied by an overflow, increasing with lengthening of the preceding ischemia to 1,270 +/- 48 pmol/g heart after 60 min of ischemia, as compared with 3.7 +/- 0.6 pmol/g during control perfusion. The kinetics of noradrenaline overflow suggest that the noradrenaline detected during reperfusion is released from the sympathetic neurons predominantly during ischemia and is then washed out from the extracellular space. The noradrenaline overflow induced by ischemia is not influenced by the lack of extracellular calcium. Blockade of neuronal uptake reduces noradrenaline overflow after ischemic periods of between 10 and 40 min (at 30 min from 481 +/- 56 to 91 +/- 12 pmol/g heart). The noradrenaline overflow after longer periods of ischemia is not affected by blockade of neuronal uptake. The results suggest that noradrenaline released from the sympathetic nerve terminals by ischemic periods of between 10 and 40 min is not due to exocytosis, but to a carrier-mediated efflux using the same carrier as is normally responsible for transporting noradrenaline from the synaptic clefts back into the neuron.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the effects of vitamin D metabolites in 29 patients established on chronic hemodialysis. The patients were divided into four groups; one was treated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 0.5 microgram/day, one with 24R,25-dihydroxyvitamin D3 [24,25-(OH)2D3] 10 micrograms/day, and one with both metabolites. The control group was not given vitamin D. Plasma levels of both metabolites were low before treatment. 1,25-(OH)2D3 levels became normal, and 24,25-(OH)2D3 increased to supranormal levels after administration of the corresponding metabolite. Combined treatment produced still higher plasma levels of 24,25-(OH)2D3, suggesting an interaction between the two metabolites. Patients receiving 1,25-(OH)2D3 alone had a greater increase in plasma calcium than those receiving both metabolites. In control patients, hyperparathyroid bone disease worsened over the 10-month observation period. 1,25-(OH)2D3 improved hyperparathyroid bone disease in most patients, as reflected by a reduction in osteoclast and osteoblast numbers, but had no demonstrable effect on mild osteomalacia. 24,25-(OH)2D3 had no significant effect on plasma biochemistry or bone histology, and the effect of combined treatment on histology was similar to that of 1,25-(OH)2D3 alone. Stainable bone aluminum increased slightly in patients given 1,25-(OH)2D3, but aluminum did not affect the response to treatment. We conclude that 1,25-(OH)2D3 is a useful agent in the treatment of renal bone disease, but no therapeutic role is apparent for 24,25-(OH)2D3.
Biochemical data and bone histology from 44 haemodialysis patients was compared using an histologic technique capable of evaluating separately the individual components of osteodystrophy. Hyperparathyroid bone disease was diagnosed by an elevated osteoclast count, and in advanced disease there was also fibrosis and woven bone. Osteomalacia, defined as an impairment in the rate of bone mineralisation, was present in two distinct forms: osteomalacia type I, characterised by wide osteoid seams, and osteomalacia type II, characterised by extensive thin, inactive osteoid. The histologic diagnoses were hyperparathyroid bone disease (15), osteomalacia type I (3), osteomalacia type II (6), hyperparathyroid bone disease and osteomalacia type I (12), hyperparathyroid bone disease and osteomalacia type II (6), normal (2). Aluminium was evident histochemically in 17 biopsies. Vitamin D metabolite levels were low in most patients and did not correlate with any biochemical or histological parameter. Parathyroid hormone levels were highly correlated with histological features of hyperparathyroid bone disease, and also correlated with plasma calcium, suggesting a degree of autonomy of parathyroid hormone secretion. Urea and creatinine were higher in the hyperparathyroid bone disease than the osteomalacia groups suggesting that poor dialysis contributes to the former. Statistical analysis showed that osteomalacia type I was associated with relatively low plasma calcium and phosphorus levels; osteomalacia type II was associated with increased bone aluminium and with the uraemic process itself, as reflected in the plasma creatinine level. This study shows relationships between renal osteodystrophy and plasma calcium and phosphorus levels, but no relationship with vitamin D metabolites. Aluminium appears to impair mineralisation even at relatively low levels of accumulation. However there are other unidentified factors associated with the uraemic process, contributing to all three components of renal osteodystrophy.
A sensitive radioimmunoassay system for 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] with an improved extraction procedure has been developed. Following one-step extraction and prepurification of 1,25(OH)2D3 by 'Extrelut-1' minicolumns final purification was achieved by high-performance liquid chromatography (HPLC) using a radial compression separation system equipped with a mu Porasil cartridge. The HPLC method applied allows the purification of 4 extracts/h. Recovery of 1,25(OH)2[3H]D3 after HPLC was 77 +/- 2.6% (mean +/- SD, n = 51). Since the recovery of 1,25(OH)2[3H]D3 was very reproducible, addition of labelled steroid to each single serum sample for monitoring recovery was omitted. The sensitivity of the assay was 0.8 pg/tube resulting in a detection limit of 3 ng/l, when 1 ml of serum was extracted. Intra-assay and inter-assay coefficients of variation were 12% and 16.8%, respectively. Serum 1,25(OH)2D3 concentration in 30 normal subjects (mean age: 25 yr) was 55 +/- 12 ng/l (mean +/- SD). In 55 elderly patients (mean age: 77 yr) the 1,25(OH)2D3 serum level was 32 +/- 12 ng/l (mean +/- SD) and in three patients with chronic renal failure on 1,25(OH)2D3 therapy 146 +/- 67 ng/l (mean +/- SD). Patients with chronic renal failure had reduced 1,25(OH)2D3 serum levels (mean 5.4 ng/l, range less than 3-11 ng/l, n = 10). In one patient with renal failure, following kidney transplantation the serum 1,25(OH)2D3 and creatinine levels were monitored from the 4th to the 12th post-surgical day: a highly significant negative correlation (r = 0.85) was found.
The biological activities of several 24-oxo and 26,23-lactone metabolites of vitamin D were determined in bone organ cultures. The 24-oxo metabolites were significantly more potent bone-resorbing agents than the lactones. 1,25-(OH)2-24-oxo-D3 had 0.18 X the bone-resorbing activity of 1,25-(OH)2D3 in fetal rat limb bones and was equipotent with 1,25-(OH)2D3 in neonatal mouse calvaria. In the limb bone system, 1,23,25-(OH)3-24-oxo-D3 had 0.08 X the activity of 1,25-(OH)2D3. 1,25-(OH)2D3 and 1,25-(OH)2-24-oxo-D3 had a similar time course of bone-resorbing effects in both bone culture systems. The most potent of the lactones, 1,25S-(OH)2D3-26,23R-lactone, had approximately 0.009 X the activity of 1,25-(OH)2D3 and approximately 500 times the activity of the 25S-OH-D3-26,23R-lactone. The 25S and 1,25S lactones were more potent than the 25R and 1,25R isomers. In experiments designed to determine whether either 1,25-(OH)2-24-oxo-D3 or 25R-OH-D3-26,23S-lactone could prevent the bone-resorbing activity of 1,25-(OH)2D3, no inhibitory effects were observed. The results suggest that conversion to the lactones represents a substantial inactivation step, whereas conversion to 24-oxo-derivatives results in less reduction in biological activity.
Within a period of twelve years, the authors have treated twelve patients with metacarpophalangeal joint luxations of thumb and long fingers which could not be reposed by conservative treatment. The case reports are presented in order to describe the problems posed by this relatively rare injury, the reasons hindering a reposition, and the treatment methods. This study is intended to underline the importance of early diagnosis and immediate surgical treatment in order to maintain the function of the joint.
The binding of the natural and unnatural diastereoisomers 25-hydroxyvitamin D3-26,23-lactone and 1,25 dihydroxyvitamin D3-26,23-lactone to the vitamin D-binding protein (DBP) and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] chick intestinal receptor have been investigated. Also, the biological activities, under in vivo conditions, of these compounds, in terms of intestinal calcium absorption (ICA) and bone calcium mobilization (BCM), in the chick are reported. The presence of the lactone ring in the C23-C26 position of the seco-steroid side chain increased two to three times the ability of both 25(OH)D3 and 1,25(OH)2D3 to displace 25(OH)[3H]D3 from the D-binding protein; however, the DBP could not distinguish between the various diastereoisomers. In contrast, the unnatural form (23R,25S) of the 25-hydroxy-lactone was found to be 10-fold more potent than the natural form, and the unnatural (23R,25S)1,25(OH)2D3-26,23-lactone three times more potent than the natural 1,25-dihydroxy-lactone in displacing 1,25(OH)2[3H]D3 from its intestinal receptor. While studying the biological activity of these lactone compounds, it was found that the natural form of the 25-hydroxy-lactone increased the intestinal calcium absorption 48 h after injection (16.25 nmol), while bone calcium mobilization was decreased by the same dose of the 25-hydroxy-lactone. The 1,25-dihydroxyvitamin D3-26,23-lactone in both its natural and unnatural forms was found to be active in stimulating ICA and BCM. These results suggest that the 25-hydroxy-lactone has some biological activity in the chick and that 1,25(OH)2D3-26,23-lactone can mediate ICA and BCM biological responses, probably through an interaction with 1,25-(OH)2D3 specific receptors in these target tissues.
A high-sodium diet accelerates the rise in blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP). The blood pressure-increasing effect of sodium loading is associated with the following abnormalities in noradrenaline metabolism: (a) noradrenaline release from sympathetic nerve endings is facilitated (especially after stimulation, such as exposure to cold); (b) noradrenaline inactivation is reduced mainly as a consequence of diminished neuronal uptake of noradrenaline; and (c) the sensitivity of vascular smooth muscle to noradrenaline is enhanced. These changes in noradrenaline metabolism are partially reversed when the concentration of potassium in a high-sodium diet is increased from 100 to 250 mmol K+/kg diet. That is, the neuronal uptake of noradrenaline is improved, the sensitivity of vascular smooth muscle to noradrenaline is attenuated, and the release of noradrenaline into the plasma is reduced. The reversal of abnormalities in noradrenaline metabolism is accompanied by a substantial blood pressure reduction following potassium repletion in SHRSP. Hence, the addition of potassium to the diet may be regarded as an antihypertensive measure which affects noradrenaline metabolism in such a way that sympathetic vasoconstriction is attenuated.
beta-Adrenoceptor blockade by propranolol (4 X 10(-6)M) was without effect on the overflow of endogenous noradrenaline from the isolated heart of the rat induced by stimulation of sympathetic nerves for 1 min at 1 and at 4 Hz. The increase in heart rate in response to such stimulation was abolished by propranolol treatment. alpha 2-Adrenoceptor blockade by yohimbine (10(-6)M) induced approximately a two fold increase in the overflow of endogenous noradrenaline induced by stimulation of sympathetic nerves for 1 min at 1 and at 4 Hz. A combination of yohimbine (10(-6)M) and desipramine (10(-7)M) induced a more than 3 fold increase in the overflow of endogenous noradrenaline produced by sympathetic nerve stimulation at 1 and at 4 Hz. Heart rate increases produced by such stimulation were intensified. These results provide no evidence for the feedback stimulation of presynaptic beta-adrenoceptors in this preparation. The action of alpha-2-blockade was equipotent at stimulation frequencies of 1 and 4 Hz.
The accumulation of endogenous catecholamines within the extracellular space of the ischemic myocardium has been studied in the isolated perfused (Langendorff) heart of the rat subjected to various periods of complete ischemia, with subsequent collection of the reperfusate. Catecholamines and deaminated metabolites were measured by radioenzymatic methods, or high pressure liquid chromatography. Ischemic periods of less than 10 minutes are not associated with an increased overflow of catecholamines or metabolites. Longer periods of ischemia are accompanied by the overflow of noradrenaline and its deaminated metabolite 3,4-dihydroxyphenylglycol. This overflow increases with lengthening of the preceding ischemic period (10 minutes: 2.5 +/- 0.6, 20 minutes: 209.8 +/- 17.2, 60 minutes: 1270.5 +/- 148.1 pmol noradrenaline/g heart). Noradrenaline concentration is highest during the first minute of reperfusion, suggesting that the noradrenaline detected during reperfusion is released into the extracellular space of the myocardium during ischemia and is subsequently eluted. Experiments with variation of extracellular calcium concentration and with neuronal uptake (uptake1) blocking agents suggest that different mechanisms of catecholamine release are acting during the course of ischemia. A calcium-independent carrier-mediated efflux of noradrenaline from the nerve terminals is of major importance, using the same carrier as is normally responsible for transporting noradrenaline from the synaptic clefts into the neuronal varicosities. Thus, various uptake1-blocking agents diminish the noradrenaline overflow following ischemic periods of between 10 and 40 minutes. The noradrenaline overflow following longer periods of ischemia is unaffected by uptake1-blocking agents, and additional noradrenaline release at this time is probably consequent upon dissolution of cell membranes. Overflow of adrenaline and dopamine occurs to a minor degree (less than 5% of the corresponding noradrenaline overflow), and only after ischemic periods of more than 15 minutes.
The contribution of centrally originating sympathetic activity to the myocardial extracellular accumulation of noradrenaline during the early phase of ischemia has been assessed in a perfused (Langendorff) rat heart preparation isolated except for its sympathetic innervation. A 10-minute electrical stimulation (4 Hz, 5 V) of the left cervicothoracic ganglion during normal perfusion causes the overflow of 177.5 +/- 13.7 pmol noradrenaline/g heart, whereas such stimulation during ischemia liberates only 21.5 +/- 3.6 pmol/g (collected during reperfusion). When neuronal reuptake is blocked by desipramine, corresponding values are 321.5 +/- 22.5 pmol/g (normal flow) and 151.8 +/- 22.4 pmol/g (ischemia). After combined blockade of neuronal uptake, extraneuronal uptake, and alpha 2-receptors, nerve stimulation liberates 674 +/- 22 pmol/g during normal flow and 206 +/- 24.3 pmol/g during ischemia. These results suggest that, in vivo, centrally originating neural activity would not lead to substantial accumulation of noradrenaline within the extracellular space of the ischemic myocardium. This failure of accumulation is due to both a functioning neuronal uptake of noradrenaline and a failure of neurotransmission.