摘要:

Abstract.The biological importance of dynamic hormonal secretion has been demonstrated [1]. There is good evidence from recent studies that parathyroid hormone (PTH) which plays an important role in bone physiology is secreted in a pulsatile manner [2–5]. In this study we performed a classification of two ‘dynamical diseases’ namely osteoporosis and hyperpara‐thyroidism by the visualization of dynamic PTH‐secretion in multidimensional phase s

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01476.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.The calcium homeostasis in eight patients with postoperative hypoparathyroidism was examined before and after 2 weeks of administration of verapamil in an oral dose of 80 mg three times daily. Serum ionized calcium increased during verapamil treatment (from mean ± SD of 110 ± 006 to 1.24 ± 0.38 mmol 1‐1;P<0.05), as well as total serum calcium corrected for protein (from 2.11±0.13 to 2.18 ± 0.13 mmol l‐1;P<0.05). During treatment with verapamil there was an increase in serum phosphate (from 1.08 ±0.15 to 1.19±0.20 mmol l‐1P≤ 0.05) and in the urinary excretion of phosphate (P/creatinine ratio from 1.22±0.69 to 1.83 ± 0.97;P≤0.05). The serum 1,25‐dihydroxyvitamin‐Dj and serum parathyroid hormone were below the detection limits both before and after verapamil treatment. There were no significant changes either of the intestinal absorption of calcium or of the urinary calcium excretion. Serum osteocalcin was insignificantly reduced after treatment (1.60 ± 0.70 before treatment and 1.25 ± 0.71 μg l‐1after treatment).Thus in patients with post‐surgical hypoparathyroidism verapamil has effects on calcium and phosphorous homeostasis. Since calcium absorption was not influenced by verapamil, it is suggested that verapamil af

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01477.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Two independent studies were designed to investigate the separate and combined effects of acipimox and cholestyramine on plasma low density lipoprotein subfractions. In the first study, normolipidaemic subjects were given cholestyramine (16 g day‐1, 4 weeks), followed, after an 8‐week wash‐out period, by acipimox (750mg day‐1, 4 weeks). In the second study, moderately hypercholesterolaemic subjects were prescribed acipimox (1250mg day‐1, 10 weeks), followed by acipimox in combination with low dose cholestyramine (12g day‐1) for a further 10 weeks. In the normal subjects, cholestyramine decreased total LDL mass (density (d)= 1.019–1.063g ml‐1) by selectively reducing the largest, least dense LDL‐I(d 1.025–1.034 gml‐1,P<0.05) and LDL‐II (d 1.034–1.044 g ml‐1,P<0.005) subfractions. The small, dense LDL‐III (d 1.044–1060 g ml‐1) showed a variable response to the resin. In the same subjects acipimox produced no overall change in total LDL mass but showed a tendency to redistribute LDL towards LDL‐I (+10%) and LDL‐II (+10%) in a manner related to the changes in plasma triglyceride (TG) (TG vs. LDL‐IIIr= 0.75,P<0.05). In the hypercholesterolaemic subjects acipimox induced a substantial redistribution of LDL subfractions (LDL‐1 + 84%P<0.05; LDL‐III‐50%) without affecting total LDL mass. The addition of cholestyramine produced a significant decrease in total LDL mass which was again confined to the LDL‐I (‐28%) and LDL‐II (‐23%) subfractions. These consistent and complementary changes in discrete LDL subfractions may, in part, explain the hypolipidaemic potency of acipimox in combination with low dose cholestyramine. In view of the association between LDL subfrac‐tion profile and coronary heart disease risk, this particular combination of drugs may represent an effective regimen for th

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01478.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.The effect of uninephrectomy (UN) at 4 months of age was studied on several parameters involved in the development of glomerulosclerosis (GS) in male spontaneously hypertensive Fawn‐Hooded rats. Protein excretion per animal was significantly more increased in UN rats at 2 months after operation compared to sham operated controls (202±104 vs. 88±37 mg 24 h‐1,P=0.005) and remained significantly higher throughout the rest of the observation period. At 11 months of age UN rats had a marked increase in the incidence of GS, 37± 16% compared to 5 ± 3% (P<0.001) in controls. No differences were observed in mean arterial blood pressure.Functional studies in separate groups of rats at 5 months of age showed an increase in single kidney glomerular filtration rate in UN rats (0.40±0.07 vs. 0.28±0.09 ml min‐1100 g,P= 0.006). Single kidney renal plasma flow and filtration fraction were not altered. Mean glomerular volume was increased 1 month after UN (1.86 ± 0.25 vs. 1.39 ± 0.25 times 106μm3,P=0.003). Urinary noradrenaline excretion per animal (24‐h) showed a high sympathic nervous tone in both sham and UN rats. Total urinary dopamine and kallikrein excretion per animal were not influenced by UN.These data indicate that after UN the development of GS in this rat strain is accelerated in association with compensatory hyperfiltration and glomerular volume expansion, which may play a role in the pa

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01479.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.In the present study we searched for restriction fragment length polymorphisms (RFLP) in the human interleukin‐1β (IL‐lβ) gene and for correlations to monocyte (Mo) function in non‐related healthy donors and insulin‐dependent diabetic patients. We demonstrated a diallelic polymorphism with the restriction enzyme TaqI consisting of fragments of 9.4 kb and 13.4 kb. No differences in allele or genotype frequencies of this RFLP were observed between randomly selected controls and randomly selected patients with insulin‐dependent diabetes mel‐litus (IDDM). However, when analysing IDDM patients negative for HLA‐DR3 and ‐DR4, our data demonstrate that the 13.4 kb allele is more frequent in this group compared to a matched control group. The functional impact of this RFLP was studied by analysingin vitrostimulated Mo IL‐1β response. An IL‐lβ allele dosage effect on secretory capacity was observed after LPS‐stimulation: 13.4/13.4 kb homo‐zygous individuals secreted significantly more IL‐lβ than 9.4/13.4 kb heterozygous individuals, who secreted significantly more than 9.4/9.4 kb homozygous individuals. Analyses of supernatants from LPS‐sti‐mulated Mo cultures from individuals with each Taql IL‐lβ genotype revealed no differences in the mouse thymocyte co‐stimulatory assay when compared on a molar basis, indicating that the Taql polymorphism gave rise only to quantitative differences in expression levels and probably not to a mutant IL‐lβ. We conclude that the 13.4 kb allele represents an IL‐1β‘high‐secretor’ phenotype, that the observed RFLP may be a genetic susceptibility marker for IDDM in non‐DR3 and non‐DR4 individuals and that high IL‐1β secretory capa

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01480.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Chronic Granulomatous Disease (CGD) manifests as a predisposition to infection as a result of defective function of the NADPH oxidase of phago‐cytic cells. Proteins identified as part of this system include two subunits of a cytochrome b (cytochrome b‐245) and two cytosolic factors. The affected oxidase component was determined in 63 CGD patients from 57 families, by Western blotting of extracts of their neutrophils with antibodies to those proteins. 38 (67%) of the families were X‐linked with a defect of the β subunit of the cytochrome. 13 (23%) lacked p47‐phox, 3 (5%) p67‐phox, and 3 (5%) the α subunit of the

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01481.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.The pathogenesis of the acute porphyric attack is not known. One hypothesis is that porphyrin precursors, especially 5‐aminolaevulinic acid (ALA), are toxic for neuronal tissue. This was tested by infusing ALA in a male volunteer after a loading dose at a rate of 50–80 mg h‐1for 92.5 h. During the experiment plasma ALA concentration was 9.11 μmol 1‐1and porphobilinogen concentration 3–6 μmol 1‐1which are the levels seen during acute attacks. Urinary excretion of these porphyrin precursors was also markedly increased. ALA infusion caused no subjective symptoms and no change in pulse rate, blood pressure, or autonomic nerve function or conduction velocity of peripheral nerves. Photosensitivity was not demonstrable. It is concluded that sustained high plasma ALA concentration does not cause porphyria

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01482.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.The role of peripheral catecholamine sensitivity in lipid mobilization was investigated in 78 healthy non‐obese subjects by comparing beta‐adre‐nergic regulation of lipolysis in isolated adipocytes with circulating catecholamines and glycerol (lipolysis index). Small intra‐individual variations (5–7%) in adipocyte lipolytic beta‐adrenoceptor sensitivity (ED50) for isoprenaline were found. However, large inter‐individual variations (almost 105‐fold) in isoprenaline ED50were observed in abdominal or gluteal adipocytes, which correlated (r = ‐0.52) negatively with the resting plasma noradrenaline levels. A correlation was also observed between circulating noradrenaline and adipocyte ED50for noradrenaline (r= ‐0.38). In subjects with high (ED5010‐10mol 1‐1) physical exercise induced a two times greater increase in plasma glycerol (P<0.01), in spite of a 50% less marked increase of plasma noradrenaline (P<0.01). Findings with beta‐adrenoceptor mRNA and with total beta‐adrenoceptor number or affinity for agonist did not show any strong correlation with the resting plasma noradrenaline level (r<0.25). In conclusion, inter‐individual variations in beta‐adrenoceptor sensitivity and its relation to circulating noradrenaline can be ascribed to specific modulations of either BAR‐subtypes or in the postreceptor activation of lipolysis. These variations in adipocyte beta‐adrenoceptor sensitivity may participate in the regulation of peripheral nervous activity and play a putative role in lipolysis during exercise when subjects with high beta‐adrenoceptor sensitivity increased their ability to mobilize lipids

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01483.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.The mutual effects of systolic ankle arterial pressures, positional manoeuvres, and calf artery occlusions on transcutaneous oxygen partial pressures (tcpO2) were studied in 388 legs of 258 patients with peripheral arterial occlusive disease (PAOD). The tcpO2‐vs‐perfusion pressure relationship could be satisfactorily fitted by a non‐linear regression model deduced from the tcpO2theory. Flow‐insensitive ranges of tcpO2‐vs‐flow hyperbolas were reduced by both leg lowering and moving the electrode towards proximal measuring sites. Lower tcpO2values were found in case of occluded compared to patent calf arteries at ankle arterial pressure indices below 0.4. The tcpO2positional variability increased with worsening hemodynamic compensation and was most pronounced in critical limb ischaemia (ischaemic rest pain, non‐healing ulcerations). According to a retrospective analysis, a critical ischaemia could be assumed if supine and sitting tcpO2‐values exceed neither 10 nor 45 mmH

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01484.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract.Antibodies directed against antigens in human neutrophils have proved to be of great diagnostic value in certain systemic vasculitides. Recent reports have focused the attention on these antigens as targets of antibodies in sera of patients with inflammatory bowel disease. We investigated the sera drawn from 60 patients suffering from biopsy proven Crohn's disease and 15 patients with active ulcerative colitis. Using sensitive enzyme‐linked immunosorbent assays with purified antigens and Western blotting the following antibodies could be demonstrated: cathepsin G (cat‐G) antibodies IgG 38.3%, IgM 13.3%, IgA 23.3% and antibodies against human leucocyte elastase (HLE) IgG, IgA, IgM 3.3%. Low but significant correlations could be found for cat‐G antibodies (IgG) and the van HEES index of activity. 73.9% of the cat‐G (IgG) positive patients had colon involvement. In the sera of patients with ulcerative colitis no antibodies to cat‐G or HLE were detectable. Only 8.3% of the patients with Crohn's disease had antibodies against proteinase 3 (C‐ANCA). Our data indicate that cat‐G among other myeloid lysosomal enzymes seems to be an important target antigen of antibodies in sera of patients with Crohn's disease. Cat‐G antibodies might be helpful to distinguish Crohn's disease from ulc

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1992.tb01485.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY