摘要:

Abstract.Lipoprotein particles were examined in plasma and ascitic fluid from nine patients (5 males and 4 females) with liver cirrhosis and in plasma from nine control subjects. LDL and HDL fractions were isolated by ultracentrifugation under rate flotation conditions in a zonal rotor. LDL size was analysed by non‐denaturing polyacrylamide gradient gel elec‐trophoresis. Plasma lipids in cirrhotic patients were markedly reduced compared to controls. Free cholesterol represented 45.3% of the total cholesterol in plasma and 70.4% of the total cholesterol in the ascitic fluid. The total cholesterol‐triglyceride ratio was three times higher in the plasma than in the ascitic fluid of cirrhotic patients. The LDL particles had the same flotation properties in plasma from cirrhotic patients as in that from controls. In cirrhotic patients the IDL concentration was higher than that in controls. In ascitic fluid the LDL particles had a higher flotation rate than in the plasma. The LDL diameter as measured by gradient gel electrophoresis was similar in both plasma and ascitic fluid of the cirrhotic patients as well as in the plasma of controls. In plasma and ascitic fluid of cirrhotic patients only a single HDL subclass (HDL1) could be identified. HDL1particles had a higher flotation rate than normal HDL particles. The plasma levels of all the apoproteins were reduced in cirrhotic subjects compared to controls, but to a variable degree; while apo CII level in cirrhosis represented only 9% of the control level, the apo E level represented 77% of the control level. Lipoprotein particles from the plasma of patients with liver cirrhosis differed in several respects not only from normal particles but also from particles isolated from ascitic fluid in the same patient. These differences may prove useful for improving our understanding of normal lipoprotein metabolism and of the mechanisms involved in ascitic fluid form

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01540.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The pathobiochemical mechanism of arteriosclerosis in hyperhomocysteinaemia has not yet been elucidated.In vitrostudies have shown that the cytotoxic properties of homocysteine can be ascribed to its generation of reactive oxygen species. We studied lipid peroxidation, bothin vivoandin vitro, in 10 homozygous cystathionine synthase‐deficient (CSD) patients and in a control group of 10 healthy subjects of comparable age and sex. The susceptibility of low‐density lipoprotein (LDL) from hyperhomo‐cysteinaemic patients to oxidation was determinedin vitroby continuously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed as total diene production) of LDL from CSD patients were not significantly different from those of LDL from controls. Furthermore, the time needed to reach maximal diene production, i.e. t(max), was similar for LDL from patients and controls. In addition, the vitamin E concentrations in LDL of CSD patients and controls were similar. The mean concentration (± SD) of plasma thiobarbituric acid reactive substances (TBARS), an indicator ofin vivolipid peroxidation, was 2.2 ± 0.7 μmol L‐1in CSD patients, a lower value than that measured in the matched controls (50± 2.0 μmol L‐1). Investigation ofin vivoandin vitroparameters of lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomocysteinaemia is unlikely to be due to increased lipi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01541.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Although a disturbed immune response to constituents of the gut mucosa has been implicated in the pathogenesis of inflammatory bowel disease, the mechanisms are still unclear. Intestinal T‐cells derived from gut biopsies were propagatedin vitroas single and co‐cultures under different experimental conditions prior to flow cytometry. Intestinal T‐cell lines from inflamed mucosa (n= 69) showed a significant (P<0.001) decrease in CD4+ T‐cells compared to T‐cells from normal (n= 49) and uninflamed (n= 29) tissue specimens. Co‐culturing of inflamed and uninflamed mucosa led to a normalization of CD4+ T‐cells in cultures derived from inflamed mucosa. Analysis of supernatants revealed a significantly (P<0.001) increased secretion of IL‐ 4 under co‐culture conditions. Moreover, stimulation of cultures derived from inflamed mucosa with rIL‐4 led to a significant (P<0.001) increase in CD4+ T‐cells, whereas anti‐IL‐4 antibodies or IFN‐γ supplementation of T‐cells derived from uninflamed mucosa significantly (P<0.001) reduced the CD4+ subset. Treatment with IFN‐γ and anti‐IL‐4 antibodies did not affect the phenotype of T‐cells derived from inflamed mucosa. These data suggest that IL‐4 might play a key role in the intestinal immune response. Furthermore, thisin vitrosystem allows the investigation of mucosal immune mechanisms in

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01542.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Hormonal and renal effects of candoxatril, a neutral endopeptidase 24.11 inhibitor, were investigated in eight subjects equilibrated on a low sodium diet (10 mmol sodium per day) and a high sodium (350 mmol per day) diet. After candoxatril treatment, plasma ANP increased to a maximum at 2–4 h and declined to baseline within 24 h. The increases were relatively greater on the high sodium diet, which was also associated with increases in urinary sodium, with highest values at 4h. On the low sodium diet, the magnitude of the changes was significantly lower (24 h cumulative sodium excretion was 11.4± 5.5 mmol on the low sodium diet and 73.1± 25.6 mmol on the high sodium diet;P<0.01). There were no significant effects on urinary potassium excretion, creatinine clearance or haematocrit. After candoxatril treatment there were reductions in PRA, especially on the low sodium diet. On either diet there were no effects on systemic blood pressure. These results demonstrate that dietary sodium intake is an important determinant of the renal and hormonal responses to neutral endopeptidase inhibit

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01543.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The effects of chronic feeding with moderate doses of ethanol (3% vol/vol in drinking water for 8 weeks), which do not induce tolerance, dependence and withdrawal, on the contractility of gastric, duodenal and ileal strips from rats were investigated. Only 50% of ethanol‐treated specimens (as compared to 100% of saccharose‐fed controls) exhibited antral phasic contractions (frequency decreased by 31% and 27% in the antrum and duodenum, respectively;P<0.03 vs. controls). The depolarizing agent potassium chloride (KG, 80 mm) produced less peak active tension in the fundus of ethanol‐fed rats (P<0.01). In alcoholic rats the sensitivity of the antrum to acetyl‐choline was fourfold less than that of control specimens. It is concluded that, in the rat, moderate doses of ethanol given chronically impair both spontaneous and tonic contractility of the stomach and duodenal muscle without affecting ileal contraction. It is possible that motility defects in the gut exposed to ethanol concentrations which do not cause tolerance, dependence or withdrawal in the rat may be due to a local rather than a systemic effect on the smooth

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01544.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (≤ 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium‐derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue‐type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post‐load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post‐load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL‐1) levels were above normal. At follow‐up, vWF levels had decreased to 170% (P= 0.01) and TM levels had decreased to 49 ng mL‐1(P= 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothel

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01545.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The cause of the digital artery spasm seen in Raynaud's phenomenon (RP) is unclear. A dysfunction of endothelium‐dependent vasodilation might contribute to the development of this spasm. We studied the digital artery responses to endothelium‐dependent and independent vasodilators in eight Raynaud's phenomenon patients and eight sex‐matched controls. A sequential series of infusions alternating with physiological saline were administered at a rate of l mL min‐1via the radial artery. The infusions contained acetylcholine chloride (ACh) 110 nm mL‐1and 550 nm mL‐1, L‐arginine 50 μmol mL‐1, prostacyclin (PGI2) 2.5 ng mL‐1and glyceryl trinitrate (GTN)4.5 nm mL‐1. Digital artery diameter (DAD) and cutaneous temperature were measured. DAD was measured using a high frequency A‐mode ultrasound scanner. There was no significant difference in mean brachial artery pressure, digital cutaneous temperature and DAD between the two groups at the start of the study. Comparing responses in the groups, there was a significantly greater increase in DAD and cutaneous temperature to Ach (endothelium‐dependent vasodilator) at both concentrations in controls. A significantly greater increase in DAD was obtained in response to GTN (endothelium‐indepen‐dent vasodilator) in the RP subjects. There was no significant difference in response to L‐arginine and PGI2 between the groups. These results suggest that a dysfunction of endothelium‐dependent vasodi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01546.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq131iodine vs. an activity calculated to deliver 100 Gy for treatment of Graves' thyro‐toxicosis. Therapeutic success was defined as the elimination of hyperthyroidism 6 months after radio‐iodine application (range 4.5–8 months). A success rate of more than 90% in eliminating hyperthyroidism was reported for both approaches, but only in retrospective investigations. Investigated prospec‐tively, hyperthyroidism was eliminated in only 71% of the patients receiving standard activity (70/98) and 58% of those randomized for calculated activity (62/107). In the patients with standard activity, therapeutic success was inversely related to thyroid size. The rate was 100% for thyroid volumes ≤15 mL, 95% for 16–30 mL, 68% for 31–45 mL, 44% for 46–50 mL, 20% for 61–75 mL and 25% for ≥75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume ≥15 mL) this size/outcome dependency was almost compensated. The rates were 86%, 65%, 45%, 61%, 41% and 45%, respectively. Furthermore, detailed statistical analysis revealed a strong correlation between the success of therapy and the radiation dose actually absorbed by the thyroid. The rate was 11 % for a target dose of 50Gy, 50% for 100 Gy, 67% for 150Gy, 80 % for 200 Gy, 84 % for 250 Gy, 88 % for 300 Gy, 90 % for 350 Gy and 93% for 400 Gy. Based on the results obtained in the present study, we strongly recommend individual calculation of the131iodine activity to be administered for treatment of Graves' hyperthyroidism. However, the target dose should be

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01547.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.In order to evaluate whether Lp(a), a lipoprotein that is potentially thrombogenic and atherogenic, is a potential risk factor for CAD in non‐insulin‐dependent diabetes (NIDDM), we compared the Lp(a) and its distribution in 145 NIDDM patients with that in 94 healthy control subjects. Furthermore, we studied the effect of insulin treatment on serum Lp(a) in 108 patients with NIDDM. Male and female NIDDM patients had similar Lp(a) concentrations to healthy controls (median value 167 mg L‐1, range 15–1550 mg L‐1vs. 157 mg L‐1, range 15–919 mg L‐1, NS and 92, range 15–1190 mg L‐1vs. 103 mg L‐1, range 15–842 mg L‐1, NS). Also, the cumulative distribution of Lp(a) did not differ between the NIDDM patients and healthy subjects. Insulin treatment increased Lp(a) in diabetics with a Lp(a) concentration of less than 300 mg‐1L, but this effect was not related to the concomitant improvement in metabolic control (mean change (±SEM) of HbA1cfrom 9.80±0.15 to 8.00±0.12;P300 mg L‐1) the Lp(a) concentration was unaffected by insulin, despite a similar improvement in glycaemic control. These results suggest that insulin may mod

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01548.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Recent studies have shown that the veno‐arterial gradient for carbon dioxide (dVVApCO2) is increased in the case of low cardiac index (CI). In order to further investigate this matter 220 haemody‐namic measurements from 34 patients with septic shock and from 28 patients in the post‐operative state without sepsis were evaluated. The arterio‐venous gradient for pH (dAVVpH) was also evaluated. CI was found to be inversely correlated to both dVVApCO2and dAVVpH when the two groups of patients were analysed separately (r= ‐0.76 andr= ‐0.78,P<0.001 for the relationship between CI and dVVApCO2, r = ‐0.58 and r = ‐0.69P10% during volume loading was 36–52%. While dAVVpH was found to be increased in non‐survivors (n= 27) when compared to survivors (0.32 ± 0.01 vs. 0.24±0.1,P<0.05) at the second day in the IUC, dVVApCO2was not a significant predictor of mortality despite the fact that CI was found to be decreased in the non‐survivors (3.5 ±0.94 vs. 4.3±1.0 L min‐1m‐2,P<0.01). In conclusion, the veno‐arterial carbon dioxide gradient was found to be inversely correlated to cardiac performance in patients both in patients with septic shock and in non‐septic post‐operative patients. The arterio‐venous gradient for pH was increased in low flow states, but this association was weaker. However of these two indices evaluated, only a raised dAVVpH was a s

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01549.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY