摘要:

Abstract.The purpose of this investigation was to determine whether an intrinsic defect in thyroid hormone production is required for the development of iodide‐induced hypothyroidism or does it also develop in TSH‐stimulated normal thyroid tissue. To answer this question, we studied the response to iodine administration (180 mg iodide daily for 3–4 months) in eight euthyroid patients who had had partial thyroidectomies 2 months to 10 years previously for benign thyroid nodules, and in three euthyroid control subjects. In all 11 euthyroid patients, basal serum TSH concentrations increased during iodide administration. In six of the eight patients who had previous thyroid operations and in two of the three control patients, basal serum TSH concentrations increased into the abnormal range (greater than 6 U ml‐1). Increased serum TSH concentrations were noted as early as 1 week after potassium iodide had been started and the increased levels persisted during the period of iodide administration. Although basal values for serum TSH concentration were initially within the normal range, those patients with highest basal serum TSH values developed the greatest increase in TSH in response to potassium iodine. Among the eight patients treated by partial thyroidectomy, serum T4concentrations decreased in five, serum T3concentration decreased in three and all five developed mild symptoms of hypothyroidism while receiving iodide. Serum T4concentrations also decreased slightly in two of the three control patients. Serum total iodine levels increased from 70pM 0.5 to 315.7 pM 108.6 g dl‐1(mean‐pM standard error) during potassium iodide administration, but there was no correlation between the level of serum iodide concentration achieved and inhibition of thyroid function. When iodide was discontinued, symptoms disappeared and thyroid function tests returned to baseline levels within 1 month in all patients, It thus appears that a restricted thyroid mass and/or a mild increase in TSH stimulation is all that is required for the development of hypothyroidism in man when exposed to exces

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01903.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The activity of cholesteryl ester transfer protein is instrumental in the distribution of cholesteryl ester between lipoproteins in plasma. We measured the activity of cholesteryl ester transfer protein in plasma, designated cholesteryl ester transfer activity, as the rate of cholesteryl ester transfer between exogenous radiolabelled low‐density and high‐density lipoproteins. The effect of hypothyroidism on cholesteryl ester transfer activity was investigated in 13 athyreotic patients who were studied in the hypothyroid condition and in the euthyroid state, after they had received triiodothyronine supplementation for 33 to 67 days.During hypothyroidism plasma total cholesterol, very‐low‐ plus low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, plasma triacylglycerol, apolipoprotein A1and B were significantly higher than in the euthyroid state. Cholesteryl ester transfer activity was 15% lower during hypothyroidism (P<0.02), and an effect of treatment duration was observed. The changes in high‐density lipoprotein total cholesterol (P<0.02), free cholesterol (P<0.001), triacylglycerol (P<0.05) and the free cholesterol/cholesteryl ester molar ratio in high‐density lipoproteins (P<0.01) were inversely related to the changes in cholesteryl ester transfer activity.We concluded that thyroid hormone is involved in the regulation of cholesteryl ester transfer protein activity, and that cholesteryl ester transfer protein activity may play a role in the alterations in high‐density lipoprotein lipids observed

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01904.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Pressure on the outside of arteries can cause physical and biochemical changes in the vessel wall of rabbits which are characteristic of atherosclerosis. It is hypothesized that occlusion of the vasa vasorum causes ischaemia of the arterial media which results in smooth muscle cell proliferation and cellular accumulation of cholesteryl esters. Hypoxia increases mRNA for platelet‐derived growth factor in arterial wall cells and increases the activity of acyl CoA: cholesterol acyltransferase (ACAT). Such a mechanism may explain many of the anatomical, actuarial and environmental risk factors for atherosclerosis. Hyperfusion of the vasa vasorum may follow thrombosi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01905.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apo B‐containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol‐induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects.Plasma CETP activity was 28% lower in the alcoholics compared with the controls (P<0.001), while the teetotallers among the latter had slightly higher CETP activity than those who consumed alcohol in moderation. CETP activity increased slowly after ethanol withdrawal, but did not reach the control level within the 7‐day observation period. A positive correlation was observed between plasma CETP activity and the LDL cholesterol/HDL cholesterol ratio (r= 0.480,P<0.002), whereas CETP activity showed a negative correlation with HDL cholesterol level (r= ‐0.467,P<0.001).The results indicate that defective transfer of cholesteryl esters from HDL to LDL contributes to the high HDL cholesterol levels in alc

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01906.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The effects of prolonged substitution of readily digested carbohydrates (wheat starch) for poorly digested carbohydrates (mixture of various fibres and crude potato starch) on plasma lipids, lipoproteins and hormones were investigated in Zucker, genetically obese rats. Lean rats were also studied in parallel. Usually, plasma lipid and insulin levels and insulin/glucose ratio were higher in obese rats vs. their lean littermates. High‐fibre diet intake led to weight loss in both obese and lean rats. With a high‐fibre diet, plasma lipid, insulin and glucose postprandial levels in both groups were reduced when compared with their respective control animals. Dietary fibre modified the lipoprotein profile. Triglycerides and cholesterol were reduced in all studied lipoprotein fractions. The study of high density lipoprotein (HDL) fraction in rats fed a high‐fibre diet demonstrated a decrease in the HDL1subpopulation and in the apolipoprotein (apo)E proportion. The findings show that a high‐fibre diet modulates plasma lipid, insulin and glucose levels and modifies the plasma lipoprotein distribution and composition in normolipaemic, lean rats as well as in hyperlipaemic, genetically obe

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01907.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Thirty‐one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine theirin vivoformation of the platelet aggregating and vasoconstricting substance thromboxane A2(TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3‐dinor‐TxB2and 2,3‐dinor‐6‐keto‐PGF1x, respectively, using gas chromatography mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2compared with age‐matched healthy controls (807 pM 163 [SEM] vs. 230 pM 15 pg mg‐1creatinine,P= 0.0000005). A significant increment of the formation of PGI2was also found (189 pM 23 (SEM) vs. 125 pM 11 pg mg‐1creatinine,P= 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2form

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01908.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.The adrenergic status was studied through evaluation of platelet α2‐adrenoceptor number ([3H]‐yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P<0.05) decreased from 144 pM 9 and 76 pM 6 mmHg in the lying position to 95 pM 12 and 60 pM 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 pM 11 pg ml‐1, (P<0.05) when compared with controls (219 pM 13 pg ml‐1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 pM 14 pg ml‐1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P<0.01) lower in Parkinsonians with orthostatic hypotension (019 pM 0.03 μg kg‐1) when compared with Parkinsonians without orthostatic hypotension (0.86 pM 0.11 μg kg‐1) or with controls (0.68 pM 0.l μg kg‐1). Plateletx2‐adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 pM 52 fmol mg‐1protein) than in Parkinsonians without orthostatic hypotension (168 pM 9 fmol mg‐1protein) or in controls (175 pM 4 fmol mg‐1protein) with no change inKd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet α2‐adrenoceptor number. These observations suggest the existence of an α‐adrenergic supersensitivity in response to the l

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01909.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Cystic fibrosis is associated with an cAMP‐regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B‐cell dysfunction potentially related to this defect, we studied thein vitroIgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co‐cultured with autologous monocytes and stimulated withStaphylococcus aureusCowan or with Nocardia‐delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10‐7mol l‐1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10‐6mol l‐1, whereas this agent induced a dose‐related enhancement from 10‐8to 10‐6mol l‐1in cultures of normal cells. Co‐culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti‐CD3 antibody‐induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 α‐ or β‐induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to ba

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01910.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Indirect evidence has suggested that intravascular coagulation may occur in patients with fulminant hepatic failure (FHF), the most severe form of acute liver disease. Thrombin is inhibited in circulation by antithrombin III, and measurement of the thrombin‐antithrombin III complex (TAT) is a direct measure of thrombin formation. Using a new rapid enzyme‐linked immunosorbent assay we have measured TAT in 54 patients on admission, with fulminant hepatic failure. TAT was significantly increased in patients with FHF compared with control subjects (25.8 pM 2.7 μg l‐1) compared with 2.6 pM 0.2 μg l‐1;n=10:P<0.001). Patients who survived had significantly lower TAT levels than those who did not (17.2 pM 2.7 μg l‐1;n= 27 compared with 34.0 pM 4.2 μg l‐1;n= 27:P<0.005) and patients with FHF caused by viral hepatitis had significantly lower TAT levels than those with FHF due to paracetamol overdose (14.6 pM 4.7 μg l‐1;n= 9 compared with 280 pM 3.1 μg l‐1;n= 45:P<0.05). Levels of TAT correlated significantly with prothrombin time (r= 0.36,P<0.01) and inversely with fibrinogen (r= ‐ 0.51,P<0.001). There was no significant correlation with antithrombin III concentration. Thus, using a simple and rapid technique, we have been able to demonstrate increased levels of TAT complex in patients with FHF. This provides more direct evidence of intravascular coagulation and thrombin generation in these patients. These results confirm that the coagulation sys

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01911.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Abstract.Plasma concentrations of atrial natriuretic factor (ANF) and cyclic 3′,5‐guanosine monophosphate (cGMP) were measured in 11 cirrhotic patients with ascites, 11 cirrhotic patients without ascites and 15 control subjects. The following were determined in 15 of the cirrhotic patients and in all the control subjects: blood volume (BV) and furosemide‐induced changes in BV, plasma values of ANF, cGMP, angiotensin II (AII), aldosterone (Aldo), arginine vasopressin (AVP) and urinary excretion rates of cGMP, prostaglandin E2(PGE2), water and sodium. Basal plasma levels of ANF and cGMP were higher in patients with cirrhosis than in controls, but were the same in both groups of cirrhotics (ANF: cirrhosis with ascites 12.7, without ascites 13.4, and in controls 5.8 pmol l‐1(medians); cGMP: 7.7, 7.4 and 4.3 nmol l‐1, respectively). BV was less reduced after furosemide in the cirrhotic patients (6.0%) than in the healthy subjects (10.1%), but basal BV did not differ. Urinary sodium excretion rates after furosemide were significantly lower in the cirrhotic patients than in the controls. PGEl excretion rate increased after furosemide in the cirrhotic patients (0.29 to 0.66 pmol minl‐1;P<0.01) but not in the controls (0.31 to 0.38 pmol minl‐1). After furosemide ANF and cGMP decreased slightly in both groups whereas AII and Aldo increased; AVP increased in the controls, but not in the cirrhotic patients.In conclusion, plasma values of ANF and cGMP are increased in liver cirrhosis both with and without ascites. This and the elevated PGEl2excretion after furosemide may be compensatory phenomena in order to facilitate renal sod

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1990.tb01912.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY