ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01369.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.We recently reported that chloride‐depletion metabolic alkalosis (CDMA) results in renal losses of Na, K, and water. In these studies we investigated whether CDMA (induced using a new model that avoids external changes in Na and water balance) was also associated with internal Na and water shifts out of the ECF. CDMA was induced using haemofiltration in functionally nephrectomized dogs. Plasma ultrafiltrate was substituted quantitatively with a solution duplicating each dog's plasma electrolyte composition in control animals, and with a solution containing HCO3as the sole anion in CDMA animals. ECF volume was estimated as the space of distribution of [3H]‐mannitol. Plasma composition and [3H]‐mannitol distribution space were unchanged in control dogs. In CDMA dogs metabolic alkalosis developed; despite the absence of external changes in Na and water balance, the space of distribution of [3H]‐mannitol decreased by 335 ± 46 ml (equivalent to 8% of baseline ECF volume), calculated chloride space fell by 304 ± 50 ml, and haematocrit increased from 45.6 to 48.5 vol%. We conclude that CDMA causes an internal shift of fluid out of the ECF. The resulting ECF volume contraction appears to be an inherent featur

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01370.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.Hyperinsulinaemia links non‐insulin dependent diabetes (NIDDM), obesity, and hypertension, each an insulin‐resistant state in its own right. Insulin resistance predicts the occurrence of NIDDM, and plays a major role in its pathogenesis. We tested the hypothesis that hyperinsulinaemia may also predict hypertension in a sample (n= 2905) of the mixed population of San Antonio, in which hyperinsulinaemia and NIDDM are more prevalent among Mexican‐Americans than non‐Hispanic whites. Whilst in the whole sample the hypertensives had significantly (P<0.001) higher plasma insulin concentrations than the normotensives, high blood pressure was significantly (P<0.01) more frequent among non‐Hispanic whites than Mexican‐Americans regardless of diabetes status. After adjusting for factors (age, sex, body mass, and body fat distribution) known to affect insulin levels, a direct relationship between post‐glucose plasma insulin concentrations and prevalence of hypertension was still present in both ethnic groups. In Mexican‐Americans, however, the standardized prevalence of hypertension was significantly (P<0.001) lower at any given insulin concentration. Post‐glucose plasma glucose levels also were directly related to hypertension prevalence in both groups; again, the regression line was shifted downward and, furthermore, less steep (P<0.02) in Mexican‐Americans, suggesting relative protection against the negative effect of hyperglycaemia on blood pressure. Dyslipidaemia (higher total cholesterol and triglyceride, and lower HDL‐cholesterol concentrations) was strongly associated with hyperinsulinaemia and blood pressure in both ethnic groups. After adjusting for plasma insulin, only hypertriglyceridaemia was associated with high blood pressure, with no inter‐ethnic difference.We conclude that in this population hyperinsulinaemia is characteristic of hypertension but does not explain its prevalence against a divergent ethnic background. Other factors that determine high blood pressure must interact with insulin resistance to determine the prevalence rate of hyperte

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01371.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.The heparin‐induced extracorporeal elimination of low density lipoproteins (LDL) is a well‐established clinical procedure to markedly reduce cholesterol levels. The biocompatibility of this artificial filter system (HELP) was investigated by quantitation of representative complement proteins within the extracorporeal circuit using established ELISA procedures, based on monoclonal antibodies recognizing exclusively either native (C6, C7) or activated proteins (act.C3, C5a, TCC). HELP was found to be a self‐limiting extracorporeal system with respect to complement activation, since act.C3 and TCC, generated mainly at the plasma filter, were partially adsorbed to the following HELP specific filters to concentrations which were lower than those obtained before the plasma filter.C5a, which increased 14.5‐fold at the plasma filter was not eliminated by the following filters; however, elevated levels were not found in the patients at the end of apheresis and no leucocytopenia was o

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01372.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high‐risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid β‐galactosidase (EC 3.2.1.23), sulpho‐ and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high‐risk group, the carcinoma carriers having intermediate values between average‐risk and high‐risk patients. In a two‐group discriminant analysis, high‐risk or carcinoma patients could be separated from average‐risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high‐risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal‐appearing left colonic and rectal mucosa by morphometric and cytochemica

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01373.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.Heparin cofactor II is a proteinase inhibitor which inhibits both chymotrypsin and thrombin, and displays great similarities with antithrombin III, the main inhibitor of thrombin in human plasma. Since acute pancreatitis is known to be associated with modification of the proteinase‐antiproteinase equilibrium, we studied heparin cofactor II and antithrombin III as well as other biochemical and haematological parameters in 10 patients experiencing attacks of acute pancreatitis. Heparin cofactor II activity decreased during the first week of illness, while its antigen concentration remained subnormal. This discrepancy between antigen concentration and activity which persisted during the first week of illness was due both to complex formation of heparin cofactor II with its target proteinases and to partial proteolysis of the inhibitor. Heparin cofactor II was shown to form a complex with chymotrypsin in the plasma of such patients. Antithrombin III levels remained unchanged throughout the study, with no discrepancy between its activity and antigen concentration. No modification of haemostasts was shown either, except for a rise in the fibrinogen level during the first days of illness. It is concluded that, unlike antithrombin III, heparin cofactor II is involved in the proteinase‐inhibitor equilibrium in patients with acute pancreatitis, and that heparin cofactor II might react as an inhibitor of pancreatic proteinases rather than an inhibitor of throm

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01374.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.Analyses of the urinary concentration relative to creatinine of the collagen crosslinks, pyridino‐line (Pyd) and deoxy‐pyridinoline (Dpd) were made in 47 patients with metabolic bone diseases to assess the validity of these assays as indicators of bone resorption. The mean values for patients with Paget's disease of bone, primary hyperparathyroidism and osteomalacia were significantly higher (P<0.001) than those for age‐matched healthy individuals. During treatment of Paget's disease with bisphosphonates, there was a steady decline in the urinary concentration of the crosslinks to the normal range; this change occurred earlier than for serum alkaline phosphatase. There were significant correlations (P<0.01) between the concentrations of both crosslinks and the corresponding values for hydroxyproline. At lower crosslink concentrations, however, these relationships were less marked due to large variations in hydroxyproline values. The results show that measurements of urinary Pyd and Dpd provide clinically applicable indices of bone resorption that are more specific than other ma

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01375.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.Since glutathione (GSH) is involved in the modulation of the function of polymorphonuclear leucocytes (PMN) such as phagocytosis and production of reactive oxygen species, the metabolism of GSH was studied in human PMN. The concentration of GSH in resting PMN amounted to 13.3 nmol 10‐7PMN and remained stable over 100 min of incubation. Upon activation of PMN with phorbol myristate acetate intracellular GSH decreased to 50% of the resting concentration within 80 min. In the presence of buthionine sulfoximine, which inhibits the synthesis of GSH, the depletion of intracellular GSH was dramatically accelerated, indicating that activation of PMN is associated with a marked stimulation of GSH synthesis. Since a similar depletion of GSH was seen in the presence of propargylglycine, an inhibitor of the cystathionine pathway, most of the cysteine required for the resynthesis of GSH must originate from methionine and not from cysteine generated by the catabolism of GSH. Further studies showed that GSH is sequentially oxidized by O2‐and HOCl, first to GSSG and then to an unidentified compound, most likely a chloramine. In the presence of an adequate supply of GSH and NADPH which is required for the reduction of GSSG ‐by glutathione reductase this further oxidation of GSSG was prevented. Thus, the highly toxic HOCl generated by PMN can be detoxified by the glutathione reductase system. The capacity of PMN to re‐synthesize GSH may be an important determinant of PMN f

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01376.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P‐III‐NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P‐III‐NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age‐matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow‐up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P‐III‐NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P=0.00097) and in 79% of patients with active liver cirrhosis (P=0.0126) but not in patients with chronic persistent hepatitis (P= 0.06). Serum concentrations (medians) of HA were increased (P= 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P<6.10‐7). The difference of HA serum concentrations but not that of P‐III‐NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P‐III‐NP serum concentrations were significantly elevated in 22 patients with acute hepatitis. Serum concentrations of P‐III‐NP in patients with autoimmune chronic liver disease significantly decreased during immunosuppressive therapy in patients with autoimmune chronic active hepatitis (P= 0.0001) and in patients with autoimmune active cirrhosis (P= 0.0039); HA serum concentration decreased to normal level in patients with autoimmune chronic active hepatitis (P= 0.0017); in contrast, when cirrhosis was present, serum HA levels decreased but remained elevated (P= 0.129).It is concluded that determination of HA serum concentrations will help to differentiate chronic active hepatitis from active cirrhosis. While elevated P‐III‐NP serum concentrations mainly correlate with inflammatory activity, elevated HA serum concentrations seem to be an expression of mainly the reduced functional (clearance function) capacity of the liver in chronic liver diseases. Therefore determination of HA serum concentration is of greater diagnostic value, especially

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01377.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.It has been reported that atherosclerotic lesions contain genomic material belonging to members of the herpes family. This suggests that latent viral infection may be one of the atherogenic triggers. In this study we show that early infection of endothelial cell monolayers with Herpes Simplex virus type 1 (HSV‐1) or Cytomegalovirus (CMV) results in an increased monocyte (MC) and polymorphonuclear leukocyte (PMN) adherence, but not in an increased platelet adhesion. Further, is demonstrated that MC and PMN respond differently to virus infected endothelial cell monolayers: PMN adhesion to CMV infected cells is approximately 430% of the control adherence, while the MC adherence is increased to 160%. Also, a difference in virus acting is observed: the adherence of MC or PMN to HSV‐1 infected endothelial cells is caused by a secreted adherence promoting factor, while the adherence of MC or PMN to CMV infected endothelial cells seems to be a cell‐bound phenomenon. In addition, it was demonstrated that the augmentation of MC or PMN adherence to virus infected endothelial cells is sensitive to tunicamycin, suggesting that both virus infections induce the expression of glycoproteins on the endothelial cell membrane, which is responsible for the MC and PMN adhesion.Thus, HSV‐1 and CMV infection of endothelium results in an increased adherence of leukocytes which is suggested, irrespective of the precise nature of the mechanism of virus induced atherosclerosis, to be the earliest event associated with endothelium cell

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01378.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY