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Biomedical subjects

F Kern

Publications and source records attributed to F Kern.

At least 109 records · Page 6Linked to original sources
PubMed1979

A trial of sulfasalazine as adjunctive therapy in Crohn's disease.

The effect of the combination of sulfasalazine and prednisone has been compared with that of prednisone and placebo in 89 actively symptomatic patients with Crohn's disease in a double-blind, randomized, multicenter controlled trial. The combination was less effective than prednisone alone in treatment of active symptomatic disease. The probability of obtaining this result, if sulfasalazine truly has a clinically useful effect equal to or greater than that specified in the calculation, is less than 1%. Patients who were in remission at the end of 8 wk were rerandomized to receive either the two drugs together or prednisone plus placebo while repeated systematic attempts to withdraw prednisone were made over the next 6 mo. Sulfasalazine showed no prednisone-sparing effect as judged either by outcome ranking or total dose of prednisone consmed by the two treatment groups. However, in this comparison the probability is greater than 5% that, given the results observed, a clinically useful effect of sulfasalazine of specified minimum degree truly exists. It was possible to withdraw prednisone from 25% of patients at the first attempt and ultimately in 37%.

Adult↗
PubMed1979

[Early diagnosis of small airways disease in young smokers (author's transl)].

Investigations during the past years have established that determinations of closing volume, flow-volume curves and frequency-dependent compliance are capable of detecting pathological changes in the bronchial system at a time when the customary lung function tests (FEV1.0 resistance as measured by bodyplethysmography) are still normal. These observations have been made use of to diagnose incipient damage in persons exposed to bronchial noxae. In the present investigation the effect of smoking on the airways was studied in a group of 25 persons aged 20-25 years by determining the closing volume and differences in ventilatory distribution (Thews method). The results were compared with those obtained in a group of 27 non-smokers in the same age group.

Adult↗
PubMed1979

Why more women than men have cholesterol gallstones: studies of biliary lipids in pregnancy.

More women than men have cholesterol gallstones. This probably to a large extent owing to ovarian hormones. Our preliminary studies suggest that the biliary lipid composition and gallbladder function may be abnormal in pregnancy. Studies are in progress to clarify these suggestive changes. We hope that the studies will allow us to determine the relevance of pregnancy to the pathogenesis of cholesterol gallstones.

Adult↗
PubMed1978

Reversal by triton WR-1339 of ethynyloestradiol-induced hepatic cholesterol esterification.

RATS TREATED WITH ETHYNYLOESTRADIOL HAVE MARKED HYPOLIPIDAEMIA: serum cholesterol is decreased to 5%, triacylglycerol to 10% and phospholipid to 70% of control concentrations. Loss of serum cholesterol follows an exponential decay, with a half-life of 1.13+/-0.09 days. After 4 days of treatment, serum cholesterol concentrations remain relatively constant (ranging from 1 to 20mg/100ml) for at least 30 days. There is a concomitant 20-fold decrease in the d<1.21 fraction of serum proteins and a similar decrease in serum apolipoproteins as measured by sodium dodecyl sulphate/10%-polyacrylamide-gel electrophoresis. The activity of hepatic microsomal acyl-CoA-cholesterol O-acetyltransferase (EC 2.3.1.26) was significantly increased by ethynyloestradiol treatment (P<0.05). This activation caused hepatic cholesteryl esters containing mainly C(18:1) fatty acids to increase linearly as serum cholesterol concentrations decreased (r=0.9675, P<0.001). Triton WR-1339, a non-ionic detergent that inhibits lipoprotein catabolism, was used to estimate hepatic lipid secretion by measuring the increment in serum lipids after its administration. At 15h after Triton WR-1339 administration, serum cholesterol concentrations were increased equally in both control and ethynyloestradiol-treated rats. In contrast, the increment of serum triacylglycerol of treated rats was 40% of that found in control rats, indicating that ethynyloestradiol inhibits hepatic triacylglycerol secretion. Triton WR-1339 inhibited the oestrogen activation of hepatic microsomal acyl-CoA-cholesterol O-acyltransferase and restored hepatic cholesteryl ester concentrations to normal values. These data suggest that ethynyloestradiol and its pharmacological ;antagonist' Triton WR-1339 alter hepatic triacylglycerol secretion via a mechanism associated with changes in hepatic cholesterol esterification.

Animals↗
PubMed1978

Alterations of hepatic Na+,K+-atpase and bile flow by estrogen: effects on liver surface membrane lipid structure and function.

Administration of the synthetic estrogen ethinyl estradiol (17alpha-ethinyl-1,3,5-estratriene-3,17beta-diol) decreases hepatic Na(+),K(+)-ATPase (ATP phosphohydrolase; EC 3.6.1.3) activity and bile flow to 50% and alters the composition and structure of surface membrane lipid in rats. Although the content of phospholipids was not changed by treatment, free cholesterol (130%) and cholesterol esters (400%) were increased in liver surface membrane fractions. These observations correlate with changes in membrane viscosity, as shown by electron spin resonance probes. Both rotational correlation time, using the isotropic probe methyl (12-nitroxyl)stearate, and the order parameter, determined by the anisotropic probe 5-nitroxylstearic acid, were significantly increased in liver surface membrane fractions from rats treated with ethinyl estradiol. Administration of Triton WR-1339, a nonionic detergent that corrects hepatic and serum lipid changes caused by ethinyl estradiol treatment, restored toward normal elevated membrane lipids and viscosity as well as Na(+),K(+)-ATPase activity and bile flow. Although restoration of normal liver surface membrane structure and function may be due to reversal of abnormal lipid composition, detergents also may directly alter membrane enzyme activity. Addition of Triton WR-1339 in vitro increased Na(+),K(+)-ATPase activity and reduced membrane viscosity of surface membranes from rats treated with ethinyl estradiol. Triton had no effect on either parameter in normal membrane preparations. Studies of membrane structure and function both in vivo and in vitro suggest that alterations in lipid composition may alter Na(+),K(+)-ATPase function and bile flow.

Animals↗
PubMed1978

Binding of bile acids by dietary fiber.

Binding of bile salts to food residue was studied in vitro and in vivo. In the in vitro experiments, residues of a number of foods were incubated with each of several bile salts at different concentrations and pHs. All food residues tested adsorbed more dihydroxy than trihydroxy bile salts. Bile salt binding increased as bile salt concentration increased and was greater at a low pH. The extent of bile salt adsorption to some food residues could be clinically important. In patients with short ileal resections, we compared the rates of fecal excretion of labelled cholic and chenodeoxycholic acids and of a nonabsorable marker during ingestion of an ordianry diet (approximately 5 g of fiber) and a residue-free liquid diet. Coefficients of bile salt adsorption were calculated. Both bile acids were absorbed more efficiently during the liquid diet. Chenodeoxycholic acid was preferentially bound to the particulate matter of stools of patients eating the fiber-containing diet. It seems possible that dietary fiber could affect the enterohepatic circulation of bile salts in certain patients with ileal resection.

Adsorption↗
PubMed1977

Minimal bile acid malabsorption and normal bile acid breath tests in cystic fibrosis and acquired pancreatic insufficiency.

This study was undertaken because of reports of a marked increase in fecal bile acid excretion by children with cystic fibrosis. We attempted to confirm this finding by performing [1-14C]cholylglycine breath tests and by measuring fecal bile acid and fat excretion in patients with cystic fibrosis and acquired pancreatic insufficiency. Studies were done when patients were taking pancreatic enzymes (Cotazym) and also without medication. 14CO2 excretion in breath was normal in patients with acquired pancreatic insufficiency and even lower in cystic fibrosis, both with and without Cotazym therapy. Fecal bile acid excretion was slightly elevated in both groups without Cotazym and became normal with Cotazym in patients with acquired pancreatic insufficiency. Steatorrhea was present in both patient groups and improved during Cotazym therapy. Bile acid malabsorption in cystic fibrosis and acquired pancreatic insufficiency is minimal and probably not clinically important.

Adult↗
PubMed1977

Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats.

Deoxycholic acid conjugation, transport capacity, and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats were found to have a lower capacity to transport deoxycholic acid than taurodeoxycholic acid, and both were decreased by ethinyl estradiol treatment. During [24-14C]sodium deoxycholate infusion, [14C]biliary bile acid secretion increased, but bile flow did not change significantly in either control or ethinyl estradiol-treated rats. Ethinyl estradiol-treated animals excreted significantly less 14C as taurocholic acid than did control animals, consistent with an impairment of 7alpha-hydroxylation of taurodeoxycholic acid. Ethinyl estradiol treatment did not impair conjugation of deoxycholic acid, but did result in an increase in sulfation of taurodeoxycholic acid from 1.5% in controls to nearly 4.0% (P less than 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. Furthermore, the rat converts deoxycholic acid, a poor choleretic, to taurocholic acid, a good choleretic. When this conversion is impaired with ethinyl estradiol treatment, sulfation may be an important alternate pathway for excretion of this potentially harmful bile acid.

Animals↗
PubMed1977

Effect of ethynylestradiol on biliary excretion of bile acids, phosphatidylcolines, and cholesterol in the bile fistula rat.

The effects of ethynylestradiol on endogenous bile acids, their capacity to conjugate and excrete intravenously infused cholic acid, the concentrations of biliary cholesterol and lecithin, and the individual molecular species of phosphatidylcholine have been determined in male and female Sprague-Dawley rats. Endogenous biliary bile acids were analyzed by gas-liquid chromatography-mass spectrometry. Eleven bile acids were identified and several minor bile acids, primarily muricholates, could not be completely characterized. After 5 days of treatment with ethynylestradiol (1 mg/kg per day), the percentage of cholic acid decreased and the percentage of 6beta-hydroxylated bile acids, including several monounsaturated species, increased. Ethynylestradiol caused a decrease in bile acid-independent bile flow. Intravenous infusion of cholic acid at a high concentration caused cholestasis in control animals but, after ethynylestradiol treatment, cholestasis developed during the infusion of a much lower concentration of cholate, indicating a lowered threshhold for bile acid-induced cholestasis. In the treated rats, there was a slight increase in excretion of unconjugated endogenous bile acids, and a striking impairment of conjugation of intravenously administered cholic acid. One of the few sex-related differences observed was an increased concentration of biliary phospholipids in untreated male rats. Both phospholipid and cholesterol concentrations in the bile were higher in the treated animals. The molar percentage of cholesterol was always 1-2%, but it was slightly higher in treated animals, especially males. Ethynylestradiol treatment also affected biliary phospholipid by causing a marked increase of phosphatidylcholine species containing palmitic and oleic acid residues and a decrease of species containing stearic and linoleic acid residues. There was no increase in biliary excretion of long chain polyunsaturated species, which might have indicated damage to membranes, in response to ethynylestradiol either alone or with cholic acid infusion. Some of these ethynylestradiol-induced changes in biliary bile acid and lipid excretion are probably peculiar to the rat, but others, such as the increase in molar percentage of cholesterol and cholestasis, may be relevant to disorders in man, especially cholesterol gallstones and idiopathic cholestasis of pregnancy.

Animals↗
PubMed1976

Allergy to insect sting. III. Allergenic cross-reactivity among the vespid venoms.

Recent reports have indicated that venoms may be more beneficial than whole body extracts for the diagnosis and treatment of Hymenoptera sensitive patients. These studies were undertaken to determine the cross-reactivity among the vespid venoms. Eighteen patients who were anaphylactically sensitive to vespid venoms were studied using in vitro leukocyte histamine release. The results (venom concentration for 50% histamine release) were analyzed by linear regression analysis; there was no allergenic cross-reactivity between any of the venoms, except for a modest association between yellow hornet and white hornet venom. In spite of this result 13 of the 18 patients studied were sensitive to three or four of the venoms tested. There is no clear explanation for this observation, but it suggests the existence of multiple major allergens in the vespid venoms, some of which are cross-reactive. Since immunotherapy with inappropriate proteins may lead to the development of IgE and the possibility of clinical sensitivity and since the majority of patients were not sensitive to all venom preparations, we suggest that appropriate diagnostic studies be carried out before the institution of therapy.

Animals↗
PubMed1976

Defective release of eosinophil chemotactic factor from peripheral leukocytes in patients with chronic urticaria.

Release of eosinophil chemotactic factor (ECF) and histamine was studied peripheral leukocytes of 16 normal and 12 ragweed allergic volunteers and compared to 15 patients with chronic urticaria. Cells were exposed to varying concentrations of anti-IgE or to ragweed antigen E in the case of allergic donors. Twelve of 15 patients with chronic urticaria showed defective release of ECF as well as histamine, while almost all normal and all allergic donors were able to release larger quantities of both mediators. Since the eosinophil is thought to have a modulating effect at sites of inflammation induced by anaphylactic mechanisms, the defective release of a factor attracting these cells may explain the persistence of symptoms in chronic urticaria.

Basophils↗
PubMed1976

Defective histamine release in chronic urticaria.

Histamine release from peripheral blood leukocytes challenged with anti-human IgE was studied in patients with chronic urticaria and nonatopic controls. 19 of 23 controls, but only 6 of 20 patients, released over 20% of the total available leukocyte histamine. The response to anti-IgE concentrations of 1.66, 0.33, 0.066, and 0.013 mug antibody N/ml was significantly lower in patients than in controls. Serum IgE levels were significantly higher in the patients but total histamine content of about 10(7) leukocytes was not. Deuterium oxide (D2O) greatly increased histamine release (in both groups), indicating that the anti-IgE interacted with the basophils of urticaria patients. Passive sensitization of leukocytes with biologically active IgE was achieved in both patients and control subjects whose cells responded to anti-IgE, but was not achieved in either patients or control subjects whose cells were nonresponsive to anti-IgE challenge. 125I-anti-IgE autoradiographic studies revealed no obvious quantitative abnormality in the amount of basophil-bound IgE in chronic urticaria patients. Ionophore stimulation of aliquots of the same leukocytes used for anti-IgE challenge demonstrated that the urticaria patients' basophils were capable of releasing normal amounts of histamine. Leukocyte cyclic AMP levels in the two groups were not significantly different either in base-line levels or in responsiveness to stimulation with isoproterenol. These data indicate that chronic urticaria patients have a (acquired?) defect in leukocyte histamine release that occurs after the anti-IgE-IgE interaction, but before the actual (second-stage) release process, and that is comparable to the phenomenon of desensitization.

Adolescent↗
PubMed1976

Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study.

Needing a single index of degree of illness in Crohn's disease, the National Cooperative Crohn's Disease Study group collected data prospectively from 187 visits of 112 patients with Crohn's disease of the small bowel, colon, or both. Information on 18 predictor variables was gathered at each visit. In addition, the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient's status with that at the previous visit. A multiple regression computer program was utilized to derive an equation for prediction of the physician's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints. This equation, numerically simplified and utilizing eight selected variables, is the Crohn's Disease Activity Index. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease, and values above 450 are seen with extremely severe disease.

Adult↗