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Biomedical subjects

K Bech

Publications and source records attributed to K Bech.

At least 37 records · Page 2Linked to original sources

Intra-arterial versus intravenous administration of gastric secretory inhibitors in conscious dogs. Effects of somatostatin, serotonin and isoprenaline on acid and pepsin secretion.

The purpose of the present study was to evaluate the effects of both intra-arterial and intravenous infusions of somatostatin, serotonin (5-hydroxytryptamine) and isoprenaline beta 1- + beta 2-adrenoceptor agonist) on gastric acid and pepsin secretion in conscious dogs with a gastric fistula. The drugs mentioned have been examined earlier for effects on gastric secretion in vivo during intravenous infusions and these effects could be hampered by the possible indirect mechanism of action as well as the different kinetics of metabolism. A catheter (vascular access port) allowed repeatedly gastric intra-arterial infusions. Somatostatin and serotonin possessed inhibitory effects on gastric acid and pepsin secretion and were without significant differences between the analyzed ways of administration. Intra-arterial infusion, isoprenaline possessed less potent inhibitory effects on gastric secretion: the effects were significant for pepsin secretion but were nonsignificant for acid secretion. The results suggest the mechanism of action of isoprenaline, somatostatin and sertonin to diverge, and for somatostatin and serotonin it was independent of the route of administration.

Animals

BRL 24924, a 5-hydroxytryptamine type 3 antagonist, and gastric secretion of acid and pepsin in vivo.

BRL 24924, a specific 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, was evaluated for effects on gastric secretion of acid and pepsin and possible influences on the effects of serotonin on gastric secretion. Experiments were carried out in conscious dogs with a gastric fistula during a background stimulation of gastric secretion by continuous infusions of pentagastrin, bethanechol or histamine. During infusion of pentagastrin or histamine, BRL 24924, by itself, influenced gastric secretion with stimulation during a low potent background stimulation and inhibition during a potent background stimulation. A serotonin-counteracting effect of BRL 24924 on gastric secretion was found only during infusion of pentagastrin. The secretory stimulation attained by BRL 24924 could be blocked by atropin suggesting a cholinergic mechanism--5-HT4 receptors? The inhibitory effects on gastric secretion and the serotonin-counteracting effects of BRL 24924 are supposed to be via 5-HT3 receptors.

Animals

Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy.

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.

Adult

Influence of interleukin 6 on the function of secondary cultures of human thyrocytes.

Interleukin 6 has been suggested as second mediator of the effects of interleukin 1 in some cell systems. Interleukin 1 has previously been shown to inhibit the function of human thyrocytes in secondary cultures. We have therefore studied the influence of interleukin 6 (10(-1)-5.10(7) U/l) on the function of thyroid cells. Recombinant interleukin 6 slightly inhibited the production of cAMP, but failed to influence the production of thyroglobulin or the DNA content. Endotoxins (lipopolysaccharides from Salmonella abortus equi or Yersinia enterocolitica) had only a slightly inhibitory effect on thyroid cell functions, and the effect of interleukin 6 could not by itself be explained by endotoxin contamination. The effect of interleukin 6 did not mimic effects on thyroid cells afforded by recombinant interleukin 1 alpha and 1 beta. Furthermore, antibodies to interleukin 6 were not able to inhibit the interleukin 1 beta-induced inhibition of thyroid cell functions. In conclusion, it is unlikely that interleukin 6 by itself mediates the biological effects of interleukin 1 on human thyroid cells.

Antibodies

Effect of maternal thyroid autoantibodies and post-partum thyroiditis on the fetus and neonate.

Thirty-five pregnant women with thyroid antibodies were followed during pregnancy and 12 month post partum. Twenty antibody-negative women served as controls and none of these developed postpartum thyroiditis in contrast to 12 of 35 antibody-positive women. Umbilical cord blood was collected at birth for measurements of thyroid antibodies, and blood samples for measurements of thyroid hormones were obtained at 5 and 30 days of age in the infants together with a clinical examination. There were no differences between the infants of antibody-positive and -negative mothers or the infants of those who developed postpartum thyroiditis with regard to gestational age at birth, birth weight, birth length or Apgar score, and no difference in thyroid function of the mothers and infants. However, serum TSH level was significantly higher in mothers who subsequently developed postpartum thyroiditis. Furthermore, a significantly lower growth during the first 30 days of life was observed in their infants. Our observations suggest a relationship between the maternal thyroid status in pregnancy and early growth in infancy.

Autoantibodies

Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1.

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.

Animals

Anti-thyroid peroxidase antibodies in thyroid disorders and non-thyroid autoimmune diseases.

A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.

Adolescent

[The pH and acidity of feces in colorectal neoplasms].

The pH and faecal titratable acidity in fresh faeces were measured in patients with colo-rectal carcinoma or adenoma and in normal individuals. Significantly higher pH values and lower acidity were found in patients with cancer than in normal individuals. Patients with cancer had pH greater than 6.90 more frequently than normal. Patients with adenomata did not differ significantly from normal individuals. These results support performance of intervention trials with lowering of the pH in the colon with the object of cancer prophylaxis even although the causal connection is obscure.

Adenoma

Differential effects of interleukin 1 alpha and 1 beta on cultured human and rat thyroid epithelial cells.

The effects of human recombinant interleukin 1 alpha (20 pg/1-2 micrograms/l) and 1 beta (200 pg/1-20 micrograms/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1 beta (20 ng/1-20 micrograms/l), but not by interleukin 1 alpha. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

Animals

Yersinia enterocolitica and thyroid autoimmunity.

The concordance rate of Graves' disease in pairs of identical twins of 30 to 60% points to the influence of environmental factors, and infections have often been incriminated in the pathogenesis. More than 15 years ago we demonstrated an increased frequency of antibodies to Yersinia enterocolitica (Y. ent.) serotype 3, which later was confirmed by others, suggesting a link between infection with Y. ent. and autoimmune thyroid diseases.

Animals

Importance of cytolytic activity and dietary iodine in the pathogenesis of postpartum thyroiditis.

The incidence of lymphocytic thyroiditis (LT) has increased since the introduction of iodine prophylaxis, and LT is claimed to represent an adverse reaction to iodine. This theory is supported by animal studies as well as experimental studies in humans. In pregnancy iodine turnover is increased. During the immunological rebound period occurring postpartum the thyroid autoantibodies increase, and may lead to postpartum thyroiditis (PPT). The iodine content within the gland may be important for this reaction. In vitro it has been shown that iodine inhibits the cAMP-dependent events of the thyroid cell function, but iodine may also stimulate the intrathyroidal immuno-competent cells leading to cytokine synthesis. Cytokines have been shown to interfer with the thyroid cell function. Iodine may thus trigger the autoreactive attack and enhance the local autoantibody production, which plays a primary pathogenic role for development of PPT.

Animals

Characterization of the natural killer cell activity in Hashimoto's and Graves' diseases.

Natural killer (NK) cell activity and blood mononuclear cell subpopulations were characterized in patients with Hashimoto's thyroiditis (n = 11), Graves' disease (n = 20), non-toxic goitre (n = 10) and in normal controls (n = 22). NK cell activity against K 562 target cells and the capability of IFN-alpha, Il-2, and indomethacin to enhance NK cell activity in vitro did not differ significantly between the groups. The percentages of large granular lymphocytes, CD5+, CD4+, CD8+ and CD16+ cells were normal in patients with non-toxic goitre, Hashimoto's and Graves' diseases. There was no correlation between NK cell activities and TgAb, MAb and TSAb. Although NK cell activity is suppressed in several autoimmune diseases, NK cell function is normal in patients with autoimmune thyroid disorders.

Adult

Repeated screening for colorectal cancer with fecal occult blood test. A prospective randomized study at Funen, Denmark.

Two screenings with Hemoccult-II were performed in a randomized study, allocating 30,970 persons to screening and 30,968 as controls in a population of 140,000 between 45 and 74 years old on the island of Funen, Denmark. The test was completed in 20,672 initially and in 18,779 of these during rescreening 2 years later. Positive H-II tests were found in 215 and 159 persons during the two screenings, respectively. A total colonoscopy was performed in 187 and 144, and cancer was detected in 37 and 13 and adenomata in 86 and 76, respectively. Interval cancers had developed in 40 persons at the end of the second screening, and 39 non-responders had developed cancer. Cancer was diagnosed in 115 controls and an adenoma in 100 during the same period. Interval cancers presented as rectal cancers more frequently than those detected by screening. Early cancers were more frequent in the screening group, and, accordingly, more patients had curative and also less extensive surgery, with a low postoperative mortality. The total number of deaths from colorectal cancer was 37 in the screening group, including interval cancers and cancers in non-responders and persons who developed cancer before they could be invited, which suggests a reduction in mortality of 27% (51 deaths among controls, compared with 37). The reduction is as yet not statistically significant, and final evaluation must await at least one more screening, ending in 1990, and a follow-up of some years. Removal of more large adenomas during screening makes it possible that the incidence of cancer will decrease.

Adenoma

Thyroid function in patients with Pendred's syndrome.

Thyroid function was studied in 17 unrelated patients with Pendred's syndrome. Fourteen patients had been treated with L-thyroxine, which was withdrawn during the investigation. Eight of the patients had previously had a thyroid resection. Thirteen patients had goiter at the time of study. The serum total thyroxine and serum total triiodothyronine concentrations were normal in 8, of whom 3 had elevated serum TSH concentrations. In the remaining 9 cases the thyroxine levels were below normal with elevated TSH. Serum reverse triiodothyronine concentrations were decreased in 8 out of 11. Median serum thyroglobulin was 973 micrograms/l (range 10.9-3200 micrograms/l) and increased in 13. Three patients had slightly positive thyroglobulin antibodies and one with normal level was thyrodectomized. Thyroid stimulating antibodies as measured by adenylate cyclase stimulation (median 114%, range 85-137%) were slightly increased in 11. When measured as TSH binding inhibiting immunoglobulins none were positive. Thyroid microsomal antibodies were negative in all. All patients with a detectable 131I uptake (n = 15) showed a pathological iodide perchlorate discharge test (median 32%, range 16-46%). These findings indicate an organification defect with impaired hormone synthesis.

Adolescent

Interleukin-1 affects the function of cultured human thyroid cells.

Cytokines are peptide hormones essential for cellular communication in the immune response. The purpose of this study was to investigate the influence of cytokines, especially recombinant interleukin 1 beta (rIL-1 beta), on human thyroid cells. Thyroglobulin (Tg) was measured by a double antibody radioimmunoassay, and cyclic AMP (cAMP) by a competitive protein binding assay. Supernatants from unstimulated and phytohaemagglutinin-stimulated blood mononuclear cells were added to human thyroid cells cultured in monolayers. A dose-dependent inhibition of the secretion of Tg and cAMP was demonstrated. Both subcultured and primary cultured cells incubated with rIL-1 beta at pharmacological levels (10(-1)-10(2) U/ml) exhibited an inhibition of Tg and cAMP secretion, while at physiological levels (10(-5)-10(-3) U/ml), the secretion of Tg was enhanced. The similar stimulation of cAMP was demonstrated in subcultures. These in vitro studies suggest that IL-1 beta may play a role in the pathogenesis of autoimmune thyroid diseases. Further, the stimulations at low concentrations indicate that IL-1 beta may regulate the function of the thyroid gland under physiological conditions.

Autoimmune Diseases

Hepatitis B in symptomless Danish homosexual men.

Forty eight symptomless homosexual men attending a sexually transmitted disease (STD) clinic and found by screening to have hepatitis B surface antigen (HBsAg) were followed up for a median of 10 (range six to 26) months to characterise their liver disease. Initially 33/50 (66%) of the men had increased serum liver enzyme activity and 19/47 (40%) had increased serum immunoglobulin G concentrations. Liver biopsy specimens showed acute hepatitis B in 12 (39%) and chronic hepatitis B in 19 (61%) of the 31 patients who underwent liver biopsy. The course of the infection was: acute hepatitis B in 14/48 (29%), chronic persistent hepatitis B in 23/48 (48%), chronic aggressive hepatitis B in 8/48 (17%), and cirrhosis in 3/48 (6%) of the patients. Antibodies against human immunodeficiency virus (HIV) were present in 16/45 (36%) of the patients, but the presence of antibodies to HIV did not influence the course of hepatitis B in the observation period.

Adult

The role of somatostatin and serotonin in the beta-adrenoceptor regulation of gastric function. An experimental study in dogs.

CHAPTER 1. The gastric functions are regulated in a complex manner by the autonomic nervous system, sympathetic and parasympathetic, and hormones and moreover by a system of peptide-containing cells and nerves. The sympathetic influence is mediated by alpha- and beta-adrenoceptors, beta-adrenoceptor agonists in general inhibit the gastric functions. The effects of the beta-adrenoceptors are probably mediated indirectly, and the responsible mechanism may be via release of and endogenous mediator--somatostatin or serotonin. The purpose of the present study, described in the survey, is to examine whether somatostatin or serotonin acts as a mediator for the gastric effects in vivo of beta-adrenoceptor agonists. The proposed mediator must present the following characteristics: A. Inhibitory effects of "physiological" doses in vivo. B. Inhibitory characteristics similar to those of the beta-adrenoceptor agonists. C. A beta-adrenoceptor mediated release. CHAPTER 2. In this chapter the known effects of beta-adrenoceptor agonists on gastric functions (acid secretion, pepsin secretion, antral motility and mucosal blood flow) are presented. The possible mechanisms mediating these effects are mentioned, and the effects of somatostatin and serotonin are reviewed. Beta-adrenoceptor agonists inhibit the acid secretion in vivo in several species, but stimulate in vitro. A similar pattern is probable as for the pepsin secretion, but sufficient results are not available in order to draw a certain conclusion. The antral motility is inhibited both in vivo and in vitro. The mucosal blood flow is increased compared to the acid secretion, however the results points to variable effects depending on the circumstances of the experiments. On the basis of the reviewed effects of somatostatin it is concluded that the effects are inhibitory, but the inhibitory characteristics are not known. A beta-adrenoceptor mediated release of somatostatin has been found, but it has not been examined selectively for the stomach. The gastric effects of serotonin has been sparsely examined and it is not possible to determine the effects as parts of a certain characteristic. It is concluded that neither somatostatin nor serotonin have been examined sufficiently to determine which is the proposed mediator. CHAPTER 3. The materials and methods used are reviewed. Dogs were used and various parameters were measured--acid secretion by titration, pepsin secretion by enzymatic process with haemoglobin as substrate, antral motility by registration of intraluminal pressure, mucosal blood flow by the clearance of neutral red, somatostatin by radioimmunoassay.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Agonists