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Biomedical subjects

U Knigge

Publications and source records attributed to U Knigge.

104 records · Page 6Linked to original sources
PubMed1984

Failure of proximal gastric vagotomy for duodenal ulcer resistant to cimetidine.

45 patients with uncomplicated duodenal ulcer who did not respond to cimetidine underwent elective proximal gastric vagotomy (PGV). 39 of these, who had received cimetidine for an average of 5.2 months before surgery, were followed up for 20-67 months postoperatively. 18(46%) of them were classified as grade IV (ie, failures) according to a modified Visick scale--17 (44%) had a recurrent peptic ulcer. Augmented histamine tests done in 17 patients showed an expected reduction of peak acid output, so maintenance of stomach acidity was unlikely to be a cause of failure of the operation. The presence of mental and social problems preoperatively was associated with a postoperative Visick grade IV. Despite repeated medical therapy, and reoperation in 6 patients, 10(26%) patients still had severe pain and/or dumping at follow up. Proximal gastric vagotomy cannot be advocated in patients with uncomplicated duodenal ulcer resistant to cimetidine, and an alternative treatment is needed for these patients.

Adult↗
PubMed1984

Modulation of basal and LRH-stimulated gonadotrophin secretion by histamine in normal men.

The effects of histamine (HA) and of HA in combination with H1- and H2-receptor antagonists on basal and LRH-receptor antagonists on basal and LRH-stimulated LH and FSH secretion were investigated in 10 normal men. HA enhanced the LH response to LRH (p less than 0.05), but had no effect on basal LH secretion. The enhancement of LRH-stimulated LH secretion was not observed when either an H1- (mepyramine) or an H2- (cimetidine) receptor antagonist was administered concomitantly with HA. Cimetidine administered alone had no effect on basal or LRH-stimulated LH secretion. HA had no effect on basal or LRH-stimulated FSH secretion. We conclude that the effect of HA on LRH-stimulated LH secretion is mediated through a combined stimulation of H1- and H2-receptors.

Animals↗
PubMed1984

Histamine-induced paradoxical growth hormone response to thyrotropin-releasing hormone in normal men.

GH responses to TRH occur in patients with certain diseases, such as acromegaly, severe liver disease, uremia, and mental disorders, and presumably reflect disruption of normal hypothalamic control of GH secretion. Since histamine (HA) inhibits hypothalamic stimulation of GH secretion, we investigated the combined effect of HA receptor activation and TRH administration on GH secretion in normal men. Eight men were given 4-h infusions of the following: saline, HA, HA plus mepyramine (Me; and H1-antagonist), HA plus cimetidine (C; an H2-antagonist), and C alone. TRH (200 micrograms) was injected iv 2 h after the start of each infusion. HA alone or in combination with either antagonist had no effect on basal or TRH-stimulated TSH secretion and no effect on basal GH secretion. However, when TRH was injected during H1 stimulation by HA plus C, GH secretion increased significantly [from 0.7 +/- 0.1 to 7.1 +/- 1.8 (+/- SEM) ng/ml; P less than 0.01] in seven of eight subjects. This GH response was reproducible and did not occur when saline was administered instead of TRH. A smaller and delayed GH response to TRH occurred during infusions of HA alone (from 0.8 +/- 0.1 to 4.9 +/- 1.0 ng/ml; P less than 0.05). No effect of TRH on GH secretion occurred during the infusion of saline (1.2 +/- 0.3 ng/ml), HA plus Me (0.9 +/- 0.1 ng/ml), or C (2.2 +/- 1.0 ng/ml). There was a significant increase in GH secretion after cessation of the infusions of HA (from 3.4 +/- 1.1 to 7.5 +/- 2.2 ng/ml) and HA plus Me (from 0.8 +/- 0.1 to 5.1 +/- 1.8 ng/ml). This rebound in GH secretion might indicate an inhibitory effect of TRH during H2-receptor stimulation. This concept is supported by the significantly smaller GH response to TRH during HA infusion than during HA plus C infusion (P less than 0.01). The study indicates that H1-receptor stimulation induces a stimulatory effect of TRH on GH secretion in normal men and that H2-receptor stimulation possibly induces an inhibitory effect of TRH on GH secretion.

Adult↗
PubMed1984

Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men.

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.

Adult↗
PubMed1984

Radioimmunoassay, pharmacokinetics, and neuronal release of gastrin-releasing peptide in anesthetized pigs.

Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.

Adrenalectomy↗
PubMed1983

The effect of histamine stimulation and H2 -receptor inhibition on the pituitary prolactin and ACTH release and on cortisol secretion in human males.

The effects of histamine (HA) on prolactin (PRL), ACTH, and cortisol secretion in human males were investigated. Specific H2 -receptor blockade caused an immediate and significant PRL release, while specific H2 -receptor stimulation (HA and mepyramine) was without effect on PRL secretion. HA significantly stimulated both ACTH and cortisol secretion, and this stimulation was probably mediated through H2 -receptors, H2 -receptor blockade caused a late, but significant ACTH release. This release was not accompanied by a release of cortisol, and might therefore be due to a spontaneous oscillation in ACTH secretion. The results support the theory that HA acts as a modulator of human ACTH secretion. A similar effect on PRL secretion as postulated by others could not be confirmed in this study.

Adrenocorticotropic Hormone↗
PubMed1983

The acute and long term effect of the H2-receptor antagonists cimetidine and ranitidine on the pituitary-gonadal axis in men.

We have investigated the effect on the human pituitary-gonadal axis of the H2-receptor antagonists cimetidine 300 mg and ranitidine 50, 100, and 200 mg by i.v. bolus, or treatment for 6 months with either cimetidine (1000 mg/day for 1.5 months followed by 400 mg/day for 4.5 months) or ranitidine (200-400 mg/day for 1.5 months followed by 100-200 mg/day for 4.5 months). Administration of the H2-antagonists (i.v.) to normal men did not cause any release of LH, FSH, or testosterone. Long-term treatment with cimetidine of duodenal ulcer patients caused a significant rise in basal LH (6 weeks) and FSH secretion (11 weeks). Following reduction of the cimetidine dose LH and later FSH returned to pre-treatment values. However, despite reduction of the cimetidine dose, the LH and FSH responses to LHRH stimulation were still significantly higher after 6 months of treatment compared with pre-treatment responses. No changes were found in basal or in LHRH stimulated testosterone or dihydrotestosterone secretion. Treatment with the more potent H2-antagonist ranitidine did not cause any change in basal or in LHRH stimulated LH and FSH secretion. The effects on LH and FSH secretion observed during cimetidine treatment might therefore be caused by other mechanisms than blockade of H2-receptors. It is possible that cimetidine, having anti-androgen properties, blocks pituitary or hypothalamic androgen receptors.

Adult↗
PubMed1982

The effect of long-term cimetidine treatment on PRL and TSH response capacity to TRH in male patients with duodenal ulcer.

The effect of long-term cimetidine treatment for 6 months on basal and thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion was studied in eight male patients with duodenal ulcer. They received 1,000 mg cimetidine orally per day until ulcer healing and thereafter 400 mg daily for the remaining period. TRH perturbation tests were performed before and after the 6 months of treatment. A significant reduction in the pituitary TSH response capacity was found. No significant changes in basal and TRH-stimulated PRL, basal TSH, thyroxine and triiodothyronine were found. It is uncertain if the reduction in pituitary TSH response capacity has any clinical implications in euthyroid patients.

Adult↗
PubMed1982

Effect of the plasma estrone/17 beta-estradiol ratio on the prolactin and TSH responses to TRH.

This study was undertaken to test whether ratios between plasma concentrations of different estrogens would be more determinant of prolactin (PRL) secretion than plasma concentrations of estrogens per se have been found to be. Oral administration of micronized 17 beta-estradiol in a dose of 2 mg b.i.d. for 1 month to 7 postmenopausal women raised plasma estrone (E1) from a median of 29 to 683 pg/ml and plasma 17 beta-estradiol (E2) from a median of 5.7 to 131 pg/ml. The E1/E2 ratios rose from a median of 4.01 to 4.92 (Pwilcoxon (Pw) greater than 0.025). Basal serum PRL increased from a median of 79.2 to 100 microIU/ml (Pw) greater than 0.025). However, the area under the curve of the PRL response to TRH increased from a median of 2,553 mm2 before to 3,919 mm2 after treatment (Pw less than 0.025). Highly significant correlations existed between the E1/E2 ratios and the PRL responses to TRH both before (rspearman (rs) = 0.964) (Pspearman (Ps) less than 0.005) and after (rs = 1.000) (Ps less than 0.00025) estradiol treatment, whereas no correlations (Ps less than 0.679) existed between plasma concentrations of E1 or E2 per se and either basal serum PRL or PRL response to TRH. The regression curves of best fit between the E1/E2 ratios and the PRL responses to TRH were hyperbolic both before (r = 0.884) and after (r = 0.996) treatment. These results, showing that the E1/E2 ratio rather than the plasma E1 or E2 concentrations per se are correlated to the PRL responses to TRH, imply that the metabolic conversion rate of estrogens modulates PRL secretion.

Estradiol↗
PubMed1982

Histamine regulation of prolactin secretion through H1- and H2-receptors.

Histamine (HA) regulates PRL secretion in the rat by a stimulatory effect through H1-receptors and an inhibitory effect through H2-receptors. The effect of HA antagonists on basal and TRH-stimulated PRL secretion was investigated in five normal men. During saline infusion, serum PRL declined, as seen normally after sleep. HA infusion caused a significantly higher PRL secretion than that observed during the saline infusion [maximum change in PRL (delta PRL), 28 +/- 20 vs. -71 +/- 30 microIU/ml; P less than 0.05]. This effect of HA on PRL secretion was inhibited during the combined infusion of HA and the H1-antagonist mepyramine (delta PRL, 28 +/- 20 vs. -77 +/- 13 microIU/ml; P less than 0.025). The PRL-stimulating effect of HA was strongly enhanced during the combined infusion of HA and the H2-antagonist cimetidine (delta PRL, -28 +/- 20 vs. 132 +/- 57 microIU/ml; P less than 0.0125). This effect of HA and cimetidine on PRL secretion was higher than the effect of cimetidine alone (delta PRL, 132 +/- 57 vs. 17 +/- 22 microIU/ml; P less than 0.05). This shows that the H2-antagonist is not the only stimulator of PRL secretion. During the different infusions, serum PRL concentrations were in the following rank order: mepyramine less than saline less than HA less than cimetidine less than HA plus cimetidine. The same rank order was found for the PRL responses to TRH during the different infusions. These data indicate a HA stimulatory effect through H1-receptors and an inhibitory effect through H2-receptors on PRL secretion in human males.

Cimetidine↗
PubMed1981

Comparison between dose-responses of prolactin, thyroid stimulating hormone and growth hormone to two different histamine H-2 receptor antagonists in normal men.

The effects of the histamine H2-receptor antagonists, ranitidine and cimetidine on prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) were studied in six normal males. Intravenous bolus injections of saline and of 50, 100, and 200 mg ranitidine and 300 mg cimetidine were tested. Ranitidine (100 and 200 mg) and cimetidine (300 mg) caused a significant increase in PRL secretion, whereas saline and ranitidine (50 mg) did not. TSH and GH secretion were unaffected by all doses. A dose-response relationship between ranitidine and PRL was established, and a dose of 65 mg ranitidine was found to be the minimal effective PRL-releasing dose. Plasma ranitidine concentration was measured by specific RIA. The results indicate an effect of H2-receptor antagonists on physiological functions in the control of PRL secretion. Histamine, therefore, may play a role in the regulation of PRL secretion.

Adult↗
PubMedDate not supplied

Effect of interleukin 1beta on the HPA axis in H1-receptor knockout mice.

OBJECTIVES AND METHODS: Circulating cytokines such as interleukin-1 (IL-1), and tumor necrosis factor-alpha as well as lipopolysaccharide (LPS) are potent ACTH secretagogues, acting via stimulation of corticotropin-releasing hormone (CRH) and vasopressinergic neurons in the paraventricular nucleus of the hypothalamus (PVN). Histamine (HA) has been shown to stimulate ACTH secretion in rats, an effect in part mediated by CRH and arginine vasopressin (AVP). We have previously shown that inhibition of neuronal HA synthesis or central blockade of H(1) receptors (H(1)R) decreased the ACTH response to LPS in male rats. To further elucidate the role of neuronal HA in cytokine-induced activation of the HPA axis, we compared the effect of H(1)R knockout on IL-1beta-induced ACTH secretion in adult male mice. RESULTS: In H(1)R knockout mice, ACTH secretion increased from basal levels of 261 to 492 pmol/l in response to IL-1beta whereas the cytokine-induced ACTH secretion increased from 140 to 406 pmol/l in wild-type mice. Plasma corticosterone (CORT) rose from basal levels of 99 to 831 nmol/l in knockout mice upon IL-1beta stimulation, whereas in wild-type mice CORT levels rose from 112 to 841 nmol/l. There was no significant difference in IL-1beta-stimulated plasma ACTH or CORT levels between wild-type and knockout mice. Furthermore, there was no significant difference in basal or IL-1beta-stimulated hypothalamic levels of histamine and tele-methyl-histamine between wild-type and knockout mice. HDC gene expression was significantly lower in knockout mice than in wild-type mice both under basal and IL-1beta-stimulated conditions, while there were no significant differences in CRH gene expression in the PVN in knockout mice under basal and IL-1beta-stimulated conditions. Increased basal expression of AVP in the PVN of knockout mice was observed in this study compared to wild-type mice. CONCLUSION: We conclude that the lack of the gene for histamine H(1)R does not seem to be crucial for the ACTH and CORT response to IL-1beta, either due to possible functional compensation in the H(1)R knockout mouse or due to activation of pathways other than the neuronal histaminergic system.

Adrenocorticotropic Hormone↗