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Biomedical subjects

H Ahlman

Publications and source records attributed to H Ahlman.

At least 127 records · Page 7Linked to original sources
PubMed1989

Expression of gastrointestinal endocrine tumours in culture systems.

Human endocrine tumours were studied in in vitro systems (cell suspensions and tissue cultures) and in in vivo systems (tumour transplants to the anterior eye-chamber of immunosuppressed rats). In the experimental systems the tumour cells were demonstrated to synthesize and secrete the same hormonal products as in the patient. Intraocular transplants of a gastrinoma secreted gastrin-17 into the chamber fluid. This molecule, normally not secreted in the rat, was also detected in the peripheral plasma of tumour-bearing rats. Intraocular transplants of midgut carcinoid tumours released serotonin (5-HT) at adrenoceptor stimulation, of a similar type as demonstrated in acute tumour cell suspensions. However, in tissue cultures genuine beta-adrenoceptors seemed to be modified, since pretreatment with beta-adrenoceptor antagonists or calcium deprivation did not prevent stimulated 5-HT release. Tachykinins were not liberated by adrenoceptor stimulation. In certain cultures of midgut carcinoid tumour cells, two different phenotypes developed: small rounded endocrine tumour cells with positive immunoreactions against 5-HT and tachykinins (TK), and large elongated neuron-like cells, which gradually lost 5-HT immunoreactivity, while TK immunoreactivity remained unchanged. These cultured tumour cells may produce an endogenous factor inducing transformation into a neuron-like phenotype. One candidate factor is nerve growth factor (NGF), since NGF-like immunoreactivity was demonstrated in cells of the endocrine phenotype.

Gastrointestinal Neoplasms↗
PubMed1989

Topical treatment of ulcerative proctitis with lidocaine.

Rectal biopsy specimens from patients with ulcerative proctitis/proctosigmoiditis (UP/PS) were investigated immunocytochemically. In general, a changed mucosal innervation was demonstrated, with a marked increase in the number of nerve fibres and terminals with neuropeptide Y and tyrosine hydroxylase. In a few patients a hyperinnervation with VIPergic or SPergic nerves was seen. These findings indicate that hyperactive local nervous reflexes are of pathogenetic importance. To silence such activity, the diseased mucosa was treated with topically applied lidocaine. Such topical treatment with lidocaine gel in 21 consecutive patients with UP/PS for 3-8 weeks caused a rapid decrease of subjective and objective symptoms. During treatment mucosal integrity was restored, accompanied by depletion of OKT4 and OKT8 lymphocytes from the mucosa. However, the hyperinnervation pattern persisted during treatment.

Administration, Topical↗
PubMed1989

Serotonin-producing carcinoid tumour cells in long-term culture. Studies on serotonin release and morphological features.

Tumour cells from a hepatic metastasis of a midgut carcinoid tumour were studied during 240 days of culture. A cell line could not be established, but the cells regularly formed large clusters and islets. The spontaneous release of serotonin (5-HT) and neuropeptide K-like immunoreactivity from cultures were followed. The amine and the peptide levels were unstable without evident covariation. The response to stimulation with noradrenaline and isoprenaline was studied during the culture period. The tumour cells released 5-HT selectively at stimulation with isoprenaline. This responsiveness also showed considerable variation with long periods of quiescence. Ultrastructurally the tumour cells showed a certain degree of polarization with apical microvilli and a supranuclear Golgi apparatus. When studied by confocal laser scanning the tumour cells were demonstrated to be cylindrical in shape with a cytoplasmic attachment to the matrix.

Carcinoid Tumor↗
PubMed1989

Surgical treatment of patients with the carcinoid syndrome.

During the last 5-year period aggressive surgical debulking was performed in 19 of 21 consecutive patients with the midgut carcinoid syndrome. Two patients were excluded due to severe cardiac disease. Fourteen of the patients had hepatic metastases. Carcinoid symptoms can occur also in patients without proven liver disease with sole lymph node metastases or retroperitoneal tumours. In 4 patients all metastatic tumour tissue could be removed resulting in biochemical cure and no symptoms. In patients with multifocal hepatic metastases surgical debulking was followed by transarterial embolisations of the hepatic arteries. All patients had good symptomatic relief of the combined surgical and radiological treatment. Five patients had currently stable disease anatomically and biochemically, 2 slowly progressive disease and one patient has a more rapid progression. Three patients have just undergone debulking and are waiting for further treatment. During the observation period 4 patients have died. Of these deaths one was related to the surgical procedures. After the introduction of somatostatin analogues major surgery can be performed safely in these patients with little risk of carcinoid crises. The role of additional drug therapy in these rare patients must be evaluated critically in randomized multicenter trials using a common surgical primary treatment.

Aged↗
PubMed1989

Treatment of the pancreatic disease of multiple endocrine neoplasia type 1 (MEN 1).

This review comprises an analysis of the treatment alternatives for pancreatic tumours of the MEN 1 syndrome presently in use at the Surgical Endocrine Unit of Sahlgrenska Hospital, Göteborg, Sweden. Patients with pancreatic tumours localized by imaging studies are offered surgical excision. Otherwise the therapy is individualized. Some patients with Zollinger-Ellison syndromes are managed with medical antiulcer treatment, others are treated with total gastrectomy. MEN 1 patients with other syndromes, e.g. insulinomas, glucagonomas and VIPomas, are offered surgery with the aim of tumour excision. Even noncurative excision might benefit the management of these cases and possibly prolong life. Asymptomatic patients with raised hormonal tumour markers in whom imaging studies have failed to reveal any tumours, are continuously followed without treatment. The malignant behaviour of the pancreatic tumours varies between different MEN 1 families. MEN 1 patients are considered for total pancreatectomy if they have multiple malignant pancreatic tumours and if the pancreatic disease has caused high morbidity and mortality in the family.

Adenoma, Islet Cell↗
PubMed1988

Carcinoid tumour cells in long-term culture: release of serotonin but not of tachykinins on stimulation with adrenoceptor agonists.

Tumour cells from a lymph-node metastasis of a midgut carcinoid tumour, immunoreactive for serotonin and substance P, were isolated and kept in culture for 2 months. The formation of large clusters or islets of tumour cells was paralleled by an increase in immunoreactive tachykinins (neuropeptide K and substance P) in the culture medium. The concentration of tachykinins declined subsequently despite good viability of the cells. Spontaneous release of serotonin into the culture medium was much greater than that of tachykinins, and remained stable throughout the study. These findings indicate different turnover rates and/or different storage sites for the peptides and the amine. In stimulation experiments, a dose-dependent release of serotonin, but not of tachykinins, was induced by a beta-adrenoceptor agonist (isoprenaline), while stimulation of alpha-adrenoceptors (noradrenaline) was not effective in releasing any of the substances. Pretreatment of the cultures with a beta-adrenoceptor antagonist (propranolol) or stimulations after calcium deprivation did not influence the isoprenaline-induced release of serotonin. These findings may indicate a modification of genuine beta-adrenoceptors during culture.

Adrenergic alpha-Agonists↗
PubMed1988

Total pancreatectomy in the MEN-1 syndrome.

A family with the multiple endocrine neoplasia Type 1 (MEN-1) syndrome, followed over three generations, is presented. In the first generation, one family member died after a history indicating Zollinger-Ellison syndrome. In the second generation endocrine pancreatic tumours were diagnosed or suspected in three out of five members. In the third generation, five out of seven members were investigated and four of these had positive tests at hormonal screening. Of particular diagnostic value in this family was the determination of peripheral serum levels of proinsulin and C-peptide, which were used as tumour markers both for diagnosis and in the postoperative follow-up. Two members in the third generation have been successfully managed by total pancreatectomy. A MEN-1 patient with malignant pancreatic tumours should be considered for total pancreatectomy if the pancreatic disease has caused high morbidity and mortality within the family. This is especially pertinent if the patient has multiple malignant tumours.

Adult↗
PubMed1988

The pentagastrin test as an indicator of a cure in surgically treated patients with advanced carcinoid disease.

A unique case of midgut carcinoid with advanced disease, engaging lymph nodes and liver but still accessible to curative surgery, is reported. Besides elevated urinary levels of 5-hydroxyindoleacetic acid, the diagnosis was based on a positive provocation test with pentagastrin, i.e., basally elevated levels of serotonin in peripheral whole blood increased twofold 3 min postinjection related to the appearance of carcinoid symptoms. After removal of primary and secondary lesions in a two-step procedure carcinoid symptoms disappeared completely. Biochemically, urinary excretion of 5-hydroxyindoleacetic acid and serotonin levels in peripheral blood before and during provocation with pentagastrin were both normalized after surgery and have remained so during 27 months of follow-up. Computed tomographies of the abdomen at regular intervals do not indicate recurrent disease. Histologically, the carcinoid lesions displayed a mixed growth pattern and signs of local aggressiveness. Immunocytochemically, the majority of the tumour cells (positive against neuron specific enolase) showed a positive reaction with serotonin antisera. Substance P-like immunoreactivity was also found in a large proportion of these cells.

Carcinoid Tumor↗
PubMed1988

In vivo motor effects of substance P on the rat urinary bladder.

Intravesical pressure recordings of the urinary bladder in anesthetized rats were performed and the role of substance P (SP) in the motor control of this organ was evaluated. Regional injection of SP (0.4 nmoles i.a.) into the superior vesical artery elicited a prompt bladder contraction; this motor response was dosedependent. The detrusor contraction could be completely inhibited by a SP-analogue, (D-Pro2, D-Trp7,9)-SP (45-90 nmoles i.a.). Furthermore, the detrusor contraction evoked by preganglionic stimulation of the pelvic nerves was partially inhibited by the same antagonist in a higher dose (65% reduction at a total dose of 150-300 nmoles). The contractile response to SP (0.5 nmoles i.a.) was also significantly reduced after blockade of muscarinic receptors with atropine (50% reduction at 1 mg/kg i.a.) or after ganglionic blockade with hexamethonium (75% reduction at 25 mg/kg i.v. + 50 mg/kg hr i.a.). Immunocytochemical studies demonstrated the occurrence of SP-immunopositive nerve terminals in the detrusor part of the rat urinary bladder. Based on these findings it is suggested that SP may act as a neurotransmitter/modulator in this organ. The mechanism of action for SP on the detrusor seems to be complex and may involve ganglionic transmission via both types of cholinoceptors as well as direct activation of smooth muscle.

Animals↗
PubMed1988

Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms.

The mechanisms controlling vagally induced release of serotonin-like immunoreactivity (5-HTLI) into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI into the portal vein. The vagally induced release of 5-HTLI into portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by previous removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animals it was shown that vagally induced release of 5-HTLI into portal circulation was mediated by adrenoceptor mechanisms, while endoluminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be quantitatively small in comparison with the release into portal circulation.

Animals↗
PubMed1988

A possible mechanism for the release of serotonin from the gut caused by pentagastrin.

Pentagastrin (PG) is a potent agent causing release of serotonin (5-HT) from patients with carcinoid tumors. The physiological release of 5-HT from gut enterochromaffin cells is controlled by beta-adrenoceptors. Studies on carcinoid tumor cell suspensions, acute or in culture, have shown that catecholamines (CA), but not PG, release 5-HT, thus indicating an indirect mode of action by the peptide. In this study the mechanism for release of 5-HT from the gut induced by PG was investigated in animal models. The test protocol for patients was used in anesthetized cats. Portal blood samples were drawn after PG injection (0.6 microgram/kg iv), which resulted in significantly increased levels of 5-HT at 3 and 5 min postinjection. The PG-induced release was totally inhibited after blockade of beta-adrenoceptors (propranolol) or of slow calcium channels (verapamil) as well as after adrenalectomy. Blockade of beta-adrenoceptors or slow calcium channels decreased the basal levels of 5-HT, while adrenalectomy caused no change. In separate experiments CA were measured after PG injection in caval blood, drawn at the level of the adrenal veins. There was a significant increase in the levels of dopamine and epinephrine postinjection, while the levels of norepinephrine were stable. The changes of CA levels after PG injection could be prevented by adrenalectomy. These results further suggest an indirect action of PG in the release of 5-HT from the feline gut via activation of beta-adrenoceptors by epinephrine released from the adrenals.

Animals↗
PubMed1988

Substance P in the control of extrahepatic biliary motility in the cat.

The effects of regional intra-arterial injections of substance P (SP) or efferent electrical stimulation of the vagal nerves on feline extrahepatic biliary motility were studied in anesthetized cats using a constant perfusion model. Each of these procedures elicited contractile motor responses of the gallbladder and the sphincter of Oddi. Since SP is present in feline vagal axons, these findings may indicate a role of SP in the vagal motor control of biliary motility. Immunocytochemically neurons with SP-like immunoreactivity were found in the smooth muscle layers of the biliary tree as well as adjacent to acetylcholinesterase-positive ganglion cells indicating either direct activation of smooth muscle cells and/or indirect activation via cholinergic neurons. Depending on the type of stimulation different SP mechanisms were demonstrated; exogenous SP induced contraction of both the sphincter and the gallbladder which were probably direct (resistant to atropine but sensitive to a SP analogue), while vagal stimulation elicited contraction of both regions via a mechanism sensitive to atropine and to a SP analogue.

Animals↗
PubMed1988

Serotonergic regulation of canine enteric motility (measured as electrical activity) and absorption: physiologic and morphologic evidence.

To explore the effect of serotonin (5-HT) on enteric electrical activity, transit and absorption, four dogs were prepared with 50 cm jejunal and ileal Vella loops. Electrodes for recording enteric electrical activity were attached to the loops and to the main small bowel. After recovery, both loops were perfused with a [14C-]PEG-glucose-electrolyte solution via the proximal stomas, while effluent was collected from the distal stomas and enteric electrical activity was monitored. Control periods were compared with periods when 5-HT was infused intravenously at a rate of 10 micrograms kg-1 min-1 for 60 min. Serotonin increased the mean +/- SEM % of jejunal and ileal pacesetter potentials with spike potentials from 33 +/- 7% and 35 +/- 9%, before infusion to 63 +/- 4% and 61 +/- 5% after infusion (P less than 0.05). Serotonin also induced distally-migrating bursts of spikes in the incontinuity small bowel. The changes were blocked by atropine, but not by ketanserin. Absorption of water, sodium and glucose from the jejunal and ileal loop and transit through the loops was not changed by 5-HT. At autopsy, all layers of the jejunum and ileum contained varicose nerve fibres with a positive immunoreaction to 5-HT, while positive nerve cell bodies were largely confined to the submucosa.

Animals↗
PubMed1988

SMS 201-995 and provocation tests in preparation of patients with carcinoids for surgery or hepatic arterial embolization.

Patients with midgut carcinoids undergoing surgical resection or ischemic treatment of hepatic metastases by embolization are at risk for development of carcinoid crises due to release of hormonally active tumor products. Eight such patients were treated on nine separate occasions with increasing subcutaneous doses of a synthetic somatostatin analogue (SMS 201-995) 4 days prior to surgery or hepatic arterial embolization. The patients were tested by pentagastrin provocation and simultaneous measurement of serotonin (5-HT) levels in peripheral blood before and after prophylactic treatment, to evaluate the efficacy of SMS 201-995. The provoked release of 5-HT was markedly diminished, and the basal levels of 5-HT were markedly reduced in patients with high initial levels. During surgery or embolization both SMS 201-995, as well as ketanserin, a 5-HT2 receptor blocker, were given. With this combined treatment all patients were hemodynamically stable during surgery or embolization. During embolization the arterial levels of 5-HT increased only moderately, while urinary excretion of 5-hydroxyindoleacetic acid remained unchanged despite a proven adequate embolization. Two patients were operated on without previous treatment with SMS 201-995; both developed severe crises at induction of anesthesia, but IV SMS 201-995 rapidly reversed the bronchoconstriction and facial flush and gradually restored arterial blood pressure, even though cardiac output remained depressed for a prolonged period. The crisis reaction correlated well with high circulating levels of 5-HT, but after treatment with SMS 201-995 these levels were still high.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Bipolarity of duodenal enterochromaffin cells in the rat.

Enterochromaffin cells of the rat duodenum have been studied immunocytochemically by use of a specific antiserum to serotonin. At the light-microscopic level serotonin immunoreactivity was observed in enterochromaffin cells located in the epithelium of the duodenal mucosa. Most of the serotonin-immunoreactive material was localized to the basal portion of the enterochromaffin cells, but small amounts of immunoreactive material were regularly observed in the apical portion. At the electron-microscopic level serotonin immunoreactivity in enterochromaffin cells was found to be concentrated over the dense cores of the cytoplasmic granules. The majority of these granules was located in the basal cytoplasm of the enterochromaffin cells, but serotonin-immunoreactive granules were also observed in the apical cytoplasm immediately beneath the microvilli. These observations indicate that duodenal enterochromaffin cells are bipolar and that they secrete serotonin both basally, to the circulation, and apically, to the gut lumen. Rat duodenal enterochromaffin cells thus appear to have an exocrine as well as an endocrine function.

Animals↗