Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 43-yr-old-man with metastatic VIPoma in whom the conventional measures of surgery, chemotheraphy, and hepatic artery embolization ultimately failed to control his severe diarrhea, resulting from vasoactive intestinal polypeptide hypersecretion, was treated with a new long-acting somatostatin analogue, SMS 201-995, for 14 mo. SMS 201-995 not only controlled the diarrhea without side effects but appeared to have possibly induced a reduction in metastatic tumor size.
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PMID:Long-term treatment of a VIPoma with somatostatin analogue resulting in remission of symptoms and possible shrinkage of metastases. 285 77

A 30-year-old man presenting with watery diarrhea, hypokalemia, and hypochlorhydria (Verner-Morrison syndrome, WDHH syndrome) had raised plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), calcitonin, and gastrin, as well as high urinary excretion of vanillylmandelic acid. A right adrenal pheochromocytoma was found and excised. The neoplastic cell population was immunohistochemically shown to contain VIP, SRIF, and calcitonin. Gross, histologic, and immunohistochemical evaluation of the pancreas revealed no abnormalities, whereas a marked hyperplasia of the gastrin-producing cells of the gastric antral mucosa was demonstrated. Postoperatively, the patient recovered from his symptoms and the plasma hormone levels returned to normal values. The clinical and histogenetic implications of this most unusual tumor of neural crest derivatives are discussed.
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PMID:Vasoactive intestinal polypeptide-, somatostatin-, and calcitonin-producing adrenal pheochromocytoma associated with the watery diarrhea (WDHH) syndrome. First case report with immunohistochemical findings. 285 7

Seven patients with gut and pancreatic endocrine tumours have been treated with a long acting somatostatin analogue (SMS 201-995), given as a twice daily subcutaneous injection. This produced dramatic improvement in their endocrine related symptoms, in association with a fall in circulating tumour peptides. One of these patients has now been treated for seven months with this analogue which has controlled his previously life threatening diarrhoea caused by a malignant VIP secreting tumour. He gives his own injections twice daily, and has returned to a full and active life. This is a promising agent both for acute treatment of peptide hypersecretion, and for the long term management of some patients who are unresponsive to other available therapy.
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PMID:Treatment of patients with pancreatic endocrine tumours using a new long-acting somatostatin analogue symptomatic and peptide responses. 286 52

Amelioration or cure of hypertension, hypercortisolism, diarrhea with steatorrhea, and massive proteinuria resulted from excision of a pheochromocytoma that contained immunoreactive ACTH, VIP, and somatostatin. Ectopic ACTH production by the tumor was clearly the cause of the hypercortisolism, and the possible involvement of VIP and somatostatin in the diarrhea and steatorrhea was considered. The response to tumor removal suggested that the mesangioproliferative glomerulonephritis shown on renal biopsy was also a paraneoplastic phenomenon.
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PMID:Hypercortisolism, diarrhea with steatorrhea, and massive proteinuria due to pheochromocytoma. 286 63

The effect of a synthetic somatostatin analog was studied in a patient with severe secretory diarrhea due to pancreatic cholera syndrome. Basal intestinal perfusion studies indicated an absence of water and sodium absorption, and active chloride secretion in the small bowel. Intravenous administration of the somatostatin analog (1 microgram/kg.h) changed zero net water movement to absorption (122 mL/30 cm of the jejunum per hour). Chloride secretion changed to absorption (5.0 to 7.9 meq/30 cm.h), and plasma vasoactive intestinal polypeptide concentration was reduced from 330 to 45 pmol/L (normal, less than 51). When the analog was given subcutaneously, 100 micrograms twice daily, stool weight decreased, and plasma vasoactive intestinal polypeptide concentration fell toward the normal range (67 pmol/L). Plasma concentration of pancreatic polypeptide was initially elevated and dropped during intravenous infusion of somatostatin analog but returned to baseline on maintenance therapy with the analog delivered subcutaneously. The patient has not had further diarrhea during 9 months of therapy.
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PMID:Pancreatic cholera syndrome: effect of a synthetic somatostatin analog on intestinal water and ion transport. 286 21

Somatostatin is present throughout the intestine, both in D cells at the luminal surface and in neural elements. It inhibits the release or action of many gut hormones known to regulate gastro-intestinal function and undoubtedly has a wide range of actions. In the intestine, available information indicates that somatostatin may have an important regulatory role for water and electrolyte absorption and secretion. The peptide affects both the epithelial transport function and the intestinal motility function. The outcome associated with administration of somatostatin is inhibition of water and electrolyte secretion. Somatostatin has been shown to effectively reduce stool output in diarrheal syndromes associated with endocrine tumor and other conditions. Clinical application of somatostatin in diarrhea still awaits development of an orally active and/or gut-specific analog. Some preliminary results indicate that this may be possible in the future.
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PMID:Intestinal somatostatin function. 286 47

Proctocolectomy (PC) with small bowel resection may lead to profuse ileostomy diarrhoea which can be difficult to treat. The effect of a recently developed long acting somatostatin analogue (SMS 201-995) on ileostomy output was investigated in 5 patients who had undergone PC and ileal resection (median 120 cm) and who suffered severe diarrhoea (4-7 litres/24 h). Gastric emptying, transit of a standard meal through the small bowel and the amounts of nutrients excreted were simultaneously determined during double blind infusion of SMS (25 micrograms/h) and placebo (isotonic saline 125 ml/h). SMS 201-995 significantly reduced ileostomy output (P less than 0.05) and water excretion (P less than 0.05) and prolonged small bowel transit time (P less than 0.05). Whilst having little effect on gastric emptying, or on the excretion of glucose or nitrogen, fat excretion was significantly increased (P less than 0.05). In two patients subcutaneous administration of SMS 201-995 (50 micrograms b.d.) has maintained a reduced ileostomy output for 4 and 6 months respectively.
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PMID:Effects of a long-acting somatostatin analogue in patients with severe ileostomy diarrhoea. 286 71

A now 61-year old man with hypersecretion of vasoactive intestinal polypeptide (VIP) due to carcinoma of the tail of the pancreas was treated and followed for nine years. Combined administration of lomustin (2.5 mg/kg on day 1) and 5-fluorouracil (30 mg/kg on days 2-6) over eight courses at six-week intervals achieved clinical remission for 13 months. No clinical improvement was observed with streptozocin (500 mg/m2 on days 1-5) for two courses four weeks apart. Treatment had to be discontinued after the second course because of the onset of (rarely observed) neurotoxic side-effect of bilateral peroneal paresis. High doses of somatostatin (6.9 micrograms/kg hourly intravenously) immediately and markedly reduced stool quantity. But at a lower dose (3.4 micrograms/kg hourly i.v.) there was no noticeable effect. In the further course of the disease, massive attacks of diarrhoea at varying intervals were best controlled in intensity and duration by prednisolone (50-60 mg daily). Other drugs which have been recommended for such cases (indometacin, lithium, trifluoperazine, nicotinic acid and clonidine) had no worth-while effect. In future long-acting somatostatin analogues may provide better prospects for long-term treatment.
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PMID:[Vipoma. 9-year observations using currently available therapy methods]. 286 74

Many of the features of the dumping syndrome may be manifestations of hypovolemia and mechanical distension of the gut, resulting from abnormal fluid secretion in the upper gastrointestinal tract. The object of the present study was to assess the effect of somatostatin, an inhibitor of upper gastrointestinal secretions, on the response to a dumping provocation test, using a double-blind, placebo-controlled method. Four patients were studied; two had undergone total gastrectomy for gastric carcinoma and two had undergone gastric bypass for morbid obesity. Each subject received, on two separate occasions, a challenge of 200 ml of 50% glucose administered orally after an overnight fast. Somatostatin in 150 mm of NaCl (250 micrograms bolus followed by 300 micrograms/hr infusion) was given intravenously during one dumping provocation test and placebo (150 mm of NaCl) during the other according to a Latin square design. When the subjects received the placebo there were significant increases in pulse rate and packed cell volume after oral glucose (p less than 0.05, paired t test), which did not occur when they received somatostatin. The glucose challenge also produced a more rapid increase in serum osmolality and blood glucose during administration of placebo than when somatostatin was given. Marked diarrhea developed in all placebo-treated subjects but in none when they received somatostatin; however, three of the subjects developed marked abdominal pain during dumping provocation tests when treated with somatostatin, which did not occur when placebo was given. Although somatostatin appears to suppress some of the objective responses to a dumping provocation test, it may not prove particularly useful in the treatment of dumping symptoms.
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PMID:The effect of somatostatin on dumping after gastric surgery: a preliminary report. 286 91

Five patients with metastatic pancreatic endocrine tumours injected a long acting somatostatin analogue (SMS 201-995) 50 micrograms subcutaneously every 12 hours and were followed up for three to six months. Treatment aimed at controlling excess secretion of hormone by the tumours thereby bringing symptomatic relief. Four patients showed a significant reduction in tumour related hormone concentrations but in none did values return to normal. All five patients, however, noted definite symptomatic improvement and in one this was dramatic (disappearance of life threatening diarrhoea and correction of metabolic acidosis and hypokalaemia within 48 hours). Mild worsening of symptoms and increasing fasting tumour related hormone concentrations after three to six months of treatment were reversed by doubling the 12 hourly dose. The treatment was well tolerated and had no deleterious effect on fasting blood glucose concentrations. This somatostatin analogue seems a promising non-invasive treatment for metastatic pancreatic endocrine tumours.
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PMID:Remission of symptoms during long term treatment of metastatic pancreatic endocrine tumours with long acting somatostatin analogue. 287 Jul 58


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