Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether measurement of serotonin in urine would give useful complementary information to the usual measurement of 5-hydroxyindoleacetic acid (5-HIAA) in urine and platelet serotonin in platelets, I measured these analytes in 75 consecutive patients with carcinoid tumors, and found that 75% had above-normal urinary 5-HIAA excretion, 64% had above-normal serotonin excretion, and 64% had above-normal platelet serotonin concentration. Six patients had increased urinary serotonin, but 5-HIAA excretion and platelet serotonin concentration were normal. Only two of a further 50 patients with solid noncarcinoid tumors--and none of 55 patients with flushing or diarrhea, who did not prove to have a carcinoid tumor--had increased urinary serotonin. Ingestion of four bananas (a food rich in serotonin) increased urinary 5-HIAA but not urinary serotonin excretion of seven normal subjects. Evidently, measurement of urinary serotonin excretion is helpful in the evaluation of patients with suspected carcinoid tumors.
 ...
PMID:Urinary serotonin in the diagnosis of carcinoid tumors. 242 46

The plasma concentrations of various tachykinins were measured before and during flushing episodes in 16 patients with metastatic carcinoid tumors. The flushing attacks were induced by iv injection of pentagastrin or ingestion of food or alcohol. Tachykinins, such as neurokinin A (NKA) and neuropeptide K (NPK), increased 2-fold during flushing episodes in 12 patients, and the plasma concentrations of substance P increased to a varying extent in 3 patients. Chromatographic analysis of plasma samples taken before and during flushing episodes in 2 patients indicated the presence of individual spectra of tachykinins. In addition, the plasma concentration of tachykinin [TKLI(K12)], using an assay that detects NKA, NPK, kassinin, eledoisin, and NKB, but not substance P and physalaemin, and the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA) were measured in 20 patients with midgut carcinoid tumors before and during treatment with human leucocyte interferon. The overall changes in the 2 tumor markers were concordant in 18 of the 20 patients. Thus, the Spearman correlation coefficient between the percent changes in urinary 5-hydroxyindole acid excretion and plasma TKLI(K12) was 0.54 (P less than 0.001). The patients who had a decrease in the tumor markers also had a decrease in flushing episodes and diarrhea. Plasma TKLI(K12) is a convenient tumor marker for the diagnosis and follow-up of patients with carcinoid tumors of midgut origin. The combined use of both tumor markers strengthens the diagnosis and may improve the evaluation of response during treatment.
 ...
PMID:Tachykinins in carcinoid tumors: their use as a tumor marker and possible role in the carcinoid flush. 242 99

The plasma concentrations of neuropeptides (neurotensin, substance P, motilin, somatostatin, vasoactive intestinal peptide and gastrin-releasing peptide), the urinary excretion of 5-hydroxyindoleacetic acid and serotonin, and the platelet concentration of serotonin were compared in 133 patients who could be assigned to one of four groups. These groups were as follows: carcinoid tumors present; history of carcinoid tumors; miscellaneous tumors present; and non-tumor diseases. The test with the most sensitivity (i.e., patients with carcinoid tumors labeled positive) and the test with the most specificity (i.e., patients without carcinoid tumors labeled negative) for the presence of carcinoid tumors was determined. Urinary 5-hydroxyindoleacetic acid excretion had a sensitivity of 73 percent and a specificity of 100 percent; the plasma concentration of substance P had a sensitivity of 32 percent and a specificity of 85 percent; and the plasma concentration of neurotensin had a sensitivity of 41 percent and a specificity of 60 percent. Even when basal plasma concentrations of substance P and neurotensin were elevated, there was no additional increase of these neuropeptides prior to ethanol-induced facial flushing. Although measurements of plasma neuropeptide levels may be helpful in occasional patients with carcinoid tumors, it is concluded that measurements of serotonin overproduction--such as 5-hydroxyindoleacetic acid excretion--are of more general value.
 ...
PMID:Role of neuropeptides and serotonin in the diagnosis of carcinoid tumors. 243 80

Malignant carcinoid tumors are remarkably varied in their biologic behavior. The disease may be indolent for years with minimal or no symptoms. On the other hand, an acute carcinoid crisis with severe diarrhea, dehydration, and hypotension may develop in the patient. Patients with flushing and/or diarrhea, not responsive to standard symptomatic measures, may benefit from chemotherapy or hormonal therapy. Chemotherapy with single agents or combination chemotherapy may be associated with response rates ranging from 20 to 40 percent. Hepatic de-arterialization by ligation or occlusion is an effective means of inducing rapid tumor shrinkage for patients who have carcinoid tumors and hepatic dominant metastases. The addition of chemotherapy after induction of a partial remission with hepatic de-arterialization may prolong the duration of response, but this remains to be proven in prospective clinical trials. Hormonal therapy with the antiestrogen tamoxifen has been unsuccessful, but treatment of the carcinoid syndrome with a long-acting analogue of somatostatin has been strikingly effective.
 ...
PMID:Metastatic carcinoid tumors and the carcinoid syndrome. A selective review of chemotherapy and hormonal therapy. 243 81

Seven patients with progressive ileal or caecal carcinoid tumors and liver metastases were treated with human recombinant alpha-interferon (IFN alfa-2b) at a dosage of 2-4 x 10(6) U daily or every other day subcutaneously. Six patients had symptoms of the carcinoid syndrome. No change of tumor size lasting 4 to 40+ months (median, 18 months) was noted in 6 patients, and 1 patient had hepatic tumor progression. A decrease in urinary excretion of 5-hydroxyindoleacetic acid by more than 50% lasting 2-11 months (median, 4) was observed in 5 patients. Four patients were completely or partially relieved of flushing, diarrhea, obstruction or abdominal pain. The side-effects were negligible with the exception of mild fever, headache and confusion only during the first days of therapy. Treatment with IFN alfa-2b offers good palliation to patients with disseminated ileal or caecal carcinoid tumor and carcinoid syndrome.
 ...
PMID:[Treatment of metastasized carcinoid tumor of the ileum and cecum with recombinant alpha-2b interferon]. 245 Mar 26

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.
 ...
PMID:Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management. 266 49

Resistance of hypoxic cells to radiation and chemotherapy remains a major limitation to effective therapy of solid tumors. Misonidazole, a 2-nitroimidazole analogue, has been studied extensively as a radiosensitizer of hypoxic cells and has been shown to undergo bioreductive metabolism to exert preferential cytotoxicity against hypoxic cells. We have investigated the effects of misonidazole on the biosynthesis of prostaglandins (PGs) in a murine mammary adenocarcinoma cell line (No. 4526) under aerobic and hypoxic conditions in attempts to exploit modulation of PG levels under hypoxia as a means of improving therapeutic approaches for the treatment of solid tumors. We report a time-dependent inhibition of PG biosynthesis by the suspended cells under hypoxia induced by flushing sealed vials with N2 (1.5 liters/min). After 30 min of hypoxia, PG formation was inhibited by 50%. Indomethacin was able to further inhibit the PG formation in a concentration-dependent manner under hypoxia. Misonidazole, however, selectively increased the PGE2 biosynthesis under hypoxia by 49% at 100 microM. This increase was concentration dependent over the range of 25 to 100 microM and was blocked by indomethacin (0.1 microM). Imidazole, the heterocyclic moiety in misonidazole without the nitro function, had no effect on PG biosynthesis at these concentrations. These data suggest that arachidonic acid metabolism is sensitive to the differential oxygen levels which exist within solid tumors and that PG levels may be modulated by electron-affinic agents in hypoxic tumor cells.
 ...
PMID:Modulation of prostaglandin biosynthesis in hypoxic murine mammary adenocarcinoma cells by misonidazole. 273 27

Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.
 ...
PMID:Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon. 273 23

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.
 ...
PMID:Somatostatinomas, PPomas, neurotensinomas. 282 62

SMS 201-995 (Sandostatin) was studied using low doses (50 to 100 micrograms) administered subcutaneously every 12 hours. A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management. Higher doses of the agent (500 to 800 micrograms per day) had no effect on metastases in one of two patients with metastatic gastrinoma. In the other patient, one tumor shrank but the other continued to grow after three months of treatment while serum gastrin levels did not change. Cultured metastatic tumor tissue from this patient released different forms of gastrin; growth rates varied, independent of uptake of SMS 201-995, and gastrin release increased. A neonate with nesidioblastosis maintained normal blood glucose levels while receiving SMS 201-995 therapy following a 95 percent pancreatic resection. In two elderly patients with organic hypoglycemia--one with a single benign adenoma and one with multiple adenomatosis--the somatostatin analogue did not prolong the hypoglycemia-free interval. In nine patients with carcinoid syndrome, flushing was uniformly controlled with 50 micrograms of SMS 201-995 administered every eight to 12 hours. One of the nine required exocrine pancreatic replacement. After six months of treatment, three of the nine had no change in tumor size and one had remission of symptoms and stopped treatment. In two patients with vipoma, SMS 201-995 controlled diarrhea and reduced levels of vasoactive intestinal peptide; tumor necrosis occurred in one patient. In a patient with diabetic diarrhea unresponsive to all treatments, SMS 201-995 therapy controlled the diarrhea but did not interfere with control of the diabetes.
 ...
PMID:Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes. 287 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>