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

An 8-month-old boy with persistent watery diarrhoea and failure to thrive developed abdominal distension, hypokalaemia, and flushing of the face and trunk. A high concentration of vasoactive intestinal peptide-like immunoreactivity was found in the serum. Soon after resection of a suprarenal mass, the serum level of vasoactive intestinal peptide became normal and the diarrhoea stopped. Histologically the tumour was a ganglioneuroblastoma: the cells showed fluorescence by the indirect immunofluorescence technique with anti-vasoactive intestinal peptide serum. Electron microscopical examination showed abundant secretory granules in the tumour cells. Reports of chronic watery diarrhoea in children due to neural crest tumours are reviewed, with particular respect to the clinical features of the syndrome.
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PMID:Watery diarrhoea with a vasoactive intestinal peptide-producing ganglioneuroblastoma. 700 19

The carcinoid syndrome is a rare clinical entity, the unique manifestations of which continue to excite the interest of physicians. Despite a common origin from neural crest tissue, the tumors are partially differentiated, as evidence by the different secretory products of foregut, midgut, and hindgut carcinoids. They also differ in their ability to metastasize, thus presenting an even more varied clinical picture. The prognosis of patients with carcinoid syndrome varies with the origin of the tumor and extent of metastases. The management of patients with carcinoid syndrome is difficult. Despite an understanding of the neurohormones that carcinoid tumors secrete, their various antagonists and inhibitors have been only partially successful in providing symptomatic relief. Carcinoid heart disease represents the most intriguing aspect of this syndrome. Although valvular dysfunction most often coexists with flushing and diarrhea, the findings of tricuspid regurgitation or stenosis occasionally provide the first clue to the presence of the disease. Despite intensive research, the definite etiology of these valvular lesions has not been established. A small group of patients has been managed by valve replacement. While surgical treatment has been successful in improving hemodynamics in most of these patients, it is expected to prolong life only in those without extensive liver metastases. In patients with extensive metastatic disease, one must carefully consider whether the risks and trauma of cardiac surgery for palliation are justified.
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PMID:Carcinoid heart disease: a clinical pathologic, and therapeutic update. 704 96

Although patients with bronchial and ovarian carcinoid tumors can develop the carcinoid syndrome (diarrhea and/or flushing) in the absence of hepatic metastasis, it is believed that development of the carcinoid syndrome in patients with carcinoid tumors of gastrointestinal origin occurs only after the patient has hepatic metastasis. This is explained by hepatic inactivation of most of the serotonin in the portal circulation or by the fact that hepatic metastases are larger than the primary tumor in the gastrointestinal tract. Three patients with ileal and jejunal carcinoid tumors who developed the carcinoid syndrome without obvious hepatic metastasis are described. Two of the patients had intra-abdominal, but extrahepatic, metastasis that probably drained directly into the systemic circulation. The third patient had an ileal carcinoid with clinical involvement limited to adjacent mesenteric lymph nodes. Following resection of her tumor, her urinary 5-HIAA excretion and platelet serotonin level returned to normal, and her attacks of carcinoid flushing virtually ceased. She has occasional spells of "blushing" that are thought to be benign; however, further close follow-up study will be needed to be certain that she is free of disease. It is suggested that each patient with the carcinoid syndrome be evaluated with CT and technetium-99 pertechnetate liver scans. If there is no liver involvement detected with these studies, one should consider hepatic arteriogram or laparotomy to determine if the patient's tumor might be totally resectable.
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PMID:Carcinoid syndrome from gastrointestinal carcinoids without liver metastasis. 709 50

Among endocrine tumors arising in the intestinal tract, midgut argentaffin EC cell carcinoids, duodenal gastrin cell tumors and rectal trabecular L cell carcinoids, in order of decreasing frequency, are those better represented. Together they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas and poorly differentiated neuroendocrine carcinomas, are also well defined tumor entities. The carcinoid syndrome with intermittent flushing, hypotension and diarrhea, and the Zollinger-Ellison syndrome with severe peptic ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome arises in about 10% of intestinal carcinoids, usually in their advanced metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of gastrin cell tumors, including small intramural growths. Tumor prognosis depends on mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases) and associated clinical syndrome or background disease.
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PMID:Endocrine tumors of the small and large intestine. 747 53

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested.
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PMID:The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid. 747 66

Iloprost is a synthetic stable analogue of prostacyclin (PGI2), which shares its antiaggregating and vasodilating properties. Iloprost has been administered by i.v. route to patients with critical limb ischaemia (CLI) of different origin (maximal dosage: 2 ng/kg/min 6 hours/day infusion for 14-28 days). In patients with claudicatio intermittens (Fontaine stage II) iloprost improved the time to claudication and the maximal walking distance on treadmill, with an effect still lasting 60 days after suspension. This benefit was not related to a significant improvement in blood flow. Five multicentric, perspective, randomized versus placebo studies in patients with more severe CLI (Fontaine stage III-IV) susceptible to surgical treatment, showed that iloprost was able to reduce pain and ulcer dimensions. Furthermore, tha amputation rate of the ischemic limb was significantly lower in patients treated with iloprost during a 6 month follow-up (p < 0.01). Iloprost was also more effective than aspirin in causing pain relief and ulcer healing in patients with thromboangiitis obliterans and more effective than nifedipine in reducing frequency, intensity and duration of ischemic episodes in patients with Raynaud's phenomenon. Minor side effects of iloprost administration are represented by facial flushing, tachycardia, headache, nausea, vomiting, abdominal cramping, diarrhoea, whose frequency ranges from 16% to 70%; major collateral effects, occurring in less than 5% of patients, are above all represented by severe hypotension and angina pectoris. Clinical data indicate therefore that iloprost treatment can allow to improve the clinical conditions and the prognosis in patients with critical ischemia of the limbs, not candidate to surgical revascularization, by causing a relief of pain, a reduction in ulcer dimensions and deferring amputation.
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PMID:[The role of iloprost in the treatment of critical ischemia of the limbs]. 750 14

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily x5 schedule has been developed further with dose escalation using granulocyte-colony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea, diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has been observed with topotecan and irinotecan in patients with a variety of solid tumors and refractory leukemia in our studies, which supports the widespread enthusiasm for this group of compounds.
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PMID:Camptothecin analogues: studies from the Johns Hopkins Oncology Center. 752 Aug 44

The carcinoid syndrome is a rare clinical entity mainly characterized by flushing and diarrhoea. It is due to different biological mediators produced by tumours that arise from enterochromaffin cells. Such tumours are typically located in the ileum, have a long course and become symptomatic only in the presence of overt liver metastases. Among the involved mediators, the role of serotonin (5-hydroxytryptamine, 5-HT) has been ascertained in the pathogenesis of diarrhoea, while it remains controversial in that of flushing. Ketanserin is a 5HT-2 antagonist with no mixed receptor agonist-antagonist activity. We report the case of a severely distressing carcinoid syndrome fully dominated by ketanserin. The patient was a 75-year-old man, who came to our attention because of marked weight loss, impossibility to feed and almost continuous diarrhoea due to liver colonization of a mid ileum carcinoid tumour, previously resected at the age of 65. Sustained facial and trunk flushing also presented several times daily. Ketanserin, 20 mg twice a day orally, was administered and then increased up to 40 mg daily with no side effects and progressive complete control of both diarrhoea and flushing. It is suggested that ketanserin, due to its availability and tolerability, should first be considered for palliative relief of carcinoid syndrome. The literature on this subject is extensively reviewed.
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PMID:[Symptomatic relief of carcinoid syndrome by ketanserin. A case]. 763 30

Melphalan has a steep dose-response curve, but the use of high doses results in unacceptable myelosuppression. Strategies to circumvent this dose-limiting myelosuppression would allow for the administration of higher, more effective doses of melphalan. Amifostine (WR-2721) has been shown in preclinical studies to protect the bone marrow from the myelotoxicity of melphalan, and in clinical trials, to protect from the myelotoxicity of other alkylating agents. A Phase I trial of the combination of amifostine and melphalan was performed in children with refractory cancers to: (a) define the acute toxicities of amifostine and its maximum tolerated dose (MTD); and (b) to determine whether the dose of melphalan could be safely escalated when administered in combination with amifostine. Amifostine was administered i.v. as a 15-min infusion 30 min before melphalan. The starting dose of amifostine was 750 mg/m2, with planned dose escalations in 30% increments. Melphalan was administered as a 5-min infusion using the previously defined MTD in heavily pretreated patients, 35 mg/m2, as the starting dose. The dose of melphalan was escalated by 30% increments. Nineteen patients, ranging in age from 3 to 24 years (median, 15 years), were entered on trial. The dose of amifostine was escalated to 2700 mg/m2, which is approximately 3-fold higher than the adult recommended dose, without reaching a MTD. Fifteen patients experienced nondose-limiting (< 25%), transient decreases in blood pressure after the amifostine infusion. Other nondose-limiting toxicities of amifostine included mild nausea and vomiting, flushing, anxiety, diarrhea, and urinary retention. Six patients, three each at the 2100 and 2700 mg/m2 amifostine dose levels were treated with an escalated dose of melphalan (45 mg/m2). All of these patients experienced grade 4 neutropenia (< 500/mm3), and five of six patients had grade 4 thrombocytopenia. The duration of this dose-limiting myelosuppression exceeded 7 days in four of six patients. Although no dose-limiting (grade 3 or 4) toxicity was attributed to amifostine, significant anxiety and reversible urinary retention occurred at the two highest amifostine dose levels. A dose of 1650 mg/m2 for pediatric Phase II trials is recommended. High doses of amifostine, however, do not appear to allow for escalation of melphalan beyond its single agent MTD of 35 mg/m2.
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PMID:A phase I trial of amifostine (WR-2721) and melphalan in children with refractory cancer. 766 82

The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.
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PMID:Treatment of carcinoid syndrome with recombinant interferon alpha-2a. 768 66


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