Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.
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PMID:Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma. 826 71

Decarbazine is an imidazole dimethyltriazene with reproducible activity in patients with metastatic melanoma. CB10-277 is a phenyl dimethyltriazene which, like dacarbazine, requires metabolic activation to its corresponding monomethyl species for antitumour activity. In preclinical models (human melanoma xenografts and transplantable rodent tumours) CB10-277 showed a similar spectrum and level of activity when compared to dacarbazine. Pharmacokinetic studies were performed with CB10-277 in mice treated i.v. at the LD10 (750 mg m-2) and plasma analysed by HPLC. The parent drug area under the plasma concentration vs time curve (AUC) was 142 mM x minutes. Drug metabolism occurred as evidenced by the HPLC identification of the monomethyl species (AUC = 8 mM x minutes) as well as other metabolites. A Phase I trial using a short infusion with doses repeated every 21 days has been performed. Thirty-six patients received 80 courses over a dose range of 80-6,000 mg m-2. The dose limiting toxicity was nausea and vomiting which occurred in 80% of the evaluable courses > or = 900 mg m-2. The only other common side effect was a flushing or warm sensation, which occurred in over 75% of courses at > or = 1,350 mg m-2. There were no hemodynamic consequences. Responses occurred in patients with melanoma (one complete, two partial, one mixed/11), sarcoma (one mixed/6) and carcinoid (one partial/l). Pharmacokinetics were performed in 46 courses. The CB10-277 AUC increased linearly with dose (r = 0.9203, P < 0.001) up to 700 mM x minutes at 6,000 mg m-2). Evidence of CB10-277 metabolism was observed, as in mice, by detection of the monomethyl species and other metabolites. However, the plasma levels of the monomethyl species in patients (1.8 and 3.7 mM x minutes at 6,000 mg m-2) were less than those predicted from studies in mice. Despite this, antitumour activity in dacarbazine sensitive histologies was observed and additional studies with CB10-277 are recommended.
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PMID:Preclinical, phase I and pharmacokinetic studies with the dimethyl phenyltriazene CB10-277. 843 67

Computed tomography during arterial portography (CTAP) and delayed high-dose iodine computed tomography (CT) have improved the preoperative localization of hepatic metastases from colon cancer. Nearly all patients presenting with malignant carcinoid syndrome have liver metastases, and removal of tumour bulk is considered the most effective means of management. To determine suitability for hepatic resection, CTAP and delayed high-dose iodine CT were used to evaluate the distribution of hepatic disease in two patients with malignant carcinoid syndrome. In both patients CTAP showed lesions not seen during recent dynamic incremented CT; the location of the lesions precluded resection. CTAP also demonstrated metastases less than 1 cm in diameter in one patient. Facial flushing (both patients) and hypotension (one) occurred during infusion of the contrast agent into the superior mesenteric artery. Because CTAP can demonstrate small hepatic metastases (less than 1 cm in diameter), it is recommended for patients with malignant carcinoid syndrome who are being considered for hepatic resection. The infusion of contrast media through the superior mesenteric artery may induce a carcinoid crisis, and prophylaxis with a somatostatin analogue is suggested.
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PMID:Computed tomography during arterial portography in malignant carcinoid syndrome: a report of two patients. 846 29

Carcinoids, tumors arising from enterochromaffin cells, represent the most common type of gastrointestinal endocrine neoplasm; they are often multiple and may appear anywhere in the gut. Carcinoid tumors may also occur in bronchi and ovaries. Classic symptomatology includes secretory diarrhea, flushing, edema, bronchospasm and cutaneous teleangectasias; however, over 30% of patients with demonstrably elevated serotonin levels may not exhibit any symptoms at all. The diagnosis of carcinoid tumor is typically made by measurement of 24-hour urinary excretion of 5-hydroxyindoloacetic acid. Commonly, tumor localisation is established with CT, US, NMR and arteriography. MIBG scintigraphy is also used to visualize tumors deriving from neuroendocrine cells as carcinoid. These tumors may express somatostatin receptors located on the cell surface. Therefore 111In Octreotide (Octreoscan), a somatostatin analogue, can be employed for tumor localisation. A 32-years-old man with liver metastases secondary to a carcinoid tumor of unknown origin is presented. Classic carcinoid symptoms were absent. Diagnosis was supported by elevated values of urinary 5-hydroxyindolocetic acid and liver fine-needle aspiration. Abdominal US and CT scan detected only liver masses but not the primary tumor. Arteriography was not performed. 131I MIBG and 111I octreotide scans both failed in locating the primary cancer too; only the second tracer showed marked uptake in liver metastases. Beside localization, these two tracers give also informations about the following therapy especially in malignant tumors where local resection isn't an adequate treatment.
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PMID:131I MIBG/111In octreotide mismatch in a patient with liver metastases secondary to a carcinoid of unknown origin. 853 97

We encountered two patients with typical bronchial carcinoid and metastases to the liver who presented with typical carcinoid syndrome. In typical bronchial carcinoid without metastases to regional lymph nodes, recurrence and distant metastasis after curative resection are generally thought to be rare. The first patient was a 62-year-old woman who was admitted to our hospital because of facial flushing and diarrhea. She had undergone curative resection of a typical bronchial carcinoid 9 years earlier, and the postsurgical pathological stage was I. On the second admission, she was found to have multiple liver metastases. The second patient was a 59-year-old woman who was admitted to our hospital because of facial flushing, dyspnea, and dehydration due to diarrhea. She had undergone curative resection of a typical bronchial carcinoid 21 months earlier, and the postsurgical pathological stage was I. On the second admission, she was found to have multiple intrabronchial, bone, and liver metastases. Both patients were treated with subcutaneous injections of octreotide, and with transhepatic arterial chemoembolization. In addition, the second patient underwent percutaneous ethanol injection under ultrasonic guidance. Signs and symptoms disappeared soon after therapy began and the patients survived longer than expected. Hepatic artery chemoembolization and simultaneous chemotherapy can relieve symptoms in patients with carcinoid syndrome and multiple liver metastases, and self-administration of octreotide is the treatment of choice for immediate relief.
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PMID:[Successful treatment of carcinoid syndrome in two cases of bronchial carcinoid]. 858 28

The classical carcinoid tumour (WHO) of the pancreas is extremely rare and its diagnosis may puzzle physicians and pathologists. Here, 29 previously published cases of pancreatic carcinoid tumours, including one new case, are reviewed. Literature research was done using MedLine from 1966 to 1995. Pancreatic carcinoids produce an atypical carcinoid syndrome. Skin flushing was reported in only 34%. The main symptom was pain, followed by diarrhoea and weight loss. Elevated urinary 5-HIAA levels were found in 85% (17/20). The immunocytochemical sensitivity for serotonin was 100% (11/11). The diagnosis of pancreatic carcinoid tumour is based on the typical endocrine histological features together with increased serotonin metabolism. Generally, the slow growth rate and late invasion of adjacent organs render local resection possible, but the high incidence of distant metastases (69%) prevents long-term survival in the majority of patients. The possible role of the Octreoscan, a new radionuclide imaging technique, is discussed with regard to this tumour entity.
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PMID:Carcinoid of the pancreas: clinical characteristics and morphological features. 875 39

Octreotide therapy is expensive, but at present it and other somatostatin analogues appear to offer the best opportunity of controlling the symptoms of flushing and diarrhoea. It may also have other properties affecting general well-being. The question of whether it changes tumour growth remains unanswered and there is no convincing evidence that it alters survival. In all published studies the numbers of patients are small and there have been no control groups. However, since no other drug has yet proved effective against flushing, the somatostatin analogues, including octreotide, remain the treatment of choice for the symptomatic control of the carcinoid syndrome. Octreotide is of great therapeutic value pre-operatively and intra-operatively and it is essential that all operating theatres have this drug available for immediate use. Surgical debulking, if feasible, provides the best outcome potential in carcinoid disease. Present evidence suggests that the place of octreotide and other somatostatin analogues is in controlling the symptoms of the disease rather than its progress and in ensuring cardiovascular and respiratory stability during surgical procedures.
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PMID:Octreotide therapy in carcinoid disease. 882 81

Tachykinins are a family of peptides that may be present in and secreted from carcinoid tumours of mid-gut origin. They are likely to play a role in the pathogenesis of, e.g. the flush, dyspnoea and valvular heart disease seen in the carcinoid syndrome. Since tachykinins are secreted from the tumour into the circulation in bursts, coinciding with flushing attacks, and have short half-lives, we anticipated that analysis of 24-h urine excretion of immunoreactive tachykinin metabolites might prove to be a more sensitive and stable parameter for monitoring than tachykinin-like immunoreactivity in plasma. The study included 48 patients hospitalized for treatment of advanced carcinoid tumours and 32 healthy controls. The urine excretion of tachykinin-like immunoreactive metabolites in the carcinoid patients (median 27.5 pmol 24 h-1, interquartile range (IQR) 8.5-51.0 pmol 24 h-1) was significantly (p<0.001) higher than that in the 32 healthy subjects (median 3.0 pmol 24 h-1, IQR 0.9-4.20 pmol 24 h-1). Of the patients, 38 (79%) had elevated 24-h urine excretion of tachykinin-like immunoreactive metabolites while 31 (64%) had elevated plasma concentrations of tachykinin-like immunoreactive metabolites. Of the patients, 27 (56%) had elevated concentrations of tachykinin-like immunoreactive metabolites both in plasma and urine, 12 (25%) had elevated concentrations only in urine excretion, 3 (6%) had elevated concentrations of only plasma tachykinin-like immunoreactive metabolites and 7 (14%) had elevation of neither plasma nor urine concentrations. Analysis by means of different column chromatographic techniques indicated that the immunoreactive material was heterogeneous, with some components co-eluting with oxidized neurokinin A (NKA) and neuropeptide K (NPK). The urine tachykinin-like immunoreactivity correlates well with that of plasma, but is a slightly more sensitive indicator of elevated tachykinin-like immunoreactivity, probably since levels of urine tachykinin-like immunoreactive metabolites reflect the overall amount of the latter secreted into the circulation during 24 h.
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PMID:Immunoreactive tachykinins in 24-h collections of urine from patients with carcinoid tumours: characterization and correlation with plasma concentrations. 890 38

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dL-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumour-to-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors experience of 131I- and 123I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131I-MIBG. Three of the seven patients with known metastatic disease had positive 131I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123I-MIBG there were four true-negative scans and one false-negative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 pentetreotide . Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111In-pentetreotide. The experience with 123I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131I-MIBG and 111In-pentetreotide relative to 131I-PIPA may be related to the fact that 131I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111In-pentetreotide binds to cell surface receptors, whereas 131I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.
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PMID:Successful and unsuccessful approaches to imaging carcinoids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue. 892 46

Carcinoid tumours derived from the neural crest are usually associated with the symptoms of flushing and diarrhoea in the presence of liver metastases. Scintigraphs with 131I-metaiodobenzylguanidine (131I-MIBG) which is accumulated in the argentaffin granules of the cell, as well as with 111In-pentetreotide for the imaging of somatostatin receptors on the cell surface, are positive in a large proportion of carcinoid patients. To evaluate the complementary role of both radionuclide tests, we studied 20 consecutive carcinoid patients: 14 with the characteristic carcinoid syndrome and 6 with tumour symptoms, such as pain or obstruction. A positive test was found in 84% with either 131I-MIBG or 111In-pentetreotide; the combination yielded a sensitivity of 95%. A positive correlation was found with the presence of the carcinoid syndrome, but not with 5-HIAA excretion. A positive test may help in adjusting treatment: either to predict the response to octreotide or to select patients for 131I-labelled MIBG treatment. Application of a therapeutic dose of 111In-pentetreotide may be limited by the high normal uptake in the kidneys.
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PMID:Combined diagnostic imaging with 131I-metaiodobenzylguanidine and 111In-pentetreotide in carcinoid tumours. 894 76


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