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)

This paper reports on the results of two controlled therapeutic trials on patients with endocrine tumours of the gastrointestinal tract. Seventeen patients were treated up to 18 months with recombinant interferon-alpha 2c (2 x 10(6) IU/m2 s.c. daily) and 16 patients are treated in an ongoing study with octreotide (3 x 200 micrograms daily). Objective response (greater than 50% reduction of hormone secretion) was observed in one of 15 evaluable patients on IFN-alpha and in 12 of 16 patients on octreotide. Reduction of tumour size was not observed in these two trials. However, the majority of patients had stable tumour size during IFN-alpha and octreotide treatment despite progressive disease before. Subjective improvement due to reduction of symptoms such as flushing, diarrhea, and dermatitis was significantly more frequent after octreotide than after IFN-alpha. Of five endocrine tumour patients with progressive disease on IFN-alpha, three responded to subsequent treatment with octreotide while one had stable disease and one progressed. Two cases are reported from the authors' series of patients treated with octreotide before start of these trials. Complete remission of the tumour by low-dose (2 x 100 micrograms daily) octreotide was observed in one carcinoid patient. This remission has now lasted for four years. In one patient with liver metastasis of a VIPoma, who had become resistant to streptozotocin, his watery diarrhoea is now completely controlled with 100 micrograms octreotide s.c. every second day.
 ...
PMID:Treatment of gastrointestinal endocrine tumours with interferon-alpha and octreotide. 171 38

Neuroendocrine gut and pancreatic tumors have over the years presented a therapeutic challenge. The patients present with a wide range of clinical symptoms related to hormone production that can sometimes be easily managed but are sometimes life threatening. The most frequent clinical symptom related to endocrine gut tumors is the carcinoid syndrome, with flushing, diarrhea, bronchoconstriction, and right heart failure. Until the middle of the 1980s, when a patient was not cured by surgery, very little could be offered except chemotherapy. Biotherapy has revolutionized the treatment of malignant neuroendocrine gut and pancreatic tumors, in which both interferon-alpha and somatostatin analogues improved the quality of life for these patients and possibly also increased survival. Chemotherapy, with response rates of 40% to 60% in endocrine pancreatic tumors, is still first-line treatment in this group of patients, whereas in patients with carcinoids of the gut, no beneficial value of chemotherapy so far has been noticed. Both interferon-alpha and somatostatin analogues provide biochemical responses in 40% to 70% of patients with carcinoid tumors, whereas significant tumor reduction is only noticed in a few cases. Development of biotherapy is just at its beginning, and in the future, when we have learned more about tumor biology and mechanisms of action of these treatments, even better therapeutic results might be encountered. Combinations of biotherapy with chemotherapy as well as combinations of different biotherapies are now under clinical investigation.
 ...
PMID:Chemotherapy and biotherapy in neuroendocrine tumors. 809 14

A 35-year-old female presented in 1989 with hepatosplenomegaly, but no conclusive diagnosis was established. From 1992, she experienced transient episodes of facial flushing and palpitations. Osteosclerotic change was detected radiologically. Colonoscopy revealed massive polypoid lesions. Mast cells were demonstrated in bone marrow smear and imprinted preparations of colon biopsy specimens by toluidine blue staining. Plasma concentrations of histamine and soluble c-kit were elevated. She was successfully treated with interferon-alpha and prednisolone, resulting in the disappearance of histamine-related attacks and a gradual decrease in tumor size. However, the remission was interferon dose dependent. This case was considered as systemic mastocytosis with massive polypoid colon lesions and showed the importance of maintenance therapy with interferon-alpha.
 ...
PMID:Systemic mastocytosis with extensive polypoid lesions in the intestines; successful treatment with interferon-alpha. 965 7

Systemic mastocytosis (SM), as opposed to cutaneous-only mastocytosis, implies the presence of neoplastic mast cell infiltration in extracutaneous tissue. Mast cell disease in adults is often systemic and often involves the bone marrow. Typical clinical and laboratory features of SM include urticaria pigmentosa, mast cell mediator symptoms (eg, headache, flushing, lightheadedness, urticaria and pruritus, nausea, diarrhea, abdominal pain, and vasodilatory shock), bone pain (eg, osteoporosis, lytic bone lesions, and fractures), hepatosplenomegaly, cytopenia, eosinophilia, elevated serum tryptase and histamine, and bone marrow fibrosis and angiogenesis. SM may be indolent (no evidence of organ dysfunction), aggressive (presence of organ dysfunction), associated with another often chronic myeloid hematologic disease (SM-AHD), or present as mast cell leukemia or sarcoma. Mast cell-mediator symptoms are treated with histamine antagonists and cromolyn sodium. Indolent SM does not require cytoreductive therapy. Aggressive SM and SM-AHD are managed based on their molecular profile. Recent information suggests that FIP1-like-1-platelet-derived growth factor receptor-alpha(+) SM responds well to imatinib mesylate, whereas interferon-alpha should be considered as a first-line treatment in all of the other cases, including patients with Asp816Val(+) SM. Cladribine has been shown to be effective in patients who develop resistance to interferon treatment.
 ...
PMID:Systemic mastocytosis: current concepts and treatment advances. 1508 68

The suitability of noncovalently bilayer-coated capillaries for the analysis of proteins by capillary electrophoresis (CE) at medium pH was investigated. Fused-silica capillaries were coated simply by successively flushing with a polybrene (PB) and a poly(vinyl sulfonate) (PVS) solution. A protein test mixture was used to evaluate the performance of the coated capillaries. Comparisons with bare fused-silica capillaries were made. Several background electrolytes (BGEs) were tested in combination with the PB-PVS coating, showing that optimum performance was obtained for the proteins using high BGE concentrations. With a 300 mM Tris phosphate buffer (pH 7.0), good plate numbers (150,000-300,000), symmetrical peaks, and favorable migration-time repeatabilities (RSDs below 0.8%) were obtained for the proteins. Using bare fused-silica capillaries, the protein peaks were significantly broadened and the migration-time RSDs often exceeded 5%. It is concluded that the PB-PVS coating effectively minimizes adverse protein adsorption and provides a very stable electroosmotic flow (EOF). We also investigated the potential of a commercially available bilayer coating (CEofix) for protein analysis. It is demonstrated that with this coating, good plate numbers and peak symmetries for proteins can be achieved when the CEofix BGE ("accelerator") is replaced by a common BGE such as sodium or Tris phosphate. Apparently, the negatively charged polymer present in the "accelerator" interacts with the proteins causing band broadening. The utility of the bilayer coatings is further illustrated by the separation of proteins such as interferon-alpha 2b, myoglobin and carbonic anhydrase, by the analysis of a degraded insulin sample in time, and by the profiling of the glycoprotein ovalbumin. In addition, it is demonstrated that even in the presence of concentrations of human serum albumin in the sample of up to 60 mg/mL, the PB-PVS coating still provides reproducible protein separations of good performance.
 ...
PMID:Noncovalently bilayer-coated capillaries for efficient and reproducible analysis of proteins by capillary electrophoresis. 1607 6

(Neuro-)endocrine tumours of the gastrointestinal tract are also called 'carcinoids'. (Neuro-)endocrine midgut tumours can be categorized according to their clinical behaviour. Most tumours are non-functioning. Functioning tumours are responsible for the carcinoid syndrome. The carcinoid syndrome is almost uniquely associated with midgut carcinoids. Symptoms of the carcinoid syndrome are caused by an excess of biogenic amines, peptides and other factors in the circulation. The typical symptoms of the carcinoid syndrome are diarrhoea, flushing, and carcinoid heart disease. Carcinoid heart disease involves the tricuspid and pulmonary valves and the endocardium. Serum chromogranin A and urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) are biochemical markers. Carcinoid tumours express large numbers of high-affinity somatostatin receptors. These can bind the currently available octapeptide somatostatin analogues. In inoperable patients, biotherapy with somatostatin analogues and interferon-alpha is the treatment of choice. Somatostatin analogues and interferon-alpha significantly improve symptoms.
 ...
PMID:Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome). 1625 95

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.
 ...
PMID:Carcinoid syndrome: diagnosis and medical management. 1644 70

Indolent systemic mastocytosis (SM) patients have a varied clinical presentation, ranging from predominantly cutaneous symptoms to recurrent systemic symptoms (eg, flushing, palpitations, dyspepsia, diarrhea, bone pain) that can be severe and potentially life threatening (anaphylaxis). Mastocytosis patients without skin involvement pose a diagnostic challenge; a high index of suspicion is needed in those with mast cell-degranulation symptoms, including anaphylaxis following Hymenoptera stings or other triggers. Modern-era molecular and flow-cytometric diagnostic methods are very sensitive and can detect minimal involvement of bone marrow with atypical/clonal mast cells; in some cases, full diagnostic criteria for SM are not fulfilled. An important aspect of treatment is avoidance of known symptom triggers; other treatment principles include a stepwise escalation of antimediator therapies and consideration of cytoreductive therapies for those with treatment-refractory symptoms. The perioperative management of mastocytosis patients is nontrivial; a multidisciplinary preoperative assessment, adequate premedications, and close intra- and postoperative monitoring are critical. Smoldering mastocytosis is a variant with high systemic mast cell burden. While its clinical course can be variable, there is greater potential need for cytoreductive therapies (eg, interferon-alpha, cladribine) in this setting. A systematic approach to the diagnosis and treatment of indolent SM using a case-based approach of representative clinical scenarios is presented here.
 ...
PMID:How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). 2342 50