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)

Hickman catheters (HC) are associated with complications, in particular infection, occlusion and thrombosis. We tested the hypothesis that regular flushing of catheters with urokinase would reduce the frequency of these complications. Patients who required a double-lumen HC for (1) bone marrow or peripheral blood progenitor cell transplantation or (2) intensive combination chemotherapy for haematological malignancies were randomised to receive twice-weekly flushes of either urokinase (5000 units) or heparin (50 units). HC-survival analysis was determined by Cox regression. 100 patients were enrolled (urokinase=52; heparin=48) and treated for a mean of 8.5 weeks. No significant difference was observed in the incidence of HC-associated septicaemic events, which occurred in 8/52 in the urokinase group and 9/48 in the heparin group (actuarial incidence 20% versus 25%, P=0.50). Similarly, there was no differences in the incidence of exit site infections (urokinase=27/52 and heparin=28/48, P=0.122); HC-septic thromboses (urokinase=2/52 and heparin=4/48, P=0.34); lumen occlusion (urokinase=30/52 and heparin=30/48, P=0.681); or venous thrombosis (urokinase=8/52 and heparin=6/48, P=0.726). Overall, a high incidence of HC-related complications was seen in both groups; 40/52 in the urokinase group and 40/48 in the heparin group (actuarial incidence 80% versus 90%, P=0.367). Despite this only 18% of HC required early removal due to complications (urokinase=8, heparin=10). There was no difference in the incidence of complications in patients undergoing transplantation (n=68) compared with chemotherapy alone (n=32). Patients with haematological malignancies were more likely to have HC-related infective complications (P=0.006), and patients with solid tumours more likely to have venous thrombosis (P=0.027). The cumulative incidence of HC-related complications in this prospective study was higher than in previously reported series. Urokinase did not appear effective in reducing the frequency of these complications.
Eur J Cancer 2001 Dec
PMID:Lack of efficacy of twice-weekly urokinase in the prevention of complications associated with Hickman catheters: a multicentre randomised comparison of urokinase versus heparin. 1172 Aug 31

Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
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PMID:[Alcohol and oropharyngolaryngeal and digestive tract cancer]. 1182 13

Carcinoid tumors are very rare and originate mainly in the gastrointestinal tract. The tumor histology is ambiguous and malignancy is determined by metastases. Carcinoid tumors affect both sexes equally and have been found in all age groups. Many carcinoid tumors are found incidentally or from symptoms related to the hormones that the tumor produces. Carcinoid syndrome occurs when vast quantities of hormones are produced from GI carcinoid metastases or a non-GI primary tumor. The classic "carcinoid triad" associated with the syndrome includes flushing, diarrhea, and cardiac involvement. The hormone largely responsible for most of these symptoms is serotonin. Treatment consists of a wide-resection for local primaries and usually palliative, medical support for patients with metastases. The tumors are very slow-growing and patients have lived for up to 30 years after metastasis is diagnosed. Somatostatin analogue (lanreotide and octreotide) administration controls many of the carcinoid symptoms. Somatostatin is a naturally occurring gastrointestinal peptide (hormone) which can augment or counteract a wide variety of other peptides. This article provides an overview of carcinoid tumor and carcinoid syndrome including diagnosis and treatment. Aspects important to patient care will also be addressed.
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PMID:Carcinoid tumors and syndrome. 1205 78

Carcinoid tumours are enigmatic, slow growing malignancies, which occur most frequently (74%) in the gastrointestinal tract. Symptoms of the carcinoid syndrome (flushing and diarrhoea) are infrequent, occurring in approximately 10% of the patients with small bowel carcinoid. A 45-year-old patient with multiple liver metastases, diagnosed in 1994 with nonHodgkin's lymphoma after undergoing surgery for a distal ileal tumour, was referred to us by the Department of Haematology. At that moment the issue of a differential diagnosis with a carcinoid tumour arose, due to the long evolution and lack of evidence to support the initial diagnosis. The carcinoid syndrome was in fact present (the patient experiencing flush after small amounts of alcohol and emotions) and also we identified elevated values of 5HIAA. Reevaluation of the histologic sections of the ileal tumour as well as an ultrasound guided fine needle aspiration of an intrahepatic lesion confirmed the diagnosis of "carcinoid tumour". This conclusion lead to new therapeutic options for this patient. One of the main therapeutic options used in treating multiple liver metastases from a carcinoid tumour is chemoembolization and this case offered an excellent opportunity to present this therapy.
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PMID:Chemoembolization in the treatment of metastatic ileocolic carcinoid. 1214 71

The aim of this study was to examine how aldehyde dehydrogenase-2 (ALDH2) genotypes and human leukocyte antigen (HLA) haplotypes contribute to the risk for esophageal cancer. We examined ALDH2 genotypes and HLA haplotypes in 29 Japanese patients with esophageal cancer. The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype. The ratio of inactive ALDH2 was significantly higher in patients with esophageal cancer than in control normal subjects, suggesting that alcoholics with inactive ALDH2 were susceptible to esophageal cancer. HLA haplotypes A24, A26, B54, B61 and DR9 were prevalent in patients with esophageal cancer (82.8, 24.1, 34.5, 37.9 and 44.8%, respectively). HLA haplotype of A24 and inactive ALDH2 were simultaneously found in 58.6% of patients with esophageal cancer. Furthermore, we found other primary malignancies in 6 of 29 (20.7%) patients with esophageal cancer, and 4 of these 6 patients had both the inactive form of ALDH2 and the HLA A24 haplotype. The present study showed the high prevalence of the inactive form of ALDH2 and HLA haplotypes A24, A26, B54, B61 and DR9 in Japanese patients with esophageal cancer. Therefore, the examination of genotypes of ALDH2 loci and HLA haplotypes may allow the early detection of esophageal cancer in the Japanese population.
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PMID:Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer. 1216 74

Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme for the elimination of acetaldehyde, an established animal carcinogen generated by alcohol metabolism. In the presence of ALDH2*2, a mutant allele that is prevalent in East Asians, this enzyme is inactive, leading to excessive accumulation of acetaldehyde. Only among Japanese alcoholic patients has the positive association between this inactive form of ALDH2 and multiple-field cancerization in the upper aerodigestive tract been demonstrated. Whether this finding could be extended to multiple-cancer patients in general is of great interest, because the prevalence of esophageal cancer with other organ cancers has increased dramatically during recent decades in Japan. This study compared the ALDH2 genotypes of groups of male Japanese drinkers who had either esophageal squamous cell carcinomas (SCCs) with (n = 26) or without (n = 48) multiplicity or oropharyngolaryngeal SCCs with (n = 17) or without (n = 29) multiplicity. After adjustments for age and drinking and smoking habits, logistic regression analysis showed significantly increased risk for each multiplicity associated with either esophageal or oropharyngolaryngeal SCCs in the presence of the ALDH2*2 allele (odds ratio, 5.26; 95% confidence interval, 1.08-51.06 and odds ratio, 7.36; 95% confidence interval, 1.29-80.70, respectively). This study is the first to strongly link inactive ALDH2 with the multiple cancer susceptibility of male Japanese drinkers with either esophageal or oropharyngolaryngeal cancers. A simple questionnaire about both current and past facial flushing after drinking a glass of beer was highly sensitive (95.6%) in detecting inactive ALDH2 in these patients and may be useful for identifying high-risk patients.
Cancer Epidemiol Biomarkers Prev 2002 Sep
PMID:Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. 1222 35

The role of genetic polymorphisms in modulating xenobiotic metabolism and susceptibility to cancer and other health effects has been suggested in numerous studies. However, risk assessments have generally not used this information to characterize population variability or adjust risks for susceptible subgroups. This paper focuses upon the aldehyde dehydrogenase-2 (ALDH2) system because it exemplifies the pivotal role genetic polymorphisms can play in determining enzyme function and susceptibility. Allelic variants in ALDH2 cause decreased ability to clear acetaldehyde and other aldehyde substrates, with homozygous variants (ALDH2*2/2) having no activity and heterozygotes (ALDH2*1/2) having intermediate activity relative to the predominant wild type (ALDH2*1/1). These polymorphisms are associated with increased buildup of acetaldehyde following ethanol ingestion and increased immediate symptoms (flushing syndrome) and long-term cancer risks. We have used Monte Carlo simulation to characterize the population distribution of ALDH2 allelic variants and inter-individual variability in aldehyde internal dose. The nonfunctional allele is rare in most populations, but is common in Asians such that 40% are heterozygotes and 5% are homozygote variants. The ratio of the 95th or 99th percentiles of the Asian population compared to the median of the U.S. population is 14- to 26-fold, a variability factor that is larger than the default pharmacokinetic uncertainty factor (3.2-fold) commonly used in risk assessment. Approaches are described for using ALDH2 population distributions in physiologically based pharmacokinetic-Monte Carlo refinements of risk assessments for xenobiotics which are metabolized to aldehyde intermediates (e.g., ethanol, toluene, ethylene glycol monomethyl ether).
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PMID:Population distribution of aldehyde dehydrogenase-2 genetic polymorphism: implications for risk assessment. 1247 14

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.
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PMID:Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers. 1267 87

There is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compounds (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine. Doxorubicin and 6-mercaptopurine are occasionally associated with hypersensitivity reaction. Comparable reactions with other chemotherapeutic agents are. uncommon; many are only anecdotal reports. Reactions associated with individual drugs are discussed in detail. The mechanisms responsible for most of these reactions are not known, as they have generally not been evaluated. The term "hypersensitivity" is widely used in the chemotherapy literature without a common definition. Hypersensitivity is defined here as an unexpected reaction with signs and symptoms not consistent with known toxicity of the drug. Most reactions are coincident with or within hours of drug administration. Almost all are associated with parenteral administration. Symptoms include flushing, alterations in heart rate and blood pressure, dyspnea and bronchospasm, back pain, fever, pruritus, nausea and all types of rashes. Some cases may be due to non-immune mediated release of histamine or cytokines, as many patients can subsequently tolerate re-exposure after pretreatment with steroids and antihistamine, and slow readministration of the drug. This is more compatible with a graded challenge, than desensitization and is generally successful for taxanes, less so for platinum compounds. In most cases hypersensitivity reactions are associated with the specific chemotherapeutic drug. Reaction rates may vary with different forms of the drugs, e.g. pegylated. Occasionally excipients such as Cremaphor EL may induce hypersensitivity reactions.
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PMID:Hypersensitivity reactions to chemotherapeutic drugs. 1272 96

Who ever is writing about standards should put himself the question: What is a standard? How is it produced? Who is defining it? How compulsory is it? A standard should only be understood as guiding principles or as following guidelines and never as a dogma, while otherwise every operative technical or therapeutical progress is prohibited. On the basis of the onco-surgical guidelines for the colo-rectal carcinoma is shown how standards can begin to sway. The Turnbull "no-touch isolation technique" does not stand up to the criteria of the evidence based medicine. The usefulness of the high ligation of the veins and the intestinal occlusion has not been proven by any studies. The central ligature of the Arteria mesenterica inferior in left resection is wrong according more recent anatomical knowledge. Ligation near to the aorta leads obligatory to lesions of the plexus hypogastricus. Animal experiments are controversial concerning the dissemination of tumour cells during crushing of the cancer. And a prospective controlled study does not show any advantage of respecting the Turnbull criteria. Independent prognostic factors are the surgeon, the frequency of performing the procedure in the hospital concerned, the pT and N stage, the R-0 resection and according to American pathologists the pre-operative CEA titre. Also are mentioned the infiltration of veins and lymph vessels, micro metastases in lymph nodes and the grading. The resection should if possible be performed in anatomical layers, specially considering the meso-rectum. What should be done in the distal 8 cm till the pelvic floor has not yet been clarified. On the contrary, the laparoscopic surgery has definitively also found its acceptance in oncological surgery. The discussions about port-metastases and tumour-cell-dissemination by the pneumoperitoneum-gas have silenced. Already, partially better long-term results are mentioned. In the beginning of 2003, the pillars of the standard technique of oncological colo-rectal surgery are besides the orthograde intestinal flushing, the pre-operative low molecular Heparin and the antibiotic prophylaxis, the open or laparoscopic R-0 en bloc resection, the minimal safety distance in the low rectum of 1 cm, the ligature of the Arteria mesenterica inferior 2-3 cm distally to its origin from the aorta in case of left resection, respectively the Arteria ilio-colica at its origin from the Arteria mesenterica superior in case of right resection, the cytotoxic intestinal flushing in case of left resection and the flushing of the abdominal cavity as well as the port-site with Taurolin 0.5%. In case of rectum-carcinoma uT3 or uN+, a neo-adjuvant radio-chemotherapy is administered and adjuvant chemotherapy is given by positive nodal colon-carcinoma.
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PMID:[Standard technique of oncologic colorectal surgery]. 1281 36


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