Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neocarzinostatin (NCS) is an antibiotic from streptomyces carzinostaticus which inhibits DNA synthesis. Clinical trials in Japan began in 1971. NCS is active against S-180, Ehrlich tumor, L1210, Yoshida sarcoma, and a range of ascitic hepatomas. In rabbit NCS is distributed at high concentrations in the kidney, skin, stomach, pancreas, lung, and muscles. The high distribution in the pancreas and the stomach suggested possible effectiveness in human tumors at these sites. In clinical studies NCS has been shown to be active against acute leukemia. As a single agent 9 out of 51 obtained a CR with 9 more achieving a PR. Anorexia, nausea, and vomiting were the most frequent side effects. NCS has been tried in combination with Ara-C, daunorubicin and prednisolone and CR was ssen in 11 out of 14. In stomach cancer responses of some kind were observed in 12 out of 141 cases, while in the case of pancreatic tumors there were 10 out of 68.
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PMID:Clinical investigations of neocarzinostatin in Japan. 15 99

Four patients, who suffered from malignant, disseminated tumors but had a morphologically intact bone marrow, where given a peroral Hydroxyurea (HU) infusion in a concentration of about 5 x 10(-4) mol over a period of 10 h. As indicator of the DNA synthesis the 3H-TdR-incorporation of bone marrow, gained by puncture before, during, and/or after HU application, was measured. While using HU, the DNA synthesis was extensively inhibited. Fourteen to 16 h after discontinuing the HU it increased by the factor 1.5 to 2 of the initial value, i.e., before treatment. This is interpreted as a partial synchronization of bone marrow cells where effects of cell depletion and recruitment are not to be entirely excluded, Toxicity, such as the decrease of peripheral blood cells or nausea, did not occur.
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PMID:[Influence of hydroxyurea on DNA synthesis of human bone marrow in vivo (author's transl)]. 51 12

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days. 133 81

It is proposed that the new American and European AIDS epidemics are caused by recreational and anti-HIV drugs rather than by human immunodeficiency virus (HIV). Chronologically, the AIDS epidemic in the 1980s followed a massive escalation in the consumption of recreational drugs that started in the 1960s and 70s. Epidemiologically, both epidemics derive about 80% of their victims from the same groups of 20-44 year-olds, of which 90% are males. In America 32% of these are intravenous drug users and their children, about 60% are male homosexuals who are long-term users of oral aphrodisiac drugs and an unknown percentage are prescribed the cytotoxic DNA chain terminator AZT, as inhibitor of HIV. Direct evidence indicates that these drugs are necessary for HIV-positives and sufficient for HIV-negatives to develop AIDS diseases. The drug-AIDS hypothesis predicts correctly that: (i) AIDS is new in the US, because the drug epidemic is new, while the HIV epidemic is old--fixed at a constant 1 million Americans since 1985; (ii) despite an increase in venereal diseases, AIDS remains restricted to long-term drug users and small groups with clinical deficiencies; (iii) over 72% of AIDS occurs in 20-44 year-old males, because they make up over 80% of hard psychoactive drug use; (iv) distinct AIDS diseases correlate with the use of distinct drugs, eg Kaposi's sarcoma with nitrite inhalants, tuberculosis with intravenous drugs, and leukopenia, anemia, and nausea with AZT; (v) AIDS diseases are only acquired after long-term drug consumption, rather than after single contacts as the virus-hypothesis predicts. The drug hypothesis can be tested epidemiologically and experimentally in animals. It predicts that most AIDS can be prevented by stopping the consumption of drugs, and provides a rational basis for therapy.
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PMID:The role of drugs in the origin of AIDS. 142 Oct 32

Turcot's syndrome is a rare, genetically transmittable disease in which patients with colonic polyposis (possibly complicated by the progression to adenocarcinoma) have malignant central nervous system neoplasms. Dominant, recessive, and sporadic cases have been described. A 26-year-old man is reported with no relevant family history who had intermittent abdominal discomfort in 1986. Sigmoidoscopy revealed numerous polyps, several of which showed carcinomatous change. Dukes' Stage C colorectal carcinoma was diagnosed. Treatment consisted of total colectomy with construction of a Koch's pouch. He remained well for 3 years until onset of headache, nausea, and vomiting. Computed tomographic scan disclosed a large, circumscribed, enhancing, right frontoparietal mass. After craniotomy and partial resection, histologic review disclosed anaplastic astrocytoma. He received cranial radiation therapy, 6000 cGy, by parallel opposed ports to the tumor bed, and carmustine 200 mg/m2 intravenously every 8 weeks. Flow cytometric DNA analysis was done on the paraffin-embedded archival material from the patient's normal colon, colonic adenocarcinoma, and anaplastic astrocytoma. DNA histograms revealed diploid distributions in all three samples. The G2/M fraction of the astrocytoma was elevated at 16%, and the S-phase fraction of the colonic adenocarcinoma was 19.4%.
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PMID:Turcot's syndrome. Flow cytometric analysis. 165

To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected.
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PMID:Positive phase II study in the treatment of advanced malignant melanoma with fotemustine. 174 55

Amonafide (benzisoquinolinedione, nafidimide, NSC 308847) is an anticancer agent that functions as a DNA intercalator. Sixteen patients with stage III or IV non-small-cell lung cancer who had not previously received chemotherapy were given amonafide at an initial dose of 300 mg/m2 i.v. daily for 5 days every 21 days. No major objective responses were observed among the 14 patients adequately treated (95% confidence limits 0-20%). Local reactions at the injection site or phlebitis were seen in 14 of the 16 patients. Leukopenia (44%), nausea or vomiting (38%), and thrombocytopenia and rash (each 25%) were also noted. With the low response rate and the toxicity observed, amonafide at this dosage and schedule has limited use in the treatment of non-small-cell lung cancer.
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PMID:Phase II trial of amonafide in patients with stage III and IV non-small-cell lung cancer. 185 87

Episodes of catastrophic entero-colitis associated with mesenteric vascular insufficiency in patients with rheumatoid arthritis(RA) have rarely been recorded thus far. We herein report two cases of RA complicated with severe attacks of entero-colitis presumably due to mesenteric vasculitis. Surgical intervention was necessary in the first case, while the second patient recovered well only through conservative therapy. Case 1: A 74-year-old man with history of RA since 1985 started to complain of abdominal discomfort and nausea early in February, 1989. On February 12, Episodes of tarry stool developed. Rapid down-hill clinical course prompted laparotomy under the clinical diagnosis of peritonitis. Ischemic changes were observed at the ileum end, the entire length of which was 120 cm orally from the cecum. The site was resected. Multiple linear and aphthoid ulcer lesions were discovered throughout the entire lumen. Histopathologically, evidence of necrotizing vasculitis such as fibrinoid necrosis and mural thrombi was demonstrated in small arteries of the submucosal layer underlying the ulcer lesion. Case 2: A 63-year-old woman who had been suffering from RA since 1980 noticed the onset of nausea, abdominal pain and bloody diarrhea in July, 1989. Colonoscopy examination revealed multiple linear and aphthoid ulcers in the sigmoid colon which was presumed to be due to ischemia. Laboratory evaluation at that time demonstrated hypocomplementemia, positive circulating immune complex and high titer of anti-DNA antibody. Corticosteroid therapy with moderate dose was successful in alleviation of all the abnormal findings and the patient fully recovered three months after her initial GI episode.
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PMID:[Two cases of rheumatoid arthritis complicated with vasculitis-induced ischemic enterocolitis]. 208 64

A 25-year-old man, who was admitted for evaluation of arthralgia and fever of 2-weeks duration, complained of a 10 kg weight loss during the previous weeks. Systemic lupus erythematosus (SLE) was diagnosed on the basis of leukopenia, LE cells, antinuclear antibodies, antibodies to double-stranded DNA, and arthritis, Malabsorption was diagnosed because of the finding of hypoalbuminemia, fat droplets in the feces, a pathological D-xylose test, and an appropriate X-ray image. Approximately half the patients with SLE develop minor expressions of gastrointestinal tract involvement, such as nausea, vomiting, and diarrhea. Major manifestations, such as intestinal obstruction or perforation, ascites, peritonitis and pancreatitis have been reported with varying frequency. Despite the frequent association of SLE with gastrointestinal manifestations, malabsorption, as in this case, has rarely been reported.
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PMID:[Malabsorption in systemic lupus erythematosus]. 235 16

Photosensitizers were first used to treat psoriasis 15 years ago when the phototoxic reaction of psoralens and UVA was found to induce remissions of the disease. The effect of this reaction on DNA, particularly the formation of cross-links, was thought to be the decisive event. Strong cross-linking agents such as 8-MOP, TMP and 5-MOP are clinically effective whereas most compounds which produce only monofunctional adducts are virtually ineffective. Orally administered 8-methoxypsoralen (8-MOP) is the most widely used compound. 4,5',8-Trimethylpsoralen (TMP) is poorly absorbed from the intestine but has marked efficacy when applied topically. 5-MOP may be a useful alternative to 8-MOP because it is less erythemogenic and does not cause nausea. These three furocoumarins appear to be similar photochemically and may introduce similar risks. However, the photobiological properties of furocoumarins can be modified by altering one or more parts of the molecule. Such modifications might yield effective analogues with reduced cytogenetic hazards. Several psoralens and angular furocoumarins are being tested for effectiveness combined with fewest long-term side-effects, especially carcinogenesis. Encouraging preliminary results have been obtained with 7-methyl-pyridopsoralen and 4,6,4'-trimethylangelicin. Other important approaches to increasing the safety of photochemotherapy may be the use of different photoactivating wavelengths or the introduction of new classes of photosensitizers.
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PMID:Photosensitizing compounds in the treatment of psoriasis. 269 31


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