Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CL 246,738 is a synthetic heterocyclic of the acridine class that has immunomodulating, interferon (IFN)-inducing, and antitumor activity by the oral route in mice. We have completed a phase I ascending dose trial to determine the maximum tolerated oral dose and biologic modifying effects. Twenty-three patients received CL 246,738 orally at five dose levels, escalating from 5 to 50 mg/kg. The major side effects were gastrointestinal disturbances such as nausea, vomiting, and diarrhea. No hematologic, hepatic, or symptomatic dose-limiting toxicities were encountered. The mean half-life of CL 246,738 in whole blood was at least 300 h and remained relatively constant over the dose range studied. Higher doses resulted in increased whole blood levels. Biologic response modification included stimulation of the IFN-induced proteins, 2',5'-oligoadenylate synthetase and beta 2-microglobulin, at higher doses of CL 246,738, and enhanced T-cell proliferation to alloantigens at lower doses. Increases in lymphocytes bearing the Leu-7 phenotypic marker were observed and some patients had enhanced natural killer (NK) cell cytotoxicity. Enhanced NK cell cytotoxicity was demonstrated in vitro. Thus, CL 246,738 was orally relatively well tolerated and has immunomodulating properties in humans.
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PMID:Biological and clinical effects of the oral immunomodulator 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride in patients with malignancy. 169 Jul 88

Forty-five patients with proved gastrointestinal amyloidosis were examined to study the clinical and pathological features and to determine the correlation with amyloid fibril proteins. The examinations included physical examination, laboratory study, plain X-ray film of the abdomen, gastrointestinal radiography, gastrointestinal endoscopy, endoscopic biopsy, surgery, and autopsy. The results were as follows: 1) Amyloid fibril proteins consisted of amyloid light chain protein (AL) in 7 patients, amyloid A protein (AA) in 36, beta 2-microglobulin (AH) in one, and prealbumin (AF) in one. 2) At the time of examination, gastrointestinal symptoms were present in 43 (96%) of the 45 patients. The incidence of diarrhea and gastrointestinal bleeding was higher in patients with the AA type than in those with other types, whereas abdominal distension, nausea, and vomiting were more frequently evident in patients with the AL type. 3) The incidence of hypoalbuminemia, hypokalemia, and positive occult blood was higher in patients with the AA type, whereas abnormal electrocardiogram and cardiac failure were more frequently observed in patients with the AL type. The thyroid gland was enlarged in 7 patients with the AA type, and the macroglossia was evident in only 2 patients with the AL type. 4) The frequency of radiographic abnormalities in the gastrointestinal tract was as follows: 79% of the patients in the jejunum and ileum, 61% in the duodenum, 53% in the stomach, 32% in the colorectum, and 14% in the esophagus. Fine granular shadows were most frequently seen in patients with the AA type, whereas multiple polypoid protrusions and thickening of the folds were characteristic in patients with the AL type. 5) Endoscopic abnormalities were found as follows: 82% in the duodenum, 81% in the jejunum, 73% in the stomach, 42% in the colorectum, and 20% in the esophagus. Endoscopy revealed fine granular appearance in 31 (86%) of the 36 patients with the AA type, whereas multiple polypoid protrusions and thickening of the folds were evident in 5 (71%) of the 7 patients with the AL type. 6) On the histological examination of the biopsy specimens, amyloid deposition was found in the duodenum in 98% of the 45 patients studied, in the jejunum in 96% of the 26 patients, in the antrum in 93% of the 41 patients, and in the rectum in 86% of the 43 patients. 7) Histological findings of the biopsy and autopsy specimens revealed that the the degree of amyloid deposition was the highest in the duodenum and jejunum of the gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Diagnosis of gastrointestinal amyloidosis with special reference to the relationship with amyloid fibril protein]. 178 55

cis-Diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA, JM8), an analogue of cisplatin showing reduced toxicity in preclinical studies, was evaluated in 60 patients. Doses were given initially every 3 weeks and escalated from 20 to 520 mg/m2. Following this, doses were given every 4 weeks and escalated from 300 to 500 mg/m2. The dose-limiting toxicity, thrombocytopoenia, occurred in four-fifths of patients treated at 520 mg/m2, with the nadir occurring 3 weeks after treatment. Leucopoenia and anaemia also occurred but were less severe. Vomiting occurred in all patients receiving over 120 mg/m2 but seldom persisted beyond 24 h. Serial measurements of 51Cr-EDTA clearances, urinary N-acetylglucosaminidase, urinary leucine aminopeptidase, and beta 2-microglobulin did not reveal significant evidence of nephrotoxicity. Detriment to the audiogram has not been seen in the first 13 patients studied. Pharmacological studies showed that most of the dose of platinum was excreted in the urine, and that impairment of renal function may be associated with drug retention and an increased risk of myelosuppression. The previous therapy and age of the patient also affected the tolerance of the drug. Clinical responses were seen in patients with ovarian carcinoma receiving greater than 120 mg/m2. A further dose escalation was performed on a 4-week schedule in patients under 65 with good renal function. The maximum dose it was possible to administer repeatedly without incurring myelosuppression was in the range 400-500 mg/m2. JM8 is not significantly nephrotoxic and is less emetic than cisplatin. It has antitumour activity in man and deserves wider evaluation, along with the other analogues under study in various centres, as an alternative to cisplatin.
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PMID:Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. 676 Oct 10

A 24 y/o male, after attempting suicide by ingesting liquid ferric chloride, presented with protracted vomiting and epigastric pain. He was noted to have leukocytosis, a metabolic acidosis and an elevated serum iron level. Hemorrhagic gastritis, coagulation defects and an increase in urine beta 2-microglobulin, indicating renal tubular damages were found in the following day. He later recovered after treatment with deferoxamine and good supportive care. This is Taiwan's first reported case of acute iron intoxication in an attempted suicide. We discussed the characteristics of this liquid form of iron intoxication, the limitations of local laboratories in providing support and how to diagnose and treat acute iron intoxication without waiting for serum iron and total iron binding capacity levels. In conclusion, to evaluate the severity of iron intoxication, a deferoxamine challenge test and the severity of symptoms and signs should be assessed without relying only on serum iron and total iron binding capacity levels. Deferoxamine and good supportive care should be given to all serious iron intoxications.
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PMID:Acute iron intoxication: a case report with ferric chloride ingestion. 825 22

Fifteen patients with stage II, IIIA, and IIIB non-small cell lung cancer (NSCLC) received subcutaneous (s.c.) recombinant, glycosylated, human interferon-beta 1a (Rebif; rHuIFN-beta 1a) on each day of conventionally fractionated radiation therapy (RT) given in 2.0 Gy fractions to 60 Gy in 6 weeks. The rHuIFN-beta 1a was generated in CHO cells by recombinant DNA technology and is identical to natural IFN-beta produced by fibroblasts in primary sequence and glycosylation. Cohorts of three patients each were treated with escalating doses of rHuIFN-beta 1a: 1.5, 3, 6, 12, and 24 MIU/m2 per treatment day. Acute toxicity was assessed according to modified WHO criteria; late toxicity was graded using RTOG late toxicity criteria. The maximum tolerated dose (MTD) of rHuIFN-beta 1a was defined as the dose level immediately below that in which dose-limiting toxicity occurred in > or = two of six patients. Immunomodulatory effects and antigenicity of rHuIFN-beta 1a were assessed by 2-5A synthetase, beta 2-microglobulin, and neopterin levels and by measurement of anti-rHuIFN-beta antibodies, respectively. Fourteen of fifteen patients experienced grades 1-3 acute (early) toxicity (< or = 90 days), which was primarily gastrointestinal: dysphagia/esophagitis (14/15), nausea/vomiting (12/15), anorexia (7/15), and liver transaminasemia (6/15). One of three patients treated with 24 MIU/m2 per treatment day (total rHuIFN-beta 1a dose 672 MIU) died of complications secondary to pneumonia, sepsis, adult respiratory distress syndrome (ARDS), and radiation pneumonitis. Twelve patients were evaluable for late toxicity (> 90 days). Maximum toxicity was grade 0 in five patients, grade 1 in four patients, and grade 5 in one patient (radiation pneumonitis). Clinical responses from the combination were 1/15 CR, 6/15 PR, 6/15 stable disease, and 1/15 progressive disease. The MTD of rHuIFN-beta 1a has been estimated at 12 MIU/m2 per treatment day when given daily during conventional RT to 60 Gy in 6 weeks. Biologic response by rHuIFN-beta 1a alone was reflected by significant and dose-related increases in 2-5A synthetase, beta 2-microglobulin, and neopterin. Radiation therapy alone had no effect on these immune response parameters and did not diminish their augmentation by rHuIFN-beta 1a. There was no association of biologic modulation with clinical response or survival.
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PMID:Recombinant human interferon-beta (rHuIFN-beta) and radiation therapy for inoperable non-small cell lung cancer. 893 64