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)

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.
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PMID:A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 151 22

Recombinant interferon-gamma was given to patients with tumours by a six-hour intravenous infusion using a portable mini-pump, to assess the side-effects of the drug. At present, 11 patients have been treated; 2 adenocarcinoma of the ovary, 3 squamous carcinoma of the bronchus, 1 adenocarcinoma of the breast, 1 adenocarcinoma of the stomach, 1 Hodgkin's lymphoma, 1 case of two primaries, adenocarcinoma of the breast and ovary, and 1 adenocarcinoma of unknown origin. Two patients received 1 X 10(6) units/m2/infusion, four received 3 X 10(6) U/m2/inf., three received 6 X 10(6) U/m2/inf. and two received 9 X 10(6) U/m2/inf. Two further dose levels will be used in the future; 27 and 51 X 10(6) U/m2/inf. Three 6-hour infusions a week were given for a four week period. The major side-effects of gamma-interferon were dose-related pyrexia with rigors to which there was no tachyphylaxis, acute and chronic tiredness, nausea with or without vomiting, headache, backache and myalgia. There was also a dose-dependent immediate but mild and transient decrease in the total white cell count. All effects have been transient, and none have been severe. We have also noticed that intravenous infusions by mini-pumps are tolerated far better by the patients than conventional drip systems, and we feel mini-pumps are the ideal way to give intravenous infusions.
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PMID:A phase 1 study of recombinant interferon-gamma given intravenously by portable mini-pump: a preliminary report. 624 30

Fifteen Indian patients with relapsing or drug-refractory visceral leishmaniasis were retreated for 30 days with antimony plus interferon-gamma (IFN-gamma). All 15 had failure of an initial course of antimony and at least one additional course of antimony or pentamidine; 7 patients had failure of three or four prior courses of therapy. During the study, treatment was discontinued in 2 patients because of anemia and congestive heart failure in 1 and intractable vomiting in the other; both subsequently died. In the remaining 13 patients, IFN-gamma plus antimony treatment was associated with daily fever but no other adverse reactions. After 30 days of therapy, 9 (69%) of the 13 patients were apparently cured. Six months after treatment, all 9 were healthy, had parasite-free bone marrow aspirate smears, and were considered cured. None have relapsed during a mean follow-up of 15.9 +/- 1.7 months. These results support the use of antimony plus IFN-gamma as an immunochemotherapeutic alternative for kala-azar patients who have repeated failures of conventional treatment.
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PMID:Successful treatment of refractory visceral leishmaniasis in India using antimony plus interferon-gamma. 807 25

Preclinical data have shown a synergism between 5-fluorouracil and interferon-gamma against human colon carcinoma cell lines. We conducted a phase II trial of this combination in 34 patients with metastatic colorectal cancer. 5-Fluorouracil was administered as an intravenous bolus of 500 mg/m2 weekly and interferon-gamma subcutaneous injection at a dose of 200 micrograms (6 x 10(6) IU) 3 times a week. Thirty-two patients were evaluable for response. There was one complete and two partial responses (response rate 9.0%, 95% CI 1.98-25.02%). Eleven patients (34%) had stable disease. Common toxicities included fever 81%, nausea/vomiting 19%, diarrhea 16%, flu-like syndrome 16%, malaise 12.5% and leukopenia 12.5%. These results indicate that the above combination of 5-fluorouracil and interferon-gamma has an unimpressive activity in patients with advanced colorectal carcinoma. Toxicity was very tolerable.
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PMID:Phase II study of 5-fluorouracil and interferon-gamma in patients with metastatic colorectal cancer. A Hellenic Cooperative Oncology Group Study. 860 43

The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted.
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PMID:Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma. 885 24

Because interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) act synergistically in vitro in the generation of lymphokine-activated killer (LAK) cells. we initiated a clinical trial of these lymphokines in combination. Twenty patients with advanced malignancy were treated at fixed dose levels of recombinant IFN-gamma given by intramuscular (i.m.) injections once a day and recombinant IL-2 given by an intravenous (i.v.) bolus injection 3 times a day for 7 days after a 3-day treatment with fixed doses (250 micrograms/m2/day) of IFN-gamma alone. A minimum of four patients were treated at each of the four dose levels studied. The side effects of the combination therapy were similar to those seen with individual lymphokines and included fever and chills, myalgia, headache, fatigue, nausea. vomiting, peripheral edema, skin rash, and hypotension. The maximum tolerated dose for the combination after a fixed dose of IFN-gamma was 2 x 10(5) U/M2/day (10 micrograms/m2/day) of IFN-gamma and 3 x 10(6) U/M2/day of IL-2, with fluid retention as the dose-limiting toxicity. Whereas natural killer (NK) or LAK activity or both were significantly increased in four of eight patients studied, only one patient with renal cell cancer had a minor response for four treatment cycles. We conclude that combination therapy with cytokines IL-2 and IFN-gamma given in this schedule had manageable toxicity and exhibited immunomodulatory effects in some patients but had no significant antitumor activity in this patient population.
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PMID:Recombinant interleukin-2 in combination with recombinant interferon-gamma in patients with advanced malignancy: a phase 1 study. 910 17

Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with renal syndrome (HFRS). To study the CNS and ophthalmic involvement in nephropathia epidemica (NE), the European type of HFRS, we included 26 patients in a prospective study. Most common CNS-related symptoms were headache (96%), insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic symptoms were reported by 82% of patients; 41% had photophobia and 50% had impaired vision. A transient loss of vision was recorded in one patient, who also had a generalized seizure. Minor white matter lesions were found in about half of the patients investigated with brain magnetic resonance imaging (MRI). Electroencephalography (EEG) showed severe alterations in only one patient, and slight and reversible patterns in another two patients. Neopterin, interleukin-6 and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which may indicate immune activation. However, we found no evidence of intrathecal NE virus replication. We conclude that CNS-related symptoms are common in NE, and transient ophthalmic involvement can be demonstrated in about half of the patients.
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PMID:Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome). 957 Jun 45

A syndrome of chronic diarrhea, vomiting, and failure to thrive was described 35 years ago. The syndrome was caused by damage in the jejunum after ingestion of cow's milk. Symptoms appeared in young infants shortly after introduction of cow's milk formula. Patients had moderate steatorrhea, decreased absorption of D-xylose, and, often, iron-deficiency anemia and hypoproteinemia. They had strong IgA and IgG antibodies to cow's milk. IgE antibodies to cow's milk were negative, as a rule. Indicators of cell-mediated immune reaction to cow's milk proteins were often positive. Patients were tolerant to cow's milk by the age of 3 years. Malabsorption was due to damage to the jejunal mucosa: Varying villus atrophy was associated with inflammation in surface epithelium and lamina propria. The epithelial cell renewal rate increased. Surface epithelial cells decreased in height, with short, furry microvilli and large aggregates of lysozymes. The number of intraepithelial lymphocytes was markedly increased, but normalized during cow's milk elimination. Most of these lymphocytes had alpha/beta T-cell receptors, and many were cytotoxic. Some specimens had an increase in gamma/delta T-cell receptor-bearing cells. In the lamina propria, CD4+ cells predominated, and some of them were activated. IgA- and IgM-containing cells were markedly increased during cow's milk exposure, but IgE cells were not abnormal. The density of eosinophils was moderately increased. Secretion of interferon-gamma by cells isolated from patients' intestines was markedly increased. Morphologic and immunologic findings suggest that T-cell-mediated reaction to proteins in cow's milk is present in the small intestines of patients with this syndrome and causes this enteropathy.
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PMID:Food-induced malabsorption syndromes. 1063 1

To develop a T-cell-based therapy for carcinomas, the superantigen staphylococcal enterotoxin A (SEA) was supplied with tumor specificity by means of a recombinant fusion of the Fab fragment of the monoclonal antibody C242 recognizing human colorectal (CRC) and pancreatic carcinomas (PC). Using this Fab-SEA fusion protein (PNU-214565), potent cytotoxicity by activation of T cells can be obtained in the targeted area. Twenty-one patients with CRC and 3 with PC were treated with single, escalating doses of PNU-214565 to establish the maximum tolerated dose (MTD) and to define toxicities. The doses ranged from 0.01 ng/kg to 4.0 ng/kg with three patients at each dose level, except for the dose of 1.5 ng/kg with which six patients were treated because of dose-limiting toxicity. Adverse events (AE) were transient: 13 patients experienced mild to moderate fever. In one patient, a grade 3 fever was followed by a grade 2 hypotension. Other mild or moderate AEs were fatigue, nausea, vomiting, diarrhea, and abdominal pain. No significant hematological toxicity occurred. Immune activation was highly variable with strong activity in peripheral blood seen only in two patients at the dosage level 1.5 ng/kg. They showed pronounced elevations of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma, 3-5 hours after the start of infusion. In one patient, IL-2 and IL-6 increased substantially (2,925 U/mL and 32,000 U/mL) concomitantly with grade 3 fever and transient grade 2 neutropenia, grade 2 lymphopenia, and grade 2 monocytopenia. In conclusion, a single 3-hour infusion of PNU-214565 could be safely administered up to 4 ng/kg. MTD was not determined. Instead, a repeat-dose trial was initiated starting at 0.5 ng/kg, considered safe in this trial, with the objective of defining the MTD.
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PMID:Phase I study of single, escalating doses of a superantigen-antibody fusion protein (PNU-214565) in patients with advanced colorectal or pancreatic carcinoma. 1068 47

The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.
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PMID:Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. 1105 8


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