Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011991 (diarrhea)
 57,543 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new viral disease (Maridi haemorrhagic fever) occurred in the South Sudan in 1976. It was obviously identical with an epidemic which occurred at the same time in Zaire. The virus is morpologically closely similar to the Marburg virus. During the Maridi epemic 124 of 238 patients died (52%). Characteristic symptoms were fever and headache (100%), diarrhoea (83%), retrosternal pain (82%), vomiting (68%), haemorrhages (62%), morbilliform or vesicular rash (52%). At post-mortem there were changes in liver, kidney, myocardium and lungs, similar to those in the Marburg virus disease, as were those observed in bone marrow and peripheral blood. Despite these analagous findings, the clinical course and results of immunofluorescence indicate that it is a new disease. The epidemic ended after suitable isolation measures had been taken. There was no specific treatment but in some cases convalescent plasma and interferon were tried. The disease is transmitted among humans by direct contact or by contact with blood or excreta of patients. No animal reservoir has been found. It is possible for this disease to be imported also into countries with a modorate climate.
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PMID:[Maridi haemorrhgic fever: a new viral disease (author's transl)]. 2 83

Biological response modifiers (BRMs) have greatly modified the immunotherapy of tumors. Interleukin-2 (IL-2) has brought about metastasis regression in some cases of malignant tumors, however, when given systemically, it results in high toxicity. More recently, the subcutaneous administration of IL-2 (combined with alpha-interferon, alpha-IFN) seems to be capable of offering the same chances of therapeutic response, but this time with a lower level of toxicity. The Authors report an evaluation of toxicity in 22 patients treated with a combination of IL-2 + alpha-IFN i.m. with or without chemotherapy. The side-effects present in the majority of cases were: fever, diarrhea and asthenia. Approximately 50% of the patients had nausea/vomiting, mucositis, skin rashes, and slight leukopenia. The following side-effects were noted to a much lesser degree, thrombocytopenia, alterations in hepatic and dizziness and cystitis. Only one patient reached 4th degree toxicity, with mucositis, asthenia and skin rash. All the other patients received the treatment without suspensions for toxicity. Biological evaluations will enable us to determine in the future, the cases which can benefit from therapeutic intensification and thus it would seem opportune at this time to use therapy with acceptable toxicity.
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PMID:Evaluation of toxicity in 22 patients treated with subcutaneous interleukin-2, alpha-interferon with and without chemotherapy. 128 42

We demonstrate here that ethanol, in contrast to heat shock (Chousterman, S., Chelbi-Alix, M.K., and Thang, M.N. (1987) J. Biol. Chem. 262, 4806-4811), induces interferon (IFN) synthesis and its related activities in Madin-Darby bovine kidney (MDBK) cells. The induced IFN is secreted maximally at 6 h, whereas the induction of 2',5'-oligoadenylate synthetase mRNA peaks between 9 and 12 h and its activity at 15 h. The appearance of both 2',5'-oligoadenylate synthetase activity and the antiviral state upon ethanol treatment is prevented by anti-bovine recombinant IFN-beta antibodies. Bovine diarrhea virus infection-free MDBK cells cultured in medium supplemented with serum substitute also gave similar results, thus indicating that IFN synthesis induced by ethanol is not mediated by the activation of bovine diarrhea virus. Together, these results show that: 1) ethanol induces the 2',5'-oligoadenylate synthetase and antiviral activities through IFN-beta production; and 2) the IFN produced does not act directly from inside the cells, but has to be first secreted to bind to its receptor. In MDBK cells, ethanol induces the synthesis of the 70-kDa protein, which precedes the expression of 2',5'-oligoadenylate synthetase; moreover, the transient nature of the synthesis of the hsp 70 in these cells is similar after both heat shock and ethanol treatment.
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PMID:Ethanol induces 2',5'-oligoadenylate synthetase and antiviral activities through interferon-beta production. 130 94

5-Fluorouracil (5-FU) is still the mainstay of chemotherapy in patients with metastatic colorectal cancer. A prolonged infusion of 5-FU is more active than any other schedule of 5-FU used to date. Cisplatin does not improve treatment results compared with 5-FU alone and is not recommended outside clinical trials. Biomodulation of 5-FU is a major step forward in the treatment of colorectal cancer patients and as the standard chemotherapy for advanced colorectal cancer. Two schedules of folinic acid daily for 5-day (low and high doses) and weekly high dose in combination with daily or weekly 5-FU are the most widely used schedules. Although the response rates to either schedule are comparable, the profile of toxicity is different, being stomatitis for the daily schedule and diarrhea for the weekly schedule as the dose-limiting toxicity. Modulation of 5-FU by methotrexate is time dependent. An interval of 24 hours between methotrexate and 5-FU is necessary for effective modulation. Other modulators, like interferon and N-phosphonoactyl-L-aspartate (PALA), are promising treatment options currently under investigation in randomized trials. The data from phase II and III trials using modulation of 5-FU by folinic acid, PALA, or methotrexate, or using continuous infusion 5-FU indicate that all of these strategies are active. Randomized trials are currently underway to further investigate these therapeutic approaches and whether a specific modulation offers more therapeutic advantages.
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PMID:Chemotherapeutic strategies in metastatic colorectal cancer: an overview of current clinical trials. 137 4

The effects of 2-mercaptoethanol (2-ME) on some in vitro functions of bovine peripheral blood mononuclear cells (PBMC) were examined. It was shown that 2-ME enhanced, in a dose-dependent manner, the production of antibodies to bovine coronavirus. In this test the optimal concentration of 2-ME was 50 microM. This molarity of 2-ME was also optimal for the pokeweed mitogen (PWM)-induced proliferation of PBMC obtained from the 7 cattle tested. Similarly, the spontaneous proliferation of PBMC from 4 out of these cattle was enhanced. Thus, 2-ME evoked an increase (up to 2.5 times) or a decrease (at most 10 times) of the quota between the PWM-induced and the spontaneous proliferation (stimulation index). In general, the presence of 50 microM 2-ME enhanced the in vitro production of interferon by bovine PBMC. On the contrary, the highest proliferative response of PBMC to stimulation with bovine virus diarrhoea virus was achieved in cultures without 2-ME or in cultures with 0.5 or 5 microM 2-ME. Since the effects of 2-ME varied, for different tests as well as for cattle tested, attention should be paid to the use of 2-ME in cultures of bovine PBMC.
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PMID:2-Mercaptoethanol influences the in vitro function of bovine peripheral blood mononuclear cells. 137 99

26 patients with progressive neuroendocrine tumours received 3 x 10(6)U/m2 interferon alfa (IFN-alpha 2b) subcutaneously thrice weekly, until progression, as outpatients with moderate toxicity. 4/16 carcinoids and none out of 10 endocrine pancreatic tumours showed objective regression. Another 17 patients (68%) had no change. For a median of 34 weeks symptom control was excellent: 9 of 17 patients had major relief from pain, 11 of 13 from diarrhoea, and 7 of 7 from flushing. Thus, low-dose INF-alpha 2b given thrice weekly might be as effective as daily treatment with higher dosages. Treatment was only administered to patients with progression or major symptoms and this did not seem to adversely affect remission quality and survival.
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PMID:Antitumour effect and symptomatic control with interferon alpha 2b in patients with endocrine active tumours. 138 94

Between February 1990 and April 1991, 59 previously untreated patients with progressive and/or symptomatic metastatic colorectal carcinoma were enrolled in a phase II study of 5-fluorouracil (5-FU) and interferon alfa-2b (IFN-alpha). 5-FU 750 mg/m2/day was administered as continuous infusion for 5 days, then weekly in a dose of 750 mg/m2 as intravenous push injection starting on day 15. IFN-alpha 9 MU was given subcutaneously three times a week. Treatment was given for a maximum of 6 months. 55 patients are evaluable for response and 51 for toxicity. 17 patients (31%) achieved a partial remission, 15 (27%) had stable disease and 21 patients (38%) had progressive disease. Median duration of remission was 5 months and median survival for all patients 10 months. Toxicity was important with two treatment-related deaths and severe leukopenia, fever, diarrhoea and mucositis in about one third of the patients. In our opinion, this regimen is effective but rather toxic in metastatic colorectal carcinoma.
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PMID:Phase II trial of 5-fluorouracil and recombinant interferon alfa-2B in metastatic colorectal carcinoma. 138 18

Because of the different sites and mechanisms of biochemical interaction among 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN), we hypothesized that the concomitant use of IFN could increase the activity of the 5-FU/LV combination in colorectal cancer patients. Forty-five patients were included in the study and all were evaluable for response and toxicity. They were treated with 5-FU 370 mg/sqm i.v. d 2-6; LV 200 mg/sqm i.v. d 2-6; IFN alpha 2b 3 million U im d 1-7 every 21 days. Six patients achieved complete responses, 17 partial responses, 14 had stable disease and 8 progressed on therapy for an overall response rate of 51%. Median survival has not been reached. At a median follow-up of 14 months 33 of 45 patients remain alive. Nine patients experienced toxicity grade 3 (6 diarrhea and 3 stomatitis). Our results seem to suggest that IFN could increase 5-FU/LV activity and that this combination is well tolerated.
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PMID:Double biochemical modulation of 5-fluorouracil by leucovorin and cyclic low dose interferon alpha 2b in advanced colorectal cancer patients. 149 68

A total of 49 patients with metastatic renal cell cancer underwent recombinant interferon-alpha 2a therapy combined with chemotherapy. Before therapy the patients without nephrectomy underwent angioinfarction of the primary renal tumor. Combined treatment included interferon at 5 x 10(6) units per m.2 intramuscularly daily, 5-fluorouracil at 750 mg./m.2 daily by continuous infusion intravenously (days 1 to 5) and mitomycin C at 5 mg./m.2 per day intravenously (days 1 and 2) repeated every 28 days. Of the patients 17 (35%, 95% confidence interval 22 to 49%) responded, and all 17 had partial remission that lasted a median of 7.1 months (range 4.2 to 20.9+ months). Response rate differed by metastatic sites: lung 46% (18 of 39 patients), lymph nodes 46% (6 of 13), mediastinum 20% (2 of 10) and liver 18% (2 of 11). Grade 3 to 4 toxicity (World Health Organization) included neutropenia (79% of the patients), thrombocytopenia (45%), stomatitis (34%), diarrhea (8%), nausea (18%) and central nervous system disorders (18%). The overall 35% response rate suggests that the combination of interferon-alpha 2a, 5-fluorouracil and mitomycin C is synergistic. Future studies are needed to confirm this finding and to assess the role of mitomycin C.
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PMID:Phase II study of interferon-alpha and chemotherapy (5-fluorouracil and mitomycin C) in metastatic renal cell cancer. 153 31

In a phase II study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous infusion of 5-fluorouracil (5-FU) 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous interferon (IFN) at 9 million units three times per week. Of 35 evaluable patients, nine (26%) achieved a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to 17+ months). Seven patients (20%) had a minor response, and 10 (28%) had stable disease. The median length of survival was 13 months (range, 2 to 19+ months). The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of 5-FU by at least 25%. We conclude that while the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen is toxic and the observed response rate (26%) is not substantially superior to alternative 5-FU programs.
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PMID:Alfa-2A interferon and 5-fluorouracil for advanced colorectal carcinoma: the Memorial Sloan-Kettering experience. 155 42


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