Gene/Protein Disease Symptom Drug Enzyme Compound
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4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A multicentre study of IL2 and IFN alpha has been performed in 58 patients with metastatic melanoma. The scheme consisted of IL2 3.0 BRMP MU/m2/d as a continuous infusion for 4 d combined with subcutaneous administration of IFN alpha 6 MU/m2/d, day 1 + 4. The cycle was repeated every 2 weeks for a maximum duration of 26 weeks. 54 patients were evaluable for response. One (2%) achieved a complete and 10 (19%) a partial response. 19 (35%) patients were stable and 24 (44%) showed progressive disease. Common side-effects included fever, chills, fatigue, skin rash, anorexia, nausea and diarrhoea. Hypothyroidism was noted in 10% of the patients. These results show that this regimen of IL2 and IFN alpha is active but, in contrast to what could be expected, not superior to IL2 alone possibly due to suboptimal dosing. In an ongoing study in Rotterdam and Nijmegen, a more intense schedule was chosen, consisting of three daily i.v. doses of IL2 4.5 BRMP MU/m2 and IFN alpha 3.0 MU/m2 for 5 d. This regimen is repeated at intervals of 3 weeks for a total of three cycles. Presently, nine patients have been entered. One patient achieved a complete response, four a partial response (overall 56%), three had stable disease and one progressed. Toxicity was severe and treatment was prematurely stopped in five patients: myocardial infarction (one patient), atrial fibrillation (one patient), negative T waves and myocardial hypokinesia (one patient) and psychosis (two patients). This regimen can only be justified if the therapeutic results are superb, which has yet to be awaited.
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PMID:Clinical experience with the combined use of recombinant interleukin-2 (IL2) and interferon alfa-2a (IFN alpha) in metastatic melanoma. 193 17

We have studied the safety, tolerance, and clinical effects of the combined administration of subcutaneous recombinant human interleukin-2 and alpha-interferon in 34 patients with metastatic renal cell carcinoma who had undergone tumor nephrectomy. Treatment courses consisted of a 2-day interleukin-2 pulse (14.4 to 18.0 million IU/m2/d), followed by 3.6 to 4.8 million IU/m2/d, 5 days per week, over 6 consecutive weeks, and alpha-interferon at 3.0 to 6.0 million U/m2, administered 2 to 3 times weekly for 6 weeks. Patients received more than 90% of the projected dose of interleukin-2 and alpha-interferon, respectively. Of 34 patients with metastatic progressive renal cell carcinoma in this study, four had complete response and six had greater than 50% reduction in tumor size (ie, partial response). There were, in addition, 13 patients with stable disease. So far, all complete responses have been durable, with a median duration of 23+ months. Clinical responses were associated with a mean peripheral blood eosinophil count of more than 1,000/microliters (P less than .05). The predominant toxicities included fever, chills, nausea, anorexia, and hypotension, and were limited to World Health Organization grades 1 and 2 in more than 80% of patients treated. No treatment-related deaths occurred. This combination of subcutaneously administered recombinant interleukin-2 and alpha-interferon has significantly reduced the side effects normally observed with high-dose intravenous recombinant interleukin-2. It can induce objective tumor regressions in patients with progressive metastatic renal cell carcinoma. Unlike the intravenous schedules developed by Rosenberg and West, which require admission to hospital, all the patients in this study were treated in an outpatient setting.
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PMID:alpha-Interferon and interleukin-2 in renal cell carcinoma: studies in nonhospitalized patients. 194 23

The safety, tolerance, and clinical effects of a home therapy regimen of recombinant human interleukin-2 (rIL-2) and interferon-alpha 2b (IFN-alpha 2b) self injected subcutaneously have been assessed in 35 patients with advanced cancer refractory to standard therapy. 52 treatment cycles were given, each consisting of a 2-day rIL-2 pulse of 9.0 million IU/m2 every 12 h, followed by 6 weeks of rIL-2 1.8 million IU/m2 twice daily for 5 days per week and of IFN-alpha 2b 5.0 million U/m2 thrice a week. The main adverse effects were fever, chills, nausea, anorexia, and hypotension and were limited to WHO grades of severity I and II in 29 of 35 patients. No treatment-related deaths occurred. The response rates among patients with renal-cell carcinoma were similar to those reported for high-dose intravenous regimens of interleukin-2 that are toxic and have to be given in hospital.
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PMID:Home therapy with recombinant interleukin-2 and interferon-alpha 2b in advanced human malignancies. 197 42

In June 1983, an outbreak of waterborne giardiasis occurred in a group of 93 university students and faculty participating in a geology field course in Colorado. All cases occurred in one subgroup of persons who were heavily exposed to untreated stream water on a field trip, and the risk of illness was strongly related to the amount of untreated stream water consumed. The median incubation period from a brief exposure to the first symptom was 7 days. The authors compared symptoms and stool sample results among 31 Giardia-positive persons in the exposed group and 36 Giardia-negative participants in an unexposed group to assess several case definitions for acute giardiasis. Diarrhea, abdominal cramps, flatulence, foul-smelling stools, nausea, excessive tiredness, bloating, anorexia, and chills were each significantly more common in the first group than in the second. A giardiasis case definition of 5 days or more of diarrhea--the definition used in many epidemiologic studies of giardiasis--had a specificity of 100 percent but a sensitivity of only 32.2 percent compared with a definition based on results of stool examinations. When a case was defined as an illness lasting 7 days or more, with a combination of two or more of six symptoms (diarrhea, flatulence, foul-smelling stools, nausea, abdominal cramps, and excessive tiredness), sensitivity rose to 73 percent, with a specificity of 88 percent. Such a case definition may be an improvement over that of 5 days of diarrhea, especially in outbreaks where there is good laboratory documentation that Giardia is the etiologic agent. The definition should be validated in other outbreaks and in situations where giardiasis must be distinguished from gastrointestinal disease caused by other agents.
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PMID:Acute giardiasis: an improved clinical case definition for epidemiologic studies. 199 3

In this study we examined the clinical and laboratory findings of 80 in-patients. There is an important difference between sexes (p greater than 0.05). Comparison of ages showed that 7-30 age is more vulnerable than the older group. We found clinical symptoms of fever, chills, headache, abdominal pain, disturbances in bowel function, nausea, vomiting, anorexia, and lassitude in the first two weeks more frequently when compared with the 3rd, 4th, 5th weeks of illness (p less than 0.001). Where physical finding of rose spots, discordant pulse rate are important in the first two weeks (p less than 0.001). Abdominal discomfort is an important symptom both in the first two and in the last three weeks (% 40.3 and % 36 respectively). Hepatomegaly and splenomegaly, were found more frequently in the last three weeks. According to laboratory findings of anemia, leukopenia, increased erythrocyte sedimentation rate and positive blood and feces cultures there is no important difference between the first two and last three weeks (p greater than 0.05). Increase in polynuclear leucocytes is important for the first two weeks, and increase in lymphocytes is important in the last three weeks (p less than 0.001). Positivity of group agglutination tests is 57%, in the first two weeks and 83% in the last three weeks. This difference is found to be important.
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PMID:[Comparison of symptoms and clinical and laboratory findings in the first and last weeks of typhoid fever]. 208 33

In a phase II study, the efficacy and toxicity of human recombinant tumor necrosis factor (rh TNF-alpha) were evaluated in patients with advanced colorectal carcinoma. Rh TNF-alpha was given as short term infusion at a dose of 3 x 10(5) U/m2 on three successive days. Treatment was repeated after a two week interval. The response was evaluated after four treatment cycles. In 15 patients entering the study, we found one partial response, one stable disease, 9 progressive diseases, and four patients who were not evaluable for tumor remission. There were numerous side effects of the treatment, mainly fever, chills, loss of appetite, leukopenia, and hepatotoxicity. In this regimen, rh TNF-alpha does not suggest a therapeutic advantage for treatment of advanced colorectal carcinoma.
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PMID:Tumor necrosis factor in advanced colorectal cancer: a phase II study. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society. 209 81

A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.
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PMID:Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma. 216 55

A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.
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PMID:Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience. 222 98

We treated 17 patients who had progressive metastatic renal carcinoma with a combination of subcutaneous recombinant human interleukin-2 (administered every 12 hours, at 9.0 million IU/m2 on days one and two, followed by 1.8 million IU/m2, five days per week, over six consecutive weeks) and interferon-alpha 2b (given at 5 million U/m2 three times weekly, for six consecutive weeks). Treatment courses were repeated in patients presenting with stable or regressive disease after the six weeks of combination therapy (11 of 14 evaluable). Two and three of 14 evaluable patients achieved complete and partial remissions, respectively. Toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (WHO) fevers, chills, malaise, nausea/vomiting, and anorexia in more than two-thirds of the patients treated.
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PMID:Treatment of metastatic renal cell cancer patients with recombinant subcutaneous human interleukin-2 and interferon-alpha. 226 78

Fourteen evaluable patients with diffuse malignant mesothelioma were treated with a once-a-day for 5 days out of 7 for 6 weeks regimen of recombinant interferon-beta (IFN-beta ser). No responses were noted. The major toxicities included fever, chills, nausea, vomiting, and anorexia. IFN-beta ser at this dose and schedule does not appear to be an active single agent for patients with refractory malignant mesothelioma.
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PMID:Phase II evaluation of recombinant interferon-beta (IFN-beta ser) in patients with diffuse mesothelioma: a Southwest Oncology Group study. 227 99


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