Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0424790 (rigors)
 822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ehrlichia are tick-borne rickettsial organisms that cause disease in animals throughout the world but that have been previously recognized as human pathogens only in Asia. We have identified six patients with serological evidence of recent infection with an Ehrlichia: a fourfold or greater rise or fall in titer to Ehrlichia canis. All of the patients reported recent tick bites. Rigors, myalgia, headache, nausea, and anorexia were each reported by five patients. Fever was present in all patients and was accompanied by relative bradycardia and leukopenia in five patients, thrombocytopenia and abnormal liver function test results in four, and anemia in three. Five of the six patients were treated with tetracycline hydrochloride, and all recovered. Infection with Ehrlichia should be considered in patients with unexplained febrile illnesses after tick exposure.
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PMID:Unexplained febrile illnesses after exposure to ticks. Infection with an Ehrlichia? 358 28

Severe renal failure caused by the mushroom Cortinarius speciosissimus was first recognised in 1972 and has been reported only from Scandinavia. In the summer of 1979 and following the consumption of the wild mushroom in Scotland, three previously healthy young adults developed the recognised features of cortinarius poisoning-namely, gastrointestinal upset after 36-38h, followed by nausea, anorexia, headache, rigors, severe burning thirst, muscle aching, and oliguria. One patient had a diuresis after 8 days and recovered completely. The two other patients did not present to hospital until 10 days after ingestion and severe renal failure had already developed. Both had a severe interstitial nephritis and neither recovered renal function. They were maintained on intermittent haemodialysis until they received renal transplants 9 months later. This form of mushroom poisoning has not so far been reported in the British Isles. With the increasing popularity of wild-mushroom eating, posters and publications on wild edible foods should contain warnings about the toxic nature of species of the genus Cortinarius.
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PMID:Poisoning by Cortinarius speciosissimus. 610 89

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
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PMID:A phase I toxicity study of human rDNA interferon in patients with solid tumours. 646 93

A single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin
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PMID:Immunomodulation by recombinant interferon-alpha 2 in a phase I trial in patients with lymphoproliferative malignancies. 660 23

A phase I study of human lymphoblastoid interferon (IFN-alpha) was undertaken in patients with acute leukaemia and other malignancies. The pharmacokinetics of intravenous IFN-alpha were also investigated. IFN-alpha was administered to two patients by intravenous (IV) bolus injection at a dose of 5 X 10(6) U/m2; and to a further 37 patients (40 cycles) by continuous intravenous infusion (IVI) for 5, 7, or 10 days at doses ranging from 5 to 200 X 10(6) U/m2/day. Pyrexia, general malaise, anorexia, and rigors were observed at all dose levels; three patients became hypotensive. Myelosuppression occurred in all patients, including seven without bone marrow infiltration. Transient rises in alkaline phosphatase and transaminases (SGOT) were observed in patients receiving daily doses greater than 30 X 10(6) U/m2. Dose-limiting central nervous system toxicity, hyperkalaemia, and hypocalcaemia were encountered at 200 X 10(6) U/m2. In six patients with acute leukaemia there was a fall in the number of circulating leukaemic blasts and in one patient with acute myelogenous leukaemia (AML) the degree of bone marrow infiltration decreased from 99% to less than 5% with cellularity returning to normal. Serum levels of IFN above 1,000 U/ml were achieved with daily doses above 30 X 10(6) U/m2 given by IVI. The maximum safely tolerated daily dose, 100 X 10(6) U/m2 administered for 7 days, is appreciably higher than that used in most previous studies, although even at this level considerable toxicity may be encountered.
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PMID:A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. 717 12

Interleukin 2 (IL-2) and interferon-alpha (IFN-alpha) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-alpha in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-alpha and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-alpha and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 x 10(6) units/m2/day or 3.0 x 10(6) units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-alpha (0.5 x 10(6) or 5 x 10(6) units/m2/day) was administered s.c. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-alpha for course 2, or IL-2/IFN-alpha in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-alpha. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-alpha. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-alpha group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum beta 2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL-2 alone and IL-2 plus IFN-alpha. No dose response effect for IFN-alpha was observed for any of the parameters assessed. Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-alpha and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A direct comparison of immunological and clinical effects of interleukin 2 with and without interferon-alpha in humans. 844 8

A 29-year-old Caucasian woman presented to hospital with a 2-day history of diarrhoea, anorexia and rigors. Investigations showed abnormal liver function tests, hyponatremia, hypoalbuminaemia and lymphopenia. The initial chest radiograph was normal. A bone marrow trephine biopsy showed non-caseating granulomata and she subsequently developed miliary shadowing on the chest radiograph. A transjugular liver biopsy confirmed the presence of acid-alcohol fast bacilli. Despite starting triple therapy for miliary tuberculosis she remained febrile and developed massive hepatosplenomegaly, jaundice and pancytopenia. Standard triple therapy was substituted with ethambutol, streptomycin and oral prednisolone and the patient made a dramatic recovery. The clinical symptoms of miliary tuberculosis are frequently non-specific and the onset of the illness is often insidious. The liver is involved in almost all patients with miliary tuberculosis, but massive hepatosplenomegaly and jaundice are rare. Standard triple-therapy should be discontinued when there is significant liver dysfunction, and corticosteroids should be considered for patients with miliary tuberculosis who fail to respond to conventional therapy.
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PMID:Massive hepatosplenomegaly, jaundice and pancytopenia in miliary tuberculosis. 957 Jun 66

This study examined the malaria situation in a malarial endemic area of Nigeria. Structured questionnaire was applied to 300 doctors practising in Enugu urban, Nigeria and confirmation of the clinical diagnosis by laboratory technique was done using 468 patients. The result shows a high prevalence of Plasmodium falciparum infection (96.4% in children, 87.0% in adults). Malaria positivity rate was 51.9% in children and 42.8% in adults. Fever, vomiting and anorexia were the commonest malaria symptoms in children, while headache, fever, chills and rigors were the commonest malaria symptoms in adults. The diagnostic practice of the doctors was clinical. Fever, vomiting and cough were found to be more associated with malaria parasitaemia in children, while in adults fever was found to be more associated with malaria parasitaemia. Chloroquine and sulphadoxine-pyrimethamine were the commonest drugs used for treating uncomplicated malaria, while quinine was the commonest drug used for treating severe malaria.
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PMID:Current clinical presentation of malaria in Enugu, Nigeria. 1562 48

On May 19, 2004, azacitidine (5-azacytidine; Vidaza(trade mark); Pharmion Corporation, Boulder, CO, http://www.pharmion.com) for injectable suspension received regular approval by the U.S. Food and Drug Administration (FDA) for the treatment of all subtypes of myelodysplastic syndrome (MDS). This report summarizes the basis for this approval. Effectiveness was demonstrated in one randomized, controlled trial comparing azacitidine administered s.c. with best supportive care (observation group) and in two single-arm studies, one in which azacitidine was administered s.c. and in the other in which it was administered i.v. The dose of azacitidine, 75 mg/m2/day for 7 days every 28 days, was the same in all three studies. In the randomized trial, study participants were well matched with respect to age, sex, race, performance status, MDS subtype, and use of transfusion during the 3 months before study entry. Patients in the observation arm were permitted by protocol to cross over to azacitidine treatment if their disease progressed according to prespecified criteria. During the course of the study, more than half of the patients in the observation arm did cross over to the azacitidine treatment arm. The primary efficacy end point was the overall response rate. Response consisted of complete or partial normalization of blood cell counts and of bone marrow morphology. The response rate in the azacitidine arm was about 16%; there were no responses in the observation arm. The response rates in the two single-arm studies were similar (13% and 19%). The responses were sustained, with median durations of 11 months and 17 months respectively. Responding patients who were transfusion dependent at study entry lost the need for transfusions. In addition, about 19% of patients had less than partial responses (termed improvement), and two-thirds of them became transfusion independent. Common adverse events associated with azacitidine treatment were gastrointestinal (nausea, vomiting, diarrhea, constipation, and anorexia), hematologic (neutropenia, thrombocytopenia), fevers, rigors, ecchymoses, petechiae, injection site events, arthralgia, headache, and dizziness. Liver function abnormalities occurred in 16% of patients with intercurrent hepatobiliary disorders and in two patients with previously diagnosed liver cirrhosis. Renal failure occurred in patients during sepsis and hypotension. There were no deaths attributed to azacitidine. Azacitidine, the first drug approved by the U.S. FDA for MDS, has a favorable safety profile and provides a clinical benefit of eliminating transfusion dependence and complete or partial normalization of blood counts and bone marrow blast percentages in responding patients.
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PMID:FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. 1579 20

Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving. Testing revealed no infection. A mesalamine-induced fever was considered, and treatment was stopped, which led to spontaneous resolution of the fever. The diagnosis was confirmed by reintroducing the mesalamine. One year later, this side effect was noticed again in the same patient after he was administered topical mesalamine. This reaction to mesalamine seems to be idiosyncratic, and the mechanism that induces fever remains unclear. Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity, an associated extraintestinal manifestation, or an infectious etiology.
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PMID:Isolated fever induced by mesalamine treatment. 2346 7


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