Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Plasmodium falciparum malaria is endemic in the northern KwaZulu areas of South Africa. The clinical morbidity produced by this parasite has not been studied since the institution of the present malaria control programme. Fifty-nine patients were prospectively studied at a peripheral clinic during the peak malaria season; symptoms and signs of the infection, parasite loads, haemoglobin values and leucocyte counts were recorded in all patients. Haemoglobin and leucocyte counts were also measured in 37 control subjects without malaria. The commonest symptoms were persistent headache (100%), rigors (98%) and myalgia (93%). None of the patients presented with coma, pulmonary oedema, hypoglycaemia or algid malaria. Splenomegaly was found in 49%, hepatomegaly in 20% and mental confusion in 5% of patients. Mean parasite load was 1.71% and 57% of patients had parasite loads of < 1%. Anaemia of < 10 g/dl was significantly more frequent (P < 0.0001) in the patient group than in the control group. Leucopenia (white cell count < 4.0 x 10(9)/l) was present in 12 of 50 patients in whom it was measured compared with 2 controls (P = 0.0175). The results show a wide range of morbidity, without severe complications as presenting manifestations. Symptomatic infection in the presence of low parasite loads suggests that there may be little or no immunity in this population.
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PMID:Morbidity from falciparum malaria in Natal/KwaZulu. 845 85

Human ehrlichiosis is a newly emergent, tick-borne, zoonotic infection caused by members of the genus Ehrlichia. These rickettsia-like, obligate intracellular, gram-negative bacteria produce two similar yet distinct diseases. Human monocytic ehrlichiosis is caused by Ehrlichia chaffeensis. Human granulocytic ehrlichiosis is caused by an organism closely related to Ehrlichia equi. The most common initial clinical findings include fever, malaise, myalgia, headaches and rigors, while the most common laboratory findings are thrombocytopenia, leukopenia, anemia and elevated liver enzyme levels. Both diseases can produce intracytoplasmic morulae, in either monocytes or neutrophils, which may be visible on Wright-stained peripheral smears. Treatment consists of tetracycline or doxycycline. Rifampin or chloramphenicol can be tried when tetracycline is absolutely contraindicated. Treatment should never be delayed pending serologic or polymerase chain reaction confirmation of the diagnosis because of the 5 to 10 percent mortality rate.
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PMID:Human ehrlichiosis. 890 Mar 57

In an attempt to restore immune competence to 12 human immunodeficiency virus-1 (HIV-1)-infected patients, lymphocytes from their HIV-1-uninfected identical twin siblings were cultured in medium supplemented with 5% fetal calf serum (FCS), anti-CD3 antibody, and interleukin-2 (100 IU/mL) for 10 days and then infused into the patients. After multiple infusions, at 6- to 8-week intervals, half of the patients developed arthus-like reactions within 4 to 12 hours of infusion consisting of fever > 39 degrees C, hypotension, rigors, arthralgias, myalgias, headache, and/or malaise. Preinfusion and postinfusion serum samples were evaluated for the presence of antibodies to FCS using double immunodiffusion. All preinfusion serum samples were negative by this method while 8 of the 12 patients developed antibodies to a single component of FCS after two or more infusions of lymphocytes cultured in FCS-supplemented medium. Prick skin testing to standardized beef extract was negative in all patients. There was a correlation between initial CD4 level and the development of antibodies to FCS (median initial CD4 count in FCS antibody positive patients = 362.0/microL v median initial CD4 count of nonresponders = 135.0/microL). There was no correlation with response to recall antigens in delayed-type hypersensitivity testing. We conclude that selected patients were sensitized to a single component of FCS carried on donor lymphocytes, despite thorough washing of the cells before infusion. The development of antibodies to FCS indicates that immune complex formation could have occurred after the cell infusions, resulting in the arthus-like reactions. These observations suggest that the therapeutic use of human lymphocytes cultured in FCS may expose the recipient to immunogenic substances with possible clinical sequelae.
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PMID:Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. 902 7

Recombinant human interleukin-1 beta (rhIL-1 beta) was evaluated in a phase 1 clinical trial in which patients with metastatic or unresectable solid tumors received carboplatin and etoposide in cycle 1 and carboplatin, etoposide, and rhIL-1 beta in cycle 2. Recombinant hIL-1 beta was given intravenously for 5 days in one of three schedules: (1) immediately postchemotherapy, (2) delayed for 5 days after chemotherapy, or (3) concurrently with chemotherapy. Four dose levels of rhIL-1 beta were evaluated: 20, 50, 100, and 200 ng/kg. The doses of carboplatin and etoposide were not changed between cycle 1 and cycle 2 so that the effect of rhIL-1 beta on chemotherapy-induced hemato-toxicity was evaluated; 54 patients were entered on study and 42 patients received at least two cycles of therapy and were thus evaluable for rhIL-1 beta toxicity and for the effect of rhIL-1 beta on hematotoxicity of carboplatin and etoposide. The major toxicities of rhIL-1 beta were chills, rigors, headache, fatigue, and hypotension. The maximum tolerated dose of rhIL-1 beta was not determined since the toxicities at all dose levels were similar. However, only 3/8 patients at the 200 ng/kg level received all 5 IL-1 beta infusions. We compared the effect of rhIL-1 beta on hematotoxicity of carboplatin/etoposide by comparing peripheral blood count parameters between cycles 1 and 2: rhIL-1 beta given postchemotherapy significantly increased absolute neutrophil count (AND) nadirs and improved neutrophil recovery times regardless of rhIL-1 beta dose level. Platelet count parameters were also improved when rhIL-1 beta was given postchemotherapy although these changes did not reach statistical significance. Thus, IL-1 beta exhibited extensive hematological effects but the usefulness of this agent in clinical practice will be limited by extensive toxicity at all tested dose levels.
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PMID:Phase 1 trial of recombinant human interleukin-1 beta (rhIL-1 beta), carboplatin, and etoposide in patients with solid cancers: Southwest Oncology, Group Study 8940. 931 21

As a result of both the constant influx of travellers and foreign workers from endemic countries and the presence of Anopheles vectors, Singapore remains vulnerable to malaria. In May and June of 1996, a localized outbreak involving 19 cases of vivax malaria was reported in central Singapore's Dairy Farm area. Resident in this area at the time were 120 foreign workers employed by and living within two nurseries. Following the outbreak, both epidemiologic and entomologic surveillance studies were conducted. The 19 cases of Plasmodium vivax involved 2 local residents of Dairy Farm Estate condominium and 17 foreign nursery workers (1 Thai, 5 Bangladeshi, and 13 Indian). The origin of the outbreak was traced to 2 foreign workers infected with Plasmodium vivax who defaulted on chloroquine treatment and relapsed within 7 months of arrival in Singapore. Malaria symptoms included fever (100%), rigors (94.7%), chills (89.5%), headache (78.9%), and sweating (42.1%). Larvae of Anopheles maculatus were found in 7 habitats: 4 seepages, 1 ground puddle, 1 earth drain, and 1 antimalaria drainage well. Transmission was interrupted within a week after the outbreak was alerted through a comprehensive strategy of active case finding, isolation and treatment of infected persons, epidemic vector control measures, and improved drainage to prevent Anopheles maculatus breeding. Malaria should always be considered in the differential diagnosis of foreign workers who present with fever.
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PMID:Local transmission of Plasmodium vivax malaria in Singapore. 949 62

The goal of our study was to determine the epidemiological and clinical features of imported malaria seen at our military hospital in Hawaii. We reviewed the records of malaria cases seen from January 1, 1979, to December 31, 1995, and compared our results with published reviews from civilian hospitals in North America. Seventy-nine patients were diagnosed with malaria by blood smears. All acquired malaria abroad, mostly in southeast Asia. Sixty-seven percent of cases were vivax malaria, 22% were falciparum malaria, and 11% were caused by undetermined species. Common symptoms were fever (100%), alternate day fever (41%), rigors (91%), headache (59%), nausea (41%), fatigue (39%), dark urine (32%), and vomiting (31%). Ninety-one percent had fever during hospitalization, but 39% were afebrile on admission. Splenomegaly was detected in 49% of cases. The white blood cell count was normal in 65%, low in 31%, and elevated in 4% of cases. Other laboratory findings were anemia (58%), thrombocytopenia (74%), and mild hyperbilirubinemia (64%). Military physicians initially considered the diagnosis of malaria in only 54% of patients. The epidemiological features of our patients differ from those described in the civilian hospitals. Most of our patients were nonimmune, U.S.-born, military personnel infected in southeast Asia, whereas patients described in reviews from U.S. civilian hospitals were usually foreign-born civilians who were infected in Africa or India. The clinical features of malaria, and the problems of initial misdiagnosis in our patients, were similar to those reported from civilian hospitals. Military physicians, like their civilian colleagues, need more training and experience in malaria.
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PMID:A review of 79 patients with malaria seen at a military hospital in Hawaii from 1979 to 1995. 950 98

The Waterhouse-Friderichsen (WFS) syndrome, also known as purpura fulminans, is described as acute hemorrhagic necrosis of the adrenal glands and is most often caused by meningococcal infection. This clinical entity is more frequently seen in the pediatric than the adult population and is associated with a high morbidity and mortality. The initial presenting complaints for patients with the WFS usually include a diversity of nonspecific, vague symptoms such as cough, dizziness, headache, sore throat, chills, rigors, weakness, malaise, restlessness, apprehension, myalgias, arthralgias, and fever. These symptoms are usually abrupt in their onset. Petechiae are present in approximately 50-60% of patients. The clinical diagnosis of WFS may be relatively straightforward or extremely challenging. Patients who appear in the initial and nontoxic-appearing stage without any skin lesions may be difficult to distinguish from a benign viral illness. When a patient presents with fever and petechiae, WFS must be considered, even when the patient has a non-toxic appearance. Due to the rapid progression and often devastating consequences, therapy should be instituted as soon as the diagnosis is suspected.
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PMID:Rupert Waterhouse and Carl Friderichsen: adrenal apoplexy. 969 86

Interleukin 1 alpha (IL-1 alpha) is a cytokine with pleiotropic effects, including cytotoxic-cytostatic activity against some tumor cell lines. We have conducted a phase I study of recombinant human IL-1 alpha (rhIL-1 alpha) in 17 patients with refractory malignancies to examine its toxicity and biologic activity. rhIL-1 alpha was given as a 2-h IV infusion daily for 5 days at five dose levels (0.08, 0.2, 0.8, 2.0, and 5.0 micrograms/m2). Seventeen patients with malignancies were treated, with no objective tumor responses noted. Common toxicities included: fever (100%), rigors and/or chills (96%), myalgia (54%), and headache (48%). Three patients developed grade III hypotension. The maximum tolerated dose was 2.0 micrograms/m2. rhIL-1 alpha induced a significant increase in absolute neutrophil count over baseline (p < 0.05), a delayed but significant increase in platelet count over baseline (p < 0.05), and there was a marked increase in the number of progenitors [colony-forming units (CFU)-G, CFU-M, CFU-GM, CFU-GEMM and burst-forming units (BFU-E)] observed in the peripheral blood. Nine of 12 evaluable patients showed an increase in bone marrow cellularity or myeloid:erthyroid ratio. Immunophenotyping did not demonstrate an increase in peripheral blood or bone marrow CD34+ cells. Interferon-gamma-mediated monocyte cytotoxicity (MCCTX) was significantly enhanced from baseline (p < 0.001), although an increase in direct MCCTX did not reach statistical significance. In summary, rhIL-1 alpha administration is well tolerated at a dose of 2.0 micrograms/m2 with fever, rigors, myalgia, and headache being the most frequent toxicities. Although there were no objective tumor responses, we have demonstrated significant biologic activity with increased neutrophil and platelet counts, increased peripheral blood progenitor cells, and enhanced interferon-gamma-mediated MCCTX.
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PMID:Biologic activity of interleukin 1 (IL-1) alpha in patients with refractory malignancies. 978 99

Murine anti-CD3 (OKT3, Muromonab-CD3) is a potent human T-lymphocyte mitogen. A previous clinical Phase I trial examined OKT3 as an immunomodulator for the treatment of cancer. However, the murine monoclonal antibody triggered a potent humoral response that neutralized the antibody activity during subsequent administration. Thus, a "humanized" form of OKT3 (hOKT3gamma4) was developed to minimize immunogenicity. The genetically engineered human anti-CD3 retained its binding activity and effectively activated T cells in vitro. Therefore, we evaluated the safety and activity of hOKT3gamma4 in a Phase I clinical trial. hOKT3gamma4 was administered as a 10-min i.v. infusion every 2 weeks for three injections (one course of therapy). Six dose levels ranging from 50 to 1600 microg/injection were evaluated. Headache and fever were common, transient toxicities but were not dose limiting. The dose-limiting toxicities were rigors and dyspnea at the 1600-microg dose level, which defined 800 microg as the maximally tolerated dose in this trial. A dose-dependent in vivo T-lymphocyte activation was produced by this treatment, and the most significant T-lymphocyte activation occurred in patients treated at the two highest dose levels (800 and 1600 microg). Persistent CD3 modulation occurred after administration of 1600 microg of hOKT3gamma4. Anti-idiotypic antibodies were detected in only 6 of 24 patients after multiple injections and were not associated with attenuation of T-lymphocyte activation. Malignant ascites resolved in three patients, one each with peritoneal mesothelioma, pancreatic adenocarcinoma, and ovarian adenocarcinoma. hOKT3gamma4 can induce T-lymphocyte activation in patients with cancer, and the immunogenicity of the "humanized" antibody is sufficiently reduced relative to its murine "parent" to permit immunostimulation by repetitive i.v. administration. The therapeutic potential of biweekly i.v. hOKT3gamma4 at a dose of 800 microg should be further evaluated.
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PMID:Phase I evaluation of humanized OKT3: toxicity and immunomodulatory effects of hOKT3gamma4. 1023 94


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