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)

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

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

A patient with malignant glioblastoma was treated with intratumoral infusions of the murine MAb425 (IgG2A) directed against the epidermal growth factor receptor. At the 10th infusion, the patient developed somnolence, fever and headache. The symptoms increased during the subsequent 48 hr but then gradually disappeared within a week. The cerebrospinal fluid (CSF) contained increased concentrations of interleukin-2. The main CSF cell subset was CD4 T-cells. A marked blood lymphocyte proliferative response against mouse IgG2A was noted. The reactive T-cell epitope(s) could be localized to a 14 amino acid (RGPTIKPCPPCKCP) long peptide of the hinge region. A B-cell response (IgG antibodies) against this peptide was also induced.
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PMID:Induction of a T- and B-cell response against a unique amino acid sequence of the mouse IgG2A hinge region in a MAb-treated patient. 939 53

Erythema migrans, the characteristic skin manifestation of acute Lyme borreliosis, is a self-limited lesion. In contrast, acrodermatitis chronica atrophicans, the typical cutaneous manifestation of late Lyme borreliosis, is a chronic skin condition. In an effort to understand pathogenic factors that lead to different outcomes in dermatoborrelioses, skin biopsy samples from 42 patients with erythema migrans and 27 patients with acrodermatitis chronica atrophicans were analyzed for mRNA expression of five pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interferon-gamma, and interleukin-2) and two anti-inflammatory cytokines (interleukin-4 and interleukin-10) by in situ hybridization with cytokine-specific riboprobes. Among the 27 patients who had erythema migrans alone with no associated signs or symptoms, the major cytokines expressed in perivascular infiltrates of T cells and macrophages were the pro-inflammatory cytokine interferon-gamma and the anti-inflammatory cytokine interleukin-10. In the 15 erythema migrans patients who had associated signs and symptoms, including headache, elevated temperature, arthralgias, myalgias, or fatigue, a larger number of macrophages and greater expression of macrophage-derived pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6, were also found. In comparison, infiltrates of T cells and macrophages in the skin lesions of acrodermatitis chronica atrophicans patients had very little or no interferon-gamma expression. Instead, they usually expressed only the pro-inflammatory cytokine tumor necrosis factor alpha and the anti-inflammatory cytokine interleukin-4. Thus, the activation of pro-inflammatory cytokines in erythema migrans lesions, particularly interferon-gamma, seems to be important in the control of the spirochetal infection. In contrast, the restricted pattern of cytokine expression in acrodermatitis chronica atrophicans, including the lack of interferon-gamma, may be less effective in spirochetal killing, resulting in the chronicity of this skin lesion. J Invest Dermatol 115:1115-1123 2000
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PMID:Differential expression of cytokine mRNA in skin specimens from patients with erythema migrans or acrodermatitis chronica atrophicans. 1112 Nov 50

Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after non-ionic dimers. The majority of late skin reactions after contrast medium exposure are probably T-cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interleukin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions.
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PMID:Late adverse reactions to intravascular iodinated contrast media. 1254 Nov 28

Intravenous high dose bolus therapy with interleukin-2 (IL2) is associated with low overall response rates (15%) and significant toxicity. Phase II and III trials of a lower dose subcutaneous regimen of IL2 administered alone (n = 152) or in combination with histamine dihydrochloride (n = 239) have recently been completed. This article describes a comprehensive safety and toxicity analysis of the results of these two trials. The phase III trial demonstrated a survival benefit in patients with liver metastases in the histamine/IL2 arm. Eligible patients had stage IV malignant melanoma with at least one measurable lesion. Toxicity was graded using the National Cancer Institute (NCI) common toxicity scale. All reported adverse events were included in the analysis. Almost all toxicities in each treatment group were NCI grade 1 or 2. The incidence of toxicities expected to occur with histamine treatment, such as hypotension/vasodilation, headache and injection site reaction, were higher among patients receiving histamine. With the exception of headache, the incidence of grade 3 or 4 toxicities was similar across the treatment groups. The addition of histamine to the subcutaneous IL2 regimen did not result in a difference in the incidence of drug interruption, dose modification or discontinuation. Study-related deaths were low and were not impacted by the addition of histamine to the IL2 regimen.
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PMID:Treatment with histamine dihydrochloride and interleukin-2 in patients with advanced metastatic malignant melanoma: a detailed safety analysis. 1277 88

Basiliximab is a chimeric anti-intcrleukin-2 receptor monoclonal antibody. Basiliximab is a glycoprotein produced by recombinant technology. It is used to prevent white blood cells from acute renal transplantation rejection. It specifically binds to and blocks the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T-lymphocytes. Due to its monoclonal nature it provides safer and more predictable therapeutic, that is, immunosuppressive response of the polyclonal antibodies. The most common adverse effects in adult patients are constipation, infections, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalacmia, hypercholesterolemia, increase in serum creatinine, and hypophosphataemia.
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PMID:Basiliximab, mechanism of action and pharmacological properties. 1564 37

We have established a novel culture system to generate effector lymphocytes designated as peptide-pulsed dendritic cell-activated killer (PDAK) cells using cultured dendritic cells (DCs), synthetic peptide, peripheral blood lymphocytes, and interleukin-2 plus immobilized anti-CD3 antibody. A feasibility study of an adoptive immunotherapy trial using PDAK cells was conducted on HLA-A2 and HLA-A24 cancer patients with antigen-positive lung metastasis that was defined by serological analysis or PCR analysis. Eleven patients with lung metastasis participated in the study: 6 with colorectal cancer, 2 with pancreatic cancer, 1 each with breast and lung cancer, and 1 with melanoma. The patients received either Muc-1, CEA, gpl00, Her-2 or SART-3-PDAK cells generated in vitro, intravenously in combination with 350,000 U IL-2 weekly for 9 weeks, together with a planned dose-escalation schedule of three transfers each of 1 x 10(7), 3 x 10(7) and 1 x 10(8) PDAK cells/kg for 6 patients, and with a uniform dose of 3 x 10(7) PDAK cells/kg for the remaining 5 patients. Peptide/HLA-specific cytotoxic activity and TCRVbeta gene usage of PDAK cells were analyzed. All transfers of PDAK cells, which showed peptide/HLA-specific lysis, were well-tolerated in all patients, and adverse effects (elevation of transaminase, fever, and headache) were observed primarily at grade 1, but in no case greater than grade 2. The generation of sufficient cells to treat the patients with 3 x 10(7) PDAK cells/kg was feasible using our culture system, but we were able to generate and administer the dose of 1 x 10(8) PDAK cells/kg in only one patient. One partial response (PR) of lung metastasis occurred in a pancreatic cancer patient who received 3 x 10(7) Muc-1-PDAK cells/kg. The cytolytic units of PDAK cells in this patient appeared to be substantially higher compared to those in PD patients. TCR gene usage analysis on PDAK cells revealed preferential usage of TCRVbeta segments. These results suggest that adoptive immunotherapy using PDAK cells for cancer patients with antigen-positive lung metastasis is safe and feasible, and tumor response should be examined in a future clinical trial
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PMID:Feasibility study of adoptive immunotherapy for metastatic lung tumors using peptide-pulsed dendritic cell-activated killer (PDAK) cells. 1608 Apr 67

Fibromyalgia syndrome (FMS) is now understood as a chronic pain syndrome, and recent evidence indicates it is not a pure psychosomatic disorder. We review the current knowledge in FMS pain pathways, focusing on the central system sensitization phenomenon and the abnormalities in the inhibitory pain systems. Chronic headache is one of the most common symptoms in FMS, and better knowledge of their common pathophysiologic features can help us understand both conditions better. These features include the nerve growth factor actions and failure of the endocannabinoid system. In addition, we review new immunological aspects of FMS, both in their humoral (autoantibodies, antipolymer antibodies) and cytokine (interleukin-2) aspects.
Curr Pain Headache Rep 2008 Oct
PMID:Fibromyalgia: an update and immunological aspects. 1876 35

In the past decades, allograft survival improved because of the development of new and more specific immunosuppressive agents. The introduction of calcineurin inhibitors was a landmark and acute rejection in organ transplantation decreased remarkably. Calcineurin inhibitor such as ciclosporin A inhibits T-cell activation by interfering with the cytosolic protein cyclophilin (immunophilin). This complex of ciclosporin and cyclophilin inhibits calcineurin, which is responsible for activating the transcription of interleukin-2. More recent research revealed a second pathway for T-cell activation, which is mediated by a specific protein kinase C., e.g., protein kinase C theta. AEB071 represents a selective protein kinase C inhibitor with promising potential for immunosuppression in organ transplantation. In pre-clinical studies, AEB071 prolonged allograft survival in kidney and heart transplant models. In human clinical studies, AEB071 reduced severity of psoriasis symptoms and has shown to be safe up to 750 mg single dose treatment. Important adverse events were gastrointestinal disorders and headaches. AEB071 inhibits early T-cell activation via a calcineurin inhibitor independent pathway and is currently investigated as a therapeutic agent to prevent allograft rejection after renal transplantation.
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PMID:AEB071--a promising immunosuppressive agent. 1993 Mar 11


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