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)

Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological and antitumor effects in vitro and in mouse models. The immunological effects of the molecule as a single agent, however, have not been well studied clinically. We conducted a Phase I trial of TNF in 53 patients with advanced malignancies in order to determine the biological and clinical effects of TNF when administered as a 30-min i.v. infusion three times/week. Dose levels of TNF ranged from 5 to 275 micrograms/m2; doses of TNF were escalated between patient groups. The most common clinical toxicities of TNF consisted of rigors, anorexia, headache, and fatigue. Dose-limiting toxicity consisted of hypotension, fatigue, and nausea. Four patients treated at the maximally tolerated dose of 225 micrograms/m2 received dexamethasone to determine whether the toxicities of TNF could be ameliorated. No significant differences in hypotension or subjective symptomatology were observed in those patients receiving dexamethasone and those who did not or between injections in which dexamethasone was administered and when it was not. One patient with colorectal carcinoma treated with 50 micrograms/m2 had a partial response lasting about 9 months. Biological responses were evaluated in 8 patients treated at the maximally tolerated dose before therapy and 24 h afterward. TNF significantly (P less than 0.05 for all) enhanced serum beta 2-microglobulin, serum neopterin, and serum interleukin-2 receptor (Tac antigen) levels. Indoleamine 2,3-dioxygenase activity was also increased 24 h following the administration of TNF, although this increase was only of borderline statistical significance (P = 0.07). TNF did not enhance granulocyte bactericidal activity. The expression of cell surface proteins on monocytes, including HLA-DR, HLA-DQ, beta 2-microglobulin, and the Fc receptor, and serum interleukin-1 activity also were not significantly increased by the administration of TNF. Thus, in humans TNF caused biological response modulation with evidence of HLA Class I (beta 2-microglobulin) increase and T-cell (Tac antigen) and monocyte (neopterin) activation.
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PMID:Biological and clinical effects of intravenous tumor necrosis factor-alpha administered three times weekly. 199 56

Twenty-six malignant lymphomas involving the central nervous system were studied. Eleven were primary (P) and 15 were systemic (S). Eight cases (3 P, 5 S) occurred in immunocompromised patients. Age at presentation in immunocompromised patients was typically younger than in the nonimmunocompromised patients. Presenting complaints of central nervous system involvement included headache, seizures, personality changes, memory lapses, ataxia, cranial nerve symptoms, and impaired consciousness. Cerebrospinal fluid involvement was seen only in 3 S cases. In 8 of the P cases, the diagnosis was first established at autopsy; in 6 of the S cases, central nervous system involvement was first documented at autopsy. Survival was longer in treated patients than in those who received no therapy (5 months in P cases and 9.3 months in S cases; 2.3 months without therapy). Regardless of therapy, the average survival of immunocompromised patients was 2.4 months. The majority of cases were multifocal. Of the P cases, 1 was of low histologic grade, 9 were of intermediate grade, and 1 was of high grade. Of the S cases, 5 were of low grade, 9 were of intermediate grade, and 1 was of high grade. Immunophenotypic studies were performed on formalin-fixed, paraffin-embedded tissue with antisera against common leukocyte antigen (all reactive), B-cell markers (L26, MB2, LN1, and LN2), T-cell markers (UCHL1 and MT1), Leu-M1, Leu-7, and HLA-DR (LN3). Two S cases were of T-cell phenotype; all others were of B-cell derivation. Eleven cases were HLA-DR positive (all of B-cell phenotype). One T-cell lymphoma was reactive for Leu-7. All cases were nonreactive for Leu-M1. All cases in immunosuppressed patients and all P cases were of B-cell phenotype.
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PMID:Central nervous system lymphomas. Immunohistochemical and clinicopathologic study of 26 autopsy cases. 252 37

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.
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PMID:A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). 254 86

A 57-year-old woman came to our hospital with complaints of neck swelling and headache in 1991. She was diagnosed as having chronic thyroiditis in euthyroidism because she had a diffuse goiter with both antithyroglobulin antibody (TGHA) and antimicrosomal antibody (MCHA). In 1992, she complained of the rapid growth of her thyroid gland and a swallowing disturbance. Atypical lymphocytes were observed in 16.5% of leukocytes in peripheral blood and similar atypical cells were found in bone marrow. Although an ultrasound scan of the thyroid gland revealed a symmetrical enlargement without a pseudocystic appearance, cytological study with fine needle aspiration biopsy of the thyroid gland demonstrated an abundance of atypical lymphoid cells. A whole body scintigram with 67gallium citrate showed no significant accumulation except in the thyroid gland. With a diagnosis of suspected primary thyroid lymphoma, total thyroidectomy was performed. However the diagnosis of malignant lymphoma was not confirmed histologically. A study of lymphocytes subset with two-color flow cytometry, which was performed for both lymphocytes in peripheral blood and infiltrating lymphocytes in the resected thyroid gland, revealed abnormal increased CD4 positive T cells and decreased HLA-DR expression. Additionally, southern blot DNA analysis for abnormal lymphocytes using restriction enzymes, EcoRI and BamHI, demonstrated rearrangement of the T-cell antigen receptor, which indicates a monoclonal proliferation of lymphocytes. After total thyroidectomy, atypical lymphocytes in peripheral blood decreased, and circulating autoantibodies including TGHA and MCHA disappeared. From these data, this patient was finally diagnosed as having a primary T-cell lymphoma of the thyroid gland, which is a very rare type of thyroid lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of primary thyroid T-cell lymphoma with infiltration of lymphoma cells in peripheral blood: diagnosed by DNA analysis]. 785 85

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

Normal volunteers received single doses of recombinant human interleukin-10 (rhIL-10; n = 6 per group) or placebo (n = 3 per group) by intravenous injection to characterize pharmacokinetics, tolerability, and immunomodulatory effects. Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 micrograms/kg. Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome characterized by fever with chills, headache, and myalgias at the highest dose. The mean terminal phase t1/2 ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose-related effects of rhIL-10 included transient increases of circulating neutrophils and monocytes and decreases of lymphocytes. rhIL-10 markedly suppressed, in a time- and dose-dependent manner, the synthesis of the inflammatory cytokines IL-1 beta and tumor necrosis factor alpha by whole blood stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of CD14+/HLA-DR+ cells at 24 hours after the dose were increased in a dose-dependent manner. Effects on expression of HLA-DR by CD14+ cells were variable. There was no apparent effect on HLA-DR expression by CD20+ cells. The immunomodulatory effects of rhIL-10 merit further clinical investigation.
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PMID:Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. 855 93

In spite of proven immunoregulatory effects in vitro of recombinant human interferon-gamma (rhIFN-gamma) in trauma, clinical trials remain inconclusive in such patients. To investigate the in vivo effect of rhIFN-gamma perioperatively in surgical patients we did a pilot study in 46 patients termed anergic by negative delayed-type hypersensitivity (DTH) skin test, who were undergoing major surgery (22 women and 24 men). They received 100 micrograms of rhIFN-gamma subcutaneously (treated [T]; n = 24) in a double-blind, placebo- (control [C]; n = 22) controlled manner on preoperative days -7, -5, and -3. Whole-blood cultures were stimulated on days -7, -1, 4, 7, and 10 for 12 h with or without LPS (1 microgram/mL). Mild side effects such as fever, headache, or chills were observed in 7/24 patients. No major complications occurred and no significant effect of rhIFN-gamma on HLA-DR, IL-1, and IL-8 was demonstrated. PGE2, TNF-alpha and IL-6 levels were elevated perioperatively in T. versus C. Neopterin, a metabolite of activated monocytes and macrophages, was significantly activated on days -1 (C: 7.6 +/- 1.2 versus T: 20.5 +/- 2.4 nmol/mL; P < 0.001), day 1 (C: 8.3 +/- 1.4 nmol/mL versus T: 24.9 +/- 2.8 nmol/mL; P < 0.001), and day 4 (C: 9.5 +/- 1.1 nmol/mL versus T: 16.0 +/- 1.8 nmol/mL; P < 0.05). Due to the overall lack of infectious complications during the investigation, no clinical effect was shown for rhIFN-gamma treatment. DTH skin testing failed to detect high-risk individuals in the patient population studied. In conclusion, we demonstrated in our pilot study that pre-operative immunomodulation with rhIFN-gamma in surgical anergic patients did not show severe side effects and modulated in vitro immunoresponse. A larger clinical trial in better-defined high-risk patients may show whether a reduction of infectious complications can be achieved.
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PMID:Perioperative treatment with human recombinant interferon-gamma: a randomized double-blind clinical trial. 1169 68

An 84-year-old woman was admitted because of anemia and marked leukocytosis. The white cell count was 237,660/microliter, with 93% abnormal lymphoid cells. The cells had abundant cytoplasm and prominent nucleoli. They were positive for CD 5, 19, 20, 22, 23, HLA-DR, IgM, IgD and kappa chain. Thus, a diagnosis of B-cell PLL was made. Chromosome analysis disclosed a complex karyotypic abnormality. Massive splenomegaly was detected by abdominal computed tomography. No external or internal lymphadenopathy was found. The patient was intermittently treated with etoposide. Although the white cell counts had been suppressed, she refused to take the drug because of side effects. When the white cell count exceeded more than 200,000/microliter again, she developed severe headache, diplopia, nausea, and vomiting. A lumber puncture disclosed infiltration of the prolymphocytes in the cerebrospinal fluid. Though intrathecal chemotherapy alleviated the symptoms and the leukemic cells disappeared, the effects were transient. When the therapy was withheld because of bone marrow suppression, the meningitis recurred and the symptoms progressed. The patient died six months after the initial presentation.
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PMID:[Leukemic meningitis in B-cell prolymphocytic leukemia]. 1222 29

We report a rare case of involvement of the central nervous system (CNS) by chronic lymphocytic leukemia (CLL). A 68-year-old man with prolymphocytic variant of B-CLL (CLL/PLL), develops CNS involvement with headache and vomiting. Computed tomography of the head showed no abnormalities. The cerebrospinal fluid (CSF) revealed numerous lymphocytoid cells of prolymphocytic appearance consistent with findings on the peripheral blood smear. Immunophenotypic analysis demonstrated that the leukemic B cells were positive for CD19, CD20, and HLA-DR, but CD5 was difficult to detect. The patient was treated with intrathecal methotrexate, cytarabine, and hydrocortisone and had improvement in symptoms and CSF findings. Although CNS involvement is an unusual manifestation in CLL, one should be aware of the possibility of this complication in cases presenting with neurological symptoms.
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PMID:Involvement of central nervous system in prolymphocytoid transformation of chronic lymphocytic leukemia. 1291 78

Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case of a patient who developed central nervous system (CNS) relapse of LBL 16 years after the onset of the primary disease. An 8-year-old girl was hospitalized with a skin tumor in the occipital region on November 27, 1984. Examination of a biopsy of the skin tumor showed typical features of non-Hodgkin's lymphoma (diffuse medium-sized cell type). She received multiagent chemotherapy and went into remission. On July 4, 2000, she was hospitalized with persistent headache. Cranial magnetic resonance imaging showed a cerebellar lesion, which was hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted images. A midline suboccipital craniotomy was performed and pathological examination revealed a diffuse proliferation of lymphoid cells, which were positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3 and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised immunohistochemistry of the primary specimens of skin tumor obtained 16 years earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain reaction products for the immunoglobulin gene from both the skin and cerebellar specimens were an identical size. Thus, the original diagnosis of diffuse medium-sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was apparent in the present case. After salvage chemotherapy, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell support and subsequent craniospinal irradiation. She went into a lasting complete remission.
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PMID:Very late central nervous system relapse in a patient with B cell lymphoblastic lymphoma. 1556 34


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