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 order to prevent the adverse effects of a first OKT3 injection in renal transplant recipients, we administered polyclonal antilymphocyte globulins (ATG Fresenius, 4 mg/kg/j) for 3 days before OKT3 injection. Compared with a historical group of 5 patients who did not receive ATG pretreatment before OKT3 injection, the patients who were pretreated by ATG had a significantly lower absolute number of circulating lymphocytes before the first OKT3 injection (363 +/- 107 vs 1,230 +/- 80/mm3, P < 0.001), a lower raise in plasma TNF-alpha level 2 hours after OKT3 injection (178 +/- 42 vs 735 +/- 127 pg/ml, P < 0.005) and a significant decrease in frequency and intensity of clinical symptoms, mainly chills, dyspnea, and headaches. However, fever and peak creatinine level were similar in both groups. A 80 percent success rate of crisis treatment was achieved in both groups and there was no increase in infectious complications. In conclusion, pretreatment with ATG induces a lymphocyte depletion, and decreases the amounts of TNF-alpha released as well as the side-effects of a first OKT3 injection.
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PMID:[Reduction of TNF-alpha release and clinical effects of the first injection of OKT3]. 129 74

Tumor Necrosis Factor-alpha/cachectin (TNF-alpha/cachectin), Lipopolysaccharide (LPS), ACTH, beta-Endorphin (beta-EPH), and Cortisol (F) levels were determined in 33 Headache patients: 22 patients were affected with Migraine (M) and 11 patients with Chronic Type Tension Headache (CTTH). TNF-alpha/cachectin serum level was detected in 15 out of 22 migraneous patients and in no CTTH patients. Plasma LPS was observed in 11 out of 15 TNF-alpha/cachectin positive migraneous patients (73%) and in 3 out of 11 CTTH patients (27%). A negative correlation was observed between TNF-alpha/cachectin values and either ACTH or beta-EPH. In the group of migraneous patients the presence of serum TNF-alpha/cachectin showed a sensibility of .6 and a specificity of 1. The endocrine and immunological implications concerning these data are discussed.
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PMID:Increased spontaneous release of tumor necrosis factor-alpha/cachectin in headache patients. A possible correlation with plasma endotoxin and hypothalamic-pituitary-adrenal axis. 166 86

A 70-year-old man was admitted to our hospital for further evaluation of recurrent fever, which had begun in October 1994. The patient had 5 to 7 days without fever, and then 2 to 3 days of fever. He had headaches during the febrile periods. On admission, he had abnormal pyramidal, extrapyramidal, and celebellar signs, and nuchal rigidity during the febrile period. However, these neurological abnormalities were completely absent during the afebrile period. Examination of cerebrospinal fluid revealed pleocytosis of mononuclear cells. During the febrile period, pleocytosis was associated with high levels of IgG, IL-6, TNF-alpha, and PGE2 in the cerebrospinal fluid. Administration of indomethacin prevented the fever, which suggests that abnormal production of cytokines in the cerebrospinal fluid contributes to fever in Mollaret meningitis.
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PMID:[Mollaret meningitis associated with a high level of cytokines in cerebrospinal fluid]. 907 8

Therapeutic applications of novel growth factors and cytokines can be limited due to the oftentimes severe inflammatory reactions that are encountered in patients following parenteral administration. These inflammatory responses, hallmarked by fever, headache, and chills are mediated by the release of inflammatory cytokines following administration of protein-based therapeutics. TNF-alpha appears to be one of the most potent and pleiotropic inflammatory cytokines released during the early stages of an inflammatory response. In the present study, we have explored the use of an in vitro assay system to determine whether the release of TNF-alpha from human PBMC could be correlated with documented inflammatory activity in humans. The cytokines tested included rhGM-CSF, rhIL-2, rhIL-3, and rhIFN-gamma, rhG-CSF, which has been shown to lack substantial proinflammatory activity in humans, was also tested. The potent macrophage activator and inflammatory agent, LPS, was used as a positive control. Results of this study demonstrate and confirm an association between the inflammatory activity of cytokines observed in patients and the stimulation of TNF-alpha release from PBMC in vitro. This assay system can be used as a predictive tool in determining the inflammatory potential of novel growth factors and cytokines.
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PMID:TNF-alpha release from human peripheral blood mononuclear cells to predict the proinflammatory activity of cytokines and growth factors. 908 89

An increasing number of persons say that they get cutaneous problems as well as symptoms from certain internal organs, such as the central nervous system (CNS) and the heart, when being close to electric equipment. A major group of these patients are the users of video display terminals (VDTs), who claim to have subjective and objective skin- and mucosa-related symptoms, such as pain, itch, heat sensation, erythema, papules, and pustules. The CNS symptoms are, e.g. dizziness, tiredness, and headache. Erythema, itch, heat sensation, edema and pain are also common symptoms of sunburn (UV dermatitis). Alterations have been observed in cell populations of the skin of patients suffering from so-called "screen dermatitis" similar to those observed in the skin damaged due to ultraviolet (UV) light or ionizing radiation. In "screen dermatitis" patients a much higher number of mast cells have been observed. It is known that UVB irradiation induces mast cell degranulation and release of TNF-alpha. The high number of mast cells present in the "screen dermatitis" patients and the possible release of specific substances, such as histamine, may explain their clinical symptoms of itch, pain, edema and erythema. The most remarkable change among cutaneous cells, after exposure with the above-mentioned irradiation sources, is the disappearance of the Langerhans' cells. This change has also been observed in "screen dermatitis" patients, again pointing to a common cellular and molecular basis. The results of this literature study demonstrate that highly similar changes exist in the skin of "screen dermatitis" patients, as regards the clinical manifestations as well as alterations in the cell populations, and in skin damaged by UV light or ionizing radiation.
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PMID:Skin changes in "screen dermatitis" versus classical UV- and ionizing irradiation-related damage--similarities and differences. 941 15

Endotoxins, cell-wall fragments of gram-negative bacteria, are found in various work environments and first measurements have been made in general indoor environments. Endotoxins cause an inflammatory response of the respiratory tract. The response is mediated by the proinflammatory cytokines IL-1, IL-6, IL-8, and TNF-alpha and gives rise to general symptoms (fever, headache, malaise), respiratory symptoms (tightness of chest, dry cough), and lung function decrements. In the work environment endotoxins have been identified in all environments which produce similar symptoms. The qualitative results of experimental and epidemiological studies agree well. The related question whether endotoxins are the biologically active component of organic dust cannot yet be answered because of the gap between the concentration of lipopolysaccharides and of endotoxins necessary to induce the same quantitative effect. Different possible explanations are discussed. Endotoxins are also found in the general environment, especially indoors. Their health relevance needs to be assessed in more detail, especially in subjects with bronchial hyperreactivity.
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PMID:[Endotoxins in the workplace and in the environment]. 1023 2

In this randomized, double-blind, parallel-group study, a commercially available human immunoglobulin-G product, IVIG, was compared with two test formulations: (1) IVIG-N, which is a nanofiltered formulation of IVIG, and (2) IVIG-L, which is a nanofiltered, liquid, ready-for-use IgG formulation containing nicotinamide, L-proline, and L-isoleucine as stabilizers. Three groups of 10 healthy subjects each received a single 0.6 g/kg dose of one of the formulations infused over 3.5 to 6.8 hours, depending on the total volume to be infused. Blood samples were obtained over a 6-week period to assess pharmacokinetics, immunogenicity, and the pharmacodynamic effects on leukocytes and TNF-alpha. A blood sample was taken at 6 months for a viral safety check. Administrations were generally well tolerated with only one reference IVIG infusion stopped prematurely due to headache. The IgG Cmax and AUC over the 6-week blood sampling period from both test formulations satisfied equivalence criteria compared with the reference formulation. In subjects receiving IVIG-L, peak concentrations of the stabilizer nicotinamide ranged from 0.34 to 0.47 mmol/L and of nicotinamide-N-oxide from 0.03 to 0.04 mmol/L, which are below those reported to cause adverse events. During the infusion of IVIG, leukocyte counts initially declined from a baseline of 5.7 +/- 1.1 x 10(9)/L to 3.7 +/- 0.8 x 10(9)/L at 2 to 4 hours and returned to baseline by 24 hours. TNF-alpha levels, reflecting activation of the monocyte-macrophage system by the infused IVIG, rose from a baseline of 13 +/- 4 pg/mL to a peak of 272 +/- 324 pg/mL at 2 to 4 hours and returned to baseline by 24 hours. These patterns were generally similar for the test formulations, with the exception that the increase in TNF-alpha levels was dampened for IVIG-N, although this was not statistically significant. There was no evidence of immunogenicity or viral transmission from any of the formulations. Hence, these three formulations were generally well tolerated, yielded similar systemic exposure to IgG over a 6-week period after administration, and did not give rise to immunogenicity or viral safety concerns.
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PMID:Product equivalence study comparing the tolerability, pharmacokinetics, and pharmacodynamics of various human immunoglobulin-G formulations. 1088 13

After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we attempted to avoid time-consuming pre-activation procedures for adoptively transferred cells by using a combination of bispecific antibodies directed to the EGF receptor (EGFR) on tumor cells and to CD3 and CD28 on T cells. Eleven patients with high-grade malignant glioma received 3 injections of 2 bispecific antibody fragments (EGFR x CD3 and EGFR x CD28) together with freshly isolated autologous lymphocytes via an Ommaya reservoir. Intracavitary fluid aspirated during immunotherapy was examined for markers of T-cell activation. Increased levels of soluble IL-2 receptor and TNF-alpha were detected in the intracavitary fluid of all patients tested. Two of the 11 treated patients experienced a beneficial response to therapy as defined by a transient contrast enhancement in subsequent MRI scans and prolonged survival. Side effects were transient and consisted of fever, nausea, headache and aggravation of pre-existing neurologic deficits. These adverse effects were most likely due to the antibody construct containing anti-CD3 specificity. Two patients developed cerebral edema and required steroid treatment.
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PMID:Local immunotherapy of glioma patients with a combination of 2 bispecific antibody fragments and resting autologous lymphocytes: evidence for in situ t-cell activation and therapeutic efficacy. 1114 49

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

Yangkyuk-Sanhwa-Tang (YS-Tang), a specific prescription composed of nine herbal mixtures, has been developed as a formula for the Soyangin cerebral infarction (CI) patients according to Sasang constitutional philosophy. However, the mechanisms by which this formula affects CI remain unknown. This study revealed changes in cytokine production in the acute stage of Soyangin constitution CI patients after YS-Tang administration. Clinical signs (vertigo, headache and slurred speech) of CI disappeared significantly in about 2 weeks after oral administration of YS-Tang (P < .05). The mean interleukin (IL)-2 plasma levels were lower by 15% in the patients with CI than in the normal groups, whereas the mean TNF-alpha, IL-4, IL-6 and IgE levels were significantly higher in the patients (P < .01). There were no significant differences in interferon-gamma (IFN-gamma) levels between the groups. Serum IFN-gamma and IL-2 levels were elevated significantly (P < .01) in the patients with CI by YS-Tang administration. Significant reduced plasma levels (P < .01) of TNF-alpha, IL-4, IL-6 and IgE were observed in the patients treated with YS-Tang. During the period of YS-Tang administration, there were no other adverse effects. The data indicate that YS-Tang has an enhancing effect on antiinflammatory cytokines and an inhibitory effect on inflammatory cytokines. These results may implicate a good CI treatment effect of YS-tang and that its action may be due to regulation of cytokine production.
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PMID:Yangkyuk-Sanhwa-Tang induces changes in serum cytokines and improves outcome in focal stroke patients. 1261 92


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