Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine patients with a recurrent malignant glioma were treated with repeated intracavitary or intracerebroventricular injections of human recombinant interleukin-2 (rIL-2) alone or in combination with systemic interferon-alpha (IFN-alpha). Five patients received only rIL-2 and four were treated with rIL-2 plus subcutaneous injections of IFN-alpha. Therapy was administered on a Monday, Wednesday, Friday schedule for up to 10 weeks, beginning with a dose of 10,000 IU rIL-2/injection. Doses were escalated every two weeks until some toxicity was apparent. The maximum amount of rIL-2 any one patient in this group received was 580,000 IU. Patients on combination immunotherapy were held at an rIL-2 dosage of 10,000 IU while IFN-alpha, which began at 3 million IU, was escalated every other week up to 18 million IU/dose. They were then held at that IFN-alpha dosage and rIL-2 was increased to 50,000 IU. The total amount of rIL-2 and IFN-alpha any one in this group received was 510,000 IU and 417 million IU, respectively. Repeated injections of 10,000 IU rIL-2 were well-tolerated by all nine patients and no change in their functional status was seen. At doses at 50,000 IU rIL-2, increased edema around the tumor cavity was observed by MRI/CT scand in 3/5 patients and clinical side-effects in the form of somnolence and headache along with some morbidity specifically associated with tumor location were also seen. Patients receiving rIL-2+ IFN-alpha showed progressive fatigue, muscle weakness, and occasionally nausea. Two of these patients showed increased peritumoral edema on MRI/CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-alpha. Results of a phase I clinical trial. 154 81

Nineteen patients with metastatic adenocarcinoma of the colon or rectum were treated with alpha (human leukocyte) interferon (alpha IFN). Patients received 3 X 10(6) IU/day of interferon im 5 days/week. Eighteen patients are evaluable for response and toxicity. There were no objective responses. All evaluable patients demonstrated progression of disease during therapy. Toxicity consisted primarily of mild granulocytopenia, thrombocytopenia, fatigue, weakness, and fever. This trial demonstrates that while alpha IFN can be administered safely as scheduled, this regimen has no activity against adenocarcinoma of the colon/rectum.
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PMID:Phase II trial of alpha (human leukocyte) interferon administered daily in adenocarcinoma of the colon/rectum. 685 Jun 64

We report a case of mononeuropathy multiplex due to interferon alpha (IFN alpha) therapy for chronic hepatitis C. A 61-year-old man received IFN alpha (natural type 6 x 10(6) IU), every day for two weeks and three times a week for 22 weeks by intramuscular injection. Seventeen weeks after the initiation of IFN alpha therapy, he noticed painful dysesthesia, muscle weakness and muscular atrophy of the left lower extremity. Neurological examination revealed weakness of the left iliopsoas, quadriceps femoris and femoral adductor muscles, hypesthesia and dysesthesia. Electromyogram showed neuropathic change in the left vastus lateralis muscle. Muscle computed tomography showed muscular atrophy of the left lower extremity. Two months after discontinuation of the IFN alpha therapy, dysesthesia and muscle weakness of the left lower extremity improved spontaneously. He was diagnosed as mononeuropathy multiplex of the left femoral nerve and obturator nerve caused by IFN alpha therapy. Attention must be paid to dysesthesia, muscle weakness and muscular atrophy when IFN alpha therapy is initiated.
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PMID:[Mononeuropathy multiplex in a patient receiving interferon alpha therapy for chronic hepatitis C]. 856 46

An interesting aspect of HIV disease is the immunoendocrine dialogue, via the hypothalamo-pituitary-adrenal axis, between glucocorticoids and cytokines and its potential role in HIV disease progression. This study reports recent data on the interaction between glucocorticoids and the immune system in AIDS patients with an acquired form of glucocorticoid resistance. Clinically, glucocorticoid-resistant AIDS patients (AIDS-GR; about 12% in our series of patients) present Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia and intense mucocutaneous melanosis) in spite of elevated values of plasma cortisol and urinary free cortisol. Monocytes from these patients have a significantly lower receptor affinity (higher Kd) for glucocorticoids and a higher receptor density than other patients and controls. Such receptor alteration is associated with higher values of plasma interferon alpha (IFN alpha). In AIDS-GR there is a significant correlation between the values of receptor Kd and of plasma IFN alpha (r = 0.77). After poly(I):poly(C) stimulation, monocytes from AIDS-GR produce much more IFN alpha than other AIDS patients. While in patients with no resistance and in control patients, monocyte production of IFN alpha is inhibited by dexamethasone (the effect being reversed by RU-486), a very slight inhibition of dexamethasone on IFN alpha production is observed in monocytes from AIDS-GR. In conclusion, these data demonstrate that the immunosuppressive mechanisms acting in AIDS may be reversed, as shown by the increased stimulus on IFN alpha production found in cortisol-resistant patients. These data also suggest that antiglucocorticoid drugs may be helpful in HIV disease as they antagonize the excessive immunosuppression induced by the increased production of glucocorticoids found at every stage of HIV disease.
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PMID:Glucocorticoids and the immune system in AIDS. 926 43

Twenty-three patients with advanced melanoma were treated with a combination of subcutaneous recombinant human interleukin-2 (IL-2), and recombinant interferon alpha-2a (IFN-alpha) with chemotherapy consisting of four cycles of carboplatin (300 mg/m2, day 1) and vinblastine (6 mg/m2, day 1), every 28 days (CV-IL-IF). IL-2 was given at a dose of 4.5 x 10(6) U twice daily on days 3-6 and days 21-24 of each cycle; IFN-alpha dose was 4.5 x 10(6) U, starting on day 2, thrice weekly. Immunotherapy was intended to continue for 6 months. Of the 23 analyzed patients, 4 (17%) achieved an objective response, including 1 complete and 3 partial responses, in nonvisceral metastatic disease. The median time to progression was 5 months and the median survival from onset of the treatment 6 months (range 1-14 months). Four patients discontinued the treatment, due to nonhaematologic toxicity; 3 for severe weakness and the 4th patient for long-lasting CNS side-effects. Other grade 3-4 toxicities included weight loss (22%), nausea and vomiting (17%) and alopecia (13%). The haematologic toxicity was acceptable. No toxic death was noted. It is concluded that the CV-IL-IF regimen has limited activity and moderate toxicity.
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PMID:Subcutaneous low doses of interleukin-2 and recombinant interferon alpha with carboplatin and vinblastine in patients with advanced melanoma. 942 75

Glucocorticoids, the final product of HPA axis, and their receptors (GRs) on mononuclear cells are crucial mediators in the endocrine-immune interaction. An alteration in GRs involving a lower receptor affinity (Kd) for glucocorticoids has been found in a group of advanced AIDS patients, who developed Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis) in spite of hypercortisolism and normal or slightly elevated values of ACTH (AIDS-GR). In these patients, data for the suppression test showed decreased cortisol and ACTH suppression in response to exogenous dexamethasone. The inhibitory effect of dexamethasone on radiolabeled-thymidine incorporation in mononuclear cells from these patients was also reduced. Monocytes of AIDS-GR patients had a receptor Kd of 10.5 +/- 4.2 nmol/l that was higher than that of other AIDS patients (AIDS-C) (2.9 +/- 0.8 nmol/l) and normal subjects (2.0 +/- 0.8 nmol/l: p < 0.01). Correlations were found between plasmatic IFN-alpha and receptor Kd on monocytes of AIDS-GR (r = 0.77). Poly (i)-poly (c)-induced IFN-alpha production by monocytes was inhibited by glucocorticoids in the AIDS-C group and controls (approx. 80% in both groups): The effect was reversed by the receptor antagonist RU-486. By contrast, glucocorticoid did not inhibit IFN-alpha production in AIDS-GR group. In conclusion, levels of plasmatic IFN-alpha, a cytokine with antiviral properties, may be increased several times, and dexamethasone fails to inhibit monocytes' IFN-alpha production only in AIDS with cortisol resistance, a disturbance that confirms an important immunoregulatory role of glucocorticoids in HIV disease.
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PMID:Glucocorticoid resistance and the immune function in the immunodeficiency syndrome. 962 9

Nine patients with onco-hematological malignancies with a poor prognosis due to high risk of relapse received immunotherapy with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) s.c. as maintenance therapy after receiving autologous bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT). All the patients were considered at very high risk of relapse. We attempted to assess the efficiency, toxicity and clinical effects of these cytokines in these patients. Five patients were treated with high-dose of IL-2 and the other four patients with escalating doses every month. Side-effects in the first group of patients consisted of fever, chills, weakness, nausea, anorexia, loss of weight and local dermatitis in the injection site. Toxicity on the WHO scale was grade II in three patients and grade IV in the other two patients. In the second group of patients, the same clinical signs of toxicity appeared, but these were grade I on the WHO scale in all patients. None of the patients had infections or died in relation to administration of IL-2. Four patients died of relapse or progression of their hematological malignancies. The other five patients are alive, one in chronic phase of CML and the other four patients are in complete remission of their malignancies.
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PMID:Treatment with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) after autologous bone marrow or peripheral blood stem cell transplantation in onco-hematological malignancies with a high risk of relapse. 1019 3

IFN-gamma can either adversely or beneficially affect certain experimental autoimmune diseases. To study the role of IFN-gamma in the autoantibody-mediated experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis in humans, IFN-gammaR-deficient (IFN-gammaR-/-) mutant C57BL/6 mice and congenic wild-type mice were immunized with Torpedo acetylcholine receptor (AChR) plus CFA. IFN-gammaR-/- mice exhibited significantly lower incidence and severity of muscle weakness, lower anti-AChR IgG Ab levels, and lower Ab affinity to AChR compared with wild-type mice. Passive transfer of serum from IFN-gammaR-/- mice induced less muscular weakness compared with serum from wild-type mice. In contrast, numbers of lymph node cells secreting IFN-gamma and of those expressing IFN-gamma mRNA were strongly augmented in the IFN-gammaR-/- mice, reflecting a failure of negative feedback circuits. Cytokine studies by in situ hybridization revealed lower levels of lymphoid cells expressing AChR-reactive IL-1beta and TNF-alpha mRNA in AChR + CFA-immunized IFN-gammaR-/- mice compared with wild-type mice. No differences were found for AChR-reactive cells expressing IL-4, IL-10, or TGF-beta mRNA. These results indicate that IFN-gamma promotes systemic humoral responses in EAMG by up-regulating the production and the affinity of anti-AChR autoantibodies, thereby contributing to susceptibility to EAMG in C57BL/6-type mice.
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PMID:Mice with IFN-gamma receptor deficiency are less susceptible to experimental autoimmune myasthenia gravis. 1020 93

Background: Essential mixed cryoglobulinemia (EMC) is a systemic disease frequently associated with chronic viral hepatitis. This study was conducted in order to assess the prevalence of EMC in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. We also evaluated the possible associations of EMC with (1) the clinical, virological, and histological status of liver disease; (2) the presence of EMC-related symptoms; and (3) the response rate to interferon-alpha (IFN-alpha) treatment, in an attempt to address whether EMC is a major problem in hepatitis patients. Methodology: A total of 154 consecutive patients (104 with HBV and 50 with HCV infection) were investigated for the presence of rheumatoid factor (RF), cryoglobulins, and EMC-related manifestations. Sixty-two HBV patients were chronic carriers of hepatitis B surface antigen, 29 had chronic hepatitis B, and 13 HBV cirrhosis. Thirty-five HCV patients had chronic hepatitis C and 15 HCV cirrhosis. HCV genotyping was performed in 44 patients. Results: The prevalence of cryoglobulins was significantly higher (P<0.001) in HCV patients (46%) than in HBV patients (13.4%). EMC was associated with a high frequency of RF detection, older age, and longer duration of viral diseases. Weakness or malaise, arthralgias, and purpura were significantly more frequent in cryoglobulin-positive patients. These manifestations, however, were mild in most of the patients. The EMC-related symptoms were significantly associated with the presence of HCV infection, increased levels of cryoglobulins, and RF detection (P<0.01, P<0.05, and P<0.000005, respectively). Worse liver histology was unrelated to a higher prevalence or increased levels of cryoglobulins in both HBV and HCV infection. There was no relationship between EMC and a specific HCV genotype. IFN-alpha therapy led to the disappearance of cryoglobulins and EMC-related manifestations in most cases. The response rate to IFN-alpha was similar in both groups of patients (with and without EMC). Conclusions: A higher prevalence of EMC was observed in HCV patients than in HBV patients. However, this finding was unrelated to overt clinical manifestations of EMC, a specific HCV genotype, or worse liver histology. The latter suggests that EMC does not contribute to liver injury and vice versa, that EMC pathogenesis is rather unrelated to the degree of liver injury. From a clinical point of view, testing for cryoglobulins seems reasonable only for HCV patients with EMC-related manifestations, since this may have therapeutic consequences. RF detection could be used primarily as a surrogate marker for the existence of cryoglobulins.
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PMID:Cryoglobulinemia due to chronic viral hepatitis infections is not a major problem in clinical practice. 1155 30

Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is a systemic vasculopathy affecting young children. Epidemiology studies documenting an antecedent illness in the 3 mo before the first definite symptom (rash and/or weakness) of JDM are supported by immunologic data that suggest that the disease pathophysiology is Ag driven. The purpose of this study was to compare the gene expression profiles in muscle biopsies of four untreated DQA1*0501(+) JDM children with profiles from children with a known necrotizing myopathy (Duchenne muscular dystrophy), as well as an in vitro antiviral model (NF90), and healthy pediatric controls. Nearly half (47%) of the dysregulated genes in JDM were associated with the immune response. In particular, increased expression of IFN-alphabeta-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-alphabeta transcription cascade seen in the in vitro viral resistance model. The IFN-alphabeta-inducible profile was superimposed on transcription profiles reflective of myofiber necrosis and regeneration shared with Duchenne muscular dystrophy. Expressed genes were confirmed by quantitative real-time PCR (6-16), immunofluorescence (thrombospondin 4), and immunolocalization (IFN-gamma, p21). We hypothesize that these data support a model of Ag (?viral) induction of an apparent autoimmune disease based on dynamic interaction between the muscle, vascular, and immune systems in the genetically susceptible (DQA1*0501(+)) child.
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PMID:Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis. 1193 76


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