Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
 4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I/II trial of the anti-CD4 monoclonal antibody (mAb) was undertaken in seven rheumatoid arthritis patients in order, (1) to investigate changes in clinical symptoms and possible side effects, and (2) to study the pharmacokinetics and to determine the dose required to achieve saturation of antibody binding sites on blood leucocytes. BL4mAb is a murine IgG2a which binds to the group 2B epitope of the V1 N terminal domain of the CD4 molecule. It inhibits syncitium formation by human immunodeficiency virus-infected cells. BL4 was administered by one hour-long intravenous infusion each day, for 10 days. Doses were steadily increased from 20 mg/d to 40 mg/d in the first three patients (group I) in an attempt to reach a serum antibody residual level sufficient to saturate CD4+ circulating cells. The three other patients (group II) received a dose of 40 mg/d during 10 consecutive days. One patient who presented chills and mild fever during the first BL4 infusion was not included in the analysis. No clinical side effects were observed in the six other BL4-treated patients. Clinical parameters of disease activity were improved within the first 14 days. Clinical improvement was still significant at day 30 in five patients, but at day 60, only the Ritchie index was still below pretreatment levels. Delayed type hypersensitivity reactions decreased in the three patients who exhibited positive reactions before BL4 administration. A transient drop in peripheral blood CD4+ lymphocyte counts occurred during each infusion in the first days of treatment. Pre-infusion CD4+ lymphocyte counts were moderately decreased within the first 8 days, but rose to pretreatment levels 3 days after the last infusion. BL4 residual levels in serum steadily increased to reach 8.0 micrograms/ml in group I and 9.8 micrograms/ml in group II. Saturation of BL4 binding sites was achieved after 2 days of treatment in all patients of group II but in only one of group I. Four out of six patients produced antibodies against the anti-CD4 mAb. Immunization appeared between days 12 and 50. This study shows that saturation of anti-CD4 mAb binding sites can be achieved by infusions of high doses (40 mg/d) of BL4 without clinical side effects. The results would encourage further placebo-controlled trials, since no definite conclusion can be drawn from the present study as regards clinical efficacy.
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PMID:Immunological effects of high dose administration of anti-CD4 antibody in rheumatoid arthritis patients. 177 12

In a series of studies, recombinant interferon-alpha 2a (rIFN alpha 2a, Roferon-A) was administered alone (273 men) or combined with vinblastine (91 men) to patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Patients were treated with daily doses of rIFN alpha 2a ranging from 3 to 54 million international units (I.U.) administered intramuscularly. A dose of 36 million I.U. daily for approximately 10 weeks followed by a three times weekly maintenance schedule with the same dose resulted in the best overall therapeutic benefit. An escalating-dose regimen of 3, 9, and 18 million I.U. daily, each for 3 days, followed by 36 million I.U. daily, produced equivalent therapeutic benefit with amelioration of acute toxicity in some patients. Response was more likely in patients without a history of opportunistic infection or B symptoms (fever, night sweats, or weight loss). Response rate increased with increasing baseline CD4 lymphocyte count and was 45.5% in patients with a CD4 count of greater than 400/mm3. Responding patients with a CD4 count of greater than 200/mm3 had a distinct survival advantage over patients who had similar CD4 counts but whose tumors did not regress with therapy. The addition of vinblastine increased toxicity and did not improve the response rate or prolong survival. Side effects included fatigue, fever, chills, myalgias, headaches, anorexia, nausea, diarrhea, and dizziness. Mild abnormalities in hematologic and liver function tests occurred in some patients. Most adverse effects diminished or resolved with continued therapy. We conclude that rIFN alpha 2a offers important therapeutic benefit in a select group of patients with AIDS-related KS.
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PMID:Interferon-alpha 2a in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 182 54

The effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion. The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks. Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens. Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04). Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients. Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02). Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion). However, it remains to be determined whether long-term remission can be induced with this therapeutic approach. The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
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PMID:Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. 199 9

A clinical trial was conducted to determine the tolerance and toxicity of recombinant tumor necrosis factor (rTNF) and recombinant interferon gamma (rIFN-gamma) when administered concurrently by continuous intravenous infusion to 11 patients with the AIDS-related complex (ARC). In addition, HIV culture, p24 antigen levels, and CD4 positive lymphocytes were monitored to obtain preliminary evidence of antiviral and immunologic effects. Two 5-day treatment cycles were separated by a 9-day washout period. Two patients were entered at each dosage level and each patient received the two 5-day treatment cycles at two sequential dose levels ranging from 1 to 25 micrograms/m2. Two patients did not complete their second treatment cycle--one due to the development of a rash, the second due to central venous catheter discomfort. The occurrence of phlebitis with peripheral vein administration of these agents necessitated administration via central venous catheter. With the exception of a single patient who developed severe headache at the 25 micrograms/m2 dose, severe clinical toxicities were not observed. Fever, chills, headache, and myalgias were the most significant clinical toxicities observed and all were dose dependent. The percentage fall in total granulocytes was dose dependent and ranged from 17% at the 1 microgram/mm2 dose to 48% at both the 15 and 25 micrograms/mm2 dose levels. The mean nadir granulocyte count was 1694/mm3. No significant renal or hepatic toxicity was observed. Of 22 treatment cycles the CD4 cell number was increased in 11, unchanged in 7, and decreased in 4. The mean CD4 cell number did not change significantly (176 +/- 143/mm3 pretherapy versus 279 +/- 305/mm3 posttherapy).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I/II study of recombinant tumor necrosis factor and recombinant interferon gamma in patients with AIDS-related complex. 256 51

OBJECTIVE--To study the effect of anti-CD4 treatment in patients suffering from refractory systemic onset juvenile chronic arthritis (JCA). METHODS--Two children were treated with the mouse CD4 antibody MAX.16H5. The effects on numbers of circulating CD4 T cells, clinical symptoms and C reactive protein (CRP) level were studied and the appearance of human antimouse immunoglobulin antibodies investigated. RESULTS--In patient one, disappearance of fever and malaise and a reduction of arthritic activity were observed together with a reduction in CRP. When disease activity returned eight weeks later, a second successful course of treatment was administered. It was possible to reduce the corticosteroid dosage permanently. In the other child, a first treatment cycle did not alter disease activity. A marked reduction in clinical and laboratory disease activity markers was observed after the second course. Only transient and mild side effects were observed. One patient exhibited a short lasting febrile reaction with chills, the other an urticarial rash. In both patients, human antibodies to mouse immunoglobulin became detectable. The decrease in the number of CD4 T cells in the peripheral blood was only short lasting and numbers returned to normal values within one to eight weeks, even after the second course of antibody treatment and under concomitant immunosuppressive treatment. No sustained clinical remissions could be achieved. CONCLUSIONS--These preliminary observations support the evidence of positive effects of CD4 antibody treatment in refractory systemic onset JCA. Long term efficacy, however, remains to be established.
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PMID:Treatment of refractory juvenile chronic arthritis by monoclonal CD4 antibodies: a pilot study in two children. 749 26

A bispecific antibody directed to T and B cells (CD3 x CD19 bsAb) was daily infused intravenously in escalating doses from 10 micrograms up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed a t1/2 of 10.5 h with peak levels of 200-300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor alpha was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon gamma. IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1 beta in serum). No gross changes in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3 x CD19 bsAb only moderate toxicity was found, probably due to CD8+ T cell activation and cytokine release, without CD4+ T cell activation.
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PMID:CD8 T cell activation after intravenous administration of CD3 x CD19 bispecific antibody in patients with non-Hodgkin lymphoma. 754 21

A 43-year-old, bisexual, black man with acquired immunodeficiency syndrome (AIDS), detected by CD4 lymphocyte criteria alone, presented with low-grade fever, chills, malaise, and watery diarrhea of 2 days' duration. Over the next 5 days, he developed a fulminant septicemia-like illness with progressive hypotension, disseminated intravascular coagulation, and very high serum lactic acid dehydrogenase (2,150 U/L) and serum creatine phosphokinase (5,395 U/L) levels, and died. The cause of this illness was not clinically apparent. A bone marrow biopsy performed on the day of his death revealed intracytoplasmic clusters of 3 microns long, oval, basophilic organisms, the exact nature of which was not evident by light microscopy. The diagnosis of disseminated toxoplasmosis (DT) was made only after electron microscopic study of the bone marrow revealed organisms with features typical of Toxoplasma gondii tachyzoites. These features included a multilayered pellicle, a pointed anterior end containing a conoid, up to nine rhoptries, sparse micronemes, and a posterior end containing a nucleus. Some of the organisms had divided by internal budding or endodyogeny. This case illustrates the value of transmission electron microscopy in making the diagnosis of DT.
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PMID:Disseminated toxoplasmosis and acquired immunodeficiency syndrome: diagnosis by transmission electron microscopy. 779 54

In June 1993, in Taiwan, a woman admitted to a local hospital with cough, fever, chills, and difficult breathing who tested positive for HIV-1 infection was transferred to Taipei Veterans General Hospital. In January 1985, at a provincial hospital, then 46 years old, she underwent an anterior total hysterectomy and bilateral salpingo-oophorectomy during which she received two units of whole blood. One of the blood donors was an AIDS patient who had been treated at the same hospital in 1991 and who had died in 1993. In the interim between hospitalizations, she had two episodes of herpes zoster infection, including oral ulcers diagnosed as herpetic gingivostomatitis, and an episode of oral candidiasis. Physicians at the Taipei Veterans General Hospital diagnosed oral candidiasis, herpes simplex type 1 virus infection forming ulcers on her lips, and Pneumocystis carinii pneumonia in June 1993. Her CD4 count was 0 and her CD8 count was 20%. Treatment consisted of intravenous (IV) trimethoprim/sulfamethoxazole (TMP/SMX) and oral zidovudine, fluconazole, and acyclovir. She continued this medication after discharge in August 1993. She was readmitted to Taipei Veterans General Hospital in February 1994 for blurred vision. She was diagnosed with cytomegalovirus retinitis. Her CD4 count was up to 1% and her CD8 count was down to 8%. The candidiasis infection had extended from her oral cavity to the esophageal mucosa. She was put on IV ganciclovir, TMP/SMX, and fluconazole. She was discharged 3 weeks after admission. Her condition deteriorated thereafter, resulting in her death in August 1994. Up until this study, this HIV/AIDS case was listed with 79 other HIV/AIDS patients as unknown cause. During the 8 years between HIV exposure and her diagnosis of AIDS, she had unprotected sexual intercourse with her husband. Neither the husband nor any of her four children have AIDS. Screening for HIV-1 in Taiwan began in January 1988. The authors urgently recommend that anyone who received a blood transfusion between 1984 and 1987 in Taiwan and who currently suffers repeated episodes of opportunistic infections undergo an HIV-1 blood test.
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PMID:Transfusion-acquired AIDS in Taiwan. 864 96

We retrospectively evaluated the clinical manifestations, diagnosis, treatment, and outcome of coccidioidomycosis in 91 patients infected with human immunodeficiency virus (HIV) at a single institution. Coccidioidomycosis was the AIDS-defining illness in 37 patients. Fever and chills, weight loss, and night sweats were the most frequent symptoms. The lung was the most frequently involved organ (80%), followed by the meninges (15%). A diffuse reticulonodular infiltrate was seen in 59 patients (65%), and 13 (14%) had focal pulmonary disease; for 15 patients (16%), the chest radiograph was normal. Coccidioidal serologies were positive for 60 patients (68%), while for 23% with proven coccidioidomycosis such tests were negative Most patients were treated with systemic amphotericin B and then an oral azole. The mortality for the whole group was 60%. Patients with diffuse pulmonary disease had the highest mortality (68%), with a median duration of survival of 54 days (P < .05; 95% confidence interval, 147-175 days). The presence of diffuse pulmonary disease and a CD4 lymphocyte count of < 50/microL were independent predictors of death. In our experience, coccidioidomycosis is an important opportunistic infection that causes substantial morbidity and mortality among HIV-infected patients living in an area of endemicity.
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PMID:Coccidioidomycosis in patients infected with human immunodeficiency virus: review of 91 cases at a single institution. 887 81

We report the immunological and clinical results of a phase II trial with intravenously administered highly purified endotoxin (Salmonella abortus equi) in patients with advanced cancer. 15 patients with non-small cell lung cancer and 27 with colorectal cancer were entered into the study. 37 evaluable patients received at least four injections of endotoxin (4 ng/kg body weight) and 1600 mg ibuprofen orally in 2-week intervals. Transient renal (WHO grade 0-1) and hepatic (WHO grade 0-4) toxicities occurred in several patients. Constitutional side-effects such as fever, chills and hypotension could not be prevented completely by pretreatment with ibuprofen. 3 patients in the colorectal cancer group demonstrated objective responses (1 complete remission (CR), 2 partial remission (PR)). The complete remission has been maintained for more than 3 years, while the partial remissions were stable for 7 and 8 months, respectively. Only marginal antitumour effects were seen in the lung cancer group. Tolerance of the macrophage system to the stimulatory effect of endotoxin, as measured by human necrosis factor alpha (TNF-alpha) release into serum, built up after the first administration and remained at a steady-state level after each subsequent injection. In constrast, rising CD4:CD8 ratio and release of tumour necrosis factor beta (TNF-beta) indicated the continuing activation of the lymphocyte system by repetitive injections of endotoxin.
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PMID:Phase II trial of intravenous endotoxin in patients with colorectal and non-small cell lung cancer. 898 79


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