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) has demonstrated antitumor activity against a variety of tumors and is particularly cytotoxic to capillary endothelial cells, which are the presumed cell of origin of Kaposi's sarcoma. We evaluated the toxicity and clinical antitumor and antiretroviral effects of recombinant TNF administered at a once weekly dose of 100 micrograms/m2 intravenously for 8 weeks in five men with AIDS-related Kaposi's sarcoma and without prior opportunistic infection. One patient was removed from study at week 4 due to rapid progression of Kaposi's sarcoma, another patient with stage IV disease and a pretreatment CD4 count of 11 developed fever, hypotension, and pneumonia at week 7 and died 8 days after discontinuing recombinant TNF. No pathogenic organisms were isolated. He had marked eschar formation of his Kaposi's sarcoma lesions, particularly in areas previously exposed to radiation therapy. Uniform toxicities included fevers, rigors, and headaches during drug infusion that were ameliorated by prophylactic meperidine hydrochloride and acetaminophen. All experienced fatigue and three had arthralgias. One patient had transient hypotension which corrected with i.v. fluids. No significant hematologic, hepatic, or renal toxicities were seen. All patients had some progression of their Kaposi's sarcoma on study. There was no change in CD4 or CD8 count or in CD4:CD8 ratios. Serum human immunodeficiency virus (HIV) p24 antigen levels increased greater than 50% in three patients. We conclude that, as a single agent, at a dose of 100 micrograms/m2 recombinant TNF by i.v. infusion has no obvious antitumor or antiretroviral effects in patients with AIDS-related Kaposi's sarcoma.
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PMID:Intravenous recombinant tumor necrosis factor in the treatment of AIDS-related Kaposi's sarcoma. 291 61

Nine patients with chronic hepatitis type B were treated with recombinant interleukin 2 (rIL-2). Side effects were limited to low-grade fever and headache, which were transient and tolerable for the patients. Seven normal volunteers and nine patients with chronic active hepatitis were administered by one bolus of 500 units of rIL-2. Acute effects of rIL-2 administration on lymphoid cells included a rapid decrease in lymphocytes, especially in cytotoxic T cells and natural killer cells. These acute effects resolved within 24 hours. There was no difference in the changes of immunological parameters between normal volunteers and patients. The same effects were seen during 28 days of rIL-2 administration. The number of lymphocytes and CD4 positive cells was increased after rIL-2 administration for 28 days (P less than 0.01). Natural killer cell activity, especially that of CD16+ and Leu-7- cells was also increased (P less than 0.05). These effects may favour the elimination of virus-infected hepatocytes.
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PMID:Immunologic effects on peripheral lymphoid cells from patients with chronic hepatitis type B during administration of recombinant interleukin 2. 297 35

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.
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PMID:The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. 329 90

In order to test whether circumvention of clinical resistance can be obtained in common solid tumours by targeting different drug resistance mechanisms, a phase I clinical and immunological study was designed. The purpose of the study was to determine the dose of cyclosporin A (CsA), in combination with doxorubicin (DOX) and ifosfamide (IFX), needed to achieve steady-state whole-blood levels of 2000 ng ml-1 and the associated toxicity of this combination. Treatment consisted of CsA 5 mg kg-1 as a 2 h loading infusion, followed by a CsA 3 day continuous infusion (c.i.) (days 1-3) at doses that were escalated from 10 to 18 mg kg-1 day-1. Chemotherapy consisted of DOX 55 mg m-2 by i.v. 24 h c.i. (day 2) and IFX 2 g m-2 i.v. over 1 h on days 1 and 3. Treatments were repeated every 4 weeks. Eighteen patients with previously treated resistant solid tumours received 39 cycles. Mean steady-state CsA levels > or = 2000 ng ml-1 were reached at 5 mg kg-1 loading dose followed by a 3 day c.i. of 16 mg kg-1 day-1 or greater. Haematological toxicity was greater than expected for the same chemotherapy alone. One patient died of intracranial haemorrhage due to severe thrombopenia. Other observed toxicities were: asymptomatic hyperbilirubinaemia (46% cycles), mild nephrotoxicity (20% cycles), hypomagnesaemia (72% cycles), mild increase in body weight (100% cycles), hypertension (15% cycles) and headache (15% cycles). Overall the toxicity was acceptable and manageable. No alterations in absolute lymphocyte number, the lymphocyte subsets studied (CD3, CD4, CD8, CD19) or CD4/CD8 ratio were observed in patients receiving more than one treatment cycle, although there were significant and non-uniform variations in the values of the different lymphocyte subsets studied when pre- and post-treatment values were compared. There was also a significant increase in the CD4/CD8 ratio. Tumour regressions were observed in two patients (epidermoid carcinoma of the cervix and Ewing's sarcoma). The CsA dose recommended for phase II trials is a 5 mg kg-1 loading dose followed by a 3-day c.i. of 16 mg kg-1 day-1 simultaneously with DOX and IFX at the doses administered in this study.
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PMID:Cyclosporin A and doxorubicin-ifosfamide in resistant solid tumours: a phase I and an immunological study. 757 85

We carried out a randomized prospective trial to compare OKT3 (5 mg/d, 51 patients) with ATG-Fresenius (ATG-F, 4 mg/kg/d, 53 patients) for induction therapy after renal transplantation, concerning side effects, rejection, and infection incidence within a one year follow-up period. Concomitant immunosuppression included azathioprine/steroids from day 0 and cyclosporine A from day 4. OKT3 patients experienced significantly more and more-severe side effects, particularly pyrexia, headache, and pulmonary fluid overload. One-year graft survival was excellent in the ATG-F group (91%), but only 78% in the OKT3 group (P < 0.05) due to a series of rejections that occurred beyond day 100; patient survival (96% and 92%) was similar in both groups. OKT3-treated patients experienced more biopsy-proven rejections (0.6 +/- 0.1/pt.) than ATG-F patients (0.3 +/- 0.1, P < 0.05), and there was a similar, albeit not significant trend in clinical rejections (OKT3: 1.1 +/- 0.2/pt.; ATG-F: 0.8 +/- 0.1/pt.). Infections were more common in the OKT3 group (OKT3: 3.2 +/- 0.3, ATG-F: 2.0 +/- 0.2, P < 0.05), although this was entirely attributable to "minor" infections. On days 1 through 6, CD3 counts were more profoundly depressed with OKT3 therapy. Beyond day 10, however, CD3 counts were lower in the ATG-F group, as were CD2 counts, CD4 counts, and the CD4/CD8 ratio, suggesting a more prolonged immunosuppressive effect of ATG-F. Sensitization occurred more frequently with OKT3 (31%) than with ATG-F (10%), but was usually irrelevant, except in two patients (one in each group), whose grafts were lost because of immunization against OKT3 and ATG-F, respectively. In conclusion, a 7-day induction therapy with OKT3 does not improve outcome or diminish immunological graft loss when compared with ATG-F, but is associated with more rejections, infections, and side effects. ATG-F appears to be preferable for induction immunosuppression after renal transplantation.
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PMID:A randomized prospective trial of prophylactic immunosuppression with ATG-fresenius versus OKT3 after renal transplantation. 770 77

Case notes of 722 HIV-infected patients who had died between March 1986 and August 1993 were analysed to evaluate the prevention and characteristic features of sinusitis associated with HIV infection. In 73 patients (10%) sinusitis had been diagnosed at least once on the basis of radiological or clear-cut clinical criteria. In addition, 15 patients with sinusitis were identified among those attending an HIV out-patient clinic. There were altogether 126 episodes of sinusitis in 88 patients (62 men, 26 women; mean age 33 [19-69] years). In 62 patients the CD4 lymphocyte count was under 100/microliters. The most commonly affected site was the maxillary sinuses. Patients with mirror formation had a significantly longer duration of illness than those without (P = 0.021). In 58 patients the symptoms of fever, headache and rhinitis were predominantly caused by the sinusitis, in 49 only partially so, and in 19 sinusitis was a chance diagnosis. In 10 of 49 attacks of sinusitis the concurrent disease (e.g. cerebral toxoplasmosis, malignant non-Hodgkin lymphoma) had not been recognized by the referring doctor. There were 1-5 recurrences over an observation period of 11.8 (0-72) months in 23 patients.-These findings show that sinusitis frequently occurs in HIV-infected patients, takes a protracted course and is difficult to distinguish from concomitant diseases by its clinical presentation. If symptoms persist, possible concurrent respiratory infection or CNS involvement must be looked for. Sinus needle aspiration is of decisive importance to ascertain the causative organism.
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PMID:[Sinusitis in HIV infection]. 773 29

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.
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PMID:Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study. 775 91

In a phase I/II trial assessing the toxicity, pharmacokinetics, and activity of the (-)enantiomer of 2'-deoxy-3'-thiacytidine (3TC, lamivudine), 97 patients with AIDS or advanced human immunodeficiency virus (HIV) disease were administered 3TC at 0.5-20.0 mg/kg/day. The cohort's median entry CD4 cell count was 128/mm3 (range, 7-357). A toxic dose was not reached, although some patients reported mild headache, insomnia, and abdominal symptoms, and there was a general downward trend in neutrophil counts at the highest doses. Although subjective and difficult to interpret, increases in energy and appetite were noted, particularly in patients receiving > or = 8.0 mg/kg/day. Immunologic and virologic parameters showed evidence of at least transient anti-HIV activity at those higher doses. Although further studies of 3TC as monotherapy are needed, its favorable toxicity profile, evidence of at least transient clinical activity, and results of in vitro resistance experiments support further clinical testing in combination therapy.
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PMID:A phase I/II study of 2'-deoxy-3'-thiacytidine (lamivudine) in patients with advanced human immunodeficiency virus infection. 776 77

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

We report a case of pneumonitis induced by PL granules. A 45-year-old man took PL granules and other drugs for fever and headache. Because he subsequently developed high grade fever, cough and diarrhea, he was admitted to our hospital. His chest X-ray film revealed multiple patchy shadows in both lung fields. Analysis of bronchoalveolar lavage fluid (BALF) disclosed a high number of cells (total), lymphocytes, and a high CD4/CD8 ratio. Microscopic examination of transbronchial lung biopsy (TBLB) specimens showed infiltration of mononuclear cells and thickening of the alveolar wall. After discontinuation of drugs, his condition (symptoms, laboratory data, and chest X-ray findings) promptly improved. Lymphocyte stimulation tests (LST) for PL granules and acetaminophen were positive and an oral challenge test with PL granules was also positive. Based on these findings, we diagnosed this as a case of pneumonitis and enteritis due to PL granules. To our knowledge, this is the first reported case of pneumonitis due to PL granules.
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PMID:[A case of pneumonitis induced by PL granules]. 785 81


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