Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99

alpha-Interferon (IFN alpha) blocks replication of human immunodeficiency virus (HIV)-1 in vitro by interfering with the release of mature virions. Clinical trials have addressed the in vivo effects of IFN alpha, both alone and in combination with other agents, in a variety of patients at all stages of HIV-1 infection. Patients with late stages of HIV-1 infection (CD4 counts under 100) show few positive results following treatment with IFN alpha. Patients with earlier stages of HIV infection, however, may benefit from treatment with this agent. Several clinical trials have demonstrated the activity of interferon in the treatment of patients with acquired immunodeficiency syndrome, Kaposi's sarcoma, and CD4 counts over 200. In these trials, response rates of approximately 40% have been reported, with the probability of response directly correlated with the level of CD4 cells. These antitumor effects have been associated with declines in the circulating levels of the HIV-1 core antigen p24. alpha-Interferon activity has also been studied in patients concomitantly receiving zidovudine. In these studies, neutropenia, reversible with the concomitant administration of granulocyte macrophage colony-stimulating factor, has been the most common dose-limiting toxicity. Both the antitumor and antiviral activities of combination therapy appear to be at least as good as those observed when single agents are used. Controlled clinical trials are currently under way to evaluate the role of interferon therapy, both alone and in combination with zidovudine, in patients with early HIV infection.
 ...
PMID:The role of alpha-interferon in patients with human immunodeficiency virus infection. 194 29

A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
 ...
PMID:Antiretroviral therapy and immunomodulators in patients with AIDS. 201 46

The possible mechanisms of neutropenia associated with both human immunodeficiency virus (HIV) infection and drug treatment in adults are examined, and the current and investigational strategies for managing neutropenia are reviewed. Neutropenia associated with HIV arises from diverse mechanisms, including cellular immune dysfunction, direct effects on progenitor cells, humoral immune dysfunction, and vitamin deficiencies. Drug-induced neutropenia may be related to direct cytotoxic effects, immunologic mediators, and the effects of vitamin depletion on the bone marrow. Bone marrow toxicity in patients receiving zidovudine appears to be more frequent in those patients with advanced disease, low CD4 cell counts, a pretreatment anemia, low serum vitamin B12 levels, and low or low normal serum folic acid levels. Patients with AIDS also are at increased risk for adverse events associated with folate antagonists and sulfonamides compared with other patient populations. Lithium therapy has improved neutrophil counts in patients receiving zidovudine; however, the toxicities associated with use of lithium, combined with the lower dosages of zidovudine now recommended, may obviate its use. The use of colony-stimulating factors appears promising for increasing the number and function of circulating neutrophils. Although concomitant use of interferon alfa and zidovudine may result in a strong synergistic anti-HIV effect, dose-limiting neutropenia has been reported in patients receiving the combination. There are currently no controlled data assessing the effectiveness of intravenous immune globulin in the treatment of HIV-related or drug-related neutropenia. In evaluating neutropenia, the clinician must attempt to discern whether the neutropenia is more likely related to disease state(s) or drug therapies. Potential management strategies include modulation of the disease state, discontinuation or dose reduction of the offending agent, or administration of exogenous immune enhancer.
 ...
PMID:Neutropenia in patients infected with human immunodeficiency virus. 203 44

Recombinant human interferon gamma (rIFN-gamma) was used for the treatment of 16 patients with various stages of cutaneous T-cell lymphoma (CTCL). All patients had been previously treated with standard topical and/or systemic therapies, and some had received experimental treatment with retinoids, recombinant human interferon alfa-2a (rIFN-alpha 2a), or radiolabeled monoclonal antibodies; most patients had an advanced stage of disease. Objective partial responses (PRs) were noted in five patients (31%) and lasted 3 months to greater than 32 months (median, 10 mo). One of these five patients had previously had disease progression after an initial PR with rIFN-alpha 2a. Six other patients (38%) showed minor or mixed responses. The most common side effects of rIFN-gamma included fever, weight loss, mild neutropenia, elevated lactate dehydrogenase, and elevated hepatic transaminases. Additionally, one episode of nephrotic syndrome and one cutaneous allergic reaction were noted. None of the toxic effects were life threatening, and all were reversible. These results suggest that rIFN-gamma has efficacy in the treatment of CTCL refractory to rIFN-alpha 2a.
 ...
PMID:Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma. 210 37

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.
 ...
PMID:Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. 221 80

In a clinical phase II study, the antitumor activity of the recently introduced combination of prednimustine and mitoxantrone (PmM) was evaluated in 17 patients with advanced low-grade non-Hodgkin's lymphoma after failure with or relapse after standard chemotherapy. The PmM regimen consisted of prednimustine 100 mg/m2/d orally on days 1 to 5, and mitoxantrone 8 mg/m2/d intravenously on days 1 and 2, giving a total dose of 16 mg/m2. Treatment was repeated every 4 to 6 weeks to a maximum of 6 cycles. Patients achieving complete remission (CR) or partial remission (PR) received two additional courses for consolidation, followed by interferon (IFN) alpha-2b 5 x 10(6) U subcutaneously three times a week until progression or relapse. Twelve of the 17 patients (71%) responded (CR, 4 and PR, 8). Side effects consisted mainly of neutropenia, which required dose reduction in 48% of treatment cycles. All 12 responders subsequently received IFN alpha-2b maintenance treatment. At present, remission duration ranges from 4.5+ to 17.5+ months (median 14.5 months). In comparison to unmaintained first remission prior to receiving PmM/IFN alpha-2b, a clear tendency towards a longer period of freedom from progression emerged in the 12 patients receiving IFN alpha-2b maintenance treatment during a second PR or CR. These data indicate a high antitumor activity of PmM in low-grade non-Hodgkin's lymphoma and suggest a beneficial effect of IFN alpha-2b maintenance. Present findings, however, will require confirmation in future investigations.
 ...
PMID:Treatment of low-grade non-Hodgkin's lymphoma by cytoreductive chemotherapy with prednimustine/mitoxantrone followed by interferon alpha-2b maintenance: results of a clinical phase II study. 225 19

Eighteen patients with advanced renal cell carcinoma were treated with human lymphoblastoid interferon (Wellferon) and continuous fusion vinblastine. All patients received vinblastine as a continuous infusion at a dose of 1.5 mg/m2/day on days 1 to 5. The interferon was given by daily intramuscular injections on days 1 to 10. Three patients were treated with a dose escalation scheme that reached a maximum daily dose by day 3 of 5 X 10(6) units/m2/day and that was then continued until day 10. Fifteen patients received 3 X 10(6) units/m2/day on day, 1, and 5 X 10(6) units/m2/day on days 3 to 10. Treatments were repeated every 28 days. Neutropenia (less than 1,500/mm3) occurred in 14 of 18 patients. Transient increases in serum glutamic-oxaloacetic transaminase levels to greater than four times baseline were noted in nine patients. Thrombocytopenia (less than 100,000 platelets/mm3) occurred in one patient. Fatigue, lethargy, and decline in performance status were marked in four of the patients. None of the patients in the low-dose interferon group and only 1 of the 15 patients in the high-dose interferon group had an objective response (7%, with a 95% confidence interval of 0 to 31%). Of the 12 patients completing at least two courses of therapy, 10 were in the high-dose group, which included the 1 objective (partial) response. This response noted at the start of the fourth course. Ten others developed progressive disease and one stopped treatment because of neurologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interferon-alpha-n1 and continuous infusion vinblastine for treatment of advanced renal cell carcinoma. 231 58

Withholding iron dextran treatment normally given to pigs at 1-3 days of age to prevent anemia resulted also in neutropenia. Polyinosinic acid:polycytidylic acid (poly I:C) at 0.5 mg/kg IV at 25 days of age resulted in induction of putative interferon 2 to 24 hours later, with significantly (P less than 0.05) lower concentrations in iron-deficient (Fe-) female pigs than in iron-supplemented (Fe+) female pigs. Poly I:C caused several transient toxic manifestations, including elevations in blood urea nitrogen, creatinine, aspartate aminotransferase, potassium (K), total bilirubin and phosphorus (P), marked leukopenia (both neutropenia and lymphopenia), and declines in serum albumin, calcium, cholesterol, glucose and globulin. Certain blood chemistries before poly I:C were significantly (P less than or equal to 0.05) different: albumin, globulin, cholesterol and K were higher in females than in males; albumin, globulin, glucose, P and K were higher in Fe- than in Fe+ pigs; and total carbon dioxide was higher in Fe+ than in Fe- pigs.
 ...
PMID:Effects of poly I:C in porcine iron deficient neutropenia. 241 Jan 86

Calves were inoculated IV with bluetongue virus (BTV), serotype 10. Titers of interferon (IFN) in serum and BTV in peripheral blood were determined. All inoculated calves produced circulating IFN that persisted for 2 to 4 days. Highest titers of BTV in peripheral blood were present after serum IFN was no longer detected. The persistence of BTV in peripheral blood, as compared with the transient IFN response, indicated that IFN was most important in the initial antiviral response of cattle to BTV infection. Bluetongue virus is probably not a suitable model inducer of circulating IFN in cattle because the profound neutropenia that accompanied BTV infection may predispose cattle to infections with other agents.
 ...
PMID:Bluetongue virus-induced interferon in cattle. 241 Nov 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>