Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxicity produced by two courses of methotrexate separated by different intervals has been studied in matched groups of rats. The maximum degree of neutropenia reached when courses were separated by 8 days or more was no greater than that seen after a single course of methotrexate. However, when courses of neutropenia following the second course of methotrexate was directly related to the level of depression of bone marrow cell numbers at the time of the second course. Conversely the anti-leukaemic effects of 2 courses of methotrexate, in terms of time of onset of leukaemia and time of death in rats transplanted with a syngeneic T-cell leukaemia, are shown to be similar when courses of methotrexate are separated by between 2 and 12 days. Thus in this system, chemotherapeutic schedules using methotrexate may be designed on the basis of minimal host toxicity without prejudicing anti-leukaemic effects. These results are discussed in relation to toxicity and anti-leukaemic effects observed during UKALL trials of treatment in acute lymphoblastic leukaemia.
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PMID:Effects of varying the interval between courses of methotrexate on its myelotoxic and anti-leukaemic activities. 83 60

Transient neutropenia developed in a 62-year-old, white male on maintenance hemodialysis being treated with cimetidine for an in tractable duodenal ulcer. The probable mechanism was peripheral destruction of the granulocyte series, unlike the marrow depression reported with metiamide, another histamine H2 receptor antagonist.
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PMID:Transient neutropenia in a patient receiving cimetidine. 89 66

Coventional kittens, 12-27 weeks old, were inoculated with cell-cultured feline panleucopenia virus and killed sequentially between day 3 and day 24 after inoculation. All developed a non-fatal mild disease between days 2 and 9, characterized by lymphopenia, neutropenia, listlessness, depression and the development of neutralizing antibodies to the virus. Small intestinal bacterial counts were reduced during the period of maximal clinical disease, presumably a result of decreased food intake. There was involution of the thymus with marked depletion of lymphocytes between days 3 and 12. Depletion of lymphocytes also characterized the lesions in the lymph nodes between days 3 and 8. At the same time crypt lesions with spotty distribution were in the small intestinal and colonic mucosa. The changes were loss of crypt epithelial cells with compensatory attenuation of the remaining epithelium. Electron microscopically, the number and size of microvilli and secretory granules were reduced but there was no change indicating lethal cell injury. There were no virus particles. The findings point to an early and transient cellular damage by the virus. Intestinal alkaline phosphatase activity disappeared from the luminal surface of the attenuated crypt epithelial cells. Otherwise, intestinal alkaline and acid phosphatase activity were not altered in inoculated cats.
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PMID:Experimental feline panleucopenia in the conventional cat. 93 27

The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect on the symptoms of recurrent aphthous stomatitis. After levamisole treatment aphthous stomatitis was milder and in the 1-year follow-up period the patient was asymptomatic several times during a phase of obvious neutrophil depression. The child no longer complained of a sore throat with swelling of the jugular glands and the recurrent staphylococcal infections of the skin disappeared. After therapy a marked increase in monocytes at the moment of neutropenia was observed.
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PMID:Levamisole treatment of a child with severe aphthous stomatitis and neutropenia. 98 Oct 93

Children with congenital neutropenia (Kostman disease) present a syndrome of recurrent and eventually fatal bacterial infections. The disease is uniformly lethal and the mean age at death is 24 months. To attempt to better understand the nature of this inborn error, we have studied marrow and peripheral blood of 3 children with the disease. Along with classic morphologic analysis we have used the technic of soft agar bone marrow culture in vitro. All 3 patients showed marked deficiency of numbers of neutrophils in the peripheral blood, intermittent monocytosis especially with infection, and predominant nitroblue tetrazolium (NBT) dye staining in monocytes during infection. The marrow of all 3 patients showed evidence of maturation arrest at the promyelocyte stage and very few or no neutrophils. Two cases showed no neutrophils in the Rebuck skin window inflammatory study. The 3rd case, however, developed small numbers of neutrophils in the peripheral blood, up to 6%, but the first 2 patients, although studied on many occasions, did not show neutrophils above 1%. Evidence from soft agar culture of bone marrow in 1 patient was compatible with the view that development of committed neutrophil stem cells is defective. This patient did not develop neutrophils in soft agar culture and showed loose colonies developing only to promyelocytes. In the 2nd case, where depression of neutrophil development was somewhat less severe clinically, culture of the marrow in soft agar yielded normal neutrophil colonies and none of the loose colonies showing arrested maturation were seen. These findings suggest that the basic mechanism underlying the congenital neutropenias may differ from patient to patient.
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PMID:Congenital neutropenia: impaired maturation with diminished stem-cell input. 109 96

Most chemotherapeutic agents are myelosuppressive and immunosuppressive. Consequently their use greatly increases a patient's susceptibility to infection. Neutropenia creates greater risk than lymphopenia and is a particular problem in patients with acute leukemia who are treated with combination chemotherapy. Chemotherapy is less immunosuppressive if given in short intensive courses rather than continuously. Continuous therapy causes severe depression of antibody production and inhibition of delayed hypersensitivity reaction.
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PMID:Effects of cytotoxic and immunosuppressive agents on the immune system. 110 94

Bone marrow culture in semi-solid agar was used to assess the proliferative activity and the response to sodium aurothiomalate of the myeloid precursor cells from patients during and after recovery from neutropenia associated with the use of this drug. Colony formation was reduced during the neutropenia and returned to normal after recovery. The rheumatoid process itself did not impair colony formation even in patients with Felty's syndrome. Sodium aurothiomalate inhibited colony formation by normal marrow in a dose-dependent manner. Bone marrow colonies from patients who had recovered from neutropenia induced by sodium aurothiomalate were not abnormally sensitive to the inhibitory effect of the drug in vitro. The metabolism of gold is probably altered in a small proportion of patients, which causes high local concentrations within the bone marrow leading directly to marrow depression.
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PMID:Depression of bone marrow colony formation in gold-induced neutropenia. 111 61

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

Myelosuppression in patients with cancer is usually the result of tumor invasion of the bone marrow, cytotoxic chemotherapy, or radiation therapy, all of which suppress bone marrow function. Anemia, thrombocytopenia, and neutropenia are the three most clinically significant complications that result from bone marrow depression. Although anemia and thrombocytopenia can produce serious clinical problems, blood-component transfusions--despite having inherent problems of their own--usually are successful in correcting or minimizing these complications. Although neutropenia is manageable in most situations, it remains a serious problem that, at its worst, can progress to life-threatening septicemia. The longer neutrophil counts remain low, the more susceptible patients become to infection by endogenous and exogenous microbial flora. Accordingly, the oncology nurse increases the frequency of patient assessment and monitoring for infection. Control measures are introduced to minimize environmental contaminants. These measures attempt to reduce the incidence of opportunistic infections that frequently occur in patients with severe or prolonged neutropenia and for which antimicrobial therapy is indicated. Implementing specific infection-control interventions and thoroughly educating the patient and his/her family help to limit the clinical problems associated with myelosuppression for most patients.
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PMID:Current strategies for managing myelosuppression in patients with cancer. 190 77

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)
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PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99


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