Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 34-year-old man presented with classic glucagonoma syndrome manifested by weight loss, dermatitis, stomatitis, anemia, and mild diabetes mellitus. The diagnosis of glucagonoma was made by light and electron microscopic demonstration of a metastatic alpha cell carcinoma in a liver biopsy specimen. Plasma glucagon concentration was abnormally high. The patient also had symptoms and signs of involvement of the central nervous system. Radionuclide and CAT scans of the brain, negative CSF cytology and myelography excluded the possibility of metastases or other space-occupying lesions. Glucagon was demonstrated in the CSF. We postulate that the neurologic symptoms were due to direct or indirect effect of this hormone on the brain. Following therapy with streptozotocin and 5-fluorouracil, the patient had a subjective and objective clinical and hormonal remission of his disease including amelioration of his neurological impairment.
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PMID:Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin. 22 32

We have previously shown that the antiviral state of explanted mouse peritoneal macrophages (PM) decays during in vitro culture and that this decay is much more rapid in Lpsd PM than it is in Lpsn PM. Moreover, Lpsn PM can transfer the antiviral state to other cells, whereas Lpsd PM cannot. In vitro treatment of Lpsn PM with different agents [i.e., bacterial lipopolysaccharide (LPS), interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, macrophage colony-stimulating factor (M-CSF) and antibody to Mac-1 antigen] induced an antiviral state to vesicular stomatitis virus (VSV) which was inhibited by antibodies to IFN-beta. Treatment of Lpsn PM with LPS or IFN-gamma resulted in greater accumulation of IFN-beta mRNA, whereas no change in the barely detectable levels of IFN-alpha mRNA was observed. Marked accumulation of IFN-beta mRNA was also observed in PM after TNF-alpha treatment. M-CSF and IFN-gamma (but not LPS) also induced an IFN-mediated antiviral state in Lpsd PM. Low levels of spontaneous transcription of IFN-beta mRNA were detected in nuclei from Lpsd PM. Treatment of Lpsd PM with IFN-gamma for 3 h resulted in the accumulation of IFN-beta mRNA without any concomitant increase in the transcription of the IFN-beta gene, as determined by run-on transcription assays with isolated nuclei. The addition of as little as I international unit/ml of IFN-gamma to PM resulted in a 100-fold inhibition of VSV yield. As antibodies to IFN-alpha/beta inhibited only a portion of the IFN-gamma-induced antiviral state, such an antiviral state might reflect the synergism between IFN-gamma and endogenous IFN-beta. In fact, the addition of low doses of both IFN-gamma and IFN-beta to either Lpsn or Lpsd PM resulted in synergistic antiviral effects. In vivo treatment of Lpsd mice with granulocyte-macrophage (GM)-CSF, M-CSF, IFN-gamma or Newcastle disease virus rendered peritoneal cells capable of transferring an antiviral state. These results indicate that (i) various stimuli can induce IFN-beta production by PM, (ii) Lpsd PM spontaneously transcribe low levels of IFN-beta mRNA, even though they cannot transfer an antiviral state, (iii) different stimuli, but not LPS, induce a normal IFN response in Lpsd PM, (iv) IFN-gamma increases the accumulation of IFN-beta mRNA in Lpsd PM by post-transcriptional mechanisms and (v) IFN-gamma may act synergistically with endogenous IFN-beta in inducing a potent antiviral state to VSV in PM.
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PMID:Effects of different biological response modifiers on interferon expression in bacterial lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive mouse peritoneal macrophages. 170 75

COP-BLAM III therapy was given to 18 patients with non-Hodgkin's lymphoma, and the therapeutic effects as well as adverse effects of the treatment were examined. Of the 18 patients 16 had a complete remission (CR) and 2 showed an partial remission (PR) with a total response rate of 100%. In terms of the stage of disease, CR was achieved in all patients in stage III and in 11 of 13 patients in stage IV. Patients with neutrophil counts less than 1,000/microliters were given rhG-CSF (1.5 micrograms/kg/day, sc), which significantly shortened the duration of neutropenia and decreased the number of days with episodes of fever when compared with those not given rhG-CSF, consequently facilitating the treatment without prolonging the dosing intervals. No serious infection was observed. Adverse effects included neutropenia of less than 1,000/microliters in 6 of the 18 patients (33.3%), thrombocytopenia less than 5 x 10(4)/microliters in 3 (16.7%), nausea and vomiting in 8 (44.4%), peripheral neuropathy in 4 (22.2%) and stomatitis in 4 (22.2%). There were no fatalities caused by the treatment. The above findings indicate that COP-BLAM III therapy is capable inducing high frequency of complete remissions in non-Hodgkin's lymphoma and that its combination with G-CSF can improve the results of the therapy and relieve adverse reactions.
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PMID:[The COP-BLAM III therapy of non-Hodgkin's lymphoma]. 172 37

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was investigated for its clinical efficacy in the treatment of various types of neutropenia (3 cases with idiopathic neutropenia of suspected drug induction, 5 cases with idiopathic neutropenia of other origin, and 2 cases with cyclic neutropenia). Treatment with glycosylated rhG-CSF produced in the Chinese Hamster Ovary cells at dose levels of 2-5 micrograms/kg/day caused rapid increases of neutrophil counts associated with an improvement of the infection. In cyclic neutropenia patients, marked reduction in the duration of the neutropenic period was observed with rhG-CSF administration started before the period. Intercurrent stomatitis, which occurred in 1 patient, was markedly milder as compared to a previous episode which occurred during an untreated neutropenic period. The treatment of rhG-CSF was well tolerated and no adverse events were observed, nor was there any detectable anti-rhG-CSF antibody in any patients studied; hence the clinical use of rhG-CSF is considered to be safe. These results suggest beneficial effects of rhG-CSF on the recovery of neutrophil counts in cyclic and other types of idiopathic neutropenias, as well as for the treatment of neutropenia-associated infection.
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PMID:Clinical effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on various types of neutropenia including cyclic neutropenia. 172 91

Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM-CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial. 185 94

Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limiting toxicity. Other toxicities included nausea and vomiting, stomatitis, erythema and phlebitis at the site of infusion, rash and skin hyperpigmentation, and elevated serum hepatic enzymes. Two drug-related deaths occurred secondary to leukopenia and sepsis. Twenty-six patients were evaluable for antitumor response. Twenty-one patients had progressive disease, while three patients had disease stabilization. There were two partial responses observed--one in a patient with breast cancer and a second in a patient with nasopharyngeal carcinoma. TMTX pharmacokinetics were studied in 15 patients. The drug had a mean terminal half-life of 13 hours. Steady-state was not achieved during the 24-hour infusions. Only 6% of the parent compound was excreted unchanged in the urine, and CSF levels averaged less than 2% of simultaneously measured plasma levels. A dose of 150 mg/m2 is recommended for phase II trials of TMTX using this 24-hour infusion schedule.
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PMID:A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule. 214

Mature macrophages, derived in vitro from bone marrow progenitors under the influence of either macrophage colony stimulating factor (CSF-1) or granulocyte-macrophage (GM)-CSF, have been shown to differ morphologically and functionally. The data presented in this report demonstrate that macrophages derived from bone marrow progenitors under the influence of CSF-1 are highly resistant to infection with vesicular stomatitis virus (VSV), and that this refractoriness can be reversed by treatment of cells with anti-IFN-alpha/beta antibody. In contrast, macrophages derived from bone marrow progenitors under the influence of GM-CSF are highly susceptible to the cytopathic effects of VSV, but can be protected by very low concentrations of exogenous IFN-alpha/beta. These findings suggest that CSF-1 derived macrophages have a greater capacity for the production and/or utilization of IFN-alpha/beta than GM-CSF-derived macrophages, which may account for many of the differentiative differences reported previously.
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PMID:Differential production of IFN-alpha/beta by CSF-1- and GM-CSF-derived macrophages. 216

Previous study has shown that the combination of mitoxantrone (Novantrone, NO) and Ara-C (AC) (NOAC) was active in refractory non-Hodgkin's lymphoma (NHL) but myelosuppression was dose-limiting. In a pilot study, we investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after NOAC chemotherapy in patients with refractory NHL. NO was applied at a dosage of 10 mg/m2/day on days 2 and 3 and AC at 3 g/m2/12h on days 1 and 2. RhGM-CSF was administered at 250 ug/m2/day as a continuous i.v. infusion from day 6 until the neutrophils were greater than 3.0/nl for 3 consecutive days. Twenty-three patients from five of the nine participating centers were treated with NOAC chemotherapy plus rhGM-CSF, whereas 14 patients from the other four centers received chemotherapy alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nl) after NOAC was 8 days versus a median of 13 days without rhGM-CSF (P = 0.0058), and that of thrombocytopenia (less than 20.0/nl), 3 days versus 7 days (P greater than 0.4, NS). The rates of infections and stomatitis were 25% and 17%, respectively, for patients treated with rhGM-CSF as compared to 53% (P = 0.0547, NS) and 60% (P = 0.0078), respectively, without rhGM-CSF. The following side effects were associated with the administration of rhGM-CSF: pleural and/or pericardial effusions in five patients, thrombosis in two patients, bone pain in two patients, and respiratory distress syndrome in one patient. A complete remission was achieved in nine of the 23 patients treated with NOAC plus rhGM-CSF, and in two of the 14 patients treated with chemotherapy alone. The median survival of patients treated with rhGM-CSF was not reached at 400 days and seemed to be longer than that of patients treated with chemotherapy alone (median, 109 days; P = 0.036). RhGM-CSF after chemotherapy can be applied safely to patients with NHL, shorten the period of severe cytopenia, reduce the rates of stomatitis, and did not seem to cause adverse effects on response.
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PMID:Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study. 219 41

Responsiveness to granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) of bone marrow cells derived from different mouse strains was investigated. There were great variations in proliferation between different strains of inbred mice. Bone marrow cells from mouse strains with a high rate of proliferation in response to GM-CSF also had a high proliferating capacity to M-CSF. The response to either CSF did not correlate with a certain H-2 haplotype. GM-CSF induced consistently higher proliferation than M-CSF. Proliferation in response to M-CSF, but not to GM-CSF, could be enhanced by the addition of antibodies against interferon (IFN). IFN is the only known inducer of (2'-5') oligoadenylate (oligo (A] synthetase. This enzyme was induced in macrophages grown in the presence of M-CSF, but not in GM-CSF promoted cells. Enzyme induction was completely abrogated by simultaneous treatment with anti-IFN alpha/beta. Infection of macrophages with herpes simplex virus type 1 (HSV) and vesicular stomatitis virus (VSV) revealed that GM-CSF-promoted cells were highly susceptible to lytic infection by these viruses. In contrast, virus titres in M-CSF-cultured cells were 100-fold lower. We conclude that, contrary to M-CSF, GM-CSF does not induce autocrine IFN during haematopoiesis. As judged from data with BALB/c mice, the sensitivity to the anti-proliferative effect of the autocrine IFN may be a factor which influences M-CSF-promoted proliferation.
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PMID:In vitro development of bone-marrow-derived macrophages. Influence of mouse genotype on response to colony-stimulating factors and autocrine interferon induction. 248 39

Inorganic bismuth salts are poorly soluble in water: solubility is influenced by the acidity of the medium and the presence of certain compounds with (hydr)oxy or sulfhydryl groups. The analysis of bismuth in biological material is not standardised and is subject to large variation; it is difficult to compare data from different studies, and older data should be approached with caution. The normal concentration of bismuth in blood is between 1 and 15 micrograms/L, but absorption from oral preparations produces a significant rise. Distribution of bismuth in the organs is largely independent of the compound administered or the route of administration: the concentration in kidney is always highest and the substance is also retained there for a long time. It is bound to a bismuth-metal binding protein in the kidney, the synthesis of which can be induced by the metal itself. Elimination from the body takes place by the urinary and faecal routes, but the exact proportion contributed by each route is still unknown. Elimination from blood displays multicompartment pharmacokinetics, the shortest half-life described in humans being 3.5 minutes, and the longest 17 to 22 years. A number of toxic effects have been attributed to bismuth compounds in humans: nephropathy, encephalopathy, osteoarthropathy, gingivitis, stomatitis and colitis. Whether hepatitis is a side effect, however, is open to dispute. Each of these adverse effects is associated with certain bismuth compounds. Bismuth encephalopathy occurred in France as an epidemic of toxicity and was associated with the intake of inorganic salts including bismuth subnitrate, subcarbonate and subgallate. In the prodromal phase patients developed problems in walking, standing or writing, deterioration of memory, changes in behaviour, insomnia and muscle cramps, together with several psychiatric symptoms. The manifest phase started abruptly and was characterised by changes in awareness, myoclonia, astasia and/or abasia and dysarthria. Patients recovered spontaneously after discontinuation of bismuth. Intestinal lavage, forced diuresis and haemodialysis have been tried without positive effects on the clinical condition of the patient or on blood bismuth concentration, and the use of dimercaprol as an antidote has produced reports of both positive and negative findings. To confirm the diagnosis of bismuth encephalopathy, it is essential to find elevated bismuth concentrations in blood, plasma, serum or CSF. A safety level of 50 micrograms/L and an alarm level of 100 micrograms/L have been suggested in the past, but no proof is available to support the choice of these levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetics and toxicity of bismuth compounds. 268 29


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