Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mast cell, equipped with enzymes, chemotactic factors, a vasoactive amine, an anticoagulant, and lipid-derived proinflammatory products, may be essential in tissue modeling as well as in defense. Its primarily perivascular location in skin and the mucosa of the respiratory tract and the gut assures its availability to counter parasites. By the same token, the mast cell is responsible for interactions with inhaled, ingested, and injected antigens that comprise IgE-mediated allergic reactions. Abnormally high numbers of mast cells in the skin, either localized or generalized, result in urticaria pigmentosa or generalized cutaneous mastocytosis, respectively. Tissue infiltration by excessive mast cells, primarily in gut, bone, liver, and spleen, results in systemic mastocytosis; this may be accompanied by myelodysplasia or lymphoma and may eventuate in mast cell leukemia. Until the etiology of mastocytosis is understood, the treatment is symptomatic: histamine antagonism by H1 +/- H2 blockade for flushing, itching, and gastric distress; cyclooxygenase inhibition to prevent prostaglandin D2 (PGD2)-induced hypotension when indicated; and oral cromolyn to prevent gastrointestinal symptoms and bone pain.
...
PMID:Mast cell disease. 149 Jun 22

Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101.
...
PMID:Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation. 348 78

The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received rhIL-3 after the second cycle of DHAP chemotherapy (cisplatin, cytosine-arabinoside, dexamethasone). Cycles 1 and 3 were given without rhIL-3. The rhIL-3 was administered as a continuous intravenous infusion for 10 days starting 48 h after chemotherapy in cycle 2. Five different dose levels of rhIL-3 (0.25, 1.0, 2.5, 5.0, and 10.0 micrograms/kg/day) were sequentially tested. At the three lowest dose levels one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to the dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven patients. Headache was dose related, with 3/4 patients at a dose of 10 micrograms/kg/day experiencing troublesome grade-2 headache precluding further dose escalation. Facial flushing developed in 3/8 patients at the highest dose levels of rhIL-3. There was a significant increase in eosinophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 cycle 2 vs cycle 3) without accompanying clinical signs of symptoms. No increase in basophil count was observed. There were no increased plasma levels of interleukin-6 or macrophage colony-stimulating factor (M-CSF) during rhIL-3. We conclude that rhIL-3 can be safely administered as a continuous intravenous infusion for 10 days after DHAP chemotherapy. Dose-limiting side effects, especially headache, occur at a dose of 10 micrograms/kg/day.
...
PMID:The tolerability of continuous intravenous infusion of interleukin-3 after DHAP chemotherapy in patients with relapsed malignant lymphoma. A phase-I study. 821 38

We have studied, as part of a group of international multicenter phase II clinical trials, the toxicity and effectiveness of CAMPATH1H administered intravenously three times a week in an outpatient setting to patients with recurrent or progressive low grade lymphoma. We report here on the toxicity and therapeutic results of the first seven patients treated before the study was closed prematurely because of unacceptable toxicity. Classical complete or partial responses of treatment were seen in three of seven patients. One complete response lasted 8.5 months and the other complete response is ongoing at 1 year. Responses occurred in nodal sites as well as in skin and peripheral blood. The first three or four antibody infusions in each patient was associated with grade 1 or 2 side-effects including rigor, fever, facial flushing, nausea, vomiting, hives, wheezes, hypotension, and/or diarrhea but these subsequently decreased or disappeared. The most significant toxicity was profound lymphopenia and associated infection, usually viral. Six of seven patients had culture or serologically documented infections and four patients had two or more such episodes. All infections responded to temporary discontinuation of antibody therapy and appropriate antiviral or antibiotic agents. We conclude that CAMPATH1H monoclonal antibody has therapeutic activity against low grade non-Hodgkin's lymphoma but that this activity is limited by marked lymphopenia and an unacceptably high frequency of serious infection at the dose and schedule used in this trial.
Leuk Lymphoma 1996 Dec
PMID:Immunosuppressive toxicity of CAMPATH1H monoclonal antibody in the treatment of patients with recurrent low grade lymphoma. 904 65

Clinical trials with 5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide (NSC-82196) given intravenously to 32 patients with various tumors suggest that the maximum tolerated dose is 5 g/m2 divided into five consecutive daily injections and repeated at 5-6-week intervals. The principal dose-limiting toxic effect was severe nausea and vomiting. Pain and flushing after administration were often severe. The time of onset and the degree of severity of delayed bone marrow toxicity (nadir, 31-35 days) were erratic, but the toxicity was reversible and usually tolerable. One patient with lymphosarcoma had an objective response. Phase II trials with NSC-82196 in patients with lymphoma and melanoma appear warranted.
...
PMID:Clinical trials with 5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide (NSC-82196) given intravenously. 1905 99

The Perdido Key beach mouse (Peromyscus poliontus trissyllepsis) is an endangered mammal indigenous to the panhandle beaches of Northwest Florida. A captive 3.5-y-old female mouse was evaluated because of severe pruritus, diffuse alopecia, skin reddening, and ulcerations over the dorsum of her body. Initial skin biopsy of the affected area suggested bacterial dermatitis but was inconclusive. Despite empiric antibiotic, anthelmintic, and antihistamine treatments, she continued to decline and developed severe ulcerations over the majority of her body. Postmortem histopathologic evaluation led to a tentative diagnosis of epitheliotropic lymphoma, suggestive of a mycosis fungoides T-cell-type cutaneous lymphoma. However, immunohistochemistry results challenged this diagnosis, indicating that the lesion was actually an epidermotropic B-cell lymphoma. Spontaneous cutaneous B-cell lymphomas are rare in rodents and had not previously been reported to occur in Perdido Key beach mice. This case report provides initial evidence that the Perdido Key beach mouse is susceptible to cutaneous B-cell lymphoma.
...
PMID:Cutaneous B-cell lymphoma in a Perdido Key Beach mouse (Peromyscus poliontus trissyllepsis). 2254 14

Red face syndrome is characterized by an erythematous dermatitis that is produced by different entities. These include rosacea, seborrheic dermatitis, contact dermatitis, atopic dermatitis, psoriasis, cutaneous lupus, photodermatosis, post-topical steroid dermatosis, demodicosis, borderline borderline (BB) leprosy, mastocytosis, carcinoid, postneoplasia flushing, cutaneous lymphoma, tineas, ulerythema ophryogenes, and psychosomatic flushing. Red face is a relatively common dermatologic manifestation. Our goal is to review tinea corporis and other fungi that affect this region causing facial erythema and its therapeutic management.
...
PMID:Red face and fungi infection. 2544 65