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)

Hexamethylmelamine (HMM) was selected for development as an antineoplastic agent because it demonstrated activity in a variety of preclinical tumor models. Its mechanism of action is unknown. It has been used in clinical trials since 1964. The clinical toxic effects have consisted of signs and symptoms involving the following systems: gastrointestinal (nausea, vomiting, anorexia), hematologic (leukopenia, mild anemia), and neurologic (critical depression, hallucinations, peripheral motor and sensory deficits). Antitumor activity against advanced ovarian cancer was demonstrated in phase I trials and the drug was quickly incorporated into trials which utilized drug combinations. The majority of these have consisted of phase II trials without an identified control population. As might be predicted, all of the HMM-containing combinations are active. However, the contribution of HMM to the antitumor activity of the combination remains conjectural. Thus, in spite of greater than 15 years of clinical trials with a drug that has single-agent activity, the questions regarding the role of HMM in the treatment of ovarian cancer remain unanswered.
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PMID:Role of hexamethylmelamine in the treatment of ovarian cancer: where is the needle in the haystack? 308 97

In our investigations the qualification of the substances 2-cyanoethyl urea, thymus extract and lithium carbonate was tested for a potential reducing or shortening of the leukocyte-depression in rats after whole-body irradiation. Intravenous applications of 2-cyanoethyl urea and intramuscular injections of thymus extract showed no effect in Wistar rats not only in increase of leukocyte number of peripheral blood, but also in variation of leukocyte portion in differential blood-count. Leukocytes depression appearing in consequence of whole-body irradiation was independent of cyanoethyl urea applications and of thymus extract, too. Lithium carbonate shows a significant increase of leukocytes in peripheral blood in dependence of dosage and frequency of applications. After whole-body irradiation with 7 Gy under lithium therapy, it was shown that on day 6 after irradiation leukocyte number was significantly higher than in controls. Radiogenic leukopenia phase was reduced significantly by lithium.
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PMID:[Effect of 2-cyanoethylurea, thymus extract and lithium carbonate on the leukocyte count in peripheral blood following whole body irradiation]. 310 Oct 18

The effect of three daily cyclophosphamide (CY) injections (doses of 0-100 mg/kg.day) on selected hematologic parameters in 7-to-8-week-old female Nicholas turkeys was examined. CY induced significant leukopenia, lymphopenia, thrombocytopenia, and heteropenia 24 to 72 hours after the initial injection; time depended on cell type and dose of CY. Significant linear correlation between increasing CY dose and increasing severity of circulating cell depression occurred. CY had no significant effect on circulating numbers of monocytes, packed cell volume, or plasma protein. Changes in basophils and eosinophils could not be identified because of their low numbers.
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PMID:Effect of cyclophosphamide on selected hematologic parameters of the turkey. 320 75

In a retrospective cohort study we reviewed our experience using D-penicillamine in children with low-level lead poisoning (whole blood lead levels 25 to 40 micrograms/dL) to determine its efficacy and the incidence of side effects. Two groups were compared: treated subjects (n = 84) were treated with penicillamine at a mean daily dose of 27.5 mg/kg; control subjects (n = 37) received no chelation therapy. Over a prechelation observation period of 60 days, lead levels (PbB) did not change in either group. With a mean period of 76 days of D-penicillamine therapy, PbB fell in treated patients by 33% (P less than 0.001). In 64 patients (76%), PbB was reduced to a currently acceptable range (less than or equal to 25 micrograms/dL). There were eight treatment failures (10%). In control subjects, mean PbB did not change significantly over 119 days of observation. Fourteen control subjects eventually required conventional chelation with calcium disodium ethylene-diaminetetraacetic acid, and 17 were lost to follow-up. Use of D-penicillamine was associated with an adverse reaction in 28 cases (33%); transient leukopenia occurred in eight, rash in seven, transient platelet count depression in seven, enuresis in three, and abdominal pain in two. Treatment was terminated prematurely in eight cases (10%) because of an adverse reaction. We conclude that D-penicillamine is effective therapy for selected children with low-level plumbism, but adverse effects can complicate or prevent its use in some patients.
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PMID:Efficacy and toxicity of D-penicillamine in low-level lead poisoning. 336 95

A phase I study with continuous administration of epirubicin for 21 days using a venous access port and a portable pump was performed. The first dose step was 2 mg/m2/d for 21 days. Interval between courses was 3 weeks. Dose increment per step was 1 mg/m2/d. Twenty-two patients entered the study and received a total of 58 courses with a median of two (range, one to nine). Up to 5 mg/m2/d no toxicity (according to World Health Organization [WHO] criteria) occurred. At 6 mg/m2/d (six pts), one patient had leukopenia grade 3. Two others had some hair loss. At 7 mg/m2/d (four patients), all patients developed mucositis (two grade 3). Three patients had bone marrow depression (one grade 3 anemia, one grade 4 leukocytopenia), and one patient developed the hand-foot syndrome. No other toxicity occurred in the patients. One patient obtained a partial response (18 weeks), ten had stable disease (12 to 54 weeks), seven had progressive disease, and four were not evaluable for response. One patient developed cellulitis around the port, responding to antibiotic treatment; one patient developed a vena cava superior syndrome that resolved with urokinase and removal of the access port. No septicemia occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with fluorometric detection. Plasma steady state was reached after 57 hours. During steady state there was a linear relationship between epirubicin dose administered and epirubicin level in plasma (r = .58, P less than .05), whole blood (r = .75, P less than .005), and in leukocytes (r = .68, P less than .05). The area under the curve in leukocytes was higher with continuous infusion of 6 mg/m2 for 21 days compared with bolus injection of 80 mg/m2. This method of continuous infusion with epirubicin may be a way to increase intracellular drug-uptake as expressed by intracellular area under curve (AUC). We recommend 6 mg/m2/d for 3 weeks for evaluation of antitumor efficacy in phase II studies.
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PMID:A phase I and pharmacokinetic study with 21-day continuous infusion of epirubicin. 347 90

2,2,2-Trifluoroethanol (TFE) is the toxic metabolite of the anesthetic agent fluroxene. TFE treatment (0.21 g/kg, ip) of male Wistar rats significantly reduced peripheral white blood cell count, bone marrow nucleated cellularity, and dry weight of the small intestine. These toxic effects of TFE were first observed at 8 to 16 hr after treatment, persisted for 96 hr, and were accompanied by severe diarrhea and edema of the small intestine. A non-lethal dose of TFE increased the sensitivity of rats to bacterial endotoxin lethality by approximately 1000-fold. Antibiotic and antiendotoxin pretreatment reduced the lethality of TFE from 80 to 20% of the rats, but did not prevent the other toxic effects of TFE. In vitro experiments with serum from TFE-pretreated rats (0.13 g/kg) supported the growth of an average of 65% fewer cultured bone marrow cell colonies compared to the number of colonies produced when serum from control rats was used. This suggests that TFE-induced bone marrow depression and leukopenia are related to a decrease in colony stimulating factor activity. Taken together these results explain the rapid development of lethal bacterial infections in TFE-treated rats. TFE-mediated damage to the small intestine combined with prolonged leukopenia decreases the resistance of the rat to endogenous pathogens leading to systemic bacterial infection. In addition, the increased sensitivity to endotoxin induced by TFE leads to lethal endotoxemia.
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PMID:Mechanism of toxicity of 2,2,2-trifluoroethanol in rats. 348 41

Case records of horses with equine ehrlichiosis (Ehrlichia equi) at the University of California Veterinary Medical Teaching Hospital and Ackerman Creek Large Animal Clinic were analyzed for evaluation of clinical signs, time of onset, hematologic values, response to treatment, and recovery. Equine ehrlichiosis was found to be seasonal in horses in the foothills of northern California, with higher incidence than reported previously. The horses developed fever, anorexia, depression, limb edema, icterus, and ataxia. Hematologic changes were leukopenia, thrombocytopenia, icterus, anemia, and inclusion bodies in the neutrophils and eosinophils. Diagnosis was made by observing the characteristic inclusion bodies, using a standard Wright's stain. Mortality was low, although complications of opportunistic secondary infection and injury due to ataxia did develop. Treatment with tetracycline resulted in prompt clinical improvement within 24 hours. Chronic cases were not detected. Equine ehrlichiosis should be differentiated from diseases with similar clinical signs including encephalitis, liver disease, purpura hemorrhagica, equine infectious anemia, and equine viral arteritis.
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PMID:Equine ehrlichiosis in northern California: 49 cases (1968-1981). 355 86

C57BL mice were injected intravenously with an antitumor immunopotentiating polysaccharide, lentinan, to assess its effect on granulopoiesis in normal mice as well as its ability to enhance the recovery from leukopenia induced by 5-fluorouracil (5-FU). Lentinan increased neutrophils and monocytes in peripheral blood as well as granulocyte-macrophage progenitor cells (GM-CFC) in spleen and bone marrow. Administration of 5-FU induced a significant decrease in GM-CFC from day 1 to day 6, and thereafter the number of GM-CFC rebounded. The administration of 5-FU also suppressed white blood cells such as neutrophils, monocytes and lymphocytes. Injection of lentinan one day after 5-FU resulted in prompt restoration of the leukopenia through the recovery of neutrophils, monocytes and lymphocytes as well as prompt and marked rebound of GM-CFC. These results suggest that lentinan may contribute to the recovery from some of the hematopoietic depression in clinical chemoimmunotherapy.
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PMID:[Granulopoietic effects of lentinan in mice: effects on GM-CFC and 5-FU-induced leukopenia]. 357 29

A phase II trial with mitozolomide was carried out in patients with malignant melanoma, since in preclinical studies this new imidazotetrazine had shown promising effects against human melanoma xenografts. Twenty-one evaluable patients with advanced malignant melanoma were treated with 115 mg m-2 of mitozolomide, given orally every 6 weeks. None of the patients had received prior chemotherapy. Two partial responses (10 and 7+ months) were observed. The responding patients had lung metastases, and one of them had, in addition, a huge (17 X 14 cm) lymph node metastasis in the groin. Also, one patient had a 48% tumour volume reduction of lung metastases. The dose limiting side effect of the treatment was bone marrow depression, with delayed leukopenia and thrombocytopenia. The median white blood cell counts and platelet nadirs were 2.5 X 10(9) 1(-1) (range 1.1-3.8) and 59 X 10(9) 1(-1) (range 14-95), respectively. Non-haematological adverse reactions were limited to mild or moderate nausea. It is concluded that orally administered mitozolomide is active against malignant melanoma and seems to have a response rate comparable to those of the most active established drugs.
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PMID:Mitozolomide (NSC 353451), a new active drug in the treatment of malignant melanoma. Phase II trial in patients with advanced disease. 358 Feb 66

Potomac horse fever was reproduced in 15 ponies by transfusion of whole blood originally from two natural cases and subsequently from ponies infected by the transfusions. Incubation periods varied from 9 to 15 days. Affected ponies developed varying degrees of fever, diarrhea, anorexia, depression, and leukopenia. Eleven affected ponies were killed, three died in the acute phase of the disease, and one did not show clinical signs. The most consistent post-mortem findings were fluid contents in the cecum and large colon, and areas of hyperemia (of inconstant degree and distribution) in mucosae of both small and large intestines. Multifocal areas of necrosis occurred in mucous membranes. Ehrlichial organisms were most common in the cytoplasm of epithelial cells, macrophages, and mast cells of the large colon.
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PMID:Enterocolitis caused by Ehrlichia sp. in the horse (Potomac horse fever). 375 Jul 39


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