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

Subacute intraperitoneal administration of the lipid portion of the unripe ackee arillus, referred to as "ackee oil", resulted in marked neutropenia (p less than 0.001) and increase in platelets (p less than 0.01) without anaemia, in rats. Blood urea, sodium and aspartate aminotransferase levels were significantly decreased but glucose and bilirubin levels were similar to those of controls. The lungs showed areas of petechial haemorrhages and a dose-related perivascular and peribronchial mononuclear cell infiltration. The pulmonary toxicity may be interpreted as a hypersensitive reaction to ackee oil. Further research is in progress on the neutropenic effects of ackee oil.
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PMID:Toxic effects of ackee oil (Blighia sapida L) following subacute administration to rats. 156 91

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)
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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.
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PMID:Effects of poly I:C in porcine iron deficient neutropenia. 241 Jan 86

Adult wild-trapped opossums were infected with Leishmania donovani (Khartoum strain, WR 378) and evaluated as an animal model of visceral leishmaniasis. All infected opossums died within 32 days. Loss of body fat, hepatomegaly, and petechiae of skin and abdominal musculature were seen at necropsy. Microscopically, numerous amastigote-laden macrophages were seen in histologic sections of liver, spleen, and lymph nodes; fewer parasite-laden macrophages were in the bronchial-associated lymphoid tissues and renal glomeruli. Hematological findings included thrombocytopenia (terminal), neutropenia, and lymphopenia. Blood lymphocyte blastogenesis in response to concanavalin A and phytohemagglutinin was decreased markedly at day 24 post-infection (PI). Serum antibodies (1:40 dilution) to promastigotes of L. donovani were detected in five of eight infected opossums tested on days 10 and 24 PI. Total bilirubin concentrations and alanine aminotransferase and aspartate aminotransferase activities were increased after day 25 PI. Activated partial thromboplastin times and one-stage prothrombin times were prolonged before death. Concurrently, factors V, VIII, and XII activities were decreased.
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PMID:Experimental visceral leishmaniasis in the opossum. 276 21

Mammary glands of 6 lactating Holstein cows were inoculated with Haemophilus somnus strain 43826. Three cows developed chronic mastitis and shed bacteria for up to 1 year. Three cows developed acute gangrenous mastitis, with evidence of bacteremia and endotoxemia. Cows with gangrenous mastitis had lower somatic cell counts early after inoculation in affected quarter secretions compared with those in cows that developed chronic mastitis. Cows with gangrenous mastitis developed hypocalcemia, hypoalbuminemia, azotemia, hyperbilirubinemia, mildly increased serum aspartate aminotransferase and creatine kinase activity, and a marked neutropenia with a degenerative left shift. Histopathologic examination of gangrenous quarters revealed edema, necrosis, and vascular thrombosis with few inflammatory cells. A limited survey failed to recover H somnus from dairy cows with clinical mastitis or from mammary secretions from 41 beef cattle at an abattoir.
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PMID:Haemophilus somnus: investigations of its potential role in bovine mastitis. 407 31

Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness.
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PMID:Clinical pathology and hemostatic abnormalities in experimental African horsesickness. 777 Oct 50

Etoposide is a schedule-dependent cytotoxic drug with high single agent activity in small-cell lung cancer and lymphoma. Despite its clear dose-dependent myelosuppressive activity, dose-dependent evidence of its anti-tumour activity is harder to demonstrate. A number of reports have correlated haematological toxicity with pharmacokinetic and physiological parameters, which explains some of the variability in dynamic effects that exists between patients. Recent reports have also suggested that anti-tumour response may be related to plasma etoposide concentration. In our own studies we have investigated factors that influence the pharmacodynamic effects of etoposide, principally with regard to haematological toxicity, and these studies have highlighted a number of patient groups who are at risk. Impaired renal function causes a reduction in clearance of etoposide, resulting in increased systemic exposure and more profound myelotoxicity. A 30% dose reduction in this group is recommended to normalise the area under the plasma concentration-time curve (AUC). Patients with low serum albumin concentrations (< 35 g/l) also showed significantly worse haematological toxicity, but with no apparent change in total drug pharmacokinetics. There was, however, an increase in the free drug fraction in this group due to decreased protein binding, such that the free drug AUC was similar to that found in patients with renal dysfunction. This would also indicate that a dose reduction of around 30%-40% is required in this patient group. Patients with normal albumin levels but liver enzyme values (aspartate transaminase or gamma-glutamyl transpeptidase) more than 3 times the upper limit of normal also had a less marked but significant increase in neutropenia. In patients with normal organ function, age was the only significant factor in predicting the degree of leukopenia/neutropenia, and increasing age was also associated with decreasing drug clearance and an increase in drug AUC. A small dose reduction and/or careful monitoring is required in this patient group. Further studies are required to elucidate further the relationship between the pharmacokinetics of etoposide and its pharmacodynamics, particularly with regard to anti-tumor activity, and to determine the role of individualised therapy, based on a pharmacokinetic parameter, in reducing the dynamic variability and optimising the use of this drug.
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PMID:Etoposide dosage and pharmacodynamics. 807 31

The experience with single-agent gemcitabine in advanced or metastatic breast cancer is reviewed. In all studies, gemcitabine was administered as a 30 min intravenous infusion in cycles once a week for 3 weeks followed by 1 week of rest. In the first European study (gemcitabine 800 mg/m2/week), of 40 evaluable patients, 14 were chemo-naive, 7 had received adjuvant chemotherapy, and 19 had received chemotherapy for metastatic disease. There were 3 complete responders and 7 partial responders (all independently validated by an external Oncology Review Board) for an overall response rate of 25.0% (95% CI: 12.7%-41.2%). The median time to declaration of response was 1.9 months and the median duration of survival for all 40 efficacy-evaluable patients was 11.5 months. Haematological and non-haematological toxicities were particularly mild. WHO grade 3 and 4 toxicities included leukopenia (6.8% and 2.3% of patients), neutropenia (23.3% and 7.0%), AST (6.8% and 2.3%), ALT (18.2% and 0%), infection (0% and 2.3%), nausea and vomiting (25.0% and 2.3%), alopecia (2.3% and 0%). There was no grade 3 or 4 creatinine, proteinuria or haematuria. In the smaller US study (18 evaluable patients, all but one having received prior chemotherapy for stage IV disease) there were no responders. However, the mean dose delivered was very low (577 mg/m2/injection). In an ongoing European trial, with a starting dose of 1000 mg/m2, a number of partial responders have been seen in soft tissue, lung and liver. Gemcitabine's modest toxicity profile and single-agent activity make it an attractive candidate for trial in combination therapy in advanced breast cancer where treatment is currently given to palliate symptoms and improve quality of life.
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PMID:Gemcitabine in advanced breast cancer. 871 26

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

The clinical trial development programme of mirtazapine (Org 3770), performed in Europe and the United States, demonstrated an outstanding safety profile of this compound. The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. A general indication of mirtazapine's safety is the significantly lower percentage of patients (65%) who complained of any adverse clinical experiences compared with the placebo- (76%) or amitriptyline-treated group (87%). Moreover, drop-out rates due to adverse clinical experiences were significantly lower than in the amitriptyline-treatment group. Mirtazapine has virtually no anticholinergic, adrenergic or typical selective serotonin reuptake inhibitor (SSRI) side effects. The only significantly higher incidences versus placebo were seen in the adverse clinical effects of drowsiness (23% versus 14%), excessive sedation (19% versus 5%), dry mouth (25% versus 16%), increased appetite (11% versus 2%) and weight increase (10% versus 1%). These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. In contrast, significantly higher incidences of headache (5% versus 10%) and weight decrease (2% versus 6%), symptoms commonly seen in depressed patients, were recorded in the placebo-treated patients. Also, typical SSRI adverse events, such as nausea, vomiting, diarrhoea and insomnia, and symptoms of sexual dysfunction were registered less frequently in mirtazapine-treated patients than in the placebo-treated patients. Approximately 10% of the mirtazapine-treated patients in the clinical trial programme were older than 65 years. The pattern of adverse clinical experiences seen in this group of patients is fully in line with that seen in the overall patient population. The analysis of vital sign indices, i.e. blood pressure and heart rate, showed that no changes occurred with mirtazapine treatment; this pattern was fully comparable to that seen with placebo. Furthermore, very low incidences of clinically relevant changes in laboratory indices, such as the liver enzymes alanine aminotransferase and aspartate aminotransferase or neutropenia, were recorded in each treatment group. Mirtazapine has a very low seizure-inducing potential: only one case was recorded in a patient with a history of seizures during previous treatment with clomipramine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. The only symptom seen in the patients taking an overdose of mirtazapine alone or in combination with other drugs was excessive but transient somnolence, which resolved spontaneously within a few hours. In conclusion, the new antidepressant mirtazapine offers clinicians a unique combination of strong efficacy and good safety.
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PMID:Safety of mirtazapine: a review. 893 8


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