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)

The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. 153 95

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

We have reviewed 10 cases of gold sodium aurothiomalate (GSTM) induced marrow suppression. All had biopsy proven marrow hypoplasia/aplasia. Anemia, neutropenia and thrombocytopenia were observed in 7 of the 10 patients. In 2 patients, hypoplastic marrow was associated with suppression of 2 of the formed elements of the blood, while in one patient, there was isolated neutropenia. Nine of the 10 patients survived. Bone marrow recovery occurred within an average of 5.4 months. A response was seen in 3 with antithymocyte globulin. One patient required an allogeneic bone marrow transplant. A combination of corticosteroids and androgens was associated with recovery in 5. Blood and platelet transfusions and antibiotics were instituted only when clinically indicated. We conclude that the prognosis of GSTM induced marrow suppression is better than previously reported.
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PMID:Gold induced marrow suppression: a review of 10 cases. 210 5

Neutrophil-specific alloantibodies and the antigens they recognize are important in clinical medicine, but little is known about the structure of these antigens. Alloimmunization to the antigen NB1 is a clinically important cause of neonatal neutropenia and febrile transfusion reactions. To study the immunochemistry of the NB1 antigen, we prepared neutrophil plasma membranes and granules by nitrogen cavitation and differential centrifugation and then analyzed them by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with alloantibodies to several neutrophil-specific antigens. Two different antisera to the neutrophil-specific antigen NB1 identified an approximately 55-Kd protein by immunoblotting on neutrophil membranes from four NB1-positive donors but not on neutrophil membranes from five NB1-negative donors. Four anti-NB1 antisera immunoprecipitated a 58- to 64-Kd protein from extracts of NB1-positive neutrophils surface-labeled with 125I using lactoperoxidase, but not from similarly treated NB1-negative neutrophils. Normal human serum did not immunoprecipitate or immunoblot any proteins from these same neutrophil preparations. The NB1 antigen was detected by immunoblotting in secondary granules but was not found in primary granules. The electrophoretic mobility of the antigen was decreased slightly by reduction, suggesting that intrachain disulfide bonds were present. After reduction, the antigen could no longer be recognized by anti-NB1 antisera, but treatment of the antigen with periodate had no effect on the ability of anti-NB1 antisera to recognize the antigen, suggesting that it is not a carbohydrate. The data suggest that the neutrophil-specific antigen NB1 is present on a 58- to 64-Kd surface glycoprotein that is also present in secondary granules, and that the NB1 epitope is not a carbohydrate but probably resides in the tertiary structure of the protein backbone.
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PMID:Biochemical characterization of the neutrophil-specific antigen NB1. 215 25

Fostriecin, a novel anticancer antibiotic produced by Streptomyces pulveraecus, is believed to act via inhibition of topoisomerase II. Single-dose intravenous administration to rats at dose levels of 8.8 to 48 mg/kg resulted in lethality at dose levels of 35 mg/kg and higher. Major toxic effects were observed primarily at 17.5 mg/kg and higher, were reversible, and consisted of bone marrow hypocellularity, leukopenia, neutropenia, thrombocytopenia, and diffuse necrosis of various lymphoid tissues. The kidney was also identified as a target organ. Renal effects were observed primarily at 20 mg/kg, were reversible, and included increases in serum BUN, creatinine, and 24-hr glucose excretion. Twenty-four-hour excretion of Na+, K+ and urine osmolality were decreased postdosing at 10 and 20 mg/kg. Renal lesions, observed primarily at 20 mg/kg, consisted of vacuolization and necrosis of proximal and distal tubular epithelium at the corticomedullary junction extending into the medulla. Repeated daily intravenous administration of fostriecin for 5 days to rats at dose levels of 2.5 to 26.5 mg/kg resulted in death at 10 mg/kg and above and similar hematologic, bone marrow, lymphoid tissue, and renal changes as observed in the single-dose study. Hematological, bone marrow, lymphoid, and renal changes observed in rats were consistent with the cytotoxic mechanism of action of the compound.
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PMID:Preclinical toxicological evaluation of fostriecin, a novel anticancer antibiotic, in rats. 222 54

Inhalation of ovalbumin by conscious, sensitized guinea pigs induced two phases of airway obstruction measured at 2 h (EAR) and at 17 h (LAR), respectively. In addition to causing airway obstruction, allergen challenge induced an accumulation in the bronchial lumen of eosinophil and neutrophil polymorphonuclear leukocytes at 17 h. Intraperitoneal injection of guinea pigs with a specific rabbit anti-guinea pig neutrophil serum 24 h before challenge reduced the number of circulating neutrophils by 94% and the airway neutrophilia after challenge by 90%, but it had no effect on the magnitude of either the EAR or the LAR. The observation that the LAR was not effected by neutropenia supports previous conclusions derived from experiments using the anti-allergic drugs, cromolyn sodium and nedocromil sodium, and the beta 2-adrenoceptor stimulant, albuterol, that, although there is a temporal relationship between neutrophil accumulation in the airways and the peak of the LAR, this polymorphonuclear leukocyte does not play a central role in the pathophysiologic processes that give rise to the late-phase response to guinea pig airways.
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PMID:Evidence that neutrophils do not participate in the late-phase airway response provoked by ovalbumin inhalation in conscious, sensitized guinea pigs. 231 88

Ethanol-induced gastric mucosal injury closely resembles an inflammatory response. Thus, in vivo and in vitro experimental models were used to assess whether ethanol is proinflammatory in concentrations likely to be encountered by the gastric mucosa during acute intoxication. Perfusing the rat gastric lumen with progressively increasing concentrations of ethanol (10%, 20%, and 30%) resulted in a dose-dependent increase in 51Cr-ethylenediaminetetraacetic acid clearance from blood-to-gastric lumen. Rendering the animals neutropenic (with antineutrophil serum) ameliorated the ethanol-induced mucosal injury; the degree of protection was directly related to the severity of neutropenia. Neither superoxide dismutase, catalase, nor sodium benzoate offered any protection against ethanol-induced injury, indicating that neither superoxide anion, hydrogen peroxide, nor the hydroxyl radical is involved. To assess further whether ethanol could exert proinflammatory effects an in vitro model consisting of cultured bovine microvascular endothelial cells and isolated human neutrophils was used. Ethanol at concentrations of 1.0%-4.0% (but not at 0.1%-0.5%) increased neutrophil adherence to endothelial cells and enhanced neutrophil-mediated endothelial cell injury. We conclude that ethanol is proinflammatory at concentrations that may be achieved in the gastric mucosa during acute intoxication. The ethanol-induced, neutrophil-mediated cell injury does not appear to involve oxy radicals.
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PMID:Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals. 231 75

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.
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PMID:[Clinical study of imipenem/cilastatin sodium in children with severe infections]. 234 51

We studied 45 patients (new-born to 12 year olds) who received 50-100 mg/kg/day chloramphenicol sodium succinate i.v. over 2-49 days for the treatment of central nervous system infections. Multiple blood samples were obtained to measure serum concentrations of chloramphenicol and its succinate ester by high pressure liquid chromatography (HPLC). Haematological parameters (haemoglobin, white cell, neutrophil, eosinophil and platelet counts) were also determined. Chloramphenicol therapy was effective in all patients. Anaemia was present in 10, leukopenia in four, neutropenia in four, and eosinophilia in 16 patients. These adverse effects occurred between 3 and 34 days after the initiation of therapy. Chloramphenicol therapy had to be discontinued only in three patients, who had absolute neutrophil counts less than 800/mm3. All adverse effects were reversible. Demographic factors, daily dose, duration of therapy, steady-state peak and trough serum concentrations, area under the serum concentration-time curve normalized for dose, and the elimination half-life were not correlated with the occurrence of adverse effects of chloramphenicol. The mean cumulative dose of chloramphenicol succinate was the only factor always higher but not statistically different in patients with adverse effects compared to those without. The mean cumulative dose of chloramphenicol succinate ranged from 1.2 to 1.8 g/kg in patients with adverse effects and 0.9-1.1 g/kg in those without. These data suggest that the adverse effects of chloramphenicol may not be predictable in paediatric patients. However, a high cumulative dose may possibly be an important factor in predisposing some patients to certain chloramphenicol toxicity.
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PMID:Lack of predictability of chloramphenicol toxicity in paediatric patients. 279 54

We report three cases of combined anemia, neutropenia and thrombocytopenia in patients with visceral leishmaniasis (kala-azar). Using immunofluorescence techniques and the common antiglobulin (Coombs') test, we showed membrane-associated antiplatelet, antineutrophil and antierythrocytic IgG antibodies in all three cases. Treatment with sodium stibogluconate raised the patients' platelet, neutrophil and erythrocyte count. At that time no antibodies were detected on peripheral blood cells. Immunological studies performed on these patients did not show marked abnormalities except for reduced T-helper cells and elevated OKM1-positive cells, which normalized after recovery. As bone marrow suppression was not found, it is suggested that pancytopenia resulted from rapid destruction of antibody-coated blood cells. Whether these antibodies are specific is not clear.
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PMID:Immunological studies of pancytopenia in visceral leishmaniasis. 283 65


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