Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An outbreak of mortality in a flock of mutton merino sheep in which 109 out of 568 sheep died in the south-western Cape Province, is described. It was characterized by haemorrhagic septicaemia, anaemia, leucocytopaenia and haemorrhagic tendencies. Mortalities followed unseasonal and heavy summer rain, extended over a period of 6 months and were associated with the uninterrupted consumption of sheep cubes processed on the farm severly fungus-infested wheat, barley and rye straw for a period of at least one month. The main clinical signs occurred in two phases: an elevated body temperature, listlessness, epistaxis and intermittent haemorrhagic diarrhoea during the first phase of the outbreak, and a progressively worsening anaemia, leucocytopaenia and less severe haemorrhagic tendencies and a terminally elevated body temperature during the second phase. The predominant autopsy findings were purpuric haemorrhage on serosal and mucosal surfaces and in most of the organs, enterorrhagia and severe pulmonary congestion and oedema during the first stage; anaemia was the predominant sign during the second stage - widespread haemorrhage still occurred but was less extensive. Pasteurella haemolytica was isolated from most of the animals autopsied during the first stage. Histologically the most salient features were atrophy and necrosis of the lymphoid tissue, aplastic anaemia and a markedly impaired inflammatory response. Extensive post-natal lamb mortalities, probably due to an Escherichia coli infection precipitated by the toxicosis, occurred during the outbreak. Toxigenic strains of Stachybotrys chartarum were isolated from the wheat and barley straw. Diethyl ether extracts of the wheat straw, sheep cubes and S. chartarum culture material elicited positive skin tests in rats following intradermal injection and the presence of 12,13-epoxytrichothecenes in these extracts were confirmed by thin layer chromatography. In feeding trials sheep cubes and wheat straw caused the death of 4/4 one-day-old Pekin ducklings and weanling Wistar rats in six and nine days, respectively. This is the first description of an outbreak of disease in sheep associated with the ingestion of S. chartarum-infested food components in the Republic of South Africa.
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PMID:A field outbreak of suspected stachybotryotoxicosis in sheep. 57 6

Flucytosine is an antifungal agent useful in combination with amphotericin B in the treatment of several deeply invasive mycoses. The potentially dose-limiting, hematologic, gastrointestinal, and hepatic toxicities of flucytosine lead to a reluctance to use it in myelosuppressed patients. To investigate the safety and tolerability of flucytosine in this setting, we evaluated its use in 17 patients with cancer or aplastic anemia during a 2 1/2-year period at our institution and reviewed the literature describing mechanisms of action, resistance, in vitro and in vivo antifungal activity, clinical antifungal activity, pharmacokinetics, and toxicity. The combination of amphotericin B plus flucytosine eradicated the mycosis in 12 (71%) of 17 patients, whereas 3 (18%) of 17 died of progressive fungal infection. Serial serum levels of flucytosine measured by a creatinine iminohydrolase assay permitted reliable dosage adjustment. During therapy, only 2 (12%) of 17 patients had elevated mean serum levels of flucytosine (> 100 micrograms/mL) and 3 (18%) other patients had transiently elevated levels. Paired serum samples (n = 45) obtained at steady state during therapy with orally administered flucytosine showed similar peak and trough levels. Adverse effects of flucytosine therapy included one case each of reversible nausea, diarrhea, elevated transaminase levels, and thrombocytopenia. No cases of bone marrow aplasia, enterocolitis, hepatitis, or death due to flucytosine toxicity were encountered. We conclude that flucytosine in combination with amphotericin B is well tolerated in myelosuppressed patients when serum flucytosine levels are serially monitored.
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PMID:Evolving role of flucytosine in immunocompromised patients: new insights into safety, pharmacokinetics, and antifungal therapy. 145 31

For treatment of steroid-resistant severe graft-versus-host disease, a murine monoclonal antibody (25.3) against the alpha chain (CD11a) of the lymphocyte function-associated antigen 1 (LFA-1) was infused into a patient with posthepatitic aplastic anemia who had undergone allogeneic bone marrow transplantation. The monoclonal antibody infusion was well tolerated and resulted in appreciable improvement in symptoms of gastrointestinal illness such as diarrhea and abdominal pain, suggesting that this antibody may be useful for controlling severe acute graft-versus-host disease.
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PMID:Anti-LFA-1 antibody treatment of a patient with steroid-resistant severe graft-versus-host disease. 148 52

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and also can be used for gonococcal infections in patients unable to tolerate penicillin. These drugs may cause gastrointestinal irritation, diarrhea, phototoxic dermatitis, and vestibular damage, and fatal reactions due to hepatotoxicity have occurred in pregnant women. Chloramphenicol has a broad spectrum of bacteriostatic activity, but its association with suppression of the bone marrow and aplastic anemia has relegated it to a historical role. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious adverse effects associated with the use of erythromycin is low; dose-related epigastric distress may occur. Clindamycin is bactericidal to most nonenterococcal gram-positive aerobic bacteria and many anaerobic microorganisms. Although historically it was a frequent cause of antibiotic-associated diarrhea and colitis, clindamycin is considered an excellent alternative to beta-lactam antibiotics for treatment of many staphylococcal infections, and it has therapeutic utility in anaerobic infections and in several protozoan infections in immunosuppressed patients. Metronidazole is efficacious for treating nonpulmonary anaerobic infections, various parasitic infections (trichomoniasis, amebiasis, and giardiasis), nonspecific vaginitis, and Clostridium difficile-mediated colitis. With use of metronidazole, mild side effects such as epigastric discomfort, diarrhea, reversible neutropenia, and allergic-type cutaneous reactions may occur.
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PMID:Tetracyclines, chloramphenicol, erythromycin, clindamycin, and metronidazole. 174 96

During the last few years the use of intravenous immunoglobulin (IVIG) has attracted increasing interest for the treatment of patients who do not have a classical humoral antibody deficiency syndrome. In certain situations this approach has revolutionized medical management, e.g. in immune thrombocytopenia. In other areas, such as in Kawasaki's syndrome, IVIG therapy have been shown to be highly beneficial in preventing long term disease sequelae by some investigators, but the field remains controversial. Conditions under which IVIG therapy has been shown to be of potential benefit are: (1) intractable childhood epilepsy; (2) autoimmune diseases, e.g. myasthenia gravis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, idiopathic neutropenia and aplastic anemia; (3) atopic allergy with IgG subclass deficiency including bronchial asthma; (4) in severe infections in combination therapy with antibiotics and as an antipyretic; (5) in Kawasaki's disease; (6) in multiple myeloma and chronic lymphocytic leukemia. Oral and intraventricular administration of IVIG have also been tried, the former for severe diarrhea and the latter to try to rescue the central nervous system from damage by a pathogen. Carefully controlled clinical trials are needed to establish the efficacy of gamma-globulin therapy in these and other conditions.
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PMID:New and controversial uses of intravenous gamma-globulin. 245 9

Cefbuperazone (CBPZ) was administered to patients with severe infections complicating hematologic diseases to assess its efficacy and safety under such clinical conditions. Primary diseases in this series of 78 cases included; acute leukemia in 41 cases, chronic leukemia in 6 cases, other leukemia in 9 cases, malignant lymphoma in 13 cases, multiple myeloma in 3 cases, aplastic anemia in 5 cases and 1 other case. Types of infection included sepsis; proven or suspected, in 59 cases, pulmonary infection in 8 cases, upper respiratory infection in 5 cases, and other cases. CBPZ was infused by an intravenous drip method at a dosage of 4-8 g daily. Patients' ages ranged from 14 to 85 years. Clinical response to the CBPZ regimen was excellent in 24 cases, good in 22 cases, fair in 2 cases, and poor in 30 cases. Thus the overall efficacy rate (percentage of cases showing an excellent or good response) was 59.0%. Efficacy rates for individual types of infection were: documented sepsis 16.7%, suspected sepsis 58.5%, lower respiratory infection 62.5%, and upper respiratory infection 100%. CBPZ also proved to be effective in 61.0% of cases with a neutrophil count of less than 500/mm3 prior to therapy. Side effects encountered were diarrhea in 1 case, gastric discomfort in 1 case and hepatic dysfunction in 5 cases. These side effects, however, were not dose-related, and none were serious. These results indicate that CBPZ has a high therapeutic efficacy even in patient with compromised immunodefenses.
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PMID:[Efficacy and safety of cefbuperazone in severe infections complicating hematologic diseases Hanshin Infection Study Group]. 304 32

Bone marrow transplantation has become an accepted treatment for malignancy (particularly leukemia and lymphoma), aplastic anemia, and certain inborn errors of metabolism. Patients require intensive care because of chemoradiation therapy toxicity, a prolonged period of immunosuppression and thrombocytopenia, graft-versus-host disease (GVHD), and the need for parenteral nutrition. Gastrointestinal and hepatic diseases are frequent post-transplant problems. They present with intractable nausea and vomiting, intestinal bleeding, diarrhea, esophageal complaints, abdominal pain, and hepatobiliary symptoms. Our clinical approach to complex transplant patients depends on the timing of signs and symptoms after marrow grafting and on the likelihood that specific disease processes are present. Each of these major problems is covered in this review.
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PMID:A problem-oriented approach to intestinal and liver disease after marrow transplantation. 304 22

Auranofin (triethylphosphine gold), an oral gold preparation, has recently been made available, and along with injectable gold preparations, is of therapeutic value for rheumatoid arthritis. Serious gold toxicity is uncommon, and drug-related deaths rare. Many potential adverse reactions are similar, including dermatitis, stomatitis, thrombocytopenia, leucopenia, and proteinuria, generally with increased incidence in the injectable gold-treated patients. Oral gold is associated with benign lower gastrointestinal side effects, including diarrhoea, loose stools and abdominal cramps that are often dose-related and resolve spontaneously. The incidence of severe reactions such as thrombocytopenia, aplastic anaemia and exfoliative dermatitis is lower with oral gold than injectable preparations, and contributes to a superior risk-benefit ratio. The treatment of gold toxicity depends on the type and extent of organ involvement.
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PMID:Adverse reactions with oral and parenteral gold preparations. 329 22

A new regimen for prevention of acute graft-versus-host disease (GvHD)--OKT3 (murine monoclonal anti-pan-T antibody), prednisone and methotrexate (OKT3-pred-MTX)--was compared with the Minnesota standard regimen--antithymocyte globulin, prednisone and methotrexate (ATG-pred-MTX)--for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post-transplant. Twenty patients (aged 25 +/- 9 years) had bone-marrow transplantation (BMT) from their HLA-MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3-pred-MTX) on days 8-22 post-transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 +/- 12 years) who received ATG-pred-MTX on days 8-22 post-transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile. Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (means 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3-pred-MTX and in eight of 19 patients who received ATG-pred-MTX (P = 0.06). The incidence of hepatic or gastrointestinal GVHD (greater than or equal to grade 2) was similar in the two groups: 4/20 OKT3-pred-MTX, 6/19 ATG-pred-MTX. Characteristics of post-transplant infections were also similar for the two prophylactic groups. Survival at 1 year post-transplant was 65% for patients who received OKT3 and 44% for patients who received ATG (P = 0.13). The use of OKT3 with prednisone and methotrexate is relatively safe and is associated with a similar incidence of moderate-severe acute GvHD to that experienced in the use of ATG with prednisone and methotrexate.
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PMID:Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation. 389 Sep 26

A three-year-old boy with severe aplastic anemia (HLA-A1,B8(Bw6), Cw7,DR3, MB2, MT2, SB4/A1,B8 (Bw6), Cw7,DR3,MB2,MT2,SB-) received a bone marrow transplant from a phenotypically HLA-identical, SB-compatible female unrelated donor. This donor was selected from eighteen HLA-A1,-B8,-blood donors after extended serotyping, mixed leukocyte culture testing and secondary proliferation assays with primed lymphocyte typing reagents specific for SB. Although patient cells proliferated well as responders in MLR, their stimulatory capability was greatly impaired. Because the patient had inherited the same serological HLA-D haplotype from each parent, it was concluded that a compatible unrelated donor must be homozygous for the same HLA-D antigens as the patient. This HLA-D homozygosity was demonstrated by the lack of MLR responses of both parents to stimulators from the donor. The SB typing results suggested SB compatibility because both the patient and the donor typed as SB4,-. Following bone marrow transplantation, there was rapid hematopoietic engraftment. The patient developed severe diarrhea caused by graft-versus-host disease of the gastrointestinal tract, which necessitated hyperalimentation. He is currently eighteen months posttransplant with full hematopoietic reconstitution and moderate chronic skin graft-versus-host disease.
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PMID:Bone marrow transplantation for severe aplastic anemia using a phenotypically HLA-identical, SB-compatible unrelated donor. 622 16


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