Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Miltefosine (2.5 mg/kg/day for 28 days) was investigated for treatment of New World cutaneous leishmaniasis in Colombia and Guatemala. The data from a controlled study was remarkably similar to the data of a prior uncontrolled pilot study. In the controlled study, the per-protocol 6-month cure rate for Leishmania panamensis disease was 91% compared with a concomitant placebo cure rate of 38%. In Guatemala, the cure rate for L. braziliensis and L. mexicana disease was approximately 50% compared with approximately 20% for placebo. In both countries, nausea but not 'motion sickness' and vomiting but not diarrhoea were experienced by approximately 30% more miltefosine patients than placebo patients. Mild elevation of creatinine, but not of aspartate aminotransferase or alanine aminotransferase, was also more frequently seen in the miltefosine group than in the placebo group. Miltefosine was well tolerated, and as effective as historic values of antimony for treatment of L. panamensis disease.
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PMID:Treatment of New World cutaneous leishmaniasis with miltefosine. 1693 Jun 49

We report a case of acute hepatotoxicity in a 42-year-old woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase (ALT), 1795 IU/L (normal range 0-40); aspartate aminotransferase (AST), 1337 IU/L (normal range 5-34); alkaline phosphatase (ALP), 339 IU/L (normal range 40-150); gamma-glutamyl transpeptidase (GGT), 148 IU/L (normal range 9-64 IU/L); total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time (PT), 13.5 s, with international normalized ratio (INR), 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixed-type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.
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PMID:Clindamycin-induced acute cholestatic hepatitis. 1787 18

A 46-year-old woman was admitted to our department with symptoms of nausea, anorexia and asthenia. Serum alanine aminotransferase and aspartate aminotransferase levels were increased; all serological tests for viral hepatitis and autoimmune disorders were negative. She had taken Lycopodium similiaplex solution as sedative for the previous 8 weeks, whose two constituents, Lycopodium serratum and Chelidonium majus, are found to be potentially toxic. After discontinuing L. similiaplex use, liver values returned to normal and she was asymptomatic. The diagnosis was definitively confirmed by liver biopsy; on the basis of the histological specimen, a hypersensitivity reaction was hypothesized as a possible pathogenic mechanism. Hepatotoxicity of phytotherapy has already been described, although so far, the true incidence and the pathogenic mechanisms are largely unknown. It is important to increase awareness of both clinicians and patients about the potential dangers of herbal remedies; surveillance systems and quality control of these products are necessary.
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PMID:Lycopodium similiaplex-induced acute hepatitis: a case report. 1840 50

Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid). In 1 study, patients could be switched to oral LEV after at least 3 days intravenously. The coprimary efficacy end points were as follows: clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). The secondary end points were as follows: microbiologic efficacy and susceptibility to TGC for CAP bacteria. Safety evaluations were included. Eight hundred ninety-one were patients screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). Most patients had Fine Pneumonia Severity Index II to IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253/282 patients (89.7%) and LEV cured 252/292 patients (86.3%); the absolute difference of TGC-LEV was 3.4% (95% confidence interval [CI], -2.2 to 9.1, noninferior [P < 0.001]). In c-mITT, TGC cured 319/394 patients (81.0%) and LEV cured 321/403 patients (79.7%); the absolute difference of TGC-LEV was 1.3% (95% CI -4.5 to 7.1, noninferior [P < 0.001]). The drug-related adverse events (AEs) of nausea (20.8% TGC versus 6.6% LEV) and vomiting (13.2% TGC versus 3.3% LEV) were significantly higher in TGC; elevated alanine aminotransferase (2.8% TGC versus 7.3% LEV) and aspartate aminotransferase (2.6% TGC versus 6.9% LEV) were significantly higher in LEV. Discontinuations for AEs were low (TGC, 26 patients [6.1%]; LEV, 34 patients [8.1%]). TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP.
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PMID:Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. 1850 26

Revision surgery for loosened hip prostheses is a heavy burden for elderly patients with comorbidity. As an alternative to surgery we performed a study to stabilize the prosthesis by percutaneous cement injection after removing inflammatory tissue with an intraarticular virus-directed enzyme prodrug approach. Twelve elderly patients with debilitating pain from a loosened hip prosthesis were included in a phase 1 dose-escalating clinical study. The patients were admitted to the hospital for 10 days for an intraarticular vector and prodrug injection, and subsequently for a percutaneous bone cement injection. This paper reports the adverse and serious adverse events of the study. After prodrug injection 9 of 12 patients had gastrointestinal adverse events (nausea, vomiting, and diarrhea), and 8 patients had hepatic adverse events (rise in aspartate aminotransferase and alanine aminotransferase). Five patients developed anemia (World Health Organization grade 1 or 2) from hematomas after cement injection. There were four serious adverse events in the first 6 months after vector injection, but these were not related to gene therapy as judged by an independent safety committee. There was no dose-limiting toxicity. However, the extensive comorbidity in these patients makes it difficult to fully establish the safety of the approach in this small and heterogeneous patient population.
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PMID:Gene therapy for the treatment of hip prosthesis loosening: adverse events in a phase 1 clinical study. 1895 51

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.
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PMID:Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China. 1985 68

A 58-year-old female patient was transferred by her general practitioner with fatigue, nausea and icterus which had begun 2 weeks prior to admission. Laboratory results revealed acute hepatitis (ALAT [alanine aminotransferase] 3,871 U/l, ASAT [aspartate aminotransferase] 2,004 U/l, bilirubin 6.7 mg/dl, gamma-GT [gamma-glutamyl transferase] 503 U/l). The patient's medical history included genetic hemochromatosis (without cirrhosis). Hepatitis A to C, infection with herpesviruses or Leptospira interrogans were excluded by serologic and molecular biological tests. There was no diagnostic evidence for underlying autoimmune or additional metabolic liver disease. Due to a trip to Africa 5 months earlier, the patient was tested for hepatitis E, leading to positive anti-hepatitis E-IgM and negative anti-hepatitis E-IgG. PCR (polymerase chain reaction) detection of hepatitis E virus (HEV) was positive as well. In conclusion, acute HEV infection was diagnosed. After close reconsideration, the nonfitting incubation period precluded a travel-associated infection. Additionally, there was no evidence for current HEV infections within the patient's social environment, so that a zoonotic origin has to be discussed.
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PMID:[Rare acute hepatitis in a female patient with hemochromatosis: a zoonosis?]. 2045 55

A 19-year-old female diagnosed with Graves' disease had treatment initiated with propylthiouracil (PTU). Pretreatment complete blood count and liver-associated enzymes (LAEs) were normal, but no further LAEs were obtained, reflecting U.S. guidelines written in 1995. Three months later, she presented with nausea, vomiting, abdominal pain, and jaundice. LAEs were markedly elevated with: total bilirubin, 6.5 mg/dl; aspartate aminotransferase (AST), 1747 IU/L; and alanine aminotransferase (ALT) 1589 UL/L. After 6 days at an outside hospital, she was transferred to our tertiary care center in acute liver failure with coagulopathy and stage II encephalopathy. Liver transplant evaluation was promptly initiated and she was listed as status 1. PTU was the only medication she had taken; and all serologic, autoimmune, and metabolic studies were negative. She demonstrated rapid clinical deterioration, and on hospital day 7 she underwent orthotopic liver transplant but succumbed to tonsillar herniation immediately after surgery. Pathology from her explanted liver revealed marked necrosis and collapse, consistent with her acute liver failure. PTU-associated hepatotoxicity and myelotoxicity have been well-recognized serious adverse effects for more than 50 years. However, as deaths related to hepatic injury from PTU are rare, American Thyroid Association guidelines do not call for routine monitoring of LAEs, although monitoring of white blood cell count levels is advised. Given the wide spectrum of PTU-related liver injury, ranging from asymptomatic elevations in ALT to fatal acute liver failure, we urge consideration of an LAE monitoring program to prevent irreversible liver damage and call for a reappraisal of monitoring guidelines in the United States.
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PMID:Gone (from the Physicians' desk reference) but not forgotten: propylthiouracil-associated hepatic failure: a call for liver test monitoring. 2057 20

Blastocystis hominis and nonpathogenic enteric protozoa were diagnosed in 300 patients with pulmonary tuberculosis mainly of its infiltrative form and 500 with Stages II and III HIV infection; the patients received antituberculosis therapy (ATT) and antiretroviral therapy (ART), respectively. Control groups included 200 Tashkent dwellers and 350 patients with various noninfectious diseases of the gastrointestinal tract. Triple coproscopy was made. B. hominis was significantly more frequently detected in patients with pulmonary tuberculosis and those with HIV infection than in healthy individuals: in 53.6 +/- 2.9, 42.2 +/- 2.2, and 18.0 +/- 2.5, respectively (P < 0.01). Only did the tuberculosis or HIV-infected patients show a high intensity of B. hominis infection, which was accompanied by recurring diarrhea and nausea. The high activity of alanine aminotransferase and aspartate aminotransferase was observed in 20% of the patients with tuberculosis + blastocytosis; that of alkaline phosphatase was seen in 25%. The tuberculosis or HIV-infected patients were more frequently found to have Chylomastix mesnili, Jodamoeba butschlii, and Endolimax nana. The specific features of intestinal colonization seem to reflect changes in local immunity; the drugs included into ATT and ART have no substantial effects on the viability of protozoa.
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PMID:[Blastocystis hominis and nonpathogenic enteric protozoa in patients with pulmonary tuberculosis and those with HIV infection]. 2087 79

Oncolytic adenoviruses are an emerging treatment option for advanced and refractory cancer. Such patients are often treated with corticosteroids to ameliorate tumor associated symptoms. Thus, it is important to evaluate whether safety is affected by immunosuppression possibly induced by corticosteroids. Concurrent low-dose cyclophosphamide, appealing for its immunomodulatory effects, could also impact safety. In a retrospective case-control study, we evaluated the effect of systemic corticosteroid use in cancer patients receiving oncolytic virotherapy. Four treatment groups were identified: (1) oncolytic adenovirus with oral glucocorticoids, (2) virus alone, (3) virus with glucocorticoids and cyclophosphamide and (4) virus with cyclophosphamide. Adverse events, neutralizing antibody titers, viral DNA in circulation and tumor responses were evaluated. The most common adverse effects were grade 1-2 fatigue, nausea, fever and abdominal pain. Common asymptomatic findings included self-limiting grade 1-3 hyponatremia and aspartate aminotransferase increase. Safety was good and no significant differences were observed between the groups. All patients had an increase in neutralizing antibody titers post-treatment, and no trends for differences between groups were observed. There were fewer post-treatment virus genomes circulating in patients receiving glucocorticoids when compared to their control groups. Overall, glucocorticoid use in cancer patients receiving oncolytic adenovirus, with or without low-dose cyclophosphamide, seems safe.
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PMID:Safety of glucocorticoids in cancer patients treated with oncolytic adenoviruses. 2096 69


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