Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the safety and efficacy of sildenafil prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with erectile dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-dose sildenafil were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinued sildenafil as a direct result of adverse events. These results suggest that sildenafil prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED.
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PMID:Post-marketing surveillance study of the safety and efficacy of sildenafil prescribed in primary care to erectile dysfunction patients. 1551 Jan 93

The purpose of this study was to evaluate the value of model-based, quantitative decision making during the development of gemcabene, a novel lipid-altering agent. The decisions were driven by a model of the likely clinical profile of gemcabene in comparison with its competitors, such as 3-hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), the cholesterol absorption inhibitor ezetimibe, and their combination. Dose-response models were developed for the lipid effects (low-density lipoprotein cholesterol [LDL-C] and high-density lipoprotein cholesterol); adverse effects, such as persistent alanine aminotransferase elevation and myalgia; tolerability issues, such as headache; and risk reduction for coronary artery disease-related events for 5 statins, ezetimibe, gemcabene, and their combinations. The integrated model was based on the joint analysis of publicly available summary-level data and proprietary patient-level data and included information from almost 10,000 patients. The model was made available and accessible to the development team by using the Pharsight Drug Model Explorer model visualization technology. The modeling greatly enhanced the understanding of the clinical profile of gemcabene when given alone or in combination with a statin. The interaction between statins and gemcabene for the LDL-C lowering effect was found to be significantly different from the interaction between statins and ezetimibe. Ezetimibe was found to have a pharmacological-independent interaction resulting in additional LDL-C lowering over the entire statin dose range. The gemcabene interaction was found to be less than independent, resulting in almost no additional LDL-C lowering at high-statin doses, although the drug has a significant LDL-C effect when administered alone or in combination with a low dose of a statin. The quick availability of the model after completion of the first phase II trial in the target patient population and the ability of the team to explore the potential clinical efficacy and safety of gemcabene in comparison with alternative treatment options facilitated a quick decision to stop development.
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PMID:Model-based development of gemcabene, a new lipid-altering agent. 1635 29

Reduced blood flow to the gut may contribute to weight loss and gastrointestinal symptoms of acute mountain sickness (AMS) at altitude. A study in humans tested the hypothesis that acute hypobaric hypoxia (ALT) would attenuate the normal postprandial hyperemia in the superior mesenteric artery (SM). Blood pressure, cardiac output (CO), and (SM) were measured with previously validated noninvasive Doppler ultrasonic flowmetry in 9 (3 women) healthy young adults (mean age: 23; range: 18-33 yr) residing at 1700 m. Baseline measurements were made after 2 h at ALT in a chamber at 430 mmHg (asymptotically equal to 4800 m = 15,750 ft) after 10-12-h fasting, and the next day the control (CON) measurements were made at 615 mmHg (1850 m). Postprandial measurements were made 45 to 60 min after ingesting a 1000-cal liquid meal under both conditions. At ALT, 5 of the 9 subjects had AMS by the Lake Louise score criteria of headache > or =1 and total score > or =3. ALT significantly reduced fasting, baseline SM relative to CON by 15%, and increased CO by 16%. The postprandial CO increase was not different between ALT and CON, but (SM) increased 115% at CON, but only 75% at ALT, the attenuation being significant (p < 0.006). Neither the diminution of fasting (SM) at ALT nor the attenuation of the postprandial increase in (SM) correlated significantly with AMS symptom scores. These results suggest that baseline and postprandial gut blood flow are altered during acute altitude exposure because of increased intestinal sympathetic tone, inferred from increased local resistance, and may be related to reduced energy intake if sustained during prolonged exposure.
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PMID:Effects of acute hypobaric hypoxia on resting and postprandial superior mesenteric artery blood flow. 1654 66

In this retrospective study, the epidemiologic and clinical characteristics of 105 adult malaria patients, who had been hospitalized between the period of 1992 and 2006 were evaluated. Nineteen percent of the patients were female, and the mean age was 28 +/- 10 years. Fifty percent of the patients acquired the infection in Southeastern Anatolia, while they were on military duty. The most common complaints were rigor (93%), fever (90%), sweating (90%), headache (76%), nausea (45%), and fatigue (38%). The most common physical examination findings were splenomegaly (86%) and hepatomegaly (62%). Anemia was detected in 23%, leukopenia in 47%, thrombocytopenia in 73%, two fold increase in ALT or AST enzyme levels in 32% of the patients. Plasmodium vivax was detected in 101 (96%) patients, whereas P. falciparum was detected in 4 patients (4%). Although the number of malaria cases in Turkey is declining in recent years, the febrile patients with a history of travel to the endemic regions should raise the suspicion of malaria.
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PMID:[Malaria in Turkey and 14 years of clinical experience]. 1700 53

We report the first case of an obstructive hydrocephalus after intraventricular hemorrhage in a woman with HELLP syndrome and eclampsia. A 25-year-old primiparaous woman had severe preeclampsia at 36 weeks of gestation. She complained of epigastric pain and nausea. The levels of AST, ALT, and LDH were 539, 560, and 1051 IU/L, respectively; the platelet count was 101 x 109/L. Cesarean section was promptly performed. Intraoperatively, she had a first convulsion. The CT scan revealed only mild brain edema. The platelet count deteriorated to 30 x 109/L at 5 hour after the operation, and she had a second convulsion with an intraventricular hemorrhage. On the 6th post-cesarean day, she complained severe headache followed by coma. The CT scan revealed the enlargement of both lateral ventricles, indicating the occurrence of obstructive hydrocephalus. Drainage into cerebral ventricle was performed, resulting in the recovery of consciousness to a normal level.
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PMID:Hydrocephalus after intraventricular hemorrhage in eclamptic woman with HELLP syndrome. 1706 45

Crimean-Congo hemorrhagic fever is a tick-borne viral disease reported from more than 30 countries in Africa, Asia, South-East Europe, and the Middle East. The majority of human cases are workers in livestock industry, agriculture, slaughterhouses, and veterinary practice. Nosocomial transmission is also well described. Clinical manifestations are nonspecific and symptoms typically include high fever, headache, malaise, arthralgia, myalgia, nausea, abdominal pain, and nonbloody diarrhea. Patients may show signs of progressive hemorrhagic diathesis. Laboratory abnormalities may include anemia, leukopenia, thrombocytopenia, increased AST/ALT levels, and prolonged prothrombin, bleeding, and activated partial thromboplastin times. Diagnostic methods include antibody detection by enzyme-linked immunosorbent assay, virus isolation, antigen detection, and polymerase chain reaction. The mainstay of treatment of Crimean-Congo hemorrhagic fever is supportive, with careful maintenance of fluid and electrolyte balance, circulatory volume, and blood pressure. The Crimean-Congo hemorrhagic fever virus is susceptible to ribavirin in vitro. There is no controlled study evaluating oral versus intravenous ribavirin in treating Crimean-Congo hemorrhagic fever patients, but few studies have evaluated oral ribavirin. This article reviews the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention, and prognosis of Crimean-Congo hemorrhagic fever with a special focus on oral ribavirin as a choice of medical treatment.
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PMID:Crimean-Congo hemorrhagic fever. 1736 25

The aim of this article is to present the manifestations of Rickettsia typhi infection in childhood. Twenty-one children under 15 years of age were hospitalised in the Department of Paediatrics of the Archbishop Makarios Hospital in Nicosia, Cyprus, from 2000 to 2006 with Rickettsia typhi infection. Ten of them were boys and 11 were girls. The median age was eight years (range four to 13 years). The most common clinical features were fever (100%) and rash (57%). Lymphadenopathy, usually cervical, was also a frequent finding (37%). Severe headache was rather infrequent (29%). Splenomegaly or hepatomegaly were less frequent findings (24% and 10%, respectively). Mild elevation of liver enzymes (AST and ALT elevated >1-fold in 81% and 75%, respectively) was the most frequent laboratory finding. Thrombocytopenia (28%) and leucopenia (17%) were less frequent. Nearly half of the patients (10/21) came from four neighbouring villages, where most residents work in agriculture. All of the children were treated with appropriate antibiotic regimens and had complete recovery. Rickettsia typhi infection should be considered in the differential diagnosis of children who present during the summer or early autumn months with prolonged fever and rash with or without lymphadenopathy.
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PMID:Murine typhus in Cyprus: 21 paediatric cases. 1755 71

A 64-year-old man visited our clinic with a 9-day history of headache and fever. He had frequent, severe, electric shock-like pain in his left eye, forehead, and scalp. The body temperature was 37.1 degrees. Cranial nerve functions were intact. Limb weakness and stiff neck were absent. There were injection of the conjunctiva, a red rash on the trunk, and an eschar in the axilla. Abnormal laboratory findings included AST 40 IU, ALT 44 IU, CRP 16.0 mg/dl, WBC 11,090/microl, and proteinuria. CT scan was unremarkable. The cerebrospinal fluid (CSF) showed 2 polymorphs/microl, 6 lymphocytes/microl, 65 mg/dl of glucose, and 42 mg/dl of protein. A diagnosis of scrub typhus was made. Treatment with minocycline brought about prompt disappearance of the fever and dramatic clinical improvement. Increased antibody titers confirmed the diagnosis. Although almost all patients present with high fever and severe headache, only a small number of patients have CSF pleocytosis. The present case illustrates that pain in scrub typhus is, on rare occasions, indistinguishable from trigeminal neuralgia. Neurologists should have a high index of suspicion in patients with fever and headache during the epidemic season and should be familiar with the systemic symptoms and signs.
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PMID:[Case of tsutsugamushi disease (scrub typhus) presenting with fever and pain indistinguishable from trigeminal neuralgia]. 1763 12

The clinical information of acute Q fever in Taiwan was limited. A clinical study of 109 adults with serologically documented acute Q fever in the past decade (1994-2005) at 3 referral hospitals in southern Taiwan was reported. Their clinical manifestations, laboratory findings, and clinical outcomes were analyzed. Males predominated (98, 90%). There is a significant correlation between monthly average temperature and case numbers of acute Q fever (r = 0.74, P = 0.006). Fever (99%), chills (69%), and headache (45%) were the common symptoms, and relative bradycardia (44/60, 73 %) was often noted. Acute hepatitis, defined as either serum aspartate aminotransferase >or=60 IU/L or alanine aminotransferase >or=78 IU/L, was found in 88 (85%) cases, and more than one-third (31/87, 36%) had hyperbilirubinemia (serum total bilirubin >or=1.4 mg/dL) at initial presentation. The intervals between initiation of appropriate therapy to defervescence were longer in patients with hyperbilirubinemia than those without hyperbilirubinemia, irrespective of tetracycline or fluoroquinolone therapy. Of note, 8 (7.3%) cases experienced a prolonged period of fever (>28 days). In southern Taiwan, the predominant presentation of acute Q fever is acute febrile illness with hepatitis with or without jaundice. Acute Q fever should be added to the list of differential diagnoses of patients with fever, headache, relative bradycardia, elevated serum aminotransferase levels, or prolongation of activated partial thromboplastin time, irrespective of jaundice.
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PMID:Acute Q fever in southern Taiwan: atypical manifestations of hyperbilirubinemia and prolonged fever. 1794 35

Interferon-alpha-n1 (lymphoblastoid interferon-alpha) is a nonrecombinant 'natural' interferon derived from lymphoblastoid cells exposed to Sendai virus. In common with endogenous and recombinant interferon-alpha molecules, interferon-alpha-n1 has antiviral, immunomodulatory and antiproliferative properties. Interferon-alpha-n1 shows some efficacy in immunocompetent adults with well-compensated chronic viral hepatitis B. Rates of complete virological response (defined as an absence of detectable hepatitis B virus-DNA in the serum) ranged from 5 to 79% of adults who received various dosage regimens of interferon-alpha-n1 in monotherapy trials. Clearance of hepatitis B 'e' antigen was reported in 5 to 70% of patients treated with the drug. Spontaneous virological responses occurred in 0 to 48% of untreated patients. The clinical efficacy of interferon-alpha-n1 in patients with chronic hepatitis B is not improved by concomitantly administered deflazacort, zidovudine or levamisole, but may be increased by a course of corticosteroid pretreatment in some patients. Interferon-alpha-n1 also shows therapeutic benefit in adults with chronic hepatitis C. Complete biochemical responses (defined as normalisation of serum ALT levels) were achieved in 27 to 60% of adult patients treated with the drug, whereas spontaneous normalisation of serum ALT levels occurred in up to 11% of untreated patients. Responses to interferon-alpha-n1 were temporary in 27 to 78% of treatment responders but were sustained in 6 to 40% of patients. Emerging data delineating baseline factors predictive of a positive response to interferon-alpha-n1 treatment may aid in the selection of patients with hepatitis B or C most likely to benefit from treatment with this drug. Most patients receiving interferon-alpha-n1 experience a transient 'influenza-like' syndrome during the first week of treatment. The syndrome, which is dose related and alleviated by paracetamol (acetaminophen), is characterised by fever, chills, and arthralgia. Dose-limiting adverse effects occurring during longer term interferon-alpha-n1 therapy include fatigue, myalgia, headache, depression, pruritus and seizures. Neutropenia and thrombocytopenia may also occur during interferon-alpha-n1 treatment. Autoimmune thyroid disease may develop in up to 9% of patients treated with interferon-alpha-n1 for >or=6 months. At present, interferon-alpha-n1 and the recombinant forms of interferon-alpha are the only drugs available for the treatment of adults with well-compensated hepatitis B or C. Interferon-alpha-n1 produces moderate response rates in adults with well-compensated chronic hepatitis B or C. Thus, it is positioned alongside recombinant interferon-alpha products as a useful first-line treatment option for patients with chronic hepatitis B or C.
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PMID:Interferon-alpha-n1: a review of its pharmacological properties and therapeutic efficacy in the management of chronic viral hepatitis. 1802 May 50


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