Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics and safety of rufloxacin were evaluated in a double-blind, placebo-controlled study. Two groups of 16 healthy volunteers were given a single oral loading dose of 400 or 600 mg of rufloxacin on day 1 of the study. A single daily maintenance dose of 200 or 300 mg was then administered for a further 9 days; in addition, four subjects in each group received placebos. Rufloxacin levels in plasma and urine were determined by high-performance liquid chromatography. Following the initial dose, the mean (+/- standard error of the mean) peak concentrations of rufloxacin in plasma were 3.35 +/- 0.12 micrograms/ml in the 400-mg group and 4.54 +/- 0.19 micrograms/ml in the 600-mg group. They were generally reached 2 to 3 h after dosing. At the end of treatment, maximum levels in plasma rose to 4.51 +/- 0.15 and 7.20 +/- 0.25 micrograms/ml in the 400-mg and 600-mg groups, with a mean extent of accumulation (fold) of 3.1 +/- 0.1 and 3.3 +/- 0.1. For the 400-mg and 600-mg groups, the elimination half-lives were 40.0 +/- 1.5 and 44.0 +/- 1.3 h, mean residence times were 57.8 +/- 2.2 and 63.7 +/- 1.8 h, apparent volumes of distribution were 132 +/- 4 and 139 +/- 5 liters, and apparent total body clearance were 39 +/- 1 and 44 +/- 4 ml/min, assuming complete bioavailability. Of the total dose administered, the percentages excreted in urine were 49.6 +/- 1.3 and 51.1 +/-2.1%, with renal clearances of 21 +/- 1 and 22 +/- 2 ml/min, for the 400-mg and 600-mg groups. On the whole, the treatments were well tolerated, but some minor adverse events (mainly headache, insomnia, or abdominal discomfort) were reported for 7 subjects on abnormalities were detected in the laboratory examinations or in ocular function tests. This study shows that a 200-mg daily oral dose of rufloxacin preceded by a loading dose of 400 mg are well tolerated and produce steady-state concentrations in plasma above the MIC for most susceptible pathogens.
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PMID:Multiple-dose pharmacokinetics and safety of rufloxacin in normal volunteers. 132 18

In this open study the efficacy and tolerability of rufloxacin in a single dose of 400 mg the first day and 200 mg the nine consecutive days was studied in 26 patients with an acute exacerbation of chronic bronchitis. Twenty-two patients were evaluable for efficacy. Four patients stopped treatment prematurely after five days because of clinical cure. At the enrollment visit a pathogen was isolated in the sputum sample in 19 of 22 evaluable patients. The predominant pathogens were Streptococcus pneumoniae and Moraxella catarrhalis. In 17 of these 19 bacteriologically evaluable patients the initial infecting organism was eradicated from specimens obtained within 48 hours after the end of therapy. There was one case of persistent infection caused by S. pneumoniae (MIC 4 mg/l), one patient had a superinfection with Serratia marcescens (MIC 1 mg/l) susceptible to rufloxacin and therapy was stopped after five days due to clinical failure. One week after the end of therapy, 15 patients remained free from infection whilst one patient experienced reinfection with Klebsiella pneumoniae (MIC 0.5 mg/l). Clinical cure or improvement was observed in 21 of 22 patients. Mild adverse events were reported by two of 26 enrolled patients. In one patient, complaining of headache and dizziness, the adverse events were considered possibly study drug related. No abnormal laboratory findings were reported. Nadir plasma levels of rufloxacin were measured and no accumulation in plasma was observed during treatment. A ten day course of an oral single dose of rufloxacin proved efficacious and was well tolerated in patients with an acute exacerbation of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rufloxacin once daily in acute exacerbations of chronic bronchitis. 191 50

Due to mass tourism and the exodus of refugees from Africa and Asia, typhoid fever, common in the tropics, has reappeared in the more temperate climates. The clinical signs of prolonged fever, headache, general malaise, anorexia and abdominal pain are not specific enough to allow diagnosis and only a blood culture will prove the presence of the disease. Unless there is resistance, which is in fact rare in Southeast Asia, chloramphenicol, an effective, well tolerated and cheap antibiotic, remains the treatment of choice for typhoid. In the search for an alternative treatment a cephalosporin, ceftriaxone (Rocephin) seems promising. It has a low MIC of 0.05 micrograms/ml for S. typhi and a high level of biliary excretion which destroys S. typhi in the bile and thus prevents relapse. In Southeast Asia three consecutive studies, of which two were randomised and comparative with chloramphenicol given for 14 days, showed that treatment for two or three days, 3 or 4 g per day of ceftriaxone was as effective as chloramphenicol and was not followed by relapse. In 46 adults there was one failure with ceftriaxone (in an immunocompromised patient) and none in the 30 patients treated with chloramphenicol, three of which, however, relapsed in the 15 days after completion of treatment. Defervescence was a little more rapid with chloramphenicol (six to seven days) than with ceftriaxone (seven to ten days) even though blood, urine and stool cultures were all negative from the third or fourth day of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of typhoid fever for three days with ceftriaxone]. 228

In a double-blind randomized study, 155 male patients with uncomplicated urethral gonorrhea were given 200 mg (one capsule with 200 mg and one capsule with placebo; n = 77) or 400 mg (two capsules with 200 mg; n = 78) of enoxacin orally. The cure rates in the 200- and 400-mg treatment groups were 90 and 92%, respectively. The enoxacin MIC for the isolated Neisseria gonorrhoeae strains ranged from 0.015 to 0.12 microgram/ml. Postgonococcal urethritis was diagnosed in 29 (42%) patients in the 200-mg treatment group and 19 (26%) patients in the 400-mg treatment group. Side effects (nausea, headache, and vomiting) occurred in 2 (3%) of the 77 patients in the 200-mg treatment group and in 3 (4%) of the 78 patients in the 400-mg treatment group.
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PMID:Comparative double-blind study of 200- and 400-mg enoxacin given orally in the treatment of acute uncomplicated urethral gonorrhea in males. 311 54

Serious infection with vancomycin-resistant enterococci (VRE) usually occurs in patients with significantly compromised host defences and serious co-morbidities, and this magnifies the importance of effective antimicrobial treatment. Assessments of antibacterial efficacy against VRE have been hampered by the lack of a comparator treatment arm(s), complex treatment requirements including surgery, and advanced illness-severity associated with a high crude mortality. Treatment options include available agents which don't have a specific VRE approval (chloramphenicol, doxycycline, high-dose ampicillin or ampicillin/sulbactam), and nitrofurantoin (for lower urinary tract infection). The role of antimicrobial combinations that have shown in vitro or animal-model in vivo efficacy has yet to be established. Two novel antimicrobial agents (quinupristin/ dalfopristin and linezolid) have emerged as approved therapeutic options for vancomycin-resistant Enterococcus faecium on the basis of in vitro susceptibility and clinical efficacy from multicentre, pharmaceutical company-sponsored clinical trials. Quinupristin/dalfopristin is a streptogramin, which impairs bacterial protein synthesis at both early peptide chain elongation and late peptide chain extrusion steps. It has bacteriostatic activity against vancomycin-resistant E. faecium [minimum concentration to inhibit growth of 90% of isolates (MIC(90)) = 2 microg/ml] but is not active against Enterococcus faecalis (MIC(90 )= 16 microg/ml). In a noncomparative, nonblind, emergency-use programme in patients who were infected with Gram-positive isolates resistant or refractory to conventional therapy or who were intolerant of conventional therapy, quinupristin/dalfopristin was administered at 7.5 mg/kg every 8 hours. The clinical response rate in the bacteriologically evaluable subset was 70.5%, and a 65.8% overall response (favourable clinical and bacteriological outcome) was observed. Resistance to quinupristin/dalfopristin on therapy was observed in 6/338 (1.8%) of VRE strains. Myalgia/arthralgia was the most frequent treatment-limiting adverse effect. In vitro studies which combine quinupristin/dalfopristin with ampicillin or doxycyline have shown enhanced killing effects against VRE; however, the clinical use of combined therapy remains unestablished. Linezolid, an oxazolidinone compound that acts by inhibiting the bacterial pre-translational initiation complex formation, has bacteriostatic activity against both vancomycin resistant E. faecium (MIC(90) = 2 to 4 microg/ml) and E. faecalis (MIC(90) = 2 to 4 microg/ml). This agent was studied in a similar emergency use protocol for multi-resistant Gram-positive infections. 55 of 133 evaluable patients were infected with VRE. Cure rates for the most common sites were complicated skin and soft tissue 87.5% (7/8), primary bacteraemia 90.9% (10/11), peritonitis 91.7% (11/12), other abdominal/pelvic infections 91.7% (11/12), and catheter-related bacteraemia 100% (9/9). There was an all-site response rate of 92.6% (50/54). In a separate blinded, randomised, multicentre trial for VRE infection at a variety of sites, intravenous low dose linezolid (200mg every 12 hours) was compared to high dose therapy (600 mg every 12 hours) with optional conversion to oral administration. A positive dose response (although statistically nonsignificant) was seen with a 67% (39/58) and 52% (24/46) cure rate in the high- and low-dose groups, respectively. Adverse effects of linezolid therapy have been predominantly gastrointestinal (nausea, vomiting, diarrhoea), headache and taste alteration. Reports of thrombocytopenia appear to be limited to patients receiving somewhat longer courses of treatment (>14 to 21 days). Linezolid resistance (MIC > or = 8 microg/ml) has been reported in a small number of E. faecium strains which appears to be secondary to a base-pair mutation in the genome encoding for the bacterial 23S ribosome binding site. At present a comparative study between the two approved agents for VRE (quinupristin/dalfopristin and linezolid) has not been performed. Several investigational agents are currently in phase II or III trials for VRE infection. This category includes daptomycin (an acidic lipopeptide), oritavancin (LY-333328; a glycopeptide), and tigilcycline (GAR-936; a novel analogue of minocycline). Finally, strategies to suppress or eradicate the VRE intestinal reservoir have been reported for the combination of oral doxycyline plus bacitracin and oral ramoplanin (a novel glycolipodepsipeptide). If successful, a likely application of such an approach is the reduction of VRE infection during high risk periods in high risk patient groups such as the post-chemotherapy neutropenic nadir or early post-solid abdominal organ transplantation.
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PMID:Treatment options for vancomycin-resistant enterococcal infections. 1182 58

A 7-year-old boy was admitted to our hospital because of headache and frequent vomiting. The patient was noted to have papilloedema and mild palsy of the right abducent nerve. Magnetic resonance image (MRI) revealed a large tumor in the frontal base with tumoral hemorrhage. Angiography showed the tumor was fed by anterior meningeal arteries. At surgery, the tumor was arising in the dura mater at the frontal base, and was removed totally. Histological examination showed the tumor to be composed of small cells with uniform round nuclei and minimal cytoplasm. Immunohistochemical studies were positive for MIC-2, NSE, C-KIT, vimentin, Class III-beta tublin and glycogen, but negative for NFP, synaptophysin, chromogranin A and GFAP. MIB-1 labeling index was 40-50%. The tumor was histologically confirmed to be peripheral-type primitive neuroectodermal tumor(pPNET). Following surgery, he underwent whole brain, whole spine and local radiation therapy(30 Gy in total respectively) and received two 5-day cycles of chemotherapy, consisting of intravenous administration of cisplatin 20 mg/m2/day, etoposide 60 mg/m2/day and IFOS 900 mg/m2/day. After these therapies, follow-up radiological examination showed there was no recurrence of the tumor for 24 months. Intracranial pPNET is rare. Ewing sarcoma and pPNET(ES/pPNET) is the designation given to a family of small round cell tumor arising in bone or soft tissues. Intracranial PNETs are devided into central nervous system PNET(cPNET) and pPNET. It is necessary that intracranial PNETs are divided into two types of PNETs because of different prognosis between these tumors. MIC-2 is a specific marker for pPNET/ES family and is useful in the differential diagnosis of these two types of tumors.
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PMID:[A case of peripheral-type primitive neuroectodermal tumor arising in the dura mater at the frontal base]. 1511 48

Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens--pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06, 0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin compared to clarithromycin remained free of exacerbations for longer periods of time (p < 0.016) and gemifloxacin had a shorter time to eradication of H. influenzae than did clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have an adverse profile that was comparable with other compounds. The most frequent side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a welcomed addition to currently available agents for the treatment of community-acquired lower respiratory tract infections. Other potential indications appear to be within the spectrum of this compound.
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PMID:Gemifloxacin: a new fluoroquinolone. 1515 13

Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent exhibiting potent activity against most gram-negative and gram-positive organisms, such as the important community-acquired respiratory pathogens Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae , and Moraxella catarrhalis . The agent's mechanism of action involves dual targeting of two essential bacterial enzymes: DNA gyrase and topoisomerase IV. Gemifloxacin was approved by the Food and Drug Administration in April 2003 for treatment of community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis. The drug has an oral bioavailability of approximately 71%. Approximately 20-35% of gemifloxacin is excreted unchanged in the urine after 24 hours. The elimination half-life of gemifloxacin is 6-8 hours in patients with normal renal function, supporting once-daily dosing. The 24-hour free-drug area under the plasma concentration-time curve:minimum inhibitory concentration ratio (fAUC(0-24):MIC) associated with efficacy, based on results from in vitro and animal models of infection, is approximately 30. With a mean fAUC(0-24) of approximately 3 microg*hour/ml (35% of total AUC(0-24) of 8.4) and a median S. pneumoniae MIC for 90% of tested strains of 0.03, a fAUC(0-24):MIC ratio of 100 would be expected after standard dosing (320 mg once/day). In clinical studies involving both hospitalized and outpatient populations, gemifloxacin has been highly effective in the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis. Clinical success rates ranged from 93.9-95.9% in patients with community-acquired pneumonia and 96.1-97.5% in those with acute exacerbation of chronic bronchitis. Gemifloxacin is well tolerated; the frequency of adverse events with this agent is low. Most adverse events are mild-to-moderate in severity, with diarrhea (< 4%), nausea and rash (< 3%), and headache (< 2%) most commonly reported. Drug interactions with gemifloxacin are not common, although absorption is greatly reduced when given with divalent and trivalent cation-containing compounds, such as antacids. Due to its potent activity against many common gram-positive and gram-negative respiratory pathogens, its proven clinical efficacy, and its favorable safety profile, gemifloxacin is a highly effective empiric treatment for community-acquired lower respiratory tract infections.
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PMID:Gemifloxacin for the treatment of respiratory tract infections: in vitro susceptibility, pharmacokinetics and pharmacodynamics, clinical efficacy, and safety. 1589 34

A 15-year-old man presented with headache. Magnetic resonance (MR) imaging revealed a large extraaxial tumor with cyst at the right frontotemporal region. The solid part of the tumor was homogeneously enhanced on T(1)-weighted MR imaging after injection of gadolinium. Digital subtraction angiography of the external carotid artery revealed sunburst appearance corresponding to the tumor, which was fed by the right middle meningeal artery. His headache worsened and computed tomography revealed enlargement of the tumor and intracystic hemorrhage, so emergent operation was performed. At surgery, the tumor strongly adhered to the dural membrane, and was obviously extraaxial. The tumor and cyst were gross totally removed. The attachment site at the dura mater was resected. Histological examination showed solid growth of small round cells with uniform round nuclei and minimal cytoplasm. Immunohistochemical staining showed the cells were positive for MIC-2 (CD99). The MIB-1 labeling index was 53%. The histological diagnosis was peripheral-type primitive neuroectodermal tumor (pPNET). Following surgery, radiation therapy and chemotherapy were given. Ewing's sarcoma and pPNET form a family of small round cell tumors arising in the bone or soft tissue. MIC-2 is a useful marker in the differential diagnosis. Good prognosis may be attained if complete surgical excision of intracranial pPNET is achieved.
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PMID:Intracranial peripheral-type primitive neuroectodermal tumor. 1829 76

Eremostachys laciniata (L) Bunge (family: Lamiaceae alt. Labiatae; subfamily: Lamioideae) is one of the 15 endemic Iranian herbs of the genus Eremostachys. A decoction of the roots and flowers of E. laciniata has traditionally been taken orally for the treatment of allergies, headache and liver diseases. Three antibacterial iridoid glucosides, phloyoside I (1), phlomiol (2) and pulchelloside I (3) have been isolated from the rhizomes of this plant. The structures of these compounds were elucidated unequivocally by a series of 1D and 2D NMR analyses. The antibacterial activity and brine shrimp toxicity of these compounds were assessed using the resazurin microtitre assay and the brine shrimp lethality assay, respectively. All three iridoid glycosides 1-3 exhibited from low to moderate levels (MIC = 0.05-0.50 mg/mL) of antibacterial activity. Of these compounds, compound 3 was the most active, and displayed antibacterial activity against 9 of 12 different strains tested. The most noteworthy activity of 3 was against Bacillus cereus, penicillin-resistant Escherichia coli, Proteus mirabilis and Staphylococcus aureus with an MIC value of 0.05 mg/mL.
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PMID:Antibacterial iridoid glucosides from Eremostachys laciniata. 1869 3


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