PubMed Health⌕ Search

Biomedical subjects

F Y Aoki

Publications and source records attributed to F Y Aoki.

At least 19 recordsLinked to original sources
PubMed2003

Early administration of oral oseltamivir increases the benefits of influenza treatment.

Our objective was to evaluate the benefit of early treatment of influenza illness using oral oseltamivir. This open-label, multicentre international study investigated the relationship between the interval from illness onset to first dose (time-to-treatment) and illness duration in the intent-to-treat infected population using accelerated failure time (AFT) modelling. A total of 1426 patients (12-70 years) presenting within 48 h of the onset of influenza symptoms were treated with oseltamivir 75 mg twice a day for 5 days during the 1999-2000 influenza season; 958 (67%) had laboratory-confirmed influenza virus infection. Earlier intervention was associated with shorter illness duration (P < 0.0001). Initiation of therapy within the first 12 h after fever onset reduced the total median illness duration by 74.6 h (3.1 days; 41%) more than intervention at 48 h. Intermediate interventions reduced the illness proportionately compared with 48 h. In addition, the earlier administration of oseltamivir further reduced the duration of fever, severity of symptoms and the times to return to baseline activity and health scores. Oseltamivir was well tolerated. The most common adverse events were nausea and vomiting, which were transient and generally occurred only with first dosing. When oseltamivir was taken with food, the tolerability was enhanced. The overall discontinuation rate was low (1.8%). In conclusion, the IMPACT study demonstrated that earlier initiation of oral oseltamivir therapy increased its therapeutic effects, which were seen at every time point of intervention and were progressive. Thus, early presentation, diagnosis and treatment of patients with influenza maximized the benefits of oseltamivir therapy.

Acetamides↗
PubMed2001

Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers.

BACKGROUND: Vitamin A is involved in normal immune function and the maintenance of mucosal integrity through complex effects on cellular differentiation. OBJECTIVE: We sought to determine whether serum vitamin A levels were associated with altered susceptibility to primary infection with HIV-1 in men with high-risk sexual behaviour and genital ulcers who presented for treatment at an STD clinic in Nairobi, Kenya. METHODS: HIV-1 seronegative men were prospectively followed. Vitamin A levels at study entry were compared among 38 men who HIV-1 seroconverted versus 94 controls who remained HIV seronegative. RESULTS: Vitamin A deficiency (retinol less than 20 microg/dl) was very common and was present in 50% of HIV-1 seroconverters versus 76% of persistent seronegatives. Seroconversion was independently associated with a retinol level greater than 20 microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04). Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23-0.93, P = 0.03). CONCLUSION: Vitamin A deficiency was not associated with an increased risk of HIV-1 infection among men with concurrent STD. A decreased risk of HIV-1 seroconversion was independently associated with lower retinol levels. The effects of vitamin A on macrophage and lymphoid cell differentiation may paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable individuals, such as men with genital ulcers. Lack of circumcision and chancroid are confirmed as important co-factors for heterosexual HIV-1 transmission. The role of vitamin A in heterosexual HIV-1 transmission requires further study.

Adult↗
PubMed2001

An outbreak of methicillin resistant Staphylococcus aureus on a burn unit: potential role of contaminated hydrotherapy equipment.

OBJECTIVE: To report a multi-institution outbreak caused by a single strain of methicillin-resistant Staphylococcus aureus (MRSA). OUTBREAK: Between September 19 and November 20, 1996 an index case and five secondary cases of nosocomial MRSA occurred on a 26 bed adult plastic surgery/burn unit (PSBU) at a tertiary care teaching hospital. Between November 11 and December 23, 1996, six additional cases were identified at a community hospital. One of the community hospital cases was transferred from the PSBU. All strains were identical by pulsed-field gel electrophoresis. MRSA may have contributed to skin graft breakdown in one case, and delayed wound healing in others. Patients required 2 to 226 isolation days. CONTROL MEASURES: A hand held shower and stretcher for showering in the hydrotherapy room of the PSBU were culture positive for the outbreak strain, and the presumed means of transmission. Replacement of stretcher showering with bedside sterile burn wound compresses terminated the outbreak. The PSBU was closed to new admissions and transfers out for 11 days during the investigation. Seven of 12 patients had effective decolonization therapy. CONCLUSION: Environmental contamination is a potential source of nosocomial MRSA transmission on a burn unit. Notification among institutions and community care providers of shared patients infected or colonized with an antimicrobial resistant microorganism is necessary.

Adult↗
PubMed2001

Oseltamivir: a clinical and pharmacological perspective.

Oseltamivir is the ethyl ester prodrug of the antiviral molecule, oseltamivir carboxylate, a potent and selective inhibitor of influenza A and B neuraminidase (NA) (sialidase). It is highly bioavailable in capsule and suspension formulations and, after conversion to the active metabolite in the liver, distributes throughout the body, including the upper and lower respiratory tract. Oseltamivir carboxylate is 3% bound to human plasma proteins and eliminated through the kidneys by a first-order process as unchanged drug by glomerular filtration and tubular secretion by an anionic transporter system. Given these characteristics, its potential for adverse interactions with other drugs appears limited to those arising from competitive inhibition of excretion by the renal tubular epithelial cell anionic transporter. The terminal plasma elimination half-life is 1.8 h in healthy adults. Renal clearance is inversely related to renal function and averages 23 h after oral administration in individuals with creatinine clearance < 30 ml/min. In vitro studies have demonstrated potent antiviral activity against all strains of influenza A and B tested including avian H5N1 and H9N2 strains recently implicated in human cases in Hong Kong. Studies of both experimental and naturally-occurring influenza in humans have demonstrated efficacy in both the prevention and treatment of influenza A and B infection. The drug is well-tolerated with the only clinically important side effect being mild gastrointestinal upset. Resistance has been uncommonly seen after clinical use; the highest incidence was 5.5% in children treated for influenza A infection for 5 days. Viruses that develop resistance appear to be less virulent in laboratory animals and to replicate less efficiently than parent strains. Although oseltamivir and the M2 ion channel inhibitors, amantadine and rimantadine, have not been directly compared in clinical trials, the greater breadth of spectrum of oseltamivir, its modest side effect profile compared to amantadine and its lesser propensity to engender the emergence of transmissible drug-resistant strains all suggest strongly that oseltamivir is a significant new agent for the prevention and treatment of influenza. A series of controlled trials comparing M2 ion channel inhibitor drugs and the new neuraminidase (NA) inhibitor agents are now needed to test this hypothesis and thereby to further advance the science of antiviral drug use to control influenza.

Acetamides↗
PubMed2001

Comparative bioavailability of acyclovir from oral valacyclovir and acyclovir in patients treated for recurrent genital herpes simplex virus infection.

The bioavailabilities of acyclovir from capsules of valacyclovir, the L-valyl ester of acyclovir, and acyclovir were compared by measuring urinary excretion of the drug in a double blind, placebo-controlled field trial of patient-initiated treatment for recurrent genital herpes. Forty-six healthy patients with recurrent genital herpesvirus infection were randomly assigned to receive acyclovir 200 mg five times daily (n=20), valacyclovir 1000 mg twice daily (equivalent to 694 mg acyclovir twice daily) (n=18) or placebo (n=6). Thirty-three patients on the active treatments provided the required 24 h urine samples for assessment of bioavailability. The acyclovir treatment group excreted 267+/-178 mg (mean +/- SD), and the valacyclovir treatment group excreted 623+/-248 mg (mean +/- SD) acyclovir over 24 h. The mean acyclovir bioavailabilities, estimated from urinary acyclovir excretion, were 26.7+/-17.8% and 44.9+/-17.9% for acyclovir and valacyclovir, respectively (P<0.007). There was no effect of sex on acyclovir bioavailability with either drug. The relative mean bioavailability of acyclovir was 68% greater from the prodrug formulation. This field trial in patients who self-initiated treatment for recurrent genital herpes confirmed that the prodrug valacyclovir provided significantly greater acyclovir bioavailability than the parent drug, as initially shown in volunteers in clinical pharmacokinetic studies.

Acyclovir↗
PubMed2001

Management of genital herpes in HIV-infected patients.

The management of genital herpes in patients infected with human immunodeficiency virus (HIV) differs from that in individuals with genital herpes because of the significant interaction between the two viruses involved. HIV-induced immunodeficiency increases the frequency and severity of recurrent anogenital herpes simplex virus (HSV) shedding and disease as well as the risk of developing drug-resistant HSV infection. HSV infection, in turn, increases HIV replication and the risk of HIV transmission. The advent of highly active antiretroviral therapy has facilitated therapy for genital herpes, but important unanswered questions remain about the optimal therapy of drug-sensitive and -resistant genital herpes and the role of antiherpes drugs in reducing HIV disease progression and the risk of HIV transmission.

AIDS-Related Opportunistic Infections↗
PubMed2000

Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group.

OBJECTIVE: To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals. DESIGN: Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter. SETTING: Forty-eight hospital-based or specialist public-health clinics in 12 countries. PATIENTS: Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions. MAIN OUTCOME MEASURES: Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures). RESULTS: Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events. CONCLUSIONS: Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.

2-Aminopurine↗
PubMed2000

Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group.

BACKGROUND: Use of some antiviral drugs for influenza infection is limited by potential rapid emergence of resistance. We studied the efficacy and safety of oseltamivir, the oral prodrug of the neuraminidase inhibitor GS4071, in adults with naturally acquired laboratory-confirmed influenza. METHODS: We did a randomised controlled trial of 726 previously healthy non-immunised adults with febrile influenza-like illness of up to 36 h duration. Patients were assigned oral oseltamivir 75 mg (n=243), oseltamivir 150 mg (n=245), or placebo (n=238) twice daily for 5 days. We assessed recovery by questionnaire and temperature recordings. The primary endpoint was time to resolution of illness in influenza-infected patients. FINDINGS: 475 (66%) patients had confirmed infection. Duration of illness was significantly shorter by 29 h (25% reduction, median duration 87.4 h [95% CI 73.3-104.7], p=0.02) with oseltamivir 75 mg and by 35 h (30%, 81.8 h [68.2-100.0], p=0.01) with oseltamivir 150 mg than with placebo (116.5 h [101.5-137.8]). The effect of oseltamivir was apparent within 24 h of the start of treatment. In patients treated within 24 h of symptom onset, symptoms were alleviated 43 h (37% reduction) and 47 h (40%) earlier with oseltamivir 75 mg and 150 mg, respectively, compared with placebo (75 mg 74.5 h [68.2-98.0], p=0.02; 150 mg 70.7 h [54.0-89.4], p=0.01; placebo 117.5 h [103.0-143.8]). Oseltamivir was associated with lower [corrected] symptom scores, less viral shedding, and improved health, activity, and sleep quality, and was well tolerated. INTERPRETATION: Oseltamivir was effective and well tolerated in the treatment of natural influenza infection in adults. The efficacy, tolerability, and ease of administration warrant further investigation in children, elderly patients, and at-risk patients.

Acetamides↗
PubMed2000

Prospects for control of herpes simplex virus disease through immunization.

Herpes simplex viruses (HSVs) can cause a variety of infections, including genital herpes. Despite effective antiviral therapy, HSV infections remain a significant worldwide public health problem. Vaccines offer the best hope for controlling spread and limiting HSV disease. This article discusses the pathogenesis and immunobiology of mucocutaneous HSV infections, summarizes the spectrum of diseases caused by HSV, and provides a review of the field of HSV vaccine research. This article also discusses what might be realistically expected of a vaccine intended for control of genital herpes and explores the question of whether a vaccine that is effective in controlling genital HSV disease might also be effective in controlling nongenital HSV disease. The efficacy of such vaccines for the full spectrum of HSV disease will eventually determine the timing and targeting of immunization, ranging from selective immunization in preadolescence to universal childhood immunization as part of the routine childhood regimen.

Female↗
PubMed2000

Impact of zanamivir treatment on productivity, health status and healthcare resource use in patients with influenza. Zanamivir Study Group.

OBJECTIVE: This study examined the impact of zanamivir treatment on patient morbidity in patients with influenza. DESIGN AND SETTING: This was a multicentre, randomised, double-blind, parallel-group study conducted in 14 countries in Europe and North America during the winter of 1995/1996. PATIENTS AND PARTICIPANTS: The study included 722 individuals with virologically confirmed influenza. INTERVENTIONS: Two different zanamivir treatment regimens [twice daily (bid) or 4 times daily (qid) for 5 days] were compared with placebo. MAIN OUTCOME MEASURES AND RESULTS: Efficacy was measured using a number of patient-assessment questionnaires. Results showed that significantly fewer patients with influenza who were treated with zanamivir had additional contacts with healthcare professionals compared with those who received placebo (8 vs 14%; p < or = 0.049, bid and qid vs placebo). Individuals treated with zanamivir also spent fewer days absent from work (placebo: mean = 3.28 days; qid: mean = 2.52 days; p = 0.031) or college/school (placebo: mean = 2.90 days; bid: mean = 2.24 days; p = 0.032), and showed significant improvements in productivity compared with placebo. The health status questionnaire revealed significant improvements in patient well-being over the first 5 days of the study in those treated with zanamivir compared with those who received placebo. CONCLUSIONS: Zanamivir treatment reduced absenteeism, improved patient productivity and well-being, and reduced the additional use of healthcare resources in patients with influenza.

Adult↗
PubMed1998

Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group.

Uveitis occurred in a substantial proportion of AIDS patients receiving rifabutin, 600 mg daily, together with clarithromycin and ethambutol for treatment of Mycobacterium avium complex bacteremia. A case-control study was undertaken to examine potential risk factors for developing uveitis. Of eight parameters examined, only baseline body weight predicted the development of uveitis by both univariate and multivariate analyses (P = .001). The incidence of uveitis was 14% in patients weighing >65 kg, 45% in patients between 55 and 65 kg, and 64% in patients <55 kg. Concomitant therapy with fluconazole, a drug known to raise serum rifabutin concentrations, was not associated with an increased incidence of uveitis. The risk of uveitis was markedly reduced when rifabutin was given at 300 mg daily in combination with clarithromycin and ethambutol.

AIDS-Related Opportunistic Infections↗
PubMed1997

Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group.

BACKGROUND: The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases. These viral enzymes are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, zanamivir has potent antiviral effects. We assessed the therapeutic activity of zanamivir in adults with acute influenza. METHODS: We conducted separate randomized, double-blind studies in 38 centers in North America and 32 centers in Europe during the influenza season of 1994-1995. A total of 417 adults with influenza-like illness of < or =48 hours' duration were randomly assigned to one of three treatments: 6.4 mg of zanamivir by intranasal spray plus 10 mg by inhalation, 10 mg of zanamivir by inhalation plus placebo spray, or placebo by both routes. Treatments were self-administered twice daily for five days. RESULTS: Of 262 patients with confirmed influenza-virus infection (63 percent of all patients), the median length of time to the alleviation of all major symptoms was one day shorter (four days vs. five days) in the 88 patients given inhaled and intranasal zanamivir (P=0.02) and the 85 patients given inhaled zanamivir alone (P=0.05) than in the 89 patients given placebo. Among the infected patients who were febrile at enrollment and among those who began treatment within 30 hours after the onset of symptoms, the median time to the alleviation of major symptoms was four days in both zanamivir groups and seven days in the placebo group (P< or =0.01). Viral titers of nasal washings in the group given inhaled and intranasal zanamivir were significantly lower than those in the placebo group. The topically administered zanamivir was well tolerated. CONCLUSIONS: In adults with influenza A or B virus infections, direct administration of a selective neuraminidase inhibitor, zanamivir, to the respiratory tract is safe and reduces symptoms if begun early.

Administration, Inhalation↗
PubMed1997

Topical undecylenic acid for herpes simplex labialis: a multicenter, placebo-controlled trial.

A multicenter, patient-initiated, double-blind, placebo-controlled trial of 15% undecylenic acid cream was conducted with 573 patients with recurrent herpes labialis. Treatment was applied 5 or 6 times daily until crusting and then thrice daily until healing. Patients were assessed daily until 48 h after crusting and then every other day until healing. Undecylenic acid significantly reduced the incidence and duration of viral shedding and the duration and severity of itching but did not increase abortive episodes or reduce times to healing, crusting, or progression of lesion size. When treatment was initiated during the prodrome, the time to crusting was reduced (P = .02) and the area under the symptom-time curve for pain and tenderness was reduced, approaching statistical significance (P = .06). Active treatment was well tolerated but caused dysgeusia and local irritation. Undecylenic acid 15% cream reduces viral shedding in recurrent herpes labialis, but clinical benefits are minimal and largely restricted to patients initiating therapy during the prodrome.

Administration, Topical↗
PubMed1997

Pharmacokinetics of antimycobacterial drugs in patients with tuberculosis, AIDS, and diarrhea.

To test the hypothesis that antituberculous drug disposition is altered in patients with AIDS, we studied the steady-state pharmacokinetics of isoniazid (300 mg/d), rifampin (600 mg/d), and pyrazinamide (1,500 mg/d) in 29 adults (14 patients infected with human immunodeficiency virus [HIV] and 15 non-HIV-infected patients) with tuberculosis in Nairobi, Kenya. Intestinal integrity was assessed with xylose. Neither HIV infection nor diarrhea accounted for the interpatient variability in the area-under-the-plasma concentration vs. time curve (AUC), the maximum concentration, or the terminal half-life (t1/2) of isoniazid, rifampin, and pyrazinamide. No significant association between HIV infection or diarrhea and pharmacokinetics was seen for any of the compounds. In addition, neither the AUC nor the t1/2 of any of these drugs reflected interpatient differences in CD4 lymphocyte counts. Xylose absorption was uniformly low. We did not demonstrate that HIV infection, diarrhea, or CD4 lymphocyte counts contributed significantly to the variability in pharmacokinetics of isoniazid, rifampin, and pyrazinamide in TB patients in Nairobi.

AIDS-Related Opportunistic Infections↗