Biomedical subjects

F Y Aoki

Publications and source records attributed to F Y Aoki.

At least 37 records · Page 2Linked to original sources

PubMed1996

Patient-initiated, twice-daily oral famciclovir for early recurrent genital herpes. A randomized, double-blind multicenter trial. Canadian Famciclovir Study Group.

OBJECTIVE: To compare the efficacy and safety of episodic patient-initiated oral famciclovir with placebo in recurrent genital herpes. DESIGN: Randomized, double-blind, frequent-observation, dose-ranging study comparing twice-daily 125-mg, 250-mg, or 500-mg oral famciclovir with placebo. Patients initiated therapy after self-culturing, reported to the clinic within 12 hours, and were assessed twice daily for at least 5 days. SETTING: Fifteen Canadian university, private practice, or public outpatient clinics. PATIENTS: A total of 692 patients with culture-proven recurrent genital herpes were randomized; 467 patients experienced a symptomatic episode and commenced treatment. MAIN OUTCOME MEASURE: Time to complete healing of all lesions. RESULTS: Famciclovir (all doses) was significantly more effective than placebo in reducing time to healing, time to cessation of viral shedding, and durations of lesion edema, vesicles, ulcers, and crusts. Times to cessation of all symptoms and of moderate to severe lesion tenderness, pain, and burning were also reduced. Patients who initiated famciclovir prior to viral shedding were more likely to not shed virus throughout. All doses were equally effective, safe, and well tolerated. CONCLUSIONS: Oral famciclovir reduced the onset and duration of viral shedding, lesion persistence, and uncomfortable symptoms. Several individual symptoms and lesion stages were also reduced in duration by this episodic therapy. Additionally, our twice-daily observation trial design proved to be a helpful tool for studying recurrent disease. Episodic oral famciclovir provides a convenient and effective alternative for those patients with recurrent genital herpes whose frequency rates do not require continuous antiviral suppression.

2-Aminopurine↗

PubMed1996

Percutaneous feeding tube changes in long-term-care facility patients.

OBJECTIVE: To compare patient outcomes when percutaneous feeding tubes were changed routinely each month or only when necessary (prn). DESIGN: Prospective, randomized, nonblinded crossover study of 6 months of routine monthly changes compared with 6 months of prn changes. SETTING: 416-bed long-term-care facility. PATIENTS: 26 permanent residents with nutrition managed through percutaneous gastrostomy or jejunostomy feeding tubes. The median age was 61.5 years; 8 (31%) also had tracheostomies, and 3 (12%) had indwelling urinary catheters. RESULTS: The frequency of feeding tube changes was 40 per 1,000 patient-days during the 6 months of routine tube changes and 14 per 1,000 when tubes were changed prn (P < .001). There were no differences between the two study periods in frequency of stoma site infections, fever, episodes of emesis, and total antibiotic courses. The median duration in situ of feeding tubes with prn changes was 104 days. For both periods, feeding tubes were significantly more likely to fall out and require replacement with-in 24 hours of previous tube replacement. CONCLUSION: There were no observed differences in clinical outcomes in long-term-care facility patients when feeding tubes were changed only as necessary as compared to routine monthly changes.

Adult↗

PubMed1995

Chronic tobacco smoking and gender as variables affecting amantadine disposition in healthy subjects.

Amantadine HCl (3 mg kg-1) was administered orally to 20 young healthy adults. Its apparent volume of distribution (V2/F) was higher in smokers than nonsmokers, 6.05 +/- 0.86 vs 4.87 +/- 0.85 l kg-1; (mean +/- s.d., 10/group, P < 0.011), and no gender-associated effect was observed. Renal clearance did not vary with time-interval, but urinary recovery at 48 h was higher in men than in women (60.2 +/- 7.5% vs 47.0 +/- 15.0%, P < 0.032). Males had higher renal clearances than females when normalised for body mass index (BMI, 0.492 +/- 0.284 vs 0.248 +/- 0.137 l-1 BMI h-1, (10/group, P < 0.032)). On combining data from a previous study, the weight normalised renal clearance was also higher in men than in women, 0.160 +/- 0.075 vs 0.102 +/- 0.053 l kg-1 h-1 (19/group, P < 0.01). Chronic tobacco smoking did not alter the plasma or renal amantadine clearance. We conclude that gender and tobacco smoking are independent variables effecting amantadine disposition.

Administration, Oral↗

PubMed1994

Pharmacokinetic disposition of loracarbef in healthy young men and women at steady state.

The pharmacokinetic disposition of 200- and 400-mg doses of a novel carbacephem, loracarbef, was determined over a dose interval on day 8, after ingestion of drug doses twice daily for 7 days, in 20 young, healthy volunteers of both genders. Drug was analyzed in plasma, urine, saliva, vaginal secretions, and fecal filtrate. Peak plasma concentration was proportional to dose for both men (4.0 +/- 1.3 and 8.8 +/- 3.4 mg/L) and women (8.0 +/- 5.6 and 15.3 +/- 3.3 mg/L), and the observed time to peak increased from 1 to 2 hours with the increased dose. Apparent volume of distribution was greater in men than women (0.385 +/- 0.114 versus 0.270 +/- 0.075 L/kg; P < .03). The drug was virtually quantitatively excreted unchanged in urine, and its renal clearance exceeded creatinine clearance in all subjects. Renal loracarbef clearance correlated with neither weight-corrected dose nor creatinine clearance in these healthy subjects. There was no evidence for drug accumulation in the body with chronic ingestion. Loracarbef was detected in the fecal filtrate of seven volunteers, but did not account for more than 7% of the daily dose. Loracarbef was detected in vaginal secretions of two of five volunteers who ingested the 400-mg dose. No drug was detected in saliva obtained just before dose ingestion. These data are consistent with complete bioavailability for an oral beta-lactam antibiotic drug that is virtually completely eliminated unchanged by the kidney.

Adult↗

PubMed1994

Influenza immunization: knowledge, attitude and behaviour of health care workers.

Knowledge, attitude and behaviour regarding influenza immunization were evaluated in 519 health care workers (HCWs) from high risk hospital areas because of this target group's historically poor acceptance rates. The results of this self-administered questionnaire survey indicated that HCWs' knowledge regarding influenza and influenza vaccine was generally satisfactory. However, only approximately one half of the HCWs knew who should receive influenza vaccine and why it is important. HCWs with good knowledge of influenza and the influenza vaccine were more likely to recommend vaccine to their patients and to their co-workers/family, but were not more likely to receive it themselves. Experiencing post-vaccine symptoms for more than one day significantly reduced the willingness of HCWs to accept and to recommend vaccine. HCWs who heard about influenza vaccine from their doctors indicated significantly more willingness to receive vaccine and to recommend vaccine to co-workers and family. Questionnaire survey of willingness to accept influenza vaccine overestimated actual acceptance, as only 35.7% of the HCWs who had positive views regarding the influenza vaccine actually received the vaccine during the following influenza season. While knowledge about the vaccine, previous experience with perceived adverse symptoms and promotion by family doctor significantly influenced questionnaire responses, hearing about the vaccine from the occupational health department, being on a geriatric ward or being a unit assistant were the most significant factors in actually being vaccinated. Thus, occupational health departments must continue their efforts to promote the influenza vaccine actively and to make it as accessible as possible.

Adolescent↗

PubMed1993

Effects of acetaminophen on adverse effects of influenza vaccination in health care workers.

OBJECTIVE: To evaluate the effects of acetaminophen on the incidence of adverse effects to, and the immunogenicity of, whole-virus influenza vaccine in health care workers. DESIGN: Prospective, randomized, double-blind placebo-controlled trial. SETTING: Health Sciences Centre, an acute care teaching hospital in Winnipeg. PARTICIPANTS: Of 474 hospital personnel who agreed to undergo influenza vaccination during the 1990-91 season 262 volunteered to participate in the study. INTERVENTIONS: A dose of 0.5 mL of inactivated trivalent whole-virus influenza vaccine was injected into the deltoid muscle. Volunteers were randomly assigned to ingest two capsules of acetaminophen in a half dose (162.5 mg per capsule) or a full dose (325 mg per capsule) or two identical placebo capsules. Capsules were to be taken at vaccination and at 4, 8 and 12 hours afterward. Subjects were asked to answer questions regarding six symptoms in a diary for the 3 days after vaccination and to record their ingestion of the study medication. MAIN OUTCOME MEASURES: Incidence of local (sore arm) and systemic (headache, fever, muscle ache, nausea and diarrhea) side effects as well as serum titres of hemagglutination inhibition (HAI) antibody to vaccine antigens before vaccination and 2 weeks and 6 months afterward. RESULTS: A total of 87, 87 and 88 subjects received the half dose, full dose and placebo respectively; 96% returned the diaries, 83% ingested all four doses of medication, and 87% volunteered all blood samples. Compared with the placebo group the incidence of sore arm was 25% to 28% lower in the half-dose and full-dose groups respectively at 24 hours after vaccination, and the rate of nausea was 90% lower in the full-dose group. The HAI titres were similar among the groups at the three test times. CONCLUSIONS: The full dose of acetaminophen significantly reduced the incidence of sore arm and nausea without affecting the antibody response. Acetaminophen use may increase the acceptance of influenza vaccine by health care workers in whom concern about side effects is an impediment to vaccination.

Acetaminophen↗

PubMed1993

Stress-induced reactivation of latent herpes simplex virus infection in rat lumbar dorsal root ganglia.

Clinical reports suggest that stress precipitates recurrent cutaneous Herpes simplex virus (HSV) infection, presumably by reactivating latent infection in sensory ganglia with subsequent centrifugal axonal spread to the skin. As an initial test of this hypothesis, rats with latent HSV, type-1, (HSV-1) infection in lumbar dorsal root ganglia (DRG) were exposed to a well-characterized acute stressor that produced gastric ulcers (U) and elevated plasma corticosterone (CS) concentrations. Stress-induced reactivation of latent HSV infection was suggested by the earlier appearance of cytopathic effect (CPE) in human foreskin fibroblast monolayers co-cultivated with ganglia from stressed rats than from nonstressed ones (4.5 +/- 0.2 and 6.4 +/- 0.4 [mean +/- SEM] days respectively; p < 0.001). No CPE was detected in monolayers co-cultivated with ganglia from non-infected rats. These initial results suggest that acute stress reactivates latent HSV-1 ganglionic infection.

Animals↗

PubMed1993

Gender and age as factors in the inhibition of renal clearance of amantadine by quinine and quinidine.

We studied the short-term effect of oral doses of quinine and quinidine on the renal clearance of amantadine in healthy young (age range, 27 to 39 years) and older (age range, 60 to 72 years) adults of both genders in a three-limbed randomized crossover study. Renal clearance of amantadine (13.2 +/- 5.8 L/hr) was significantly inhibited by quinine (9.7 +/- 4.8 L/hr) and quinidine (8.9 +/- 4.0 L/hr) only in male subjects and was not associated with age. The chiral selectivity for the renal clearance of quinidine over quinine was confirmed and extended with the suggestion of both age- and gender-associated changes on the renal clearance ratio for these two diastereomeric drugs. These data support the continued use of amantadine for studies on the renal elimination of organic cationic drugs.

Adult↗

PubMed1993

Immunohistological characterisation of acute herpes simplex virus infection of lumbar dorsal root ganglia in the rat.

After inoculation of herpes simplex virus (HSV) into the dorsal skin of the hind paw of rats, HSV antigen was detected in dorsal root ganglion neurones by immunohistochemistry. Antigen was first detected 2 days after inoculation. Between 2 and 4 days after inoculation, numerous small-type unmyelinated neurones gave positive staining reactions for HSV antigens. Necrosis of neuronal cells was evident by 4 days. Antigen was not detected 6 or 9 days after inoculation. Immunohistological studies of co-cultivated ganglia removed from the infected monolayers, immediately after cytopathic effect first appeared or 24 h later, uniformly revealed virus antigen staining of small-type unmyelinated neuronal cells.

Acute Disease↗

PubMed1993

A placebo-controlled dose-finding study with bambuterol in elderly patients with asthma.

A new long-acting bronchodilator prodrug, bambuterol hydrochloride, was tested in a randomized, crossover, and double-blind study in elderly asthmatic patients (aged 64 to 82 years). They received placebo and 5-mg, 10-mg, and 20-mg tablets once daily for a week at each dose. The plasma concentration of the active metabolite, terbutaline, increased linearly with the dose of drug (p < 0.001). Peak expiratory flow rate increased with dose in the morning (p < 0.001 for 10-mg and 20-mg doses) and afternoon (p < 0.05 for 10 mg; p < 0.001 for 20 mg) and was different from placebo for the 10-mg/d and 20-mg/d regimens. The use of supplemental inhaled beta 2-adrenergic agonist therapy was reduced during the night for the 10-mg (p < 0.05) and 20-mg (p < 0.01) doses in comparison to placebo. No significant effects of treatment on blood pressure and pulse were demonstrated. Tremor and palpitations were mild and related to the dose. These data suggest that treatment once daily with bambuterol hydrochloride in a dose of 10 or 20 mg improves pulmonary function and is well tolerated as bronchodilator therapy in elderly patients with asthma.

Aged↗

PubMed1993

Frequency of changing enteral alimentation bags and tubing, and adverse clinical outcomes in patients in a long term care facility.

Enteral alimentation, given via nasogastric or gastrostomy tubes, is a well established practice to provide nutrition for patients with significant neurological injury. The frequency with which enteral feeding bags and tubes require change and potential adverse effects associated with bacterial contamination of tube feeds remain controversial. The authors studied different times between enteral feeding bag and tube changes, and the effect on adverse clinical outcomes in residents of a long term care facility. In the first study, residents were randomized to 24 h (n = 2), 48 h (n = 3) or 72 h (n = 6) tube feeding and bag changes with clinical status monitored in a standardized fashion for six months. In the second study, patients were randomized to 24 h (n = 6) or 72 h (n = 6) changes. Patient-days of follow-up were 382, 574 and 1000 for the three arms of the first study period and 556 and 496 for the two arms of the second study. No differences in potential clinical adverse events--including fever, gastrointestinal symptoms or pneumonia--were observed with different durations of tubing change. This study suggests it is appropriate to change alimentation tube and feeding bags every 72 h (rather than every 24 h). The less frequent changes will decrease supply costs and free nursing time for other activities.

Aged↗

PubMed1992

In vitro reactivation of latent herpes simplex virus by the demethylating compound hexamethylene-bis-acetamide.

We have characterized previously a model of herpes simplex virus (HSV) infection of rat dorsal root ganglia (DRG) following cutaneous infection. During acute infection HSV can be isolated from co-cultivated rat ganglia in (mean +/- S.E.M.) 4.8 +/- 0.33 days (d) and from latently infected ganglia in 7.8 +/- 0.53 (d) (P < or = 0.0001). We treated co-cultivated rat ganglia from acute and latent infected rats with the demethylating compound hexamethylene-bis-acetamide (HEX) to see what effect, if any, it would have on HSV infection. HEX-treated ganglia from rats with acute infection did not differ significantly from controls in the proportion of rats, skin or ganglia positive for HSV. The mean time to detect virus was not different between treated (3.6 +/- 0.38 d) and control (3.1 +/- 0.46 d) (P > 0.05) groups. In latent infected rats there was no difference between treated and controlled groups in the proportions of rats, skin and ganglia positive for HSV. There was a significant difference in the mean time to CPE between the HEX and control groups respectively (4.5 +/- 0.72 d vs 8.92 +/- 1.42 d, P < 0.01). We conclude that HEX converted latent HSV infection to a productive one.

Acetamides↗

PubMed1992

Effects of chronic amantadine hydrochloride ingestion on its and acetaminophen pharmacokinetics in young adults.

The authors studied the effect of chronic amantadine ingestion on its own disposition and that of acetaminophen in five healthy young adults. The half-life of amantadine after 42 days ingestion was 15.1 +/- 2.3 hours and was not different from 14.8 +/- 4.4 hours after an acute ingestion (mean +/- SD). However, chronic amantadine ingestion was associated with an increased apparent volume of distribution for acetaminophen, 1.1 +/- 0.1 L/kg compared with 0.9 +/- 0.1 L/kg, when the two drugs were concurrently ingested after a 2-week washout period. This difference in kinetic distribution was not reflected in terminal acetaminophen half-life, 149 +/- 54 versus 151 +/- 55 minutes for chronic and acute amantadine ingestion, respectively. Plasma acetaminophen clearance with chronic amantadine ingestion (5.8 +/- 2.6 mL/min/kg) was not different from that determined after acute coingestion of both drugs (4.3 +/- 1.1 mL/min/kg). Thus, no change in recommended dose is necessary when these two drugs are coingested.

Acetaminophen↗

PubMed1992

Rabies neutralizing antibody in serum of children compared to adults following post-exposure prophylaxis.

Rabies neutralizing antibody concentrations in serum (SRNA) elicited by experimental post-exposure prophylaxis (PEP) regimens are used to assess their potential clinical efficacy. Although PEP with human rabies immunoglobulin (HRIG) plus human diploid-cell culture vaccine (HDCV) is almost completely protective, the limited availability of these components has stimulated the search for alternative regimens. Since 33% to over 60% of PEP is administered to children, a need exists for data on the SRNA response to HRIG plus HDCV in children, to be used to assess the potential value of alternative PEP treatments. We measured SRNA by the rapid fluorescent focus inhibition test on days 0, 1, 3, 7, 14, 28, 56 and 90 after initiation of PEP with HRIG (20 IU/kg) and HDCV (1.0 ml on day 0, 3, 7, 14, 28) in 10 children [8 +/- 4 (mean +/- SD) years of age] and 32 adult control patients (38 +/- 16 years of age). Early, uniform appearance of SRNA was observed with no differences between groups. These data are consistent with the demonstrated efficacy of PEP with HRIG plus HDCV in children as in adults and provide results that can be used for initial evaluation of experimental pediatric PEP regimens in the future.

Adult↗

PubMed1992

Pharmacokinetics and pharmacodynamics of bambuterol, a long-acting bronchodilator pro-drug of terbutaline, in young and elderly patients with asthma.

Disposition and efficacy of bambuterol were studied in 10 younger (20 to 37 years) and 10 older (69 to 76 years) patients with asthma (nine men and 11 women) at steady state, after single daily doses of 20 mg (50 mumol) for 1 week. There was a greater area under the concentration versus time curve for terbutaline during a dose interval in older patients compared with younger patients (558 +/- 171 and 376 +/- 149 nmol.hr/L, respectively [mean +/- SD], p less than 0.021). This was reflected in a lower apparent plasma terbutaline clearance in older patients compared with younger patients (1.22 +/- 0.33 and 2.32 +/- 1.26 L/hr/kg, respectively, p less than 0.023). Peak drug concentration was not different by age. Plasma cholinesterase levels were depressed by about 70% in both groups compared with pretreatment activity. Peak expiratory flow rate increased in both groups. Improvement in forced expiratory volume in 1 second and forced vital capacity was detected only in the younger patients. A small decrease in heart rate and diastolic blood pressure occurred in both patient groups. Bambuterol appears to offer the possibility of once-daily therapy in both younger and older patients with asthma.

Adult↗

PubMed1991

Long-term captopril in young and old patients with mild hypertension.

The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (less than 50 years) and old (greater than 65 years) hypertensive patients. Captopril effectively decreased blood pressure in both groups (diastolic blood pressure less than 90 mm Hg), with the young patients requiring a lower dose (.7 mg/kg) than the elderly patients (1.2 mg/kg). Creatinine and para-aminohippurate clearances were maintained in both groups, with a decrease in renal vascular resistance being observed in the younger patients. Serum aldosterone levels fell significantly after each dose of captopril at all phases of the study, with no change observed in plasma renin levels. Atrial natriuretic peptide (ANP) level was increased in the elderly patients receiving placebo (48.8 +/- 8 pg/mL) when compared with the young subjects (24 +/- 3.8 pg/mL). Captopril did not alter ANP levels in either group.

Adult↗

PubMed1991

Randomized, double-blind, placebo-controlled, clinic-initiated, Canadian multicenter trial of topical edoxudine 3.0% cream in the treatment of recurrent genital herpes. Canadian Cooperative Study Group.

Treatment for recurrent genital herpes using edoxudine 3% cream for 5 days was evaluated in 200 patients in a randomized, multicenter, double-blind, placebo-controlled, clinic-initiated trial. Lesion tenderness was predictive of and more sensitive and longer-lasting than the symptom of pain. Among patients receiving placebo, times to crusting (P = .043), cessation of investigator-observed signs (P = .005), lesion-associated signs (P = .02), and groin signs (P = .05) were longer in women. Edoxudine reduced viral shedding in men (mean 2.7 vs. 3.4 days, P = .009) and women (2.0 days vs. 3.5 days, P = .0001). Loss of investigator-observed signs (4.4 vs. 6.2 days, P = .002), investigator-observed lesion tenderness (P = .01), lesion signs (P = .02), groin adenopathy (P = .01), and tenderness (P = .01) occurred earlier in women taking edoxudine. Edoxudine was well-tolerated and reduced several signs of herpes in women. Its clinical role in recurrent genital herpes remains to be fully determined.

Administration, Topical↗

PubMed1991

Prescribing patterns for older heavy drug users living in the community.

We report an analysis of prescription drugs claimed under a government-sponsored, universal Pharmacare program for community-dwelling adults aged greater than or equal to 50 years in Manitoba during 1975, 1978, 1981, and 1984. We limited our analysis to claimants who reported over six drugs in a year in order to control for effects of inflation and a changing deductible. The median number of prescribed drugs and the percent of claimants over age 50 years receiving prescriptions from multiple physicians decreased during the course of our study. In this sample of heavy drug users, age and sex did not consistently correlate with overall drug use, although there was correlation for specific drug groups. The relative ranking of prescribed drugs changed over the years, although benzodiazepines, thiazide diuretics, topical steroids, and codeine-containing analgesics remained near the top. Barbiturates and topical antibiotics showed the greatest drop in prescription rates; acetaminophen and beta-blockers increased the most. Using these community data, we project the prevalence of drug-related adverse events to be highest with beta-blockers, nonsteroidal antiinflammatory drugs, thiazide diuretics, and benzodiazepines.

Age Factors↗