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Biomedical subjects

F Y Aoki

Publications and source records attributed to F Y Aoki.

At least 55 records · Page 3Linked to original sources

Characterization of acute and latent herpes simplex virus infection of dorsal root ganglia in rats.

The characteristics of HSV type-1 infection following subcutaneous inoculation in the dorsum of one hind paw of Sprague-Dawley rats were studied to determine whether infection in rats might more closely parallel the infection in man than is seen in other animals. The serologic and virologic characteristics of acute and latent ganglion infection conformed to those of human infection. Immunohistochemical studies suggested that sensory ganglion infection arose via centripetal axonal migration of virus as is hypothesized in man. In rat, small type B neuronal cell bodies appeared central to the maintenance of latent infection and reactivation observed during cocultivation of lumbar ganglia. Acute and latent lumbar sensory ganglion infection in rats after subcutaneous hind paw injection of HSV-1 appears to be another suitable model of this infection in man.

Acute Disease↗

Effect of acute experimental influenza A virus pneumonia on concentration of alpha 1-acid glycoprotein in mouse serum.

In mice, the mean serum concentration of the acute-phase reactant alpha 1-acid glycoprotein increased 34-48% over 14 days following experimental induction of pneumonitis by intranasal inoculation of influenza A virus. Inoculation of undiluted (hemagglutination titer 640) and 10(-1) dilution of virus was followed by development of maximum concentrations of alpha 1-acid glycoprotein in serum at seven days, of 334 micrograms/ml, compared to a concentration in control mice inoculated with irradiated inactivated virus of 225 micrograms/ml (P = 0.002). Infection with 10(-2) virus yielded a peak serum alpha 1-acid glycoprotein of 301 micrograms/ml at four days, 34% higher than in control mice at four days (P = 0.04). There were no differences in alpha 1-acid glycoprotein concentrations among virus-infected mice. Influenza A virus pneumonitis was confirmed histologically, by virus isolation, and by serologic testing, but no inoculum-dependent differences were observed. On day 7, there was a direct relationship demonstrated between the severity of pneumonitis evaluated histologically and the serum alpha 1-acid glycoprotein concentration (r = 0.50; P less than 0.02). Influenza A pneumonia in mice is associated with increased concentrations of alpha 1-acid glycoprotein in serum; the increase may be directly related to the severity of the pulmonary inflammation.

Acute Disease↗

Intravenous human rabies immunoglobulin for post-exposure prophylaxis: serum rabies neutralizing antibody concentrations and side-effects.

The beneficial effect of passive immunization for post-exposure rabies prophylaxis is associated with the appearance of serum neutralizing antibody (SNA) earlier than occurs with vaccine alone. We compared the SNA response and the side-effects in 30 previously unimmunized healthy volunteers given a commercially available human rabies immunoglobulin (HRIG) intramuscularly (i.m.) or an experimental HRIG prepared by DEAE Sephadex column chromatography, intravenously (i.v.) with or without human diploid-cell culture rabies vaccine (HDCS). The subjects were divided into five equal groups: HDCS alone, HDCS + i.m. HRIG 20 IU/kg (currently recommended), i.v. HRIG alone 15 IU/kg, HDCS + i.v. HRIG 15 IU/kg or HDCS + HRIG 5 IU/kg i.v. plus 10 IU/kg i.m. to simulate local bite wound infiltration. HDCS, 1.0 ml, was injected subcutaneously (s.c.) on days 0, 3, 7, 14 and 28. Only local discomfort at injection sites was observed without differences between groups. SNA was demonstrated in all HRIG recipients at day 1, but the concentrations were higher in those receiving it intravenously. No difference in the SNA response to vaccine was observed between the i.v. and i.m. HRIG groups given the same vaccine lot. It would appear that i.v. HRIG 15 IU/kg can be substituted for i.m. HRIG 20 IU/kg for post-exposure prophylaxis. Since the current regimen is almost 100% protective, there is no way of proving that i.v. HRIG 15 IU/kg is more efficacious. The immediate SNA level and economy are the chief advantages of i.v. HRIG 15 IU/kg.

Antibodies, Viral↗

Nadolol antihypertensive effect and disposition in young and elderly adults with mild to moderate essential hypertension.

Nadolol was effective and well tolerated as once-daily monotherapy for mild to moderate essential supine diastolic hypertension (SDBP) in 10 young (mean age, 39 years) and 12 elderly (mean age, 68 years) patients in a single-blind, placebo-baseline, escalating-dose study. Doses required to reduce SDBP to 90 mm Hg were not different in young (1.08 +/- 0.21 mg/kg/day) and elderly (0.82 +/- 0.14 mg/kg/day) patients (mean +/- SE). Trough plasma nadolol concentrations at steady state were similar and were linearly related to dose in both groups. More unchanged nadolol was recovered in 24-hour urine samples from young subjects (15.6% +/- 1.9%) than from elderly ones (10.7% +/- 1.1%) (p = 0.028). With increasing nadolol doses, plasma norepinephrine concentration increased and isoproterenol sensitivity decreased in both young and elderly subjects, and creatinine clearance and plasma active renin levels were unchanged; plasma inactive renin levels increased in the young, and aldosterone concentration declined in the elderly with the lowest nadolol dose.

Adult↗

Efficacy and safety of foscarnet for recurrent orolabial herpes: a multicentre randomized double-blind study.

Foscarnet sodium (trisodium phosphonoformate hexahydrate) has been shown to inhibit herpes simplex virus (HSV) in vitro and to be efficacious for topical treatment of experimental HSV infection in animals. To assess its clinical efficacy in the treatment of recurrent orolabial herpes a multicentre collaborative, double-blind, placebo-controlled trial was conducted. The study patients were randomly assigned to receive either 3% foscarnet cream (78 patients) or placebo (cream vehicle) (75 patients) and were asked to start treatment at the earliest indication of a recurrence. Efficacy was evaluated in 143 patients (74 in the foscarnet group and 69 in the placebo group). There was no significant difference in time to healing or duration of virus shedding between the two groups. However, in the subgroup of patients who started treatment before vesicles appeared, the duration of virus shedding was shorter in the foscarnet group than in the placebo group (p = 0.04), and the proportion of lesions that evolved to the vesicular stage was smaller (p = 0.03). No significant difference in the incidence of local or systemic adverse effects was noted between the two groups. We conclude that the beneficial effect of foscarnet was limited to a subgroup of patients who started treatment in the prevesicular stage.

Administration, Topical↗

Drug-associated hospital admissions in older medical patients.

A survey of drug-related admissions of patients aged 50 years and older was conducted at the Health Sciences Centre, Winnipeg to determine the interrelationship of risk factors, and isolate the effect of age. All nonelective medical admissions were prospectively assessed to determine the role of drug therapy as a contributory factor. Of the 863 eligible admissions, 162 exhibited at least one drug-related adverse patient event (DRAPE) at the time of hospitalization. This accounted for 19% of the admissions (23% of 718 admissions that involved prescription drugs). Although adverse drug reactions were responsible for many DRAPEs (48%), intentional noncompliance (27%), treatment failure (19%), alcohol (14%), and medication error (10%) were also frequent contributing causes. Drugs commonly implicated in DRAPEs were systemic steroids, digoxin, nonsteroidal anti-inflammatory agents, alpha-methyldopa, calcium channel blockers, beta-blockers, theophylline, furosemide, sympathomimetics, thiazides, and benzodiazepines. The risk of a DRAPE was related to the number of diseases prior to admission (r = 0.81; P less than .026) and the number of drugs used (r = 0.77; P less than .001). Age was not correlated with the risk of a DRAPE. Females had significantly more adverse drug reactions, although sex was not a predictor for overall DRAPE risk.

Aged↗

Clinical pharmacokinetics of amantadine hydrochloride.

Amantadine is a drug with diverse uses ranging from prevention of influenza A illness to the treatment of patients with Parkinson's disease. It is available only in oral formulations from which it is well absorbed and widely distributed, little drug being present in the circulation. Apparent volume of distribution is inversely related to dose over the therapeutic range and accounts in part for a noteworthy logarithmic increase in plasma concentration as a function of dose. Elimination is primarily by renal clearance by both glomerular filtration and tubular secretion. Amantadine accumulates in patients with renal dysfunction. Hence, doses must be reduced in such patients to avoid toxicity. Interactions with other drugs appear uncommon. Relationships have been demonstrated between amantadine therapeutic effects and plasma concentrations in different study cohorts, but not in individual patients. Dose schedules have been suggested for individuals in whom amantadine kinetics are different from healthy subjects. However, these schedules are controversial in their choice of target concentrations and in being untested as to predictive value.

Administration, Inhalation↗

Factors indicative of outcome in a comparative trial of acyclovir and vidarabine for biopsy-proven herpes simplex encephalitis.

A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.

Acyclovir↗

Partial characterization of alpha 1-acid glycoprotein isolated from mouse serum.

AGP was purified from mouse serum by perchloric acid treatment and CM-Sepharose chromatography. Induction of inflammation with turpentine resulted in a 10-fold increase in the serum level of mouse AGP, indicating mouse AGP is an acute phase reactant. Biochemical characterization of mouse AGP indicated similarity with human and rat AGP.

Amino Acids↗

Immunologic studies in subjects with a serum sickness-like illness after immunization with human diploid cell rabies vaccine.

Ten patients developing a serum sickness-like hypersensitivity reaction to human diploid cell rabies vaccine were studied and compared with control subjects matched for previous vaccination history and level of rabies virus-specific IgG response to immunization. The clinical reaction consisted of delayed onset, generalized urticaria, and angioedema, with some arthralgias. Skin biopsy specimens demonstrated a leukocytoclastic vasculitis. Individuals reacting to the vaccine possessed IgE antibodies to human diploid cell rabies vaccine, to mock vaccine lacking viral antigen, and to fetal calf serum (FCS), a vaccine trace contaminant. Increased levels of IgG antibodies to FCS, mock vaccine, and beta-propiolactone-modified FCS, and human serum albumin were also found. Such humoral responses to vaccine components other than rabies virus might be responsible for the hypersensitivity reactions developing after rabies vaccination.

Antibodies, Viral↗

Clinical course of recurrent genital herpes and treatment with foscarnet cream: results of a Canadian multicenter trial.

Clinic-initiated topical treatment of recurrent genital herpes with foscarnet cream (concentration, 0.3% in men and 1% in women) was compared with a placebo in a Canadian multicenter trial involving 309 patients. Culture-positive episodes of herpes took significantly longer to heal than did the others. Lesions in men were larger and lasted longer but were less symptomatic than those in women. Foscarnet did not statistically improve the times to healing or the loss of symptoms overall but did result in a higher proportion of symptom-free individuals after one day of treatment. Foscarnet-treated patients had a reduced duration of shedding of virus, and this was significant for men. These clinical benefits do not, however, warrant general use of this agent for established lesions. Earlier, prodromal treatment might have been more effective, but patient-initiated studies include a greater proportion of culture-negative (shorter) episodes that often make results difficult to interpret.

Administration, Topical↗

Enprofylline disposition in the presence and absence of amoxycillin or erythromycin.

1 The kinetic disposition of a novel xanthine bronchodilator, enprofylline, was determined in young healthy male volunteers in the presence and absence of amoxycillin or erythromycin. These data were compared to those derived from a similar study of theophylline disposition in the presence and absence of erythromycin. 2 Erythromycin inhibited theophylline disposition only in those subjects in whom the control kinetic study was done after antibiotic ingestion, but the effect was modest. Erythromycin had no effect on enprofylline disposition. 3 Amoxycillin reduced the renal clearance of enprofylline, but the change was not statistically significant.

Adult↗

Vidarabine versus acyclovir therapy in herpes simplex encephalitis.

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

Acyclovir↗

Fatal diphtheria in an older woman.

A previously healthy 68-year-old woman presented with fever and sore throat. Her condition was initially diagnosed as necrotizing streptococcal tonsillitis and was treated with penicillin G, given intravenously. A swab of her throat taken for culture at the time of admission yielded Corynebacterium diphtheriae 48 hours later. At that time an electrocardiogram showed new T-wave inversion--evidence of diphtheritic myocarditis. She was immediately given 60 000 units of equine diphtheria antitoxin (following a test dose), but later that day she began choking, became apneic and died. The patient had not received any immunizing agents as a child, and no antitoxin was detected in a blood sample obtained prior to administration of the antitoxin. Her death re-emphasizes the seriousness of diphtheria, an infection to which many elderly people are susceptible.

Aged↗