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Biomedical subjects

F G Hayden

Publications and source records attributed to F G Hayden.

At least 91 records · Page 5Linked to original sources
PubMed1994

Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans.

The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge. The rates of virus shedding (100% in both groups), days of viral shedding (3.1 +/- 1.3 for the LY217896 group; 2.8 +/- 1.3 for the placebo group), and titers of virus in nasal washings did not differ between the groups. Mild upper respiratory tract illness (72% in the LY217896 group; 69% in the placebo group) developed in similar proportions of each group. LY217896 was associated with asymptomatic rises in serum uric acid levels and was ineffective in modifying the virologic or clinical course of experimental influenza A (H1N1) virus infection.

Adolescent↗
PubMed1994

Comparative antirhinoviral activities of soluble intercellular adhesion molecule-1 (sICAM-1) and chimeric ICAM-1/immunoglobulin A molecule.

We conducted a comparative study of the antirhinovirus activities of soluble intercellular adhesion molecule-1 (sICAM-1) and a chimeric ICAM-1/immunoglobulin A (IgA) molecule (ICI-5D/IgA) for nine major receptor group human rhinovirus (HRV) serotypes and for a variant of HRV-39 relatively resistant to inhibition by sICAM-1. ICI-5D/IgA inhibited the infectivity of eight of the nine wild-type HRVs and the resistant HRV-39 variant and was 60 to 170 times more potent than sICAM-1 on a molar basis. In contrast to sICAM-1, ICI-5D/IgA directly neutralized the infectivity of the representative HRVs by approximately 1 log10. These results expand on the antirhinovirus spectrum of ICI-5D/IgA, confirm that dimeric forms of sICAM-1 have a higher antirhinoviral potency than monomeric sICAM-1, and indicate that cross-linking of two adjacent receptor binding sites on the virus capsid by a divalent receptor enhances the direct inactivation of viral infectivity.

Antiviral Agents↗
PubMed1993

Detection of human rhinovirus RNA in nasal washings by PCR.

A PCR assay was developed to detect human rhinovirus (HRV) RNA in nasal washings from individuals experimentally infected with HRV-39 or HRV strain Hanks. Total RNA was purified from samples stored in the presence of vanadyl ribonucleoside complex (VRC) by one of two methods: proteinase K digestion followed by multiple extractions with phenol/chloroform (PK-PC); or denaturation with guanidinium thiocyanate followed by one phenol/chloroform extraction (GTC). The limit of detection of HRV in nasal washings spiked with HRV-39 was lower with the GTC method (1 TCID50) than with the PK-PC method. In a study of 31 nasal washings extracted by the PK-PC method, the sensitivity (93%) and negative predictive value (94%) were sub-optimal in comparison to cell culture. In a study of 60 nasal washings extracted by the GTC method, the number of samples positive by PCR (25) exceeded by two the number positive by isolation in cell culture. A GTC-based method for HRV RNA extraction in nasal washings was superior to a proteinase K-phenol/chloroform-based method in regard to sensitivity, consumption of reagents, material and time.

Base Sequence↗
PubMed1993

Comparative anti-influenza virus activity of 2'-deoxy-2'-fluororibosides in vitro.

The anti-influenza virus activity of 2'-deoxy-2'-fluoroguanosine was determined in cell culture and in explants of human respiratory epithelium by yield reduction assay. The concentration causing at least 1.0 log10 reduction in influenza A (H3N2) virus yield (EC90) at 24 h was 2.5 micrograms/ml in primary rhesus monkey kidney and 12 micrograms/ml in Madin-Darby canine kidney (MDCK) cells, compared to 0.5 micrograms/ml and 0.9 micrograms/ml, respectively, for ribavirin. The estimated therapeutic ratios for both compounds were low (< 5 to 25) in these cell types. In contrast, the EC90 values at 48 h for influenza A and influenza B virus were < or = 0.1 micrograms/ml in human respiratory epithelial explants, and concentrations up to 100 micrograms/ml did not inhibit explant outgrowth. Ribavirin was approximately 50-fold less active in this system and inhibited outgrowth at 10 micrograms/ml. 2'-deoxy-2'-fluoroguanosine was also approx. 45-fold more potent than the corresponding adenosine and inosine compounds in explant cultures. Partially resistant variants, with approximate 5-fold increases in EC50 values, could be selected by serial influenza A virus passage in MDCK cells in the presence of 2'-deoxy-2'-fluoroguanosine, which indicated that its antiviral activity is at least partially virus specific. The exceptional activity of 2'-deoxy-2'-fluoroguanosine in human respiratory epithelial cells against both influenza A and B viruses makes this compound an interesting candidate for further investigation.

Adenoids↗
PubMed1993

Adenovirus type 8 epidemic keratoconjunctivitis in an eye clinic: risk factors and control.

Epidemic keratoconjunctivitis (EKC) due to adenovirus type 8 affected 126 (7%) of 1870 ophthalmology clinic patients during an outbreak. Risk factors and mode of transmission were studied by comparing cases (n = 58) and controls (n = 200) for exposure to risk factors. Pneumotonometry (odds ratio [OR], 10.5; 95% confidence interval [CI], 4.0-27.7), multiple clinic visits (OR, 5.9; 95% CI, 3.3-10.6), and contact with an infected physician (OR, 3.3; 95% CI, 1.2-9.0) were significant risk factors for infection. The hands of 3 patients and 3 physicians with EKC were cultured before and after hand washing to assess adenovirus removal; 3 had hand cultures positive for adenovirus after hand washing. In conclusion, this outbreak appeared to be due to inadequate disinfection of instruments, especially pneumotonometers, and finger-to-eye transmission by health care workers. Hand washing did not reliably remove adenovirus from contaminated fingers. Gloving for exam of eyes with EKC may help prevent transmission. Ophthalmologists with EKC were a significant risk factor for patients and should be furloughed for the duration of communicability.

Adenovirus Infections, Human↗
PubMed1993

Middle ear abnormalities during natural rhinovirus colds in adults.

To determine middle ear pressure (MEP) changes during natural rhinovirus colds, adults with illness for < or = 3 days were tested by digital tympanometer daily for 5 days (study 1) or every other day for 7 days (study 2). Abnormal MEPs (< -50 or > +20 mm H2O) were found in 72% of 36 patients in study 1 (P < .001, vs. baseline of 11%) and 76% of 55 patients in study 2 (P < .001, vs. 15% of 103 healthy controls). Major abnormalities (> or = +100 or < or = -100 mm H2O) were found in 61% of patients in study 1 (P < .001, vs. baseline of 0) and 47% in study 2 (P < .001, vs. control of 5%). MEP abnormalities usually resolved by day 14. Only 1 subject developed clinically apparent otitis media. Earache or respiratory symptom scores did not correlate with MEP abnormalities. These results indicate that natural rhinovirus colds in adults are frequently associated with marked but transient MEP abnormalities.

Adult↗
PubMed1993

Efficacy of oral WIN 54954 for prophylaxis of experimental rhinovirus infection.

The efficacy of oral WIN 54954 for the prevention of rhinovirus infection and illness was tested in two randomized, double-blinded, placebo-controlled volunteer challenge studies. Volunteers were inoculated with rhinovirus type 39 (MIC of WIN 54954, 0.17 microgram/ml) or rhinovirus type 23 (MIC, 0.016 microgram/ml). The volunteers received two doses of drug (600 mg per dose) or placebo on the first day; this was followed by three doses on each of the subsequent 5 days. All volunteers were challenged with virus after the third dose of study drug. No significant antiviral or clinical effect was detected in either study. Pharmacokinetic studies revealed that on the last day of drug administration, 38 of 39 (97%) volunteers had trough levels of WIN 54954 in plasma greater than the MIC for the respective virus. Nasal wash specimens collected on the same day revealed a detectable level in only 6 of 24 (25%) volunteers at the peak (range, 6 to 24 ng/ml) and in only 2 of 14 (14%) volunteers at the trough (range, 6 and 7 ng/ml). These results suggest that the lack of efficacy of WIN 54954 against rhinovirus may be related to an inability to deliver sufficient drug to the site of viral infection.

Adult↗
PubMed1993

Therapeutic effects of an anticholinergic-sympathomimetic combination in induced rhinovirus colds.

This study's objective was to determine if the combination of pseudoephedrine hydrochloride and atropine sulfate attenuates the symptomatic and pathophysiologic response of individuals to experimental rhinovirus infection when given after illness begins. Forty-three susceptible adult volunteers were challenged with rhinovirus type 39 and randomly assigned to 1 of 2 treatment groups. Twenty-one subjects were treated with the active medication (0.3 mg atropine sulfate and 60 mg pseudoephedrine) and 22 subjects were treated with inert capsules identical in appearance. Treatments were administered 4 times daily beginning approximately 24 hours after rhinovirus challenge and extending for 5 days. Before challenge and on each of 5 treatment days, all volunteers were asked to rate symptom severity and were evaluated for secretion production (weighted tissues), nasal patency (active posterior rhinomanometry), nasal clearance (dyed saccharin technique), eustachian tube function (9-step test), and middle ear status (tympanometry). Twenty subjects in each group were infected with rhinovirus type 39 and were included in the efficacy analysis. Between-group comparisons showed no significant differences in total symptom scores, combined nasal symptom score, secretion production, or the frequencies of persons with eustachian tube obstruction or abnormal middle ear pressures. However, an objective measure of nasal congestion was significantly lower in the active treatment group. The nasal mucociliary clearance rate was significantly more impaired in that group. Side effects consistent with anticholinergic activity were reported more frequently in the active treatment group.

Administration, Oral↗
PubMed1993

Risk factors for acute wheezing in infants and children: viruses, passive smoke, and IgE antibodies to inhalant allergens.

OBJECTIVE: To examine the prevalence of viral infection, passive smoke exposure, and IgE antibody to inhaled allergens in infants and children treated for acute wheezing. DESIGN: Case-control study of actively wheezing children who were compared with children without respiratory tract symptoms. SETTING: University of Virginia Pediatric Emergency Room. PATIENTS: Convenience sample of 99 wheezing patients (2 months to 16 years of age) and 57 control patients (6 months to 16 years of age). MEASUREMENTS AND RESULTS: Serum IgE antibody to inhalant allergens, measured by radioallergosorbent test (RAST), was uncommon in wheezing and control patients under age 2. After 2 years of age, the percentage of RAST-positive patients increased markedly and was significantly higher in wheezing patients than controls after age 4 (72%, n = 54, and 30%, n = 40, respectively, P < .001). Total IgE levels and nasal eosinophilia were strongly correlated with a positive RAST after age 2. Viral pathogens, predominantly respiratory syncytial virus, were identified in nasal washes from 70% (n = 20) of wheezing patients younger than 2 years of age compared with 20% of controls (n = 10), P < .05. After age 2, viruses, particularly rhinovirus, were isolated in washes from 31% (n = 70) of wheezing patients, 64% of whom were also RAST-positive. Levels of cotinine, a nicotine metabolite, were elevated (> or = 10 ng/mL) in saliva from a large percentage of smoke-exposed, wheezing patients under 2 (74%, n = 19) compared with those over 2 (14%, n = 51), P < .001. Odds ratios for wheezing were significant for virus (8.2, confidence interval [CI] = 1.3 to 5.0), and cotinine (4.7, CI = 1.0 to 21.3) in children under 2, and IgE antibody by RAST (4.5, CI = 2.0 to 10.2), virus (3.7, CI = 1.3 to 10.6), and the combination of IgE antibody and virus (10.8, CI = 1.9 to 59.0) were significant risk factors after age 2. CONCLUSION: Wheezing children younger than 2 years of age had a high rate of viral infection and a low rate of IgE antibody to inhalant allergens. When these children were exposed to passive smoke, salivary cotinine levels were elevated suggesting heavy exposure. After 2 years of age, sensitization to inhaled allergens became increasingly important and viruses remained a significant risk factor for wheezing. These data support recommendations to reduce tobacco smoke exposure at home, especially for young patients, and to consider sensitization to inhaled allergens and allergen avoidance in wheezing children at an early age, particularly after age 2 years.

Adolescent↗
PubMed1992

Effects of naproxen on experimental rhinovirus colds. A randomized, double-blind, controlled trial.

OBJECTIVE: To determine whether naproxen, a propionic acid inhibitor of cyclooxygenase, alters the course of experimental rhinovirus colds. DESIGN: A randomized, double-blind, controlled trial. SETTING: Rhinovirus challenge model in volunteers cloistered in individual hotel rooms. VOLUNTEERS: Eighty-seven healthy young adults with serum neutralizing antibody titers of less than or equal to 1:2 to the challenge virus; 79 were evaluable. INTERVENTION: Thirty-nine participants received naproxen (loading dose, 400 mg or 500 mg followed by 200 mg or 500 mg three times daily for 5 days). Forty participants received placebo. Treatment was started 6 hours after viral challenge. MEASUREMENTS: Daily measurement of viral titers, symptoms, nasal mucus production, and nasal tissue use; incidence of infection and illness; and measurement of homotypic serum neutralizing antibody responses. RESULTS: Viral titers and serum homotypic antibody responses were similar in the naproxen and placebo groups. Significant reductions in headache, malaise, myalgia, and cough occurred in the naproxen group. A 29% reduction was noted in the total (5-day) symptom score in the naproxen group (95% CI, 16% to 42%). CONCLUSION: Naproxen treatment did not alter virus shedding or serum neutralizing antibody responses in participants with experimental rhinovirus colds, but it had a beneficial effect on the symptoms of headache, malaise, myalgia, and cough. Prostaglandins may be among the inflammatory mediators that play a role in the pathogenesis of rhinovirus colds.

Adult↗
PubMed1992

Otologic effects of interferon beta serine in experimental rhinovirus colds.

To evaluate the efficacy and otologic effects of recombinant interferon beta serine for experimental rhinovirus colds, 38 healthy adults received nasal drops of recombinant interferon beta serine, 12 x 10(6) U, or placebo three times daily for 4.3 days beginning 36 hours after infection. Illness rates and severity did not differ between the groups, but the frequency of virus shedding was reduced on the fourth (37% vs 74%) and sixth (11% vs 42%) postchallenge days in recipients of recombinant interferon beta serine. Abnormal eustachian tube function in at least one ear was identified by the inflation-deflation test during 44% of observations in 13 infected recipients of recombinant interferon beta serine compared with 62% of observations in five placebo recipients. Tympanometry revealed middle-ear pressure abnormalities (less than -50 or greater than 20 mm H2O) in at least one ear during 18% of observations in recipients of recombinant interferon beta serine compared with 38% of observations in placebo recipients. These results suggest that antiviral therapy may alter the course of middle-ear dysfunction associated with experimental colds.

Administration, Intranasal↗
PubMed1992

Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine.

Amantadine- and rimantadine-resistant viruses have been recovered from approximately 30% of patients treated for acute H3N2 subtype influenza and less often from their close contacts receiving drug prophylaxis. The limited data suggest that resistant viruses can emerge rapidly during drug therapy, as early as 2-3 days into treatment. These viruses retain their resistance phenotype during multiple passages in the laboratory and appear to be genetically stable in this regard. Studies in families and in nursing homes indicate that resistant isolates appear to be transmissible from treated patients and cause typical influenza in contacts receiving drug prophylaxis. It is unknown whether resistant human viruses are capable of competing with wild-type ones during multiple cycles of infection in the absence of the drug. These viruses appear to be pathogenic, and no evidence indicates that they differ from wild-type strains. Thus, these viruses clearly possess the biologic properties that are associated with clinically important drug resistance. However, limited information is available to assess their actual impact. It is unknown what degree of selective drug pressure would be required to cause substantial transmission of resistant viruses during community outbreaks. Natural selection of antigenic variants and disappearance of previous variants may prevent the emergence of viruses that have been altered in the genes coding both for the surface glycoproteins and for the M2 protein. However, the emergence of drug-resistant influenza viruses appears to pose potential clinical problems in certain epidemiologic situations involving close contact with treated patients.

Amantadine↗
PubMed1992

Physiologic abnormalities in the paranasal sinuses during experimental rhinovirus colds.

Six (18%) of 34 healthy, asymptomatic young adults had mucosal thickening or fluid in the paranasal sinuses on screening magnetic resonance imaging (MRI) examination. When 19 of these subjects were challenged with rhinovirus, 18 became infected. Twelve of the 18 infected subjects had technically satisfactory serial MRI examinations, and four (33%) of these developed MRI abnormalities of the ethmoid or antral sinuses that were temporally associated with the acute infection. The mean total nasal secretion weights were 22 gm/5 days in the four subjects whose MRI abnormalities were associated with the acute infection compared with 5.5 gm/5 days in the eight subjects who had normal MRI examinations during the acute infection (p = 0.06). Abnormalities of the paranasal sinuses, which were associated with increased volumes of nasal secretion, were detected by MRI examination during rhinovirus infection. These abnormalities may have a role in the pathogenesis of acute sinusitis associated with colds.

Acute Disease↗
PubMed1992

Serologic response and reactogenicity to booster immunization of healthy seropositive adults with live or inactivated varicella vaccine.

The immunogenicity and reactogenicity of live and heat-inactivated varicella vaccine were evaluated in 95 healthy seropositive adults (mean age, 32 yrs). Live-attenuated vaccine containing 28,000 pfu, 2800 pfu, or 280 pfu of Oka/Merck strain virus (8.4, 0.84, and 0.08 antigen units, respectively) or heat-inactivated vaccine with comparable antigen content (7.1, 0.71, and 0.07 antigen units) was administered subcutaneously to 15 to 16 adults per group in a randomized, single-blind study. ELISA antibody responses were dose-dependent but independent of whether the vaccine was live or inactivated. Mean titers reached a peak on day 14 and remained elevated through day 42 in recipients of the highest dosages but declined by followup at eleven months. A minority of vaccinees developed a four-fold or greater increase in antibody titer on day 14 (25 to 31 percent in the high-dose groups [greater than or equal to 7.1 antigen units], less than or equal to 7 percent of other groups). The vaccine was generally well tolerated. Localized erythema and swelling occurred at the injection site in 44 to 56 percent of the high- and middle dose recipients [greater than or equal to 0.71 antigen units], compared with 0 to 6 percent of those receiving the lowest dose. Although statistically significant increases in varicella antibody titer were observed after immunization with high doses of live or inactivated vaccine, the duration and clinical significance of this booster effect remains to be determined.

Adolescent↗
PubMed1992

Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events.

Previous studies of rhinovirus infection indicate that about one third of the persons with confirmed viral infection do not show evidence of cold symptoms. Factors that determine which infected individuals will develop colds are not known. Using a rhinovirus inoculation protocol, the authors explored the possible role of recent life events, current mood, and perceived stress in the development of symptoms in individuals known to be infected. As part of a larger study, 17 subjects were exposed to a rhinovirus and were individually isolated for 5 consecutive days; cold symptoms, mucus weights, and tissue use were monitored on a daily basis during this period. Although all 17 subjects had confirmed rhinovirus infection, only 12 subjects developed clinical colds, as indicated by self-reported symptoms and by objective symptom indices. The average number of reported major life events for the previous year was significantly higher for those who developed colds than for those who did not (p < .05). Measures of affect and perceived stress before the inoculation were not different for those who did and did not develop colds. Complementing recent research demonstrating psychosocial influences on experimental infection rates, these results provide evidence that the development of cold symptomatology in experimentally infected individuals is related to prior life events.

Adolescent↗
PubMed1992

Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection.

Pirodavir (R77975) is a capsid-binding, antipicornaviral agent with in vitro activity against most rhinovirus (RV) serotypes. We conducted four double-blind, controlled trials to assess the efficacy of intranasal pirodavir in experimentally induced RV infection of susceptible volunteers. Intranasal pirodavir (2 mg per dose) or the hydroxypropyl-beta-cyclodextrin vehicle as a placebo was given by metered pump spray. In three prophylaxis trials, subjects were inoculated with RV within 10 min of the second and third doses. When sprays were given six times per day for a total of 25 doses, infection, detected by either virus shedding or seroconversion, developed in 100% of the 13 placebo-treated subjects and 58% of the 12 pirodavir-treated subjects (P = 0.015). Clinical colds developed in 54% of placebo-treated subjects and 8% of pirodavir-treated subjects during drug administration (efficacy = 85%, P = 0.03), although late-developing colds developed in several subjects in both groups. Significant reductions in morning symptom scores and in the frequency of abnormal middle-ear pressures were also found in the pirodavir group. In contrast, in two prophylaxis studies using three doses daily, no significant antiviral or clinical benefits were observed. When frequent sprays were initiated at 24 h after RV challenge, significant reductions in virus shedding but no clinical benefits were found. Intranasal pirodavir was generally well tolerated but was associated with an excess rate of transient unpleasant taste. The findings indicated that frequent intranasal sprays of pirodavir were effective in preventing experimentally induced RV illness.

Administration, Intranasal↗