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Biomedical subjects

F G Hayden

Publications and source records attributed to F G Hayden.

At least 73 records · Page 4Linked to original sources
PubMed1997

Frequency and natural history of rhinovirus infections in adults during autumn.

Human rhinovirus (HRV) accounts for a significant portion of common-cold illness, with the peak incidence being in the early fall. Three hundred forty-six adults who had self-diagnosed colds of 48 h or less were enrolled in a study during September and October 1994 to determine the frequency and clinical course of HRV infections. Nasal wash specimens for viral culture and reverse transcription-PCR (RT-PCR) for HRV RNA and human coronavirus OC43 and 229E RNA detection were collected on enrollment, and participants recorded their symptoms twice daily for 14 days. Middle ear pressure (MEP) was measured with a digital tympanometer on days 1 and 7. Picornaviruses (224 HRV and 7 enterovirus isolates) were detected by culture in 67% (231 of 346) of the subjects. Among 114 samples negative by culture, HRV was detected by RT-PCR in 52 (46%) for an overall picornavirus infection rate of 82% (283 of 346 subjects). Among the remaining 62 negative samples, human coronavirus RNA was detected by RT-PCR in 5 patients, so that 288 (83%) of patients had documented viral infection. The first symptom noticed most often was sore throat (40%) in HRV culture- or PCR-positive patients and stuffy nose in HRV-negative patients (27%). No differences in symptom scores over time or in the presence of individual symptoms were noted between groups. The median duration of the cold episodes was 11 days in HRV culture-positive patients, 9.5 days in HRV RT-PCR-positive patients, and 11.5 days in HRV-negative patients. On enrollment, abnormal MEPs (< or = -100 or > or = +100 mm of H2O) were found for 21% of HRV culture-positive patients, 14% of HRV RT-PCR-positive patients, and 10% of HRV-negative patients. No important differences in the clinical course of HRV culture-positive, HRV culture-negative and RT-PCR-positive, or HRV-negative colds were found. These results represent the highest frequency of virologically confirmed natural colds to date and document the importance of rhinoviruses as the cause of colds during fall months.

Adolescent↗
PubMed1997

Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR.

Of 20 adults with acute community-acquired sinusitis (ACAS), rhinovirus was detected in specimens from 10 (50%) patients, including maxillary aspirates from 8 (40%) patients and nasal swabs from 9 (45%) patients, by reverse transcription-PCR (RT-PCR). Human coronavirus was detected by RT-PCR in nasal swabs from 3 of 20 patients but in no sinus secretions. These findings suggest that rhinovirus is an important cause of ACAS and that viral invasion of the sinus cavity itself may be a common event during the disease.

Adult↗
PubMed1996

Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the tolerability and clinical effectiveness of intranasal ipratropium bromide for the treatment of symptoms of common colds. DESIGN: Multicenter, double-blind, randomized trial. SETTING: 3 university student health services. PATIENTS: 411 previously healthy persons 14 to 56 years of age who had cold symptoms that had lasted for no more than 36 hours, rhinorrhea subjectively judged to be of at least moderate severity, and documented nasal discharge of at least 1.5 g over a 1-hour observation period. INTERVENTION: Either 1) ipratropium bromide nasal spray 0.06% in buffered salt solution, two 42-micrograms sprays per nostril administered by metered pump spray; 2) control nasal spray, which consisted of buffered salt solution; or 3) no treatment. Treatments were self-administered three or four times daily during waking hours for 4 days. After receiving their morning dose, patients stayed at the study center for 6 hours on study day 1 and 3 hours on study day 2; symptom severity was recorded and nasal mucus discharges were collected and weighed hourly during these periods. RESULTS: Ipratropium recipients had 26% less nasal discharge than controls (P = 0.0024) and 34% less nasal discharge than untreated patients (P = 0.0001). Severity of rhinorrhea as judged subjectively was reduced in ipratropium recipients by 31% compared with controls and by 78% compared with untreated patients (P = 0.0001 for both comparisons). In addition to being associated with reductions in daily assessments of the severity of rhinorrhea (P < or = 0.003), ipratropium was associated with reduced sneezing on study days 2 (20% difference; P = 0.03) and 4 (30% difference; P = 0.02) but not with reduced nasal congestion compared with the control spray. Ipratropium was generally well tolerated but was associated with higher rates of blood-tinged mucus (16.8% in the ipratropium group compared with 3.6% in the control group; P = 0.01) and nasal dryness (11.7% in the ipratropium group compared with 3.6% in the control group; P = 0.021) than the control spray. Patient assessments of the overall effectiveness of treatment were more favorable for ipratropium than for the control spray (P < or = 0.026) or for no treatment (P < or = 0.002) on each day of inquiry (study days 1, 2, and 5). CONCLUSIONS: Intranasal ipratropium bromide provides specific relief of rhinorrhea and sneezing associated with common colds.

Administration, Intranasal↗
PubMed1996

Combination antiviral therapy for respiratory virus infections.

A limited number of antiviral drug combinations have been shown to have enhanced activity for important human respiratory viruses. Rimantadine or amantadine combined with ribavirin shows increased antiviral effects in vitro and in experimental animal models. This combination warrants testing in human influenza. Immunoglobulin containing neutralizing anti-RSV antibody combined with ribavirin shows enhanced antiviral effects in experimental animal infections and provides clinical benefit in severe RSV infections of transplant patients. Generally, more effective treatments for acute respiratory viral infections will likely involve combinations of both antivirals and agents that modulate host inflammatory responses to infection.

Amantadine↗
PubMed1996

Oral prednisone therapy in experimental rhinovirus infections.

This study was designed to test the effects of oral steroid therapy on the kinin levels and symptoms of experimental rhinoviral colds. Forty-seven men were randomized to receive prednisone (20 mg) or placebo. Therapy was administered three times a day for 5 days, after one dose was given 11 hours before inoculation with rhinovirus. Viral titers, symptom scores, and kinin and albumin concentrations in nasal washes were monitored. The mean kinin levels were lower in the steroid group (287 vs 449 pg/ml, p = 0.005) with significant differences in kinin levels on days 3 and 4 (p < 0.01). No significant difference in total symptom scores was seen between the two groups. Except for increased sneezing (p < 0.01) and mucus weights (p < 0.05) on day 1 in patients treated with prednisone, there were no significant differences in individual symptom scores. Headache tended to be less prominent in steroid recipients. Mean viral titers were higher in the steroid group (1.13 vs 0.79, p = 0.03) with significant differences in the daily viral titers on days 3 (p < 0.05) and 4 (p < 0.01). Steroids reduced kinin levels in rhinoviral infections, but that reduction was not associated with a significant reduction in symptoms. This study also provides evidence for the enhancement of viral growth in steroid recipients.

Administration, Intranasal↗
PubMed1996

Prevention of nosocomial influenza.

OBJECTIVE: To study compliance with preventive strategies at a university hospital during an outbreak of nosocomial influenza A during the winter of 1988, and the rates of vaccination of healthcare workers and of nosocomial influenza following changes in vaccine practices after the outbreak. DESIGN: Retrospective review of employee health, hospital epidemiology, hospital computing; and clinical microbiology records. SETTING: A university hospital. INTERVENTIONS: Unvaccinated personnel with exposure within the previous 72 hours to an unisolated case of influenza were offered influenza vaccine and 14 days of amantadine hydrochloride prophylaxis. Personnel with exposure more than 72 hours before evaluation were offered vaccine. A mobile cart was introduced for vaccinating personnel after the 1988 outbreak. RESULTS: An outbreak of influenza with 10 nosocomial cases occurred in 1988. Only 4% of exposed employees had been vaccinated previously and 23% of exposed, unvaccinated employees agreed to take vaccine, amantadine, or both. A mobile-cart vaccination program was instituted, and annual vaccination rates steadily increased from 26.3% in 1989 to 1990 to 38% in 1993 to 1994 (P < .0001). The relative frequency of documented cases of influenza in employees with symptoms of influenza decreased significantly during this period (P = .025), but nosocomial influenza rates among patients did not change significantly. CONCLUSION: A mobile-cart influenza vaccination program was associated with a significant increase in compliance among healthcare workers, but a majority still remained unvaccinated. The rate of nosocomial influenza among patients was not reduced by the modest increase in the vaccination rate, but influenza rates remained acceptably low, perhaps due to respiratory isolation of patients and furlough of employees with influenza.

Adolescent↗
PubMed1996

The immunogenicity of influenza virus vaccine in solid organ transplant recipients.

We monitored the responses of solid organ transplant recipients (SOTs) to influenza vaccine during consecutive influenza seasons. Standard 1993-1994 trivalent influenza vaccine was given to 68 SOTs and 29 healthy young adults, and hemagglutination-inhibition (HI) antibody titers were determined pre- and post-immunization. Significant rises in geometric mean antibody titers occurred post-immunization for all three antigens in both groups. However, the magnitude of the rise was lower in SOTs (1.5-2.3-fold vs. 8.7-10.4-fold, depending on the antigen) (P < .05), and significantly fewer SOTs had protective HI titers (> or = 1:40) for B/Panama/45/90 antigens (50% of SOTs vs. 76% of healthy subjects) and for A/Texas/36/91 (H1N1) antigens (60% vs. 90%). After exclusion of persons with high preimmunization titers, SOTs had significantly reduced frequencies of > or = 4-fold antibody responses compared with those of healthy subjects (23%-38% vs. 86%-100%) (P < .05 for each antigen). When a series of two injections of standard 1994-1995 vaccine was given to 23 SOTs, there was no significant improvement in vaccine response with the second dose. Some SOTs have deficient responses to inactivated influenza vaccines.

Adult↗
PubMed1996

Comparative susceptibilities of human embryonic fibroblasts and HeLa cells for isolation of human rhinoviruses.

The recovery of human rhinovirus (HRV) from nasal washings and nasal and pharyngeal swabs from volunteers with naturally acquired colds was compared in different cell types. Human embryonic lung fibroblast (HELF) strain WI-38 (sensitivity, 61 to 84%) and HeLa-I, an HRV-susceptible HeLa clone (sensitivity, 86 to 94%), were the most sensitive cell types used. HELF-WI-38 cells showed a cytopathic effect earlier than the other cells used, and the different strains of HRV-susceptible HeLa cells varied in their sensitivities for HRV isolation. HRV was detected in a single cell type in 20 to 35% of the positive samples, suggesting that use of a combination of different HRV-susceptible cell lines is the best approach for the recovery of HRV. Although nasal washings tended to yield more HRV isolates than nasal and pharyngeal swabs, the two sampling methods were not found to be significantly different.

Cell Line↗
PubMed1996

Intravenous ribavirin by constant infusion for serious influenza and parainfluenzavirus infection.

Three patients with severe lower respiratory tract influenza or parainfluenzavirus infections were treated with continuous ribavirin infusion, given as a 5 mg/kg/hour (h) loading infusion for 8 h followed by 1.5 mg/kg/h for 2 to 6 days. This regimen was generally well tolerated. Plasma ribavirin concentrations were 40 to 60 microM in two patients during the continuous infusion phase and lower concentrations were detectable in tracheobronchial secretions. In temporal association with ribavirin administration, viral shedding diminished in one patient and ceased in two patients, one of whom had developed virus resistant to amantadine. The strategy of continuous ribavirin infusion warrants controlled testing for its antiviral and possible clinical effectiveness.

Adult↗
PubMed1995

Localization of human rhinovirus replication in the upper respiratory tract by in situ hybridization.

To localize the sites and determine the extent of human rhinovirus (HRV) replication in the upper respiratory tract, biopsies of nasal and nasopharyngeal epithelia were collected from 26 HRV- or 7 sham-inoculated volunteers on days 1, 3, and 5 and on days 12, 20, or 33 after inoculation and analyzed by in situ hybridization. HRV-infected cells were detected on at least 1 day in 22 of the 23 HRV-infected subjects and in 1 of the 7 sham-inoculated subjects who developed a cold and had nasal secretions positive for a picornavirus by polymerase chain reaction. Low numbers of in situ hybridization-positive ciliated cells were present in nasal biopsies. In the nasopharynx, most HRV-infected cells were ciliated, but infected nonciliated epithelial cells were also detected. Our results indicate that HRV replicates in a very small proportion of cells in the nasal epithelium and in both ciliated and nonciliated cells in the nasopharynx of experimentally infected humans.

Adult↗
PubMed1995

Influenza A virus--induced acute otitis media.

To better understand the significance of viral upper respiratory tract infections in the pathogenesis of acute otitis media (OM), 27 adults underwent intranasal inoculation with influenza A virus. Monitoring consisted of antibody titer determination, tympanometry, and otoscopy. Microbiologic analysis consisted of cultures and polymerase chain reaction (PCR)-based detection for influenza A virus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All subjects became infected with the challenge virus. By day 4, 16 (59%) developed middle ear pressures of -100 mm H2O or below and 4 (25%) of them developed OM. One subject (4%) developed purulent OM requiring myringotomy for pain relief. Middle ear effusion cultures were negative. PCR analysis of that subject's middle ear effusion and nasal washes were positive for influenza A virus and S. pneumoniae. These findings support a causal role for viral upper respiratory tract infections in the pathogenesis of OM, possibly mediated by middle ear underpressures and viral and bacterial middle ear infection.

Acute Disease↗
PubMed1995

Prolonged shedding of amantadine-resistant influenzae A viruses by immunodeficient patients: detection by polymerase chain reaction-restriction analysis.

Consecutive A (H3N2) influenza virus isolates from 2 influenza virus-infected immunodeficient patients treated with amantadine were examined using a novel polymerase chain reaction (PCR)-restriction analysis for resistance to this antiviral compound. The data indicate that immunodeficient patients may shed resistant viruses for prolonged periods and with different drug resistance mutations present at different times. This PCR-restriction technique allows rapid detection of amantadine- or rimantadine-resistant strains.

Adult↗
PubMed1995

Intranasal pirodavir (R77,975) treatment of rhinovirus colds.

A randomized, double-blind, placebo-controlled trial assessed the therapeutic efficacy of intranasal pirodavir in naturally occurring rhinovirus colds. Adults with symptoms of < or = 2 days' duration were randomly assigned to intranasal sprays of pirodavir (2 mg per treatment) or placebo six times daily for 5 days. In people with laboratory-documented rhinovirus colds (53 in the pirodavir group, 55 in the placebo group), no significant differences in the resolution of respiratory symptoms were apparent between the groups. The median duration of illness was 7 days in each group. Similarly, scores for individual symptoms found no differences in favor of pirodavir during or after treatment. In contrast, reduced frequencies of rhinovirus shedding were observed in the pirodavir group on day 3 (70 versus 23%; P < 0.001) and day 5 (38 versus 12%; P = 0.002) but not after the cessation of treatment, on day 7 (19 versus 21%). No pirodavir-resistant viruses were recovered from treated individuals. The pirodavir group had higher rates of nasal dryness, blood in mucus, or unpleasant taste on several study days. In summary, intranasal sprays of pirodavir were associated with significant antiviral effects but no clinical benefit in treating naturally occurring rhinovirus colds.

Administration, Intranasal↗
PubMed1995

Orthomyxoviral and paramyxoviral infections in transplant patients.

In summary, orthomyxo- and paramyxoviruses cause clinically important infections in transplant patients. Patients often develop lower respiratory tract involvement and sometimes respiratory failure, which almost is uniformly fatal. Bone marrow transplant recipients appear to be at higher risk of severe disease than are solid-organ recipients, but well defined criteria to predict those patients who will be severely affected are not available. Factors associated with more severe disease include the type of viral pathogen, with pneumonia occurring more commonly with RSV and PIV infection, and the degree of immunosuppression of the patient, particularly the pre-engraftment phase in bone marrow transplant recipients. Because mortality is associated with development of pneumonia, prompt diagnosis and studies for concurrent infections are essential. Evaluation of fever and upper respiratory tract symptoms in patients in the peritransplant period should include sampling of nasopharyngeal and throat for virus isolation and antigen detection for respiratory viruses. If patients develop lower respiratory tract symptoms, early bronchoscopy with BAL is indicated. No specific antiviral therapy has proved effective in the treatment of established respiratory viral infections of transplant patients. Aerosolized ribavirin or, in the instance of influenza A virus infection, oral rimantadine might be considered as early therapy to prevent severe lower respiratory disease. Intravenous ribavirin, currently available on a compassionate use basis, might be considered for treating measles virus infection. In patients with lower tract disease due to RSV, the addition of immunoglobulin with high neutralizing antibody titers to RSV or intravenous ribavirin are additional considerations to forestall respiratory failure. Controlled studies of these interventions are needed in transplant patients before their use can be recommended routinely.

Antiviral Agents↗
PubMed1994

Anti-influenza virus activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en in cell culture and in human respiratory epithelium.

The anti-influenza activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en (4-G-NAc) was determined in Madin-Darby canine kidney (MDCK) cells by yield reduction and ELISA and in explants of human respiratory epithelium by yield reduction. In MDCK cells, 50% inhibitory concentrations (EC50) averaged 0.5 microgram/ml for influenza A/Virginia/88(H3N2) and 0.04 microgram/ml for A/Texas/36/91(H1N1) by ELISA, and < 0.01 microgram/ml for influenza A/Virginia by yield reduction. In human adenoid explants, concentrations causing at least 1.0 log10 TCID50/ml decrease in yield (EC90) at 48 h were < 0.01 microgram/ml for A(H1N1) and A(H3N2) viruses and 0.25 microgram/ml for B/Hong Kong/5/72. 100 micrograms/ml 4-G-NAc did not inhibit outgrowth of human adenoid epithelium at 6 days, whereas ribavirin 10 micrograms/ml reduced outgrowth by > 50%. 4-G-NAc is a potent and selective inhibitor of clinical isolates of influenza A and B viruses in human respiratory epithelium.

Animals↗
PubMed1994

In vitro selection of human rhinovirus relatively resistant to soluble intercellular adhesion molecule-1.

Variants of human rhinovirus serotype 39 (HRV-39) relatively resistant to inhibition by soluble intercellular adhesion molecule-1 (sICAM-1) were selected by serial passages in HeLa or WI-38 cells in the presence of sICAM-1. Moderate resistance (four- to fivefold increases in 50% effective inhibitory concentrations [EC50s]) was observed after the second passage in HeLa cells and remained constant during six further passages in the presence of 10 micrograms of sICAM-1 per ml. A 7- to 17-fold increase in EC50s was observed in WI-38 cells during passage with 10 micrograms/ml, and reversion to a nonresistant phenotype was not observed after four passages in the absence of sICAM-1. Resistance of a higher degree was obtained by passing HRV-39 in the presence of 100 micrograms of sICAM-1 per ml in HeLa cells (30-fold EC50 increase). The sICAM-1-resistant phenotype was estimated to constitute 1 in 10(4) to 1 in 10(5) PFU of a nonexposed HRV-39 population. Low to moderate levels of resistance to sICAM-1 inhibition emerge readily during in vitro passage in the presence of sICAM-1 and appear to be phenotypically stable.

Cell Adhesion Molecules↗