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Biomedical subjects

F G Hayden

Publications and source records attributed to F G Hayden.

At least 163 records · Page 9Linked to original sources
PubMed1984

Combined interferon-alpha 2, rimantadine hydrochloride, and ribavirin inhibition of influenza virus replication in vitro.

Recombinant DNA-produced human interferon-alpha 2 inhibited the replication of influenza A and B viruses in primary rhesus monkey kidney cells (RMK). Human interferon-alpha 2 interacted additively or synergistically with rimantadine hydrochloride or ribavirin in reducing the yield of clinical isolates of either H3N2 or H1N1 subtype influenza A viruses. The combination of human interferon-alpha 2 and ribavirin also inhibited the replication of an influenza B virus to a greater extent than either single agent. In addition to drug concentration, the virus inoculum and duration of culture were important variables in determining the degree of inhibition. Single drugs or combinations did not significantly inhibit the growth of uninfected RMK cells, which indicated that the observed interactions with respect to antiviral activity were not due to cell cytotoxicity.

Adamantane↗
PubMed1984

Intranasal interferon-alpha 2 for prevention of natural rhinovirus colds.

The prophylactic activity of intranasal human interferon-alpha 2 (HuIFN-alpha 2) against natural rhinovirus colds was determined in a randomized, double-blind, placebo-controlled trial. A total of 304 working adults self-administered sprays of HuIFN-alpha 2 (10(7) IU/day) or a placebo once daily. During 22 days of treatment, 13 (8.5%) placebo recipients but no HuIFN-alpha 2 recipients had respiratory illnesses documented secondary to rhinovirus infection (P = 0.0002). The occurrence of illness with symptoms of tracheobronchitis was lower in HuIFN-alpha 2 recipients (one eposide) than in placebo recipients (eight episodes, P = 0.04). In contrast, the frequency of nasal symptoms and the overall rate of respiratory illness were significantly higher in HuIFN-alpha 2 recipients during weeks 2 and 3 of treatment. Symptoms (obstruction, discomfort, blood-tinged nasal mucus) or signs (punctate bleeding sites, erosions, superficial ulcerations) of nasal irritation occurred in 40 HuIFN-alpha 2 recipients during week 3 (P less than 0.0001 versus placebo recipients). Although the results of the current study were partially confounded by the nasal side effects of prolonged administration, they showed that intranasal HuIFN-alpha 2 was efficacious in preventing rhinovirus colds under natural conditions.

Administration, Intranasal↗
PubMed1983

Anti-interferon antibody increases rhinovirus isolation rates from nasal wash specimens containing interferon-alpha 2.

Isolation of rhinoviruses from nasal secretions may be delayed or prevented by exogenously applied interferon which is carried over into nasal wash specimens. In studies of interferon-alpha 2 treated volunteers with experimental rhinovirus infection, we determined that incorporation of antiinterferon antibody into collection broth significantly increased isolation rates (84% increase) and the proportion of monolayers positive for CPE (155% increase), as compared to plain collection broth.

Antibodies↗
PubMed1983

Modification of encephalomyocarditis virus-induced diabetes in mice by antiviral agents.

The current study used a murine model of diabetes induced by the D variant of encephalomyocarditis virus (DEMC) to determine the protective effect of exogenous antiviral agents. Antivirals, which were found to inhibit the development of DEMC virus cytopathic effect in L-929 cell monolayers, were administered intraperitoneally beginning 12 h prior to DEMC virus challenge. Arildone (500 mg/kg per day) or murine interferon (3.2 X 10(6) IU/kg per day) significantly reduced the incidence of hyperglycemia at 4 days after virus challenge. The incidences of hyperglycemia were 96% in untreated, 62% in arildone, and 0% in interferon treated mice. In other experiments we found that interferon (1.6 X 10(6) IU/kg per 12 h X 3) significantly protected mice against diabetes when administered at the time of virus infection or beginning 12 h afterwards. This effect was associated with reductions in average viral titers in the heart and pancreas of infected animals relative to untreated, infected mice. The results of these studies suggest that picornavirus induced diabetes may be prevented or ameliorated by the use of antiviral agents.

Animals↗
PubMed1983

Intranasal interferon alpha 2 for prevention of rhinovirus infection and illness.

In two placebo-controlled, double-blind studies, the prophylactic efficacy of recombinant DNA-produced interferon alpha 2 (IFN-alpha 2) against induced rhinovirus (RV) type 39 infection in susceptible volunteers was assessed. IFN-alpha 2 was given by intranasal drops in either multiple treatments (11.4 X 10(6) IU four times per day for four days) or one treatment daily (42.8 X 10(6) IU once per day for five days) starting before RV type 39 challenge. The efficacy rates of multiple-dose IFN-alpha 2 for preventing infection, virus shedding, and RV type 39-specific colds were 78%, 78%, and 100%, respectively. The corresponding rates for one daily treatment were 45%, 64%, and 75%, respectively. Both dosage regimens were associated with significant reductions in days of virus shedding and nasal mucus production. In the second study, three IFN-alpha 2 recipients developed transient leukopenia (less than 4,000 leukocytes/mm3). The results suggest that intranasal IFN-alpha 2 may prove to be a safe and effective method of preventing rhinovirus infection and illness.

Administration, Intranasal↗
PubMed1983

Human tolerance and histopathologic effects of long-term administration of intranasal interferon-alpha 2.

Fifty-two healthy adults were randomly assigned interferon-alpha 2 (HuIFN-alpha 2), 8.4 X 10(6) U/day, or placebo by intranasal spray for 28 days. Symptoms, nasal examinations, and histologic analysis of nasal biopsy specimens obtained three days before and one day after exposure were evaluated under blind conditions. HuIFN-alpha 2 was associated with signs of mucosal irritation (dry mucous membranes, crusts, and friability) and/or symptoms (blood-tinged mucus) in 23% of recipients. Moderate or marked epithelial acute inflammation with ulceration occurred in 19% of HuIFN-alpha 2 recipients. Pronounced submucosal lymphocytic and mononuclear cell infiltrates developed in 58%. These histopathologic abnormalities resolved within eight weeks of stopping exposure. These results indicate that long-term or indefinite intranasal administration of HuIFN-alpha 2 at the dosages used in this study is not feasible strategy for prophylaxis of respiratory viral infections.

Administration, Intranasal↗
PubMed1983

Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics.

In a double-blind, placebo-controlled study, the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined. Healthy, working adults ingested either 200 (n = 52) or 300 mg (n = 196) per day in divided doses for 4.5 days. Mean plasma drug concentrations at 4 h after the first dose were lower in rimantadine recipients given 100- (140 versus 300 ng/ml for rimantadine and amantadine, respectively; P less than 10(-5)) or 200-mg doses (310 versus 633 ng/ml; P less than 10(-5)). The plasma drug concentrations after the first dose correlated significantly with total symptom sources for both amantadine and rimantadine, but the plasma levels of toxic and nontoxic subjects overlapped extensively. At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms (33% of amantadine versus 9% of rimantadine recipients; P less than 0.001) and sleep disturbance (39 versus 13%; P less than 0.001), but not gastrointestinal symptoms (19.5 versus 16.0%). However, no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations. Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations.

Adamantane↗
PubMed1983

Human polymorphonuclear neutrophil functions are unaffected by human interferon-alpha 2.

Leukocyte-derived interferons have been reported to enhance the functions of polymorphonuclear neutrophils. This study reveals no effect of the highly purified recombinant DNA-produced human interferon-alpha 2 on the oxidative, chemotactic, adherent, phagocytic, and bactericidal activities of human polymorphonuclear neutrophils in vitro.

DNA, Recombinant↗
PubMed1983

Comparison of the Immulok cultureset kit and virus isolation for detection of herpes simplex virus in clinical specimens.

The Immulok test performed at 24 h after inoculation had a 73% sensitivity and 97.5% specificity for detecting herpes simplex virus in clinical specimens, as compared with viral culture in human embryonic lung fibroblasts. The test increased the proportion of positive specimens reportable at 24 h by 48% (P less than 0.01) but failed to detect 4 of 31 (13%) specimens positive for cytopathic effect at 24 h and 13 of 32 (41%) specimens positive at greater than or equal to 48 h after inoculation.

Antigens, Viral↗
PubMed1983

Counterimmunoelectrophoresis of urine for diagnosis of bacterial pneumonia in pediatric outpatients.

Thirty-eight pediatric outpatients with pneumonia were studied by counterimmunoelectrophoresis for the presence of Haemophilus influenzae type b or pneumococcal antigenuria. Of the 38 patients eight (21%) had H influenzae type b antigenuria and two (5%) had pneumococcal antigenuria. H influenzae type b antigenuria was detected more frequently in patients less than 2 years of age than in older children. Urine counterimmunoelectrophoresis appears to be a useful tool for the etiologic diagnosis of bacterial pneumonia and should facilitate further studies of the epidemiology, pathogenesis, and clinical spectrum of this disease.

Antigens, Bacterial↗
PubMed1982

Comparative therapeutic effect of aerosolized and oral rimantadine HCl in experimental human influenza A virus infection.

Thirty-six adult volunteers were inoculated intranasally with 7.2 log10 egg infectious doses 50% of an attenuated A/Khabarovsk/77/H1N1 virus. Twenty-four hours later volunteers were begun on both aerosol treatments (rimantadine HCl 25 mg in saline or saline, 10 min exposure twice daily) and oral medications (rimantadine HCl 50 mg or placebo every 6 h, three times daily) which were administered for 5 days. Virus-positive volunteers receiving placebo by both of the two routes had a peak in clinical illness scores on the second treatment day (mean score 5.3), which was not observed in either the aerosol rimantadine (0.6) or oral rimantadine (0.9) treated volunteers. On the second treatment day, the proportion of virus-positive volunteers with elevated axillary temperature measurements and the mean peak temperature measurement were also significantly reduced in both drug groups. No significant effects on the duration of virus shedding were noted. In experimental influenza A virus infection, characterized by mild clinical illness and short duration of virus shedding, low doses of aerosolized rimantadine had a therapeutic effect comparable to that found with larger doses of oral rimantadine.

Adamantane↗
PubMed1982

Prophylactic activity of intranasal enviroxime against experimentally induced rhinovirus type 39 infection.

Intranasal administration of enviroxime by aerosol spray was associated with drug levels in nasal secretions that 1 h later averaged 750-fold higher than those inhibitory for rhinoviruses in vitro (0.2 microgram/ml). However, administration of intranasal enviroxime (one spray per nostril, five times per day) to susceptible volunteers, beginning 1 day before and continuing for 4 days after virus exposure, did not significantly reduce infection or illness due to experimentally induced rhinovirus type 39 infection. The combined results of two separate trials yielded an infection rate of 100% for 21 placebo-treated and 89% for 19 enviroxime-treated subjects. Approximately one-half of the volunteers in each group had seroconversion to the challenge virus. Overall, 52% of the placebo-treated and 53% of the enviroxime-treated subjects developed colds. No significant differences in symptom scores, nasal mucus weights, or numbers of nasal tissues used were observed between the two groups. Two-thirds of the enviroxime-treated volunteers noted intranasal irritation immediately after sprays, as compared with only one-third of the placebo-treated subjects.

Administration, Oral↗
PubMed1982

Activity of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) against picornaviruses in vitro.

The newly synthesized compound 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (MDL-860) has been found to inhibit picornavirus replication. In multiple growth cycle experiments, 1 microgram of MDL-860 per ml caused a reduction in virus yield of at least 1.0 log10 50% tissue culture infectious doses per 0.2 ml for 8 of 10 enteroviruses and 72 of 90 rhinovirus serotypes. This antiviral activity was dependent on both compound concentration and virus inoculum size. At concentrations that had no toxic effects on cell cultures, MDL-860 did not inhibit cytopathic effect or hemadsorption activity due to coronavirus 229-E, vesicular stomatitis virus, herpes simplex virus type 1, adenovirus, influenza virus A, or parainfluenza virus 1. Compound concentrations up to 25 micrograms/ml did not cause cytopathic effect in short-term cultures of rhesus monkey, WI-38, or HeLa cells; 10 micrograms/ml did not inhibit the replication of HeLa cells. The mechanism of action of MDL-860 has not been defined, although it was not directly virucidal and appeared to inhibit picornaviruses specifically at an early step in the virus-host cell interaction.

Antiviral Agents↗
PubMed1981

Successful treatment of naturally occurring influenza A/USSR/77 H1N1.

Forty-five university students with proved influenza A/USSR/77 H1N1 infection were randomly treated with either amantadine hydrochloride (14 students), rimantadine hydrochloride (19 students), or placebo (12 students). By 48 hours after initiation of therapy, amantadine and rimantadine recipients had significantly less fever and greater improvement compared with subjects given the placebo. Minor reversible CNS side effects at the end of the five-day course of therapy were observed in one third of the amantadine-treated subjects. However, both amantadine and rimantadine recipients returned to classes earlier and shed smaller amounts of virus than placebo recipients. Thus, both drugs exerted a notable therapeutic effect. Hence, during an influenza outbreak, five days of empirical therapy with amantadine or rimantadine for persons with an influenza-like syndrome should ameliorate clinical symptoms and might decrease spread of virus.

Adult↗
PubMed1981

Etiology of acute conjunctivitis in children.

To determine the etiology of acute conjunctivitis in children seen in pediatric practice, 99 patients with conjunctivitis and 102 age-and season-matched controls were cultured for aerobic bacteria including Haemophilus influenzae, and for viruses, Chlamydia trachomatis, and mycoplasmas. Agents statistically associated with conjunctivitis included H. influenzae (42% vs 0%), Streptococcus pneumoniae (12% vs 3%), and adenoviruses (20% vs 0%). One of these three etiologic agents was isolated from 71 (72%) of the patients. Simultaneous infection with two pathogens was uncommon. Staphylococcus aureus was equally prevalent in diseased and control eyes; one strain of C. trachomatis was isolated from a control eye. Although there were variations in the clinical features of viral and bacterial conjunctivitis, differentiation in an individual patient was difficult. An adenovirus was isolated from 11 (65%) of 17 patients who had pharyngitis in addition to conjunctivitis. H. influenzae was isolated from 14 (74%) of 19 children who had both otitis and conjunctivitis. Adenovirus conjunctivitis was common in the fall and H. influenzae in winter.

Acute Disease↗
PubMed1981

Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults.

The relative toxicities of amantadine and rimantadine were compared in a double-blind, placebo-controlled study involving healthy adults. In separate studies, drugs were administered at a dosage of 200 mg/day (52 volunteers) or 300 mg/day (196 volunteers) for 4.5 days. Both drugs were well tolerated at the lower dosage. At 300 mg/day amantadine recipients had a greater frequency and severity of central nervous system (nervousness, lightheadedness, difficulty concentrating) and sleep (insomnia, fatigue) complaints compared with rimantadine or placebo recipients. Amantadine recipients also performed less well on an objective test measuring sustained attention and problem-solving ability. Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients. Because of better tolerance at higher dosage, rimantadine offers more promise than amantadine for treatment of influenza A virus infections.

Adamantane↗