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Biomedical subjects

F G Hayden

Publications and source records attributed to F G Hayden.

At least 127 records · Page 7Linked to original sources
PubMed1989

Modulation of thymosin alpha 1 and thymosin beta 4 levels and peripheral blood mononuclear cell subsets during experimental rhinovirus colds.

Cellular immune response to localized upper respiratory viral infection was studied in two groups of healthy volunteers infected with an unnumbered rhinovirus serotype (Hanks). In the first group of 18 volunteers, serum levels of thymosin alpha 1 rose on day 5 following rhinovirus challenge. This observation was confirmed in a second group of 20 normal volunteers inoculated with the same rhinovirus strain; there was a slight increase in thymosin alpha 1 levels on day 3 and a significant rise on day 5 (p less than .001). There was also a significant rise in serum thymosin beta 4 levels on day 5 (p less than .001). Serum cortisol rose in parallel with thymosin alpha 1 on day 5 after rhinovirus inoculation, but there was no direct relationship between individual changes in cortisol and thymosin alpha 1 levels. Enumeration of peripheral blood mononuclear cell subpopulations during rhinovirus infection revealed a significant increase in total lymphocytes on day 5 (p less than .01), but not on day 3. The rise in total lymphocyte count was attributable to an increase in T lymphocytes (CD3+) (p less than .05), cytotoxic/suppressor (CD8+) cells (p less than .01) and natural killer (CD16+ cells) (p less than .05). This is the first report of thymic hormone modulation by a virus, and suggests that local rhinovirus infection of the upper respiratory tract has systemic effects and induces cellular immune responses.

Adult↗
PubMed1988

Intranasal tolerance and histopathologic effects of a novel synthetic interferon, rIFN-alpha Con1.

In a double-blind trial 119 adults were randomly assigned to receive daily sprays of placebo (N = 30) or rIFN-alpha Con1 3 MU (N = 29), 9 MU (N = 30), or 30 MU (N = 30) per day for 25 consecutive days. Fifty-nine subjects were removed from treatment because of abnormal nasal exams (N = 56) or irritative symptoms (N = 3). The fraction of drop-outs in the placebo group (30%) was significantly different (P less than 0.05) from that in the 3 MU (55%), 9 MU (57%), or 30 MU (67%) groups. Nasal mucosal biopsies collected 1-2 days after completing spray use detected moderate or marked lymphocytic infiltration in 10% of placebo (N = 10), 90% of 3 MU (N = 9), 85% of 9 MU (N = 13), and 70% of 30 MU (N = 10) subjects (P less than 0.05, placebo vs each rIFN-alpha Con1 group). All 3 dose levels of rIFN-alpha Con1 were associated with significant clinical and histopathologic signs of nasal irritation. The findings suggest that intranasal rIFN-alpha Con1 does not have a more favorable therapeutic index than rIFN-alpha 2 and that the risk of nasal irritation relates more closely to the anti-viral activity than the protein content of the rIFN-alpha administered.

Adult↗
PubMed1988

Relapse of herpes simplex encephalitis after conventional acyclovir therapy.

Acyclovir sodium is the drug of choice for the treatment of herpes simplex encephalitis. We treated an immunocompetent patient with a ten-day course of intravenous acyclovir sodium at the recommended dosage of 10 mg/kg every eight hours for clinically apparent herpes simplex encephalitis. After marked improvement, his condition deteriorated four days after completing acyclovir therapy. A subsequent brain biopsy specimen disclosed acyclovir-sensitive herpes simplex virus type 1. A longer duration of acyclovir therapy (14 to 21 days) should be considered for treating herpes simplex encephalitis.

Acyclovir↗
PubMed1988

Modification of experimental rhinovirus colds by receptor blockade.

Human rhinovirus (HRV) infection can be inhibited in vitro by antibody directed against the cellular receptor for the major HRV group representing 90% of serotypes. We assessed the prophylactic effectiveness and safety of intranasally administered rhinovirus receptor murine monoclonal antibody (RRMA) in two double-blind, place-controlled, randomized studies of volunteers experimentally inoculated with HRV-39. In the first study, RRMA administration (135 micrograms/subject in 9 applications, -17 to +48 h) did not reduce infection (RRMA 12/15 vs. placebo 13/15) or illness (8/12 vs. 7/13) rates or modify the clinical course of experimental HRV-39 colds. In the second trial, a higher RRMA dosage (1 mg/subject in 10 applications, -3 to +36 h), similarly did not reduce overall infection (11/13 vs. 12/13) or illness (7/11 vs. 9/12) rates, but was associated with a 1-2 day delay in the onset of viral shedding and cold symptoms and with significant reductions in viral titers and nasal symptoms on the second day after challenge and in mucus weights on the third day after challenge. No toxicity related to RRMA was recognized. The results indicate that intranasal RRMA modified infection and illness after experimental HRV-39 challenge and suggest that blockade of host cell receptors offers a novel antiviral approach against HRV infections.

Administration, Intranasal↗
PubMed1988

Tolerance and efficacy of intranasal administration of recombinant beta serine interferon in healthy adults.

We performed two studies to determine the dose-related tolerance and the efficacy of recombinant beta serine interferon (rIFN-beta ser) in experimental rhinovirus infection. In the tolerance study, 120 healthy adults received intranasal sprays of rIFN-beta ser or placebo daily for 25 d. No differences in nasal symptoms were found. Rhinoscopy detected more mucosal bleeding sites in high-dose (38%) versus low-dose (12.5%) or placebo (12.5%) recipients. There were more subepithelial lymphocytes in nasal biopsy specimens in the high-dose (54%) than the low-dose (17%) or placebo (17%) groups. In the efficacy study, 34 volunteers received daily nasal drops of IFN, beginning 36 h before challenge and for three days afterwards. The numbers of infections and days of shedding of virus were not reduced, but colds occurred less often in the high-dose (25%) than in the low-dose (55%) or placebo (64%) recipients. Nasal mucus weights were lower in the high-dose (mean +/- SD g per five days; 5 +/- 4) than placebo (31 +/- 37) recipients. Thus, rIFN-beta ser may have a more favorable therapeutic ratio than do previously tested alpha interferons.

Administration, Intranasal↗
PubMed1988

Ineffectiveness of oral terfenadine in natural colds: evidence against histamine as a mediator of common cold symptoms.

The role of histamine in the pathogenesis of infectious rhinitis is unclear, as is the efficacy of antihistaminic drugs in the treatment of the common cold. This study evaluated the short-term efficacy of oral terfenadine (Seldane) in the treatment of the common cold. Over a 5-week period, the authors recruited 250 adults who had developed cold symptoms within 6 to 48 hours prior to enrollment. Volunteers had a primary complaint of runny or stuffy nose; at least one other respiratory symptom; no fever or exudative pharyngitis; and no history of atopy, sinusitis, or use of cold preparations within 1 week of enrollment. Out of the eligible subjects, 126 were randomly assigned terfenadine (60 mg), and 124 received placebo. Volunteers self-administered either terfenadine or placebo twice a day on Days 1, 2 and 3, and a final dose on the morning of Day 4. They also recorded the severity of their clinical symptoms (runny nose, sniffles, sneezing, postnasal drip, cough and sore throat) on symptom cards. Both groups reported similar severity scores throughout the treatment period. Average symptom burdens declined at almost identical rates for both groups. Terfenadine was well tolerated and had a low incidence of side effects. According to subject evaluation, terfenadine was no more effective than placebo. The mean +/- SD score of global efficacy was 2.2 +/- 1.1 in the terfenadine group and 2.1 +/- 1.3 in the placebo group (P = NS). Slightly fewer terfenadine recipients (41%) than placebo recipients (48%) said they would use the study medication again for treating cold symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Ipratropium bromide treatment of experimental rhinovirus infection.

The importance of parasympathetic-cholinergic mechanisms in the production of common cold symptoms is not clear. The quaternary ammonium anticholinergic antagonist ipratropium bromide was intranasally administered under double-blind, randomized, placebo-controlled conditions to assess its tolerance and efficacy in reducing nasal hypersecretion in adult volunteers with experimental rhinovirus colds. Ipratropium was sprayed intranasally three times daily (80 micrograms per treatment) for 5 days beginning 24 h after intranasal inoculation of rhinovirus type 39. Clinical colds occurred in 50% of 30 infected ipratropium recipients and in 76% of 33 infected placebo recipients (P = 0.04). The nasal mucus weights tended to be lower for ipratropium-treated persons (mean +/- standard deviation, 14.7 +/- 15.1 g/5 days) than for placebo-treated recipients (24.7 +/- 28.0 g/5 days; P = 0.076). Whereas total nasal symptom scores were similar between the two groups, the rhinorrhea score analyzed for each day of treatment showed nonsignificant trends favoring the ipratropium group over the last 4 days of treatment. Ipratropium was generally well tolerated. The results suggest that cholinergic mechanisms are at least partially responsible for nasal mucus production in rhinovirus colds but that the effect of anticholinergic compounds alone is insufficient to be of practical use in treatment, although they may have value as components of multi-ingredient preparations.

Administration, Intranasal↗
PubMed1988

Multiple-dose pharmacokinetics of rimantadine in elderly adults.

To assess the possible effect of aging on rimantadine hydrochloride pharmacokinetics, single- and multiple-dose kinetics were determined in 18 healthy adults with ages between 51 and 79 years. Subjects ingested single 100-mg oral doses of rimantadine after an overnight fast, followed after 5 days by a dosage of 100 mg twice a day for 9.5 days. No differences were observed among the age-stratified groups in measured or derived pharmacokinetic parameters. Peak concentrations in plasma (mean +/- standard deviation) following the single- and multiple-dose regimens, respectively, were 89 +/- 25 and 417 +/- 129 ng/ml for subjects who were 50 to 60 years of age (group 1), 92 +/- 24 and 401 +/- 84 ng/ml for those 61 to 70 years of age (group 2), and 100 +/- 14 and 538 +/- 51 for those 71 to 79 years of age (group 3). The elimination half-life in plasma following multiple doses averaged 33.5 h for group 1, 32.5 h for group 2, and 38.6 h for group 3. Steady-state concentrations in nasal mucus developed by day 5 of dosing (1.5-fold higher than concentrations in plasma), and rimantadine remained detectable in secretions for 5 days after the last dose in 65% of subjects. Stepwise regression analysis suggested that changes in maximum concentration in plasma and area under the concentration-time curve at steady state may be related to creatinine clearance. The results indicate that no important differences in rimantadine multiple-dose pharmacokinetics exist among healthy elderly adults with ages between 51 and 79 years.

Adamantane↗
PubMed1988

Intranasal recombinant alfa-2b interferon treatment of naturally occurring common colds.

In a double-blind, placebo-controlled study, patients with naturally occurring common colds of less than or equal to 48 h duration were randomly assigned to receive nasal sprays of recombinant alfa-2b interferon at 10 or 20 MU/day or placebo four times per day for 5 days. The 10-MU (n = 74), 20-MU (n = 74), and placebo (n = 72) groups had comparable frequencies of documented rhinovirus colds (50 to 65%) and mean durations of pretreatment symptoms (26 to 27 h). The median duration of colds tended to be longer in the 20-MU group (10 days) than the 10-MU group (8 days) or placebo group (8 days) (P = 0.06). In those with proven rhinovirus colds treated within 24 h, the median duration was significantly longer in the 20-MU group (9 days) than in the placebo group (6 days). No differences favoring interferon treatment were found in respiratory symptom scores or resolution of specific symptoms. On days 5 and 7, nasal washings from compliant subjects with proven rhinovirus colds yielded rhinoviruses more often in placebo (47 and 48%, respectively) than in interferon (15 and 16%, respectively) recipients (P less than 0.02), but no differences in new respiratory illness occurrence were observed in household contacts. Interferon recipients had significantly higher frequencies of blood in nasal mucus (16 to 18%) than did placebo recipients (4%) during treatment. Antibiotics for presumed secondary infections were given more often in the 20-MU group (11%) than in the placebo group (0%) (P less than 0.01). Nasal sprays of recombinant alfa-2b interferon were not an effective treatment for natural colds and were associated with toxicity.

Administration, Intranasal↗
PubMed1988

Rapid diagnosis of influenza A and B by 24-h fluorescent focus assays.

Murine monoclonal antibodies directed against type-specific antigens of influenza A and B viruses have been shown to be useful diagnostic reagents for the detection of influenza viruses by immunofluorescence testing of nasopharyngeal cells. We have developed fluorescent focus assays utilizing these antibodies in cell culture chamber slides and shell vials for the rapid diagnosis of influenza A and B. Chamber slide assays were compared with virus isolation in 160 specimens from 135 patients with symptoms of influenza. Virus isolation was compared with immunofluorescence testing in 38 of the 160 specimens. Compared with virus isolation, 24-h cell culture chamber slide assays had a sensitivity of 75% and a specificity of 96%. Immunofluorescence testing of nasopharyngeal cells was only 38% sensitive and 91% specific. Shell vial assays were compared with virus isolation for 89 specimens. At 16 to 18 h postinoculation, the shell vial assay was 84% sensitive and 100% specific. We conclude that both chamber slide and shell vial assays are rapid, sensitive, and specific techniques for the diagnosis of influenza.

Animals↗
PubMed1988

Measurement of rimantadine in plasma by capillary gas chromatography/mass spectrometry with a deuterium-labeled internal standard.

Rimantadine is a synthetic antiviral agent used in prophylaxis and in treating the early stages of uncomplicated influenza A illness. We describe a stable isotope-dilution assay involving capillary gas chromatography/mass spectrometry. We used 200 ng of d3-rimantadine, added to 1 mL of plasma, as the internal standard. The rimantadine was extracted from the plasma with a Bond-Elut CN column, the column was washed with water, and the rimantadine was eluted with methanol, dried, and treated to form the t-butyldimethylsilyl derivative. The mass spectrometer was operated in the selected ion monitoring mode. Ions at m/z 236 and m/z 239 were monitored, corresponding to the loss of C4H9 from the rimantadine derivative and d3-rimantadine, respectively. Within-run precision (CVs) ranged from 8.9% at 29 micrograms/L to 3.2% at 1666 micrograms/L. Corresponding data for between-run precision were 5.4% and 1.7%. Treated volunteers (n = 86) provided plasma samples with a concentration range of 153 to 1127 micrograms/L. This simplified method allows rapid, precise assay of rimantadine in plasma.

Adamantane↗
PubMed1987

Lymphocyte subsets in normal airway mucosa of the human nose.

The distribution and number of lymphocytes, monocytes/macrophages, and cells expressing HLA-DR antigen were studied in frozen biopsy sections of nasal mucosa from 40 healthy adults, using monoclonal antibody avidin-biotin immunoperoxidase techniques. The lymphocyte to monocyte/macrophage ratio was estimated to be 10:1; the T cell to B cell ratio was 3:1; and the T helper/inducer cell to T suppressor/cytotoxic cell ratio averaged 2.5:1. Regional differences were observed with a relatively increased number of T suppressor/cytotoxic cells around submucosal glands, and a relatively large number of B cells in lymphocyte aggregates in the lamina propria. The HLA-DR antigen was expressed in epithelial cells, suggesting involvement of surface epithelium of human airway in local immune responses.

Adult↗
PubMed1987

Tolerance and nasal histopathologic effects of long-term, low-dose intranasal recombinant interferon alpha-2A (Roferon-A).

The dose-related tolerance and histopathologic effects of intranasal recombinant interferon alpha-2a (rIFN-alpha 2a) were determined in a blind study in which healthy subjects were randomized to receive sprays of interferon (IFN) (3 or 6 MU/day) or placebo for 28 days. Adverse nasal symptoms (bleeding, obstruction, irritation) tended to occur more often in the IFN 6 MU/day group. Blind analysis of biopsy samples collected before and after IFN treatment revealed that both IFN groups had significant histologic changes, most commonly an increased degree of lymphocytic infiltration in the subepithelium and underlying glandular zones. Changes developed in 61% of 18 recipients of IFN 6 MU/day, 37% of 19 recipients of IFN 3 MU/day, and 6% of 18 placebo recipients. Serum antibodies to rIFN-alpha 2a detectable by EIA were found in 4 recipients of IFN 3 MU/day and 2 recipients of IFN 6 MU/day, one-third of whom were positive by neutralization bioassay. The findings would predict that these rIFN-alpha 2a dosages would be associated with an excess of adverse side effects during long-term use in healthy adults.

Administration, Intranasal↗
PubMed1987

Comparison of radioactive (32P and 35S) and biotinylated probes for detection of cytomegalovirus DNA.

Cytomegalovirus (CMV) DNA was detected in a dot-blot assay by hybridization to a DNA probe labeled with radioisotopes (32P or 35S) or biotin. Limits of detection were established for both the radioisotopically labeled DNA probes as well as the biotin-labeled probe. Hybridization of the radioisotopically labeled probes was detected by autoradiography and liquid scintillation while the biotin-labeled probe was detected after coupling to one of three enzymes (e.g., horseradish peroxidase, alkaline phosphatase, or acid phosphatase). In addition, several different substrates were evaluated with the nonisotopic detection enzymes. Detection limits (and times for detection) were 1 pg (4 h) for 32P, approximately 1 pg (96 h) for 35S, 5 pg (1-3 h) for the phosphatases, and 25-50 pg for peroxidase. Thus, 32P-labeled probes appear to provide the best sensitivity whereas the avidin-linked phosphatases provide the best sensitivity among the nonisotopic detection systems.

Autoradiography↗
PubMed1987

Human nasal mucosal responses to topically applied recombinant leukocyte A interferon.

Healthy adults were randomly assigned to receive intranasal sprays of recombinant leukocyte A interferon (IFN; 9 X 10(6) U per day) or placebo once daily for four or 10 days. Scrape nasal biopsy specimens stained by hematoxylin and eosin and mucosal punch biopsy specimens stained by immunoperoxidase techniques with monoclonal antibodies to lymphocyte subsets were collected before and after exposure. Blinded analysis of the punch biopsy specimens by two pathologists found increased degrees of lymphocyte infiltration compared with preexposure samples in 56% of IFN vs. 0% of placebo recipients at four days (P = .008) and 60% of IFN vs. 10% of placebo recipients at 10 days (P = .057). By immunoperoxidase staining the cellular infiltrates were primarily in the subepithelium and comprised principally (mean, greater than or equal to 84%) T lymphocytes. In the 10-day IFN recipients, subepithelial T helper (Leu-3):T suppressor (Leu-2) cell ratios ranged from 2:1 to 5:1. The number of distribution of B (Leu-14) or natural killer (Leu-7) cells did not appear affected by IFN.

Administration, Topical↗
PubMed1987

In vitro activity of zinc salts against human rhinoviruses.

The antiviral activity of zinc salts against rhinovirus types 1A and 39 was assayed by yield reduction and inhibition of cytopathic effect in cell culture. The findings indicate that the zinc salts tested have low in vitro therapeutic indices and suggest that the possible beneficial effects of zinc lozenges in reducing cold symptoms may not be related to selective antirhinovirus activity.

Cell Line↗