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Biomedical subjects

R G Douglas

Publications and source records attributed to R G Douglas.

At least 91 records · Page 5Linked to original sources
PubMed1981

Responses of elderly subjects to monovalent A/USSR/77 (H1N1) and Trivalent A/USSR/77 (H1N1)-A/TEXAS/77 (H3N2)-B/Hong Kong/72 vaccines.

Antibody responses to vaccination with monovalent A/USSR/77 (H1N1) and trivalent A/USSR/77 (H1N1)-A/Texas/77 (H3N2)-B/Hong Kong/72 vaccines were examined in a group of elderly persons most of whom had received more than 1 influenza vaccination in the previous 5 yr. Seventy-two per cent had a fourfold or greater increase in hemagglutination inhibition (HA1) titer to A/USSR and 92% had postvaccine titers equal to or greater than 1:40. There were no differences in antibody responses to A/USSR between recipients of monovalent and trivalent vaccines. No booster effect of a second injection of A/USSR was observed in subjects who had failed to respond to the first injection. Although there was a significant correlation between postvaccine HAI titers to A/USSR and to A/Texas, the responses to A/Texas and B/Hong Kong were modest or minimal compared with those to A/USSR. This serologic data may be relevant to the results of surveillance studies that suggest a limited advantage of repeated vaccinations with H3N2 subtypes and should help in evaluating the results of this practice.

Adult↗
PubMed1981

Interferon production in adults with respiratory syncytial viral infection.

Respiratory syncytial virus may cause repeated infections and appreciable illness in adults as well as children. Factors associated with immunity and recovery are poorly understood. We studied 37 adults with natural respiratory syncytial viral illness and eight experimentally infected volunteers for nasal interferon production. Their response was compared to that of 25 adults with influenza. Interferon was detected in only six of those with natural respiratory syncytial virus and in none of those with experimental infection. The quantities of interferon were low (geometric mean, 6 U/mL) and did not appear to affect viral shedding. In contrast, 24 of influenza patients produced interferon and in greater quantities (geometric mean, 116 U/mL). This suggests that interferon is not involved in recovery from respiratory syncytial viral infection and might indicate a lack of a local cell-mediated response that could relate to the often prolonged course and shedding observed with respiratory syncytial virus.

Adult↗
PubMed1980

Genetic approaches to attenuation of influenza A viruses for man.

The explosion of new information concerning the influenza A viral genome provides a basis for deliberate manipulation of its genes with the intent of introducing specific mutations that render influenza virus attenuated and useful for prevention of disease. Currently there is considerable effort to develop a defined set of mutant genes that confer a specific and desired level of attenuation upon any viral recombinant into which they are transferred. In this manner new antigenic variants of influenza A virus may be satisfactorily attenuated after transfer of the mutant genes. The mutant genes must be readily identifiable by simple in-vitro techniques, thus enabling the genetic basis of attenuation to be monitored directly during all phases of vaccine development, manufacture and utilization in man. We describe our experience with two sets of ts mutant genes which affect viral RNA transcription or synthesis and which effect a reproducible level of attenuation in wild-type influenza A virus.

Animals↗
PubMed1980

Mitogen responses and interferon production after exposure of human macrophages to infectious and inactivated influenza viruses.

Human macrophages were exposed to two influenza A viruses representing different subtypes. The donors were likely to have been exposed to one subtype (H3N2) but not to the other (H0N 1). Similar effects upon the macrophages were observed for both subtypes: macrophage enhancement of mitogen-stimulated lymphocyte transformation responses was depressed, and the macrophages produced interferon. In contrast, macrophages exposed to inactivated virus exhibited normal enhancement of lymphocyte transformation response, yet produced interferon, although in lower titers than did macrophages exposed to infectious virus.

Hot Temperature↗
PubMed1980

Temperature-sensitive mutants of influenza A virus: evaluation of the Alaska/77-ts-1A2 temperature-sensitive recombinant virus in seronegative adult volunteers.

An influenza A virus recombinant bearing the surface antigens of the A/Alaska/6/77 (H3N2) wild type virus ands the two ts genes of the A/Udorn/72-ts-1A2 (H3N2) virus was evaluated for attenuation, antigenicity, and transmissibility in 28 adult volunteers all of whom possessed a preinoculation serum hemagglutination-inhibiting (HAI) antibody titer of less than or equal to 1:8 and 18 of whom also possessed a serum neuraminidase-inhibiting (NI) antibody titer of less than or equal to 1:4. The Alaska/77-ts-1A2 recombinant, which had a 37 degrees C shutoff temperature for plaque formation and ts mutations on the genes thought to code for the P1 and P3 polymerase proteins, infected 71 percent of the vaccinees when administered at a dose of 10(6.5) TCID50. Only 3 percent of the vaccinees developed symptoms in contrast to 50 percent of volunteers who received 10(4.2) TCID50 of wild type virus. Vaccinees shed virus for a shorter interval and at a lower titer than the volunteers who received wild type virus. Each ts-1A2 isolate retained the ts phenotype indicating that the recombinant was stable genetically in seronegative adults. An immunological response, as measured by a rise in serum HAI and/or NI antibody, was detected in 71 percent of the vaccinees and 87 percent of the recipients of wild type virus. Transmission of vaccine virus to susceptible contacts was not observed. The two ts-1A2 ts genes have now been transferred to two variants within the H3N2 subtype, the Vic/75 and Alaska/77 viruses, and have rendered the viruses satisfactorily attenuated for adults. The level of infectivity of the Alaska/77-ts-1A2 virus appeared to be low, however.

Adult↗
PubMed1980

Possible transmission by fomites of respiratory syncytial virus.

To test whether nosocomial spread of respiratory syncytial virus (RSV) could occur through contact with environmental surfaces contaminated by RSV-infected nasal secretions, survival in the environment of RSV isolated from media, pooled adult secretions, and secretions from hospitalized infants was examined. RSV in freshly obtained infant secretions was recovered from countertops for up to 6 hr, from rubber gloves for up to 1 1/2 hr, from cloth gowns and paper tissue for 30--45 min, and from skin for up to 20 min. RSV in media and pooled secretions survived for slightly longer periods. Further experiments demonstrated that infectious virus could be transferred to hands touching these contaminated surfaces and could be recovered from these hands for up to 25 min. These studies suggest that survival of RSV in the environment of infected infant secretions is sufficient to allow transfer of infectious virus to the hands of hospital personnel. Thus, self-inoculation by contact with contaminated infant secretions may be a potential mode of nosocomial transmission of RSV.

Child↗
PubMed1980

Therapeutic effects of aerosolized amantadine in naturally acquired infection due to influenza A virus.

The effect of small-particle aerosol therapy with amantadine was assessed in a randomized, double-blind study of 20 patients with naturally acquired influenza A virus infection. Aerosol treatments of 20 min with either distilled water or with amantadine hydrochloride (1.0 g/100 ml of distilled water) were given three times a day for four days. The amantadine-treated patients experienced a significantly more rapid resolution of clinical signs and symptoms when compared with placebo-treated patients. The resolution of fever was similar for both groups. Aerosol delivery of amantadine did not affect the frequency of viral isolation from upper respiratory tract secretions but was associated with a trend toward reduced quantity of viral shedding. Serial pulmonary function tests found no important differences between the groups. Amantadine-treated patients experienced a greater frequency of mild local side effects (rhinorrhea, nasal irritation) during aerosol exposures, but aerosol treatments did not cause any apparent decline in pulmonary function.

Adult↗
PubMed1980

Effects of ribavirin on respiratory syncytial virus in vitro.

Ribavirin was demonstrated to have an antiviral effect on respiratory syncytial virus in vitro. A 50% reduction in plaque number was observed at concentrations of 3 or 10 micrograms of ribavirin per ml. This effect was observed when the drug was added as late as 12 h postinfection. At concentrations of greater than 10 micrograms of ribavirin per ml, the size of the syncytial plaque also noticeably decreased. Ribavirin similarly decreased the number of infectious units released into the culture supernatant. The antiviral effect was observed to be inversely related to the size of the viral inoculum, although all concentrations above 3.2 micrograms of ribavirin per ml visibly lessened the cytopathic effect regardless of the inoculum. Cloning of respiratory synctial virus in inhibitory concentrations of ribavirin failed to show increased resistance to the drug.

Cytopathogenic Effect, Viral↗
PubMed1980

Plaque inhibition assay for drug susceptibility testing of influenza viruses.

The relative antiviral activities of four drugs against contemporary strains of influenza A and B viruses were determined in Madin-Darby canine kidney cell monolayers with a plaque inhibition assay. This assay proved to be a reliable, rapid method of determining 50% inhibitory concentrations that correlated well with clinically achievable drug levels and the results of clinical trials. Contemporary strains of influenza A viruses (subtypes H1N1, H3N2, HSW1N1) required amantadine hydrochloride and rimantadine hydrochloride 50% inhibitory concentrations in the range of 0.2 to 0.4 microgram/ml, whereas 50% inhibitory concentrations ranged from approximately 50 to 100 micrograms/ml against influenza B viruses. Ribavirin was approximately 10-fold less active than amantadine hydrochloride against influenza A viruses, and the ribavirin 50% inhibitory concentrations against both influenza A and B viruses ranged from 2.6 to 6.8 micrograms/ml. Inosiplex had no antiviral activity in this test system.

Amantadine↗
PubMed1980

Enhancement of activity against influenza viruses by combinations of antiviral agents.

In an investigation of alternative therapeutic approaches for the treatment of influenza virus infections, the antiviral activities of rimantadine hydrochloride, amantadine hydrochloride, ribavirin, and combinations of these drugs were assessed in vitro. Madin-Darby canine kidney cell monolayers were inoculated with recent isolates of influenza viruses at low multiplicities of infection, and virus titers were determined after 24 h. The combination of rimantadine and ribavirin resulted in an enhanced antiviral effect (a decrease in virus titer of > 1.0 log10 plaque-forming unit per ml at 24 h relative to the maximal effect of a single drug) against A/USSR/90/77/H1N1, A/Texas/1/77/H3N2, A/New Jersey/76/HSW1N1, and A/PR/834/H0N1 viruses. The degree of inhibition depended on the virus strain used, the drug concentrations, and the virus inoculum. Amantadine and ribavirin showed enhanced activity. Ribavirin in combination with high (50 micrograms/ml), but not low (1.56 to 25 micrograms/ml), concentrations of rimantadine showed an enhanced antiviral effect against B/Hong Kong/72 virus. An assay of Madin-Darby canine kidney cell proliferation in the presence of drugs showed that the enhanced inhibitory effect of drug combinations was not due to increased cytotoxicity.

Antiviral Agents↗
PubMed1980

Evaluation of influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and cold-adapted recombinant viruses in seronegative adult volunteers.

Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID(50)) for each recombinant was approximately 10(5.0) 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID(50) and approximately 70% of ca or ts vaccinees who received 10 to 32 HID(50) of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.

Adult↗
PubMed1980

Airway reactivity in subjects with viral upper respiratory tract infections: the effects of exercise and cold air.

To define airway hyperreactivity further in symptomatic upper respiratory tract infection (URI), we compared in the setting of viral URI the respiratory effects of inhaling histamine to that of exercising with room air (993 +/- 300 kpm/min; 22 degrees +/- 2 degrees C), cold air breathing (-8 +/- 2 degrees C), and exercising with cold air (993 +/- 300 kpm/min; -8 degrees +/- 2 degrees C). Thirteen previously healthy, nonsmoking, nonatopic adults with URI were evaluated at the time of presentation and 1, 3, and 6 wk thereafter. At the initial presentation there was a 28 +/- 14% decrease in mean airway conductance (SGaw) after inhalation of histamine (p > 0.001). By 6 wk, airway reactivity to histamine decreased in 9 of 13 subjects. After exercise with cold air, there was a 12.5 +/- 7.5% decrease in mean SGaw (p < 0.001). By 6 wk, exercise with cold air no longer produced a decrease in SGaw (p > 0.05). In 5 additional subjects this airway reactivity to exercise with cold air was blocked by previous administration of atropine and by oropharyngeal anesthesia. We conclude that during viral URI there occurs transient airway hyperreactivity ot the combination of exercise with cold, dry air and that the upper airway and parasympathetic nervous system have important roles in these responses.

Adult↗
PubMed1980

Diffuse pneumonitis due to adenovirus type 21 in a civilian.

A patient with severe pneumonitis due to adenovirus type 21 responded to oxygen delivered by continuous positive airway pressure through a face mask. Pulmonary function studies over ten months demonstrated resolving, restrictive lung disease. The prognosis of severe adenovirus pneumonia may be better than expected based on previous reports.

Adenoviridae Infections↗
PubMed1980

Infection control committee reviews policies, cuts costs.

Working in cooperation with other hospital departments, especially nursing, the members of an infection control program were able to review and change hospital policies and procedures without compromising patient care. This collaboration resulted in hospital policies that are more uniform, rational, and workable and a savings of $63,000.

Cost-Benefit Analysis↗