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Biomedical subjects

R G Douglas

Publications and source records attributed to R G Douglas.

At least 73 records · Page 4Linked to original sources

Serological diagnosis of influenza A/USSR/77 H1N1 infection: value of ELISA compared to other antibody techniques.

Serologic diagnosis of influenza is an important but imperfect tool. During an outbreak of natural H1N1 A/USSR/77 infection, volunteers who received either amantadine, rimantadine, or placebo were tested to determine serologic response to infection by four different antibody techniques. Hemagglutination inhibition (HAI) and complement fixation (CF) were least sensitive, detecting only about half of the virus-positive subjects, whereas neutralization detected 81% and enzyme-linked immune peroxidase (ELISA) detected 95%. Failure to detect significant antibody response was associated with a higher titer of antibody in acute serum specimens and with a history of receipt of A/New Jersey/76 Hsw1N1 vaccine. Although antibody response measured by ELISA was of lower magnitude in vaccinees, it still was sufficient to be diagnostic. Thus, in situations where there is no access to viral isolation facilities, ELISA antibody techniques appear to be an excellent measure of assessing the rate of influenza infection.

Adolescent↗

X-chromosome hyperploidy in couples with multiple spontaneous abortions.

From 1973 to 1983, cytogenetic analyses were performed on blood samples from 144 couples referred because of two or more spontaneous abortions. Any couple with abnormal offspring in addition to the miscarriages was excluded from the study. Two balanced translocations were found in the 288 individuals examined (0.7%). There was a high frequency of phenotypically normal individuals with cells hyperploid for the X chromosome. This may be a manifestation of an impaired genetic control of chromosome disjunction in these patients.

Abortion, Habitual↗

Antiviral drugs 1983.

A number of antiviral compounds are currently available, and several others are of great interest. Trifluridine, idoxuridine, and vidarabine are effective topically in herpes simplex virus keratoconjunctivitis infection. Vidarabine (and presumably acyclovir) is effective in herpes simplex virus encephalitis and in herpes zoster infections in the immunocompromised host. Acyclovir is effective topically, orally, and intravenously in primary herpes genitalis, and the oral and intravenous forms are effective in recurrent herpes genitalis as well. Amantadine and rimantadine are effective prophylactically and therapeutically in influenza A infections. Ribavirin and interferon, although not licensed, are of great interest. Ribavirin may be useful in respiratory syncytial virus infections, and interferon may be of benefit in common colds and related disorders.

Acyclovir↗

Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine.

During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improvement. Bothersome side effects resulted in discontinuation of therapy by 35% of the aspirin treatment group but only 3% of the amantadine treatment group (P less than 0.05). Individuals who present to a physician during an influenza A epidemic with characteristic symptoms will experience symptomatic benefit from amantadine treatment, with negligible toxicity.

Adolescent↗

Responses of elderly subjects to a new subunit influenza virus vaccine.

The serologic responses and the side effects resulting from the administration of a new subunit vaccine against influenza were compared with those of a currently available whole-virus vaccine in an elderly population. The subunit vaccine is prepared by cleavage of the hemagglutinin and neuraminidase surface antigens from the virus with a cationic detergent, cetyltrimethylammonium bromide. The resulting vaccine is more selectively reduced to these primary antigens than are the available subunit vaccines produced by the use of lipid solvents that disrupt the viral membrane [1]. Previous studies in younger individuals with new subunit preparations of earlier H3N2-subtype viruses as well as influenza A/New Jersey/76 (HswN1) and B/Hong Kong/73 viruses indicated that antibody responses in primed, although not in unprimed, populations wee comparable to those induced by whole-virus vaccines and that side effects were few [2,3]. There were not statistically significant differences in the serologic responses of the vaccine recipients except that the percentage of recipients who achieved titers of HAI antibodies of 1:10 or 1:20 to influenza B/Singapore/222/70 virus after vaccination was greater in the subjects who received the subunit vaccine. There were no statistically significant differences in the percentage of recipients with an antibody response (fourfold or greater in titer) or in the geometric mean titers of HAI antibodies after vaccination between those who had received the trivalent influenza virus vaccine in 1979 and those who had no history of vaccination in 1979. Mild redness and/or tenderness were noticed at the injection site between 6 and 48 hr after vaccination in 16 subjects who received the subunit vaccine and in four subjects who received the subunit vaccine and two who received the whole-virus vaccine (P less than 0.01 by chi 2 test). One patient in each group complained of headache; four subjects who received the subunit vaccine and two who received the whole-virus vaccine complained of fatigue.

Aged↗

In vivo inhibition of respiratory syncytial virus by ribavirin.

Ribavirin reduced the amount of respiratory syncytial virus in nasal turbinates and lung tissues of experimentally infected cotton rats by over 90%. An effect was seen when the drug was given either intraperitoneally or by aerosol; however, the antiviral effect was achieved at much lower doses when delivered by the aerosol route. No animal deaths due to the drug were seen.

Aerosols↗

Antibody responses in adult volunteers to pneumococcal polysaccharide types 19F and 19A administered singly and in combination.

The immunogenicity of the two major group 19 pneumococcal polysaccharides, types 19F and 19A, was studied in human volunteers. Antibody responses after vaccination with either 50 micrograms of type 19F polysaccharide, 50 micrograms of type 19A polysaccharide, or 25 micrograms of both polysaccharides premixed in a single injection revealed that the combined vaccine was immunogenic for both types, but that the optimal immunogen for each was the homologous polysaccharide. We concluded that vaccination with type 19F polysaccharide antigen, included in the current pneumococcal vaccine, does not induce a satisfactory heteroimmunogenic response to type 19A.

Antibodies, Bacterial↗

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↗

Nosocomial respiratory syncytial viral infections. Should gowns and masks be used?

The efficacy of infection control procedures utilizing gowns and masks in the control of nosocomial respiratory syncytial virus (RSV) infections was evaluated by comparing the rate of nosocomial RSV infections in infants and ward personnel during two sequential periods when gowns and masks were used (period 1) and not used (period 2). All patients (162) and staff (36) on our infants' ward were examined for signs of respiratory infection and had nasal washes obtained for viral isolation every two to four days for two months. Nosocomial RSV infection was identified in a total of 19 infants. Eight of these occurred in period 1 for a nosocomial infection rate of 32% of contact infants who were hospitalized for seven or more days. In comparison, 11 (41%) of the contact infants hospitalized for seven or more days in period 2 became infected. These findings suggest that the additional routine use of masks and gowns does not result in measurable benefit in controlling the nosocomial spread of RSV infection to infants or to ward personnel.

Child, Preschool↗

Interferon production by human mononuclear leukocytes: differences between respiratory syncytial virus and influenza viruses.

The ability of respiratory syncytial virus (RSV) to induce interferon production by human mononuclear leukocytes was compared with that of influenza viruses. Cell culture fluids were assayed for interferon activity 1, 3 and 7 days after exposure to RSV or to one of two subtypes of influenza A virus (H0N1 and H3N2). RSV induced interferon production inconsistently and in low titers. Varying the multiplicity of infection did not improve the ability of RSV to induce interferon production. In contrast, influenza viruses were effective inducers of interferon production. Seropositivity to the influenza virus strains was not associated with increased interferon titers. Interferon produced after exposure to RSV or to the influenza viruses was resistant to low pH treatment. The data suggest that interferon production may not be a major component of human immunological defense against RSV infection.

Adult↗

Evaluation of A/Alaska/6/77 (H3N2) cold-adapted recombinant viruses derived from A/Ann Arbor/6/60 cold-adapted donor virus in adult seronegative volunteers.

The influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) virus was evaluated as a donor of attenuating genes to new variants of influenza A virus. This ca donor virus was mated with the A/Alaska/6/77 (H3N2) wild-type virus, and three A/Alaska/6/77 (H3N2) ca recombinant viruses were produced. The parental origin of the genes in the three ca recombinants had been determined previously (2), and their virulence for adult seronegative volunteers was assessed in the present study to identify the genes present in the ca donor virus that confer attenuation. Each of the recombinants received the hemagglutinin and neuraminidase genes from the A/Alaska/6/77 (H3N2) wild-type parent. One ca recombinant (CR-29) received all six transferable genes from the ca parent and was found to be satisfactorily attenuated in the volunteers. The two other ca recombinants received five of the six transferable genes with a wild-type gene at the M or NS locus. The pattern of infection in humans with these latter two ca recombinants was similar to the CR-29 ca recombinant. These findings demonstrate that inheritance of a gene in ca recombinants at the M or NS locus segregates independently of attenuation and suggest that the M and NS genes present in the ca donor virus are not the major determinants of attenuation conferred by this virus.

Antibodies, Viral↗

Infectivity of respiratory syncytial virus by various routes of inoculation.

To understand the transmission of respiratory syncytial virus, we examined the frequency of infection in volunteers after inoculation by different routes with varying doses of virus. Thirty-two adult volunteers received serial dilutions of a safety-tested live strain of respiratory syncytial virus instilled into nose, eye, or mouth. The highest inoculum, 5.2 log10 50% tissue culture infective dose (TCID50), was administered to four groups of four subjects each, by nose to one group, by eye to one group, and by mouth to two groups. Subsequently, 1:100 and 1:1,000 dilutions of this inoculum were administered by nose and eye. At the highest inoculum, infection occurred in three of four subjects inoculated by nose and in three of four subjects inoculated by eye. Infection occurred in one of eight subjects inoculated by mouth, but this subject most likely was infected by secondary spread. With an inoculum of 3.2 log10 TCID50, the proportion of subjects infected by either route diminished to 25%. When the inoculum was further reduced to 2.2 log10 TCID50, no infections occurred by either route. Infections after the highest inoculum were characterized by earlier and greater shedding. These findings suggest that respiratory syncytial virus may infect by eye or nose and that both of these routes appear equally sensitive. In comparison, the mouth appears to be an insensitive route of inoculation. This is of potential import in infection control procedures and in the development of vaccines or other prophylactic measures.

Antibodies, Viral↗

Influenza A/Brazil/78(H1N1) infection in the elderly.

Although influenza A/H1N1 virus has caused both sporadic illness and epidemics throughout the world, there have been few cases and no outbreaks reported in older persons. Using a surveillance program for detection of viral respiratory tract illness, we documented an outbreak of influenza (A/Brazil/78(H1N1) infection in one floor of a chronic disease hospital. We prospectively studied all 32 patients and 16 personnel on that floor. Infection was proved in 11 subjects by serology and/or virus isolation, including 9 patients (median age, 84 yr) and 2 personnel (36 and 58 yr of age), for attack rates of 28% and 12.5%, respectively. Six patients had fever, 38 degrees C to 39 degrees C, lasting for 1 to 5 days (median, 4), and/or respiratory and constitutional symptoms lasting for 2 to 17 days (median, 13). Bacterial pneumonia occurred in 1 patient 12 days after the onset of upper respiratory tract illness. Risk factors for acquisition of infection in patients included a nonvaccinated state (p = 0.03) and a preinfection antibody titer of less than or equal to 32 (p = 0.02). These findings indicate that older persons are at risk for infection with influenza A/H1N1 virus, which may also cause outbreaks of respiratory illness in the elderly institutionalized population similar to other influenza viruses.

Adult↗