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Biomedical subjects

R F Betts

Publications and source records attributed to R F Betts.

At least 73 records · Page 4Linked to original sources
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

Cytolytic IgM antibody to cytomegalovirus in primary cytomegalovirus infection in humans.

Suspensions of cytomegalovirus (CMV)-infected human foreskin fibroblasts were used to measure cytolytic antibody (CyA) to CMV in serum by a 51Cr release assay. CyA was associated with IgM but not with IgG antibody to CMV, required rabbit or human complement, and was directed at a surface antigen. CyA was detectable for one to three months in the sera of 16 patients with community-acquired CMV infection and in the sera of 20 of 22 renal transplant recipients with primary CMV infection. CyA was found less frequently in the sera of renal transplant recipients with reactivated CMV infection and occurred almost exclusively when the donor was seropositive for CMV. One individual, unlike many patients with CyA, was free of symptoms. Sera from patients with either rheumatoid factor-positive arthritis or heterophil-positive infectious mononucleosis and from 70 of 71 control patients with other types of antibody to CMV yielded no 51Cr release.

Animals↗
PubMed1981

Cefamandole failure in ampicillin-resistant Haemophilus influenzae b pneumonia.

A woman with rheumatoid arthritis and ampicillin-resistant Haemophilus influenzae type b (Hib) pneumonia complicated by bacteremia and empyema is reported. Initial therapy with cefamandole failed to eliminate bacteria from the pleural space and did not substantially affect the clinical course. However, cultures became negative and fever resolved when therapy was changed to chloramphenicol. Ampicillin-resistant Hib pneumonia in adults is an increasing problem and may be a difficult diagnosis to establish initially. Counterimmunoelectrophoresis may be useful in adults with pneumonia. If Hib antigen is detected, or if H influenzae is suspected on the basis of Gram stains and cultures, chloramphenicol should be given until the isolate is shown to be sensitive to ampicillin.

Ampicillin↗
PubMed1981

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↗
PubMed1981

Interaction of cytomegalovirus immune complexes with host cells.

After adsorption to host cells of a mixture of cytomegalovirus (CMV) and immunoglobulin G (IgG)-anti CMV, at least 99% of the surviving fraction consisted of infectious virus-antibody complexes which could be neutralized by anti-human IgG antibody. The virus-antibody complexes penetrated into cells and were uncoated more slowly than native virus. When the virus-antibody complexes were treated with anti-human IgG antibody before adsorption was allowed to take place, anti-human IgG antibody immune complexes were adsorbed to host cells less readily and uncoated less efficiently than were untreated complexes. Furthermore, after adsorption, anti-human IgG antibody-IgG-CMV complexes were further retarded in their penetration and uncoating. These observations suggest that neutralization of CMV by IgG-anti-CMV resulted from interference with the normal mechanisms of penetration and uncoating. Anti-human IgG antibody enhanced the degree of neutralization by augmenting the inhibitory effect of antibody on these stages of virus-host interaction and also reduced adsorption of the complex.

Adsorption↗
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↗
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

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

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

Physical properties of cytomegalorvirus immune complexes prepared with IgG neutralizing antibody, anti-IgG, and complement.

Human cytomegalovirus (CMV) strain AD 169 was reacted with IgG antibody (ab) from a CMV-infected renal transplant patient. A portion of he virus was neutralized, but infectious CMV-ab complexes that could be neutralized by adding rabbit anti-human IgG (A-IgG) or complement (C) were also generated. The immune complexes were examined, and the following observations were made: 1) CMV ab sufficient to cause 94% neutralization did not induce measurable changes in virion size or density. 2) The CMV-ab complexes increased slightly in size after reaction with A-IgG. 3) C increased the size and density of CMV-ab complexes to a greater degree than A-IgG. Virus aggregation did not occur with ab alone or with ab + A-IgG. However, clumping may have occurred in the presence of ab + C. 4) C also damaged virus envelopes, rendering viral DNA sensitive to DNase. 5) CMV-ab complexes absorbed to host cells as efficiently as native CMV. A-IgG or C partially inhibited complex attachment to the cells and increased the rate of release of cell-attached CMV. These findings suggest that virus neutralization may occur in a multistage process by more than one mechanism depending on the immune reagents employed. The physical changes in virus particles caused by A-IgG or C may be contributing factors in the neutralization process.

Animals↗
PubMed1979

Epidemiology of cytomegalovirus infection in end stage renal disease.

Since primary cytomegalovirus (CMV) infection is a cause of morbidity among renal transplant recipients, we undertook a prospective study of our maintenance hemodialysis patients and personnel to determine whether these sources posed a risk for transmission of CMV. Our study of 85 patients and 49 personnel showed that CMV was detected in eight nontransplanted, older dialysis patients and 13 patients who had lost their allograft. In spite of the presence of CMV on the unit, no patient or staff member developed primary infection from interpersonal transmission or from transfused frozen red blood cells. All primary infections in renal transplant patients could be accounted for by acquisition from the transplanted kidney, thus eliminating the dialysis unit or frozen blood as a risk to either patients or personnel.

Antibodies, Viral↗
PubMed1979

Lack of effect of an interferon inducer, N,N-dihexadecyl-m-xylylenediamine, on rhinovirus challenge in humans.

CP-28,888-27 and placebo nasal sprays were compared in 62 normal volunteers challenged with rhinovirus type 13 or 21 in two randomized, double-blind studies. Half of the subjects received CP-28,888-27 and half received nasal placebo administered at 24, 20, and 16 h before challenge and 4 and 8 h after challenge. In each study, the number of subjects shedding virus in nasal washes, the number developing fourfold or greater serum antibody responses, and the number developing afebrile or febrile upper respiratory tract illness were not significantly different comparing subjects given CP-28,888-27 and those given placebo. Interferon was detected in nasal washes from 5 of 15 volunteers tested in the CP-28,888-27 group compared to 2 of 15 volunteers from the placebo group.

Adult↗
PubMed1979

Temperature-sensitive mutants of influenza A virus: evaluation of the A/Victoria/75-ts-1A2 temperature-sensitive recombinant virus in seronegative adult volunteers.

An influenza A virus recombinant bearing the surface antigens of the A/Victoria/3/75 (H3N2) strain and the two ts genes of the A/Udorn/72-ts-1A2 virus was evaluated for attenuation, antigenicity, and protective effect in 42 doubly seronegative adult volunteers (i.e., individuals who lacked detectable serum antibodies for the hemagglutinin and neuraminidase antigens). This 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 90% of the volunteers. Of the volunteers, 5% developed mild coryza or rhinitis but other signs or symptoms were not observed, indicating that the A/Victoria/75-ts-1A2 recombinant was more attenuated than the A/Victoria/75-ts-1[E] recombinant. Vaccinees shed virus for a shorter interval and at a lower titer than did the A/Victoria/75-ts-1[E] vaccinees. Each ts-1A2 isolate retained the ts phenotype indicating that the recombinant was stable genetically in doubly seronegative adults. Finally, the ts-1A2 recombinant induced significant resistance to subsequent challenge with A/Victoria/75 wild-type virus.

Adult↗