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Biomedical subjects

R F Betts

Publications and source records attributed to R F Betts.

At least 37 records · Page 2Linked to original sources
PubMed1992

Detection of influenza A and B in respiratory secretions with the polymerase chain reaction.

Influenza A and B are RNA-containing viruses that frequently infect humans. Currently, sensitive detection of these viruses requires fresh respiratory secretions and special facilities for culture. To facilitate diagnosis of influenza, the polymerase chain reaction (PCR) was used in the present studies to detect DNA produced by reverse transcription of influenzal RNA in vaccines, tissue culture fluids, and stored respiratory secretions. Primers were directed at targets on the highly conserved segment 7 (matrix gene) of influenza A (212-bp product) and B (365-bp product). The primers were completely type specific. Critical variables in the assay were the concentration of pleotropic salts used during preparation of samples, the use of carrier RNA and RNase inhibitors during sample preparation, and the use of optimum K+ and Mg2+ levels at each step. Studies of 33 patients with symptoms of viral respiratory infection whose nasal washes had been cultured and frozen for up to 1 year before assay showed that PCR provided type-specific detection of influenza with a sensitivity comparable to that of culture of the fresh secretions. The assay offers a powerful test for detection of devitalized influenza viruses and may be useful in both diagnostic work and epidemiological studies of influenza.

Base Sequence↗
PubMed1992

Viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings.

OBJECTIVE: To prospectively evaluate the incidence and impact of viral respiratory infection in the institutionalized elderly during a winter season. DESIGN: Prospective descriptive study, without intervention. METHOD: Patients with respiratory illnesses were evaluated by a directed history and physical examination. Nasopharyngeal secretions for viral culture were obtained, and acute and convalescent serum samples were obtained for analysis. Serologic evidence of infection with respiratory syncytial virus (RSV) and parainfluenza were determined by enzyme immunoassay (EIA), and influenza by hemagglutination-inhibition assay and EIA. SETTING: A 591-bed nursing home. PARTICIPANTS: Residents with signs or symptoms of acute respiratory illness (nasal congestion, pharyngitis, cough, wheezing, or respiratory difficulty) were eligible for study. RESULTS: A viral etiology was documented in 62 out of 149 illnesses (42%). RSV was the most common virus associated with illness; it was documented in 27% of respiratory illnesses, followed by rhinovirus (9%), parainfluenza (6%), and influenza (1%). RSV was associated with significantly more severe disease when compared with rhinovirus. Clustering of specific viral infections occurred, suggesting nosocomial transmission. CONCLUSIONS: Viruses are an important cause of acute respiratory infections in the institutionalized elderly during the winter months.

Acute Disease↗
PubMed1991

Antiviral agents in respiratory infections.

Viral respiratory illnesses are among the most common afflictions in the United States. Until recently, few agents were available to control these infections. Now, there are specific and nonspecific agents either to prevent or treat viral respiratory infections. For example, a better understanding of the pathogenesis of the common cold provided new insights into therapeutic intervention for that entity. In other instances (eg, influenza), the antiviral agent is so specific that there is a need for diagnostic information to guide therapy. Epidemiological clues, clinical symptoms, and some newer laboratory methods all contribute to the clinician's understanding of the cause of an individual respiratory illness and guide the choice of therapy. In other circumstances, information is being gradually developed that points toward the availability of a broad-spectrum antiviral drug with activity against at least five of the important respiratory viruses; its major limitation is that a cumbersome and expensive means of delivery to the patient is required. For such a drug to gain widespread use, a more practical method of delivery is necessary.

Antiviral Agents↗
PubMed1990

Use of live cold-adapted influenza A H1N1 and H3N2 virus vaccines in seropositive adults.

To investigate the immunogenicity and protective efficacy of cold-adapted influenza vaccine in individuals with underlying immunity to influenza A virus, we administered cold-adapted H1N1 and H3N2 vaccines to adults with prevaccination serum hemagglutination inhibition antibody titers of 1:16 or more and challenged them 1 month afterwards with homologous wild-type influenza A virus. Both cold-adapted vaccines were immunogenic in seropositive adults. In addition, individuals receiving cold-adapted vaccines had lower rates of virus shedding and illness following challenge with wild-type influenza virus than did unvaccinated seropositive volunteers.

Administration, Intranasal↗
PubMed1989

Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen unterminally coupled to the diphtheria protein CRM197.

Vaccines consisting of oligosaccharide (OS) derived from Haemophilus influenzae type b capsular polysaccharide and conjugated to carrier proteins had been shown capable of eliciting memory-type capsular polysaccharide of H. influenza type b antibody responses in human infants, but the structural variables governing immunogenicity were not defined. Here a series of conjugates were made with the diphtheria protein CRM197 and with uniterminally coupled OS haptens that varied in chain length, exposed terminal residue, or multiplicity of loading as defined by ribose/protein ratio. Adults were given a single injection, 1-yr-old infants were given a two-injection sequence, and capsular polysaccharide of H. influenzae type b antibody responses were assessed by radioantigen binding. Vaccines C-4r, C-6r, and C-12r, in which ribitol-ended OS of mean length 4, 6, or 12 repeat units were coupled at low hapten loading, were about equally immunogenic (geometric means 2 to 5 micrograms/ml in infants, 5 to 9 micrograms/ml in adults). Vaccine C7p was made with a higher loading of OS having mean length 7 repeat units and having mainly phosphate monoester at the exposed termini Vaccine C-7R was made from a portion of C-7p by enzymatic removal of most of the terminal phosphates. Compared to the C-4r, C-6r, and C-12r series, vaccines C-7p and C-7R induced geometric means about 10-fold higher in adults and 20-fold higher in infants. Thus OS chain length (in the range studied) and exposed terminus are less critical variables in this system than the extent of hapten loading.

Adult↗
PubMed1989

Amantadine and rimantadine for the prevention of influenza A.

Influenza is a leading cause of morbidity and mortality in the United States, particularly among persons with cardiac and/or pulmonary disease and those over age 65. Vaccine is effective but not completely protective. Prophylaxis with one of the antivirals, amantadine or rimantadine, has proven efficacy against influenza A virus infections. It should be considered for high-risk patients both in the community and in health care facilities where these subjects are concentrated. Prophylaxis also has potential benefit in the home when an index case of acute influenza has been identified. The dose of drug that is most appropriate is under study. Based on observations made in young patients, it is hoped that rimantadine will be better tolerated by the elderly than has been the case with amantadine. Assessment of efficacy in outbreaks caused by viruses of different antigenic make up and elevation of the significance of drug resistance will be important in judging the true value of prophylaxis of influenza with either of these antivirals.

Adamantane↗
PubMed1988

Atypical invasive external otitis from Aspergillus.

We report a rare case of invasive external otitis caused by aspergillosis in an elderly nondiabetic patient. Amphotericin B therapy was curative. Atypical features of the presentation delayed diagnosis. Early use of tissue biopsy and culture to guide prompt initiation of therapy is recommended. The clinical spectrum and microbiology of invasive aspergillosis are also reviewed.

Aged↗
PubMed1988

Enzyme-linked immunosorbent assay of core antigens for clinical diagnosis of influenza.

A solid-phase enzyme-linked immunosorbent assay (ELISA) with monoclonal secondary antibodies was used to detect matrix protein and nucleoprotein of influenza A. The sensitivity of the ELISA for highly purified A/Brazil nucleoprotein and matrix protein was 0.05 and 1.0 ng, respectively. Nasal washes from 10 of 20 adult subjects with culture-proven, naturally acquired infection caused by A/Brazil/11/78-like influenza virus were positive in the test, and 2 of 13 subjects with rhinovirus infection were falsely positive. To determine if ELISA results could be improved, nasal washes were obtained from 21 adult volunteers who had been inoculated intranasally with wild-type A/Korea/1/82 (five subjects) or A/Korea recombinants with matrix protein or RNA-2 protein of A/Ann Arbor/6/60 (16 subjects), and the nasal washes were processed by a variety of methods. Prompt addition of sodium azide to the nasal washes to limit bacterial growth, avoidance of freezing, and the use of an antiproteolytic agent all failed to improve ELISA results noticeably. Under the best conditions, ELISA was positive in only 12 of the 21 experimentally infected subjects and in 1 of 15 uninfected controls. Positive ELISA results in experimentally infected subjects correlated significantly with the titer of live virus in the nasal washes (r = +0.506; P less than 0.001). Detection of gradient-purified whole influenza virus or isolated core antigen in ELISA was inhibited by prior incubation with nasal washes, and the inhibitory activity was only partly decreased by heat treatment of the secretions. At present, the use of ELISA for detection of influenza antigens in respiratory secretions is not sufficiently sensitive or specific for routine laboratory diagnosis of influenza.

Adult↗
PubMed1988

Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold-adapted vaccine recombinant in which vaccine-associated illness occurred in normal volunteers.

Live attenuated cold-adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold-adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten- and 100-fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold-adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.

Adult↗
PubMed1988

Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults.

The infectivity, immunogenicity, and efficacy of live, attenuated influenza A/Texas/1/85 (H1N1) and A/Bethesda/1/85 (H3N2) avian-human (ah) and cold-adapted (ca) reassortant vaccines were compared in 252 seronegative adult volunteers. The immunogenicity and efficacy of the H1N1 reassortant vaccine were also compared with those of the trivalent inactivated virus vaccine. Each reassortant vaccine was satisfactorily attenuated. The 50% human infectious dose was 10(4.9) for ca H1N1, 10(5.4) for ah H1N1, 10(6.4) for ca H3N2, and 10(6.5) TCID50 for ah H3N2 reassortant virus. Within a subtype, the immunogenicities of ah and ca vaccines were comparable. Five to seven weeks after vaccination, volunteers were challenged with homologous wild-type influenza A virus. The magnitude of shedding of virus after challenge was greater than 100-fold less in H1N1 vaccinees and greater than 10-fold less in H3N2 vaccinees compared with unimmunized controls. The vaccines were equally efficacious, as indicated by an 86%-100% reduction in illness. Thus, the ah A/Mallard/New York/6750/78 and the ca A/Ann Arbor/6/60 reassortant viruses are comparable.

Adult↗
PubMed1988

Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines.

Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.

Adult↗
PubMed1987

Two randomized controlled trials of zinc gluconate lozenge therapy of experimentally induced rhinovirus colds.

The therapeutic efficacy of zinc gluconate lozenge therapy in experimentally induced rhinovirus infection was assessed in two randomized controlled trials in susceptible adult volunteers. In trial 1, lozenges containing either zinc gluconate (23 mg of elemental zinc) or placebo were given 36 h after nasal inoculation of rhinovirus type 39 and administered eight times per day for 5 days. All of the volunteers had early cold symptoms at the time that treatment was begun. In trial 2, the same lozenge regimen was used, beginning 2 h after nasal inoculation with rhinovirus type 13, and continued for 7 days. Zinc therapy did not reduce the severity or duration of cold symptoms or the frequency or duration of viral shedding in either trial. Viral titers were measured in trial 2 and were shown to be unaffected by zinc therapy. Nasal mucus weights and the numbers of paper tissues used were slightly higher in zinc recipients. A statistically significant increase in levels of zinc in serum was documented in zinc recipients after 5 days of therapy. These data suggest that zinc gluconate lozenge therapy is not therapeutically useful in the treatment of rhinovirus colds.

Administration, Oral↗
PubMed1986

The use of eye-nose goggles to control nosocomial respiratory syncytial virus infection.

We evaluated an eye-nose goggle to determine its usefulness in reducing nosocomial RSV infection in patients and staff members on our infant ward. During a community outbreak of RSV in 1984, infection was assessed by biweekly routine viral cultures on all ward personnel and patients and also by seroconversion in personnel. For three weeks staff members wore the goggles; two (5%) adults and one (6%) child acquired nosocomial infection. During the subsequent three-week study period, goggles were not used and 34% of personnel and 43% of susceptible infants became infected. The use of the disposable eye-nose goggles was associated with a significant decrease in nosocomial RSV infections (P less than .003 for staff and P less than .05 for contact infants).

Adult↗
PubMed1986

Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS.

Primary cultures from a brain biopsy specimen of a human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) seropositive patient with progressive dementia contained small numbers of monocytoid cells and showed reverse transcriptase activity that persisted for as long as 100 days. Electron microscopy of these cells revealed the presence of HTLV-III/LAV virions. Subcultured cells removed from primary cultures by trypsinization were nonspecific esterase negative and did not express virus or show evidence of HTLV-III/LAV proviral sequences, while those remaining in the original flasks were nonspecific esterase positive and continued to produce virus. Virus from primary cultures was transmitted to peripheral blood-derived monocyte-macrophages and T cells. Virus production in T-cell cultures was transient while the monocyte-macrophages, like the primary cultures, produced virus for at least 120 days. Infection of several brain-derived cells with this and another HTLV-III/LAV isolate failed to demonstrate virus replication. These results indicate that the HTLV-III/LAV-infected cells recovered from the brain of this patient are cells of the mononuclear phagocyte series.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Normal T cell subsets in homosexual men living in a community without endemic AIDS.

The cause of the abnormal T lymphocyte subsets reported in healthy homosexual men is not known. Frequent sexually transmitted infections including human T cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) are possible causes. To determine if the T lymphocyte subsets were abnormal in this population in an area without endemic acquired immune deficiency syndrome (AIDS), T lymphocyte subsets of 52 homosexual men in Rochester, New York, were enumerated, and evidence of infections known to cause these abnormalities was sought. Unlike the findings in previous reports, relative numbers of T helper and T suppressor cells and helper/suppressor T cell ratios were normal. Prevalence of cytomegalovirus infection (86 percent) was similar to that found in analogous populations, but only 9 percent had seropositive results for HTLV-III/LAV. Men with serologic evidence of nonprimary cytomegalovirus disease had lower helper/suppressor T cell ratios (1.5 +/- 0.2 versus 2.2 +/- 0.2; p less than 0.01). Hence, despite frequent infections with cytomegalovirus and other sexually transmitted pathogens, T cell subsets are normal in homosexual men in an area without endemic AIDS. Therefore, HTLV-III/LAV is primarily responsible for the T cell abnormalities observed elsewhere.

Adult↗