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Biomedical subjects

R F Betts

Publications and source records attributed to R F Betts.

107 records · Page 6Linked to original sources
PubMed1976

Temperature-sensitive mutants of influenza A virus. XII. Safety, antigenicity, transmissibility, and efficacy of influenza A/Udorn/72-ts-1[E] recombinant viruses in human adults.

The influenza A/Hong Kong/68-ts-1[E] virus (shutoff temperature, 38 C), which possesses many characteristics desirable in a vaccine virus, was used as a donor of its two temperature-sensitive (ts) lesions to the antigenically divergent influenza A/Udorn/72 wild-type virus. Two subsets of Udorn/72-ts-1[E] recombinant viruses were evaluated in seronegative volunteers (serum titer of hemagglutination-inhibiting antibody, less than or equal 1:8). The first subset, represented by clone 13, possessed a shutoff temperature of 39 C and only one of the two ts lesions; this virus was insufficiently attenuated for use in humans. The other subset, represented by clones 16 and 24, possessed both ts lesions and a shutoff temperature of 38 C, like that of its Hong Kong/68-ts-1[E] parent. This subset, also like its ts-1[E] parent, was adequately attenuated, nontransmissible, and protective against intranasal challenge with wild-type Udorn/72 virus. The attenuation manifested by the ts mutants was not a result of their cloning in bovine kidney tissue or replication in eggs. The results suggest that the Hong Kong/68-ts-1[E] virus can be considered for use as a master strain for donation of ts lesions and thus could bring about predictable attenuation of new wild-type influenza A viruses.

Antibodies, Viral↗
PubMed1975

Lymphocytic choriomeningitis in university hospital personnel. Clinical features.

Clinical manifestations of lymphocytic choriomeningitis (LCM) virus infection in 15 patients are described. These patients were University Hospital personnel who had had contact with hamsters, subsequently shown to harbor the virus. Fever with striking myalgias, headache and rigors were the most common symptoms. Only 2 of the 15 patients had clinically overt and documented aseptic meningitis. Leuikpenia was observed in 10 of 11 patients and thrombocytopenia in 8 of 8 patients tested. A biphasic illness was seen in eight patients. In a patient who has been exposed to laboratory animals, particularly to hamsters, a nonspecific influenza-like febrile illness accompanied by leukopenia and thrombocytopenia may represent LCM virus infection.

Animals↗
PubMed1975

Transmission of cytomegalovirus infection with renal allograft.

Fifty-four patients who received a renal allograft between October 1971 and October 1974 were followed prospectively to correlate pretransplant serum antibody to cytomegalovirus (CMV) with shedding of CMV following transplantation. Twenty-five of 54 patients had antibody demonstrable to CMV using immunofluorescent techniques, but only 20 of 54 using complement-fixing techniques. All 24 who had antibody and survived one month or longer, and seven of nine without antibody but who received a kidney from a seropositive donor shed virus after transplantation, whereas none of 12 individuals without antibody and who received a kidney from a seronegative donor (P less than 0.005) shed virus. Three of eight other seronegative patients for whom donor sera were not available for analysis shed virus. Viremia occurred in eight of ten individuals who developed new antibody after transplantation, versus seven of 24 with antibody prior to transplant (P less than 0.02), and virus shedding in seroconverters from other sites was significantly more persistent than in pretransplant antibody-positive patients. Thus, CMV infection was due either to reactivation of latent infection or was transmitted along with the renal allograft and manifested as a primary infection.

Adult↗
PubMed1975

Varicella-zoster virus and subcutaneous cytarabine: correlation of in vitro sensitivities to blood levels.

The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 mug of cytarabine per ml or less. Cytarabine levels in sera of 12 patients after a single subcutaneous injection of 50 mg/M(2) exceeded this inhibitory level for a period of 75 min. Thus, the subcutaneous route is a potentially useful method of administration of cytarabine for antiviral drug trials.

Cytarabine↗
PubMed1975

Evaluation of a topical interferon inducer in experimental influenza infection in volunteers.

The prophylactic and/or therapeutic effect of a low-molecular-weight interferon inducer, CP-20,961, was tested in a double-blind placebo controlled study of experimental influenza A/England/42/72 (H(3)N(2)) infection in normal volunteers. Ten volunteers received CP-20,961 and 10 received placebo. Interferon was detected in nasal secretions of nine of the former and three of the latter group (P < 0.05). Seven in each group became ill, and severity of illness was not different. Also, quantitative virus shedding patterns and antibody response were not different between the two groups. The negative result may have been due to the relatively low quantities of interferon induced.

Administration, Topical↗
PubMed1975

Ineffectiveness of subcutaneous cytosine arabinoside in localized herpes zoster.

Cytosine arabinoside (cytarabine) was evaluated in a randomized double-blind controlled study for the treatment of localized herpes zoster. Cytarabine was administered subcutaneously in a dose of 50 mg/m-2 body surface area once daily for 4 days, always within 14 days of onset of the first symptom and usually within 7 days. Thirty patients given cytarabine and 30 patients given placebo were well matched with respect to age, sex, and length and severity of presenting rash and pain as well as underlying disease. There was no difference in the rate of disappearance of pain or rash in either treatment group. More patients given cytarabine than patients given placebo had minimal pain and significantly more cytarabine-treated patients had persistence of neurological symptoms at 6 months' follow-up. Acute side effects, though mild, were significantly increased in the cytarabine-treated patients especially with respect to nausea and vomiting and decrease in platelet count. Cytarabine administered in this dose subcutaneously had no beneficial effect and was associated with mild side effects and persistence of neurological symptoms.

Adult↗
PubMed1974

Effect of induced interferon in experimental rhinovirus infections in volunteers.

Nasal administration of an interferon inducer, CP-20,961 (N, N-dioctadecyl-N', N'-bis(2-hydroxyethyl)propanediamine), was evaluated in a double-blind, placebo-controlled study of experimental rhinovirus infection in 29 volunteers. Detectable nasal interferon developed in 10 of 15 subjects treated with CP-20,961, and 2 of 14 in the group receiving placebo (P < 0.006). Titers of CP-20,961-induced interferon ranged from 10 to 250 international units, concentrations similar to those observed in rhinovirus infections. Ten in the CP-20,961 group and eight in the placebo group became ill (P > 0.05). However, mean total sign scores were significantly diminished among CP-20,961-treated subjects as compared with placebo-treated subjects (P < 0.025). No significant effect was noted on quantitative virus shedding patterns or neutralizing antibody responses. These findings suggest that such concentrations of induced interferon do not protect against rhinovirus infection, and that factors other than interferon may be important in recovery from rhinovirus infection.

Administration, Intranasal↗
PubMedDate not supplied

Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults.

OBJECTIVE: Cases of varicella pneumonitis were reviewed to examine the effects of acyclovir therapy on outcome. METHODS: A retrospective chart review was done of all admissions of adults to two hospitals, between 1985 and 1995, because of complications of chickenpox. RESULTS: Fifteen patients were hospitalized for varicella pneumonitis during this period. No patient had a history of chickenpox as a child; all had a recent history (within 2-4 weeks prior to admission) of exposure to chickenpox in their family or neighborhood and developed respiratory symptoms 1 to 4 days after the appearance of the rash. Twelve patients (80%) had a history of cigarette smoking, and seven patients had a platelet count below the normal range. All patients were treated with intravenous acyclovir within 24 hours of admission, and all but one survived and were discharged from the hospital without comorbid conditions. The one mortality was attributed to bacterial superinfection. CONCLUSIONS: Acyclovir treatment may be of benefit for varicella pneumonitis, but no controlled trial has been performed to definitively answer this question.

Acyclovir↗
PubMedDate not supplied

Nosocomial viral infections: II. Guidelines for prevention and control of respiratory viruses, herpesviruses, and hepatitis viruses.

This article reviews the most likely mechanisms of transmission of the commonly encountered respiratory viruses (influenza, respiratory syncytial virus, parainfluenza, rhinovirus), herpesviruses, and hepatitis viruses, and presents the guidelines used currently for prevention and control that are in use at Strong Memorial Hospital.

Cross Infection↗
PubMedDate not supplied

Communitywide laboratory-based influenza surveillance focused on older persons, 1989-1992.

We collected surveillance data as part of the Medicare Influenza Vaccine Demonstration to describe communitywide epidemiology of influenza, focusing on the elderly. Laboratory-based surveillance was established in medical practices, hospitals, and nursing homes in a two-county demonstration in upstate New York. Time course and intensity of epidemic influenza were compared between counties, between influenza A and B epidemics, and among several levels of surveillance involving elderly persons as well as children during the years 1989-1992. The counties experienced parallel epidemics during each of the three demonstration years. Influenza A/H3N2, predominant in 1989-1990 and 1991-1992, was equally intense among young and old, accounted for 11%-28% of acute cardiopulmonary hospitalizations of older persons, and caused focal outbreaks in 30%-40% of nursing homes in the respective epidemics. Influenza B, predominant in 1990-1991, showed modest impact among the elderly as compared with children. Influenza A/H1N1 occurred among children each year but was virtually absent among the elderly. Systematic surveillance during the "influenza season" consistently confirms widespread infection among older patients, both in the community and in institutions. However, much febrile respiratory illness in this age group during periods of epidemic influenza is culture-negative for influenza virus and thus may be caused by other respiratory pathogens.

Aged↗
PubMedDate not supplied

Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza.

OBJECTIVE: The current study evaluated whether intranasal administration of the sialic acid analog 4-guanidino-Neu5Ac2en (GG167), an inhibitor of influenza virus neuraminidase, was effective and safe in either preventing or treating experimental human influenza. METHODS: Four randomized, double-blind, placebo-controlled trials involving three prophylaxis limbs, two early treatment limbs, and one delayed treatment limb were conducted. SETTING: Isolation in individual rooms. PARTICIPANTS: Susceptible (serum hemagglutination-inhibition antibody titer < or = 1:8) adult volunteers (n = 166) were inoculated intranasally with 10(5) TCID50 influenza A/Texas/91 (H1N1) virus. INTERVENTION: GG167, 3.6 to 16 mg, was administered intranasally two or six times daily beginning 4 hours before inoculation (prophylaxis) or 1 or 2 days afterward (early or delayed treatment). MAIN OUTCOMES: Virological measures were frequency of infection based on viral shedding and/or seroconversion (prophylaxis) or quantitative viral shedding based on titers and duration of virus recovery (treatment). Clinical measures were the frequency of febrile illness and symptom severity scores. RESULTS: Intranasal GG167 was well tolerated for both prophylaxis and therapy. For all dose groups combined, GG167 prophylaxis was 82% effective in preventing laboratory evidence of infection and 95% effective in preventing febrile illness (P < .01 vs placebo). Early treatment with GG167 reduced peak viral titers by 2.0 log10, the median duration of viral shedding by 3 days, and the frequency of febrile illness by 85% (P < .05 for each comparison). Other measures of illness were reduced by approximately 50% to 70% in the GG167 dosing groups. Twice daily dosing was as effective as six times daily. CONCLUSIONS: Direct respiratory administration of the selective neuraminidase inhibitor GG167 appears safe and effective for both prevention and early treatment of experimental influenza. Influenza virus neuraminidase is important for viral replication in humans.

Administration, Intranasal↗