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Biomedical subjects

R F Betts

Publications and source records attributed to R F Betts.

At least 91 records · Page 5Linked to original sources
PubMed1979

Live Victoria/75-ts-1[E] influenza A virus vaccines in adult volunteers: role of hemagglutinin immunity in protection against illness and infection caused by influenza A virus.

To explore the relationship between neuraminidase immunity and the degree of attenuatíon of live influenza A virus vaccines, a comparative evaluation of three Victoria/75-ts-1[E] (Vic/75-ts-1[E]) recombinant viruses in serum hemagglutination-inhibiting-negative (titer, </=1:8) adult volunteers was performed. These three ts-1[E] viruses had a similar restriction of replication at 38 degrees C in vitro, and each possessed the two attenuating genes of the ts-1[E] donor strain (13). However, Vic/75-ts-1[E] recombinants 81 and 113 possessed both Vic/75 hemagglutinin (H3(75)) and Vic/75 neuraminidase (N2(75)), whereas Vic/75-ts-1[E] recombinant 67 had Vic/75 hemagglutinin but the N2(65) neuraminidase. Vic/75-ts-1[E] recombinant 67 was significantly more attenuated than Vic/75-ts-1[E] recombinants 81 and 113 in that fewer local and systemic signs and symptoms of illness were observed in those volunteers who received clone 67. These findings were consistent with our previous observations which suggested that the following two factors contribute to the attenuation of ts-1[E] vaccine strains in adults: (i) the attenuating effect of the two ts-1[E] genes and (ii) the neuraminidase immunity of the host. Vic/75-ts-1[E] recombinant clone 67 vaccinees developed an immunological response to the H3(75) hemagglutinin in the absence of a response to the N2(75) neuraminidase. To assess the role that anti-hemagglutinin immunity induced by an attenuated live virus vaccine plays in resistance to influenza A virus, vaccinees who received recombinant 67 were challenged with Vic/75 wild-type virus, and their responses were compared with those of Vic/75-ts-1[E] vaccinees who received recombinant 81 or 113. Each of the three groups of ts-1[E] vaccinees was significantly protected against illness induced by wild-type virus infection, although resistance was not complete. However, the clone 67 vaccinees were protected less against infection. The infection-permissive resistance induced by clone 67 resembled that previously described for inactivated neuraminidase-specific vaccines. These results suggested that a ts-1[E] recombinant that possessed the hemagglutinin of a new pandemic variant, the neuraminidase of the preceding subtype, and the two ts-1[E] ts genes would be satisfactorily attenuated for children and adults with neuraminidase immunity and could induce resistance to illness caused by the new pandemic wild-type influenza A virus.

Adolescent↗
PubMed1979

Cytomegalovirus infection blocks the beneficial effect of pretransplant blood transfusion on renal allograft survival.

Two factors which have gained attention as possible contributors to success of renal allografts are freedom from infection with cytomegalovirus (CMV) after transplant and administration of multiple blood transfusions pretransplant. In order to determine the interrelationship of these two variables, we analyzed 55 recipients of well matched (at least two antigens) cadaveric kidneys. In this study, absence of CMV infection and receipt of multiple transfusions both provided favorable outcomes. When patients were grouped by both factors, those who were free of infection and received multiple transfusions did significantly better than any other combination. Infection with CMV decreased the frequency of allograft survival in multiply transfused patients to a point intermediate between the above group and those who had not been multiply transfused. Since CMV infection can be predicted by measurements made pretransplant, and since up to one-quarter of CMV infection which develops post-transplant is transmitted with the allograft, administration of multiple transfusion to all patients and the use of donors who are free of latent CMV infection for CMV antibody-negative potential recipients should increase allograft success. For those potential recipients who already have latent CMV infection, further study will be necessary to determine what stimuli can be given pretransplant to prevent the interference with the beneficial effect of multiple transfusion.

Blood Transfusion↗
PubMed1978

An analysis of cytomegalovirus infection and HLA antigen matching on the outcome of renal transplantation.

Eighty-five recipients and donors of renal allografts were examined for evidence of cytomegalovirus infection before and repeatedly after transplantation. The recipients were also divided into two group on the basis of HLA antigen matching. Better allograft survival was noted in patients well matched for HLA antigens (0-2) mismatched antigens) compared to those poorly matched (three or more antigens mismatched), and in patients free of cytomegalovirus compared to those infected. Cytomegalovirus infection had a more marked influence on allograft survival than did HLA antigen matching. The differing rates of success of transplantation, apparently dependent on blood relationship between donor and recipient, have been assumed largely to be due to inherited factors. This study, however, revealed an important factor to be the disparate incidence of cytomegalovirus infection in sibling, parental, and cadaveric categories of transplantation. The mechanism of this disparity can be explained on the basis of the incidence of latent CMV infection in the recipients and various categories of kidney donors.

Adult↗
PubMed1978

Recurrent disseminated histoplasmosis.

A patient who has had three distinct recurrences of disseminated histoplasmosis over 22 years is presented. Measurements of cellular and humoral immune response to histoplasmin antigens were compared with previously reported data. Although initially sulfisoxazole therapy led to regression of disease, over the past 13 years she has required three courses of amphotericin B, each time with resolution of signs and symptoms. Despite minimal evidence of a cellular or humoral immune response to this organism, the patient has done well. Although disseminated histoplasmosis is often a fatal disease, this woman has tolerated the infection well.

Adult↗
PubMed1978

Temperature-sensitive mutants of influenza A virus: evaluation of A/Victoria/3/75-ts-1[E] recombinant viruses in volunteers.

The Hong Kong/68-ts-1[E] virus and its Udorn/72 and Georgia/74 recombinants, which have a 38 degrees C shutoff temperature and a ts lesion(s) on the genes coding for the P3 and NP proteins, were adequately attenuated and immunogenic in adult volunteers who lacked serum hemagglutination-inhibiting antibody (titer, </=1:8), but who possessed serum neuraminidase-inhibiting antibody. Two Victoria/75-ts-1[E] clones that also had a 38 degrees C shutoff temperature and a ts lesion(s) on the same two genes were administered to adult volunteers who lacked both serum hemagglutination-inhibiting antibody (titer, </=1:8) and neuraminidase-inhibiting antibody (titer, </=1:4). In contrast to the behavior of the earlier ts-1[E] recombinants, the Vic/75-ts-1[E] recombinants retained the capacity to cause febrile, systemic illness. However, the recombinants were attenuated compared with wild-type virus. The Vic/75-ts-1[E] virus vaccinees shed a larger amount of virus for a longer time than the previous ts-1[E] vaccinees, but they shed less virus than volunteers infected with wild-type virus. The ts-1[E] virus shed retained its ts phenotype in most instances and failed to spread to susceptible contacts. Vaccinees were partially protected against homologous wild-type virus challenge. The failure of HK/68, Udorn/72, and Georgia/74 ts-1[E] vaccinees to develop systemic reactions may reflect the presence of neuraminidase immunity before infection. In this situation, attenuation probably resulted from the degree of defectiveness of the ts-1[E] recombinant virus and the existence of neuraminidase immunity in the recipients. The 50% human infectious dose of the Vic/75 ts-1[E] virus was less than 10(5.2) 50% tissue culture infective doses. This suggests that at the time of a pandemic shift involving both the hemagglutinin and neuraminidase glycoproteins, a small amount of live virus vaccine might be effective in initiating infection.

Antibodies, Viral↗
PubMed1978

Studies with live attenuated influenza vaccines.

Inhibitor-resistant and temperature-sensitive live attenuated influenza virus vaccines were administered to normal volunteers and elderly and chronically ill persons to assess safety, antigenicity, and transmissibility. Recombinants of both types of vaccine were made using currently prevalent influenza virus strains (A/Hong Kong/68, A/England/42/72, A/Scotland/74, A/Victoria/75) over a five-year period to keep the vaccine relevant with regard to antigenic drift. The results indicate that both vaccine types are safe, antigenic and non-transmissible and that for both types of vaccines, recombinants can be made to new antigenic drifts. The inhibitor-resistant vaccine replicates to lower titers in the nasopharynx than the temperature-sensitive virus, and this is considered an advantage, whereas the genetic defect of the temperature-sensitive virus is better defined than that of the inhibitor-resistant vaccine.

Administration, Intranasal↗
PubMed1977

Clinical manifestations of renal allograft derived primary cytomegalovirus infection.

Seventy seven patients, thirteen younger than 20 years of age, were followed up prospectively for the first three months after renal transplant for evidence of infection and illness due to cytomegalovirus (CMV). Thirty-two developed reactivation of latent CMV and 29 did not develop any CMV infection and wn, five had pneumonia, and four underwent nephrectomy. Of these, 16, eleven received a kidney from a parent, whereas of the other 61 patients, five received parental kidneys (P less than .001). Hence, CMV seronegative individuals who received a kidney from a CMV seropositive parent developed clinical illness and sometimes lost the allograft.

Adolescent↗
PubMed1977

Efficacy of live attenuated influenza A/Scotland/74 (H3N2) virus vaccine against challenge with influenza A/Victoria/3/75 (H3N2) virus.

For evaluation of heterologous protection by live attenuated influenza virus vaccine, 42 healthy volunteers with low titers of or no antibody to A/Scotland/74 (H3N2) and A/Victoria/3/75 (H3N2) influenza viruses were given live attenuated A/Scotland/74 (H3N2) virus vaccine or placebo by the intranasal route with no resultant vaccine-related illness. Seventeen of 21 vaccine recipients and none of 21 placebo recipients developed antibody conversion. Thirty-seven days after administration of vaccine or placebo, all subjects were challenged intranasally with wild-type A/Victoria/3/75 influenza virus. Five placebo recipients and no vaccine recipients developed moderately severe illness, whereas 10 vaccine recipients and three placebo recipients developed no illness (p less than 0.025). Although 16 of 21 vaccine recipients fulfilled criteria of infection with the challenge virus, shedding of virus was significantly less frequent, less prolonged, and of significantly lower magnitude than that in the placebo recipients. Thus, live attenuated influenza virus vaccine showed a significant protective effect against illness following challenge with heterologous wild-type virus. The protective effect and the negligible side effects of this vaccine merit consideration of its use in a large-scale field trial.

Adolescent↗
PubMed1977

Comparative study of reactogenicity and immunogenicity of influenza A/New Jersey/8/76 (Hsw1N1) virus vaccines in normal volunteers.

Local and systemic reactions and antibody responses to three different doses of influenza virus vaccine (A/New Jersey/76 [Hsw1N1]) produced by four different manufacturers were studied. Local and systemic reactions that peaked between 8 and 24 hr after vaccine administration were related to the source of the vaccine more than to the dose. Antibody conversion occurred in almost 90% of subjects over the age of 25 years but in only 61% of subjects 25 years or younger. This low response rate was due almost entirely to the lack of response of volunteers who received split-product vaccine (only 49% of subjects became seropositive). In addition, individuals with symptoms of local reaction had a rate of antibody conversion and magnitude of antibody response that were significantly higher than those observed in subjects who did not have local reactions. These findings suggest that in subjects older than 25 years, all four vaccines produced a high frequency of antibody response with a minimum of side effects. In addition, split-virus vaccine is less immunogenic than whole-virus vaccine in subjects younger than 25 years. Production of a vaccine devoid of local reaction may not be advisable.

Adolescent↗
PubMed1977

Double-blind evaluation of oral ribavirin (Virazole) in experimental influenza A virus infection in volunteers.

The prophylactic effectiveness of oral administration of ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) against experimentally induced influenza A infection was evaluated in a double-blind clinical trial in normal volunteers. Fourteen men received ribavirin capsules (1,000 mg/day in four divided doses) and 15 other men received identical-appearing placebo capsules beginning 6 h after the intranasal inoculation of 3.4 log(10) 50% tissue culture infectious doses of influenza virus A/Victoria/3/75 H3N2 and continuing for 5 days after challenge. The total number of moderate-to-severe symptom scores and the total number of temperatures >/=100 degrees F (37.8 degrees C) were significantly lower in the ribavirin group compared with the placebo group. The mean quantity of virus shed in nasal wash specimens and the total number of days that there were viral titers greater than 1.0 log(10) 50% tissue culture infectious doses per ml were significantly greater in the placebo group. There was no difference between the frequencies of virus isolated or the antibody responses in the two groups. Therefore, prophylactic ribavirin ameliorated symptoms and fever indicative of moderate-to-severe illness, but had no effect on the manifestations of mild illness in response to influenza A challenge. A transient rise in total serum bilirubin occurred in 29% of the ribavirin-treated volunteers and in none of the placebo-treated volunteers.

Adult↗
PubMed1977

Cytomegalovirus (CMV) in the compromised host(s).

Cytomegalovirus infection in compromised hosts occurs most frequently as asymptomatic shedding of a reactivated virus. Reactivation occurs when cellular immunity is compromised owing to either immune-deficiency disease or iatrogenic intervention. When intervention is modest, most antibody-positive patients do not shed virus (19); when the group is treated with a higher mean dose of cytotoxic agents, almost all antibody-positive patients shed virus (6). In the instance where the chemotherapeutic program includes massive doses of these agents, as in heart or marrow transplantation, or when dysfunction of all cellular activity is extreme, as in the case of severe combined immune deficiency and far-advanced neoplasia, dissemination of infection with multiple-organ involvement ensues (17, 20-22). Primary infection may occur in some patients with neoplasia or in marrow-transplant recipients from either blood transfusions or from marrow, although data are insufficient to be certain (22). It has been conclusively shown, however, that seronegative renal-allograft recipients usually develop primary infection when they acquire a kidney from a seropositive donor. Clinical illness related to virus infection in the first few months after transplantation occurs in almost all patients with primary infection and seldom in those with reactivation infection (6, 25, 26). Three very intriguing observations have been made that should suggest avenues for future research: (a) Since illness occurs more closely related to development of antibody than it does to onset of virus shedding, this suggests that host response plays an important role in the disease that is obviously caused by a virus; a definition of the mechanism of this interaction could lead to an understanding of host-induced disease processes in man; (b) Graft-versus-host disease in marrow transplantation; and (c) allograft rejection in renal-graft recipients correlate with development of CMV infection (16, 22, 24, 26). Taken together, these observations are consistent with the hypothesis that virus antigens interrelate with most antigens in such a way as to lead to immune response to both antigens. Exploration of this clinical observation could lead to a greater understanding of the function of the HL-A system in man.

Adult↗
PubMed1976

Malignant external otitis: a severe form of otitis in diabetic patients.

Two cases of malignant external otitis are presented and the literature is reviewed. The disease seems to occur exclusively in elderly diabetic patients. Diagnosis is mostly a clinical one, and requires a high index of suspicion. The characteristic clinical manifestations are pain and severe tenderness of the tissues around the ear and mastoid, persistent drainage and the presence of granulation tissue at the junction of the osseus and cartilagenous portions of the external ear. Roentgenographic findings are not helpful in the early stages. The pathogenesis of this disease depends on the presence of clefts in the cartilage forming the floor of the external auditory canal at its junction with the osseus portion through which infection can spread from the external ear to the deep soft tissues. Serious and often fatal complications may ensue. The most common and earliest symptom to appear if facial nerve palsy. Pseudomonas aeruginosa has been isolated uniformly, in pure or mixed cultures. This entity, therefore, should be borne in mind whenever an elderly diabetic patient presents with external otitis not amenable to the usual methods of therapy. Ps. aeruginosa should be strongly suspected, and its isolation should prompt vigorous systemic treatment with gentamicin and carbenicillin before extensive necrosis of cartilage and bone takes place. Any delay in diagnosis and management will lead to a serious and often fatal complications.

Age Factors↗
PubMed1976

Safety and efficacy of "Alice" influenza virus vaccine in normal healthy adults.

A live influenza virus candidate vaccine, "Alice" strain, was evaluated in normal healthy adults. It proved to be safe, with minimal clinical reactions. Thirteen of 21 volunteers (61.9%) with pre-existing titers of hemagglutination-inhibiting antibody of less than or equal to 1:4 and three of nine (33.3%) with initial titers of 1:8-1:16 had four-fold increases in titers of serum antibody. A second dose of vaccine did not increase the frequency or the magnitude of the serum antibody response. Nasal neutralizing antibody responses occurred in six of 18 subjects tested (38.8%). The vaccine virus appeared to produce its effect by replication since vaccine virus was recovered from six of 17 subjects (35%), administration of a vaccine inactivated by ultraviolet irradiation did not produce a response, a 1:10 dilution of virus infected two of five subjects, and a 1:100 dilution infected none of six subjects. The virus was not transmitted to the antibody-negative controls who were confined with infected volunteers. Challenge of 20 volunteers and 26 control subjects with wild-type influenza A/Udorn/307/72 (H3N2) virus revealed a significant reduction in the frequency of infection and illness among subjects who responded to "Alice" vaccine compared with the frequency among unvaccinated controls.

Adult↗
PubMed1976

In vitro susceptibility of common clinical anaerobic and aerobic isolates against josamycin.

The in vitro susceptibility of 145 anaerobic clinical isolates and 96 gram-positive aerobic clinical isolates to josamycin, a new macrolide antibiotic, was studied using the agar dilution technique. Ninety-five of the aerobes were susceptible to 1.56 mug or less of josamycin per ml. The median minimal inhibitory concentration of these organisms was </=0.39 mug/ml. The in vitro activity of josamycin against the anaerobes was compared with that of erythromycin, clindamycin, penicillin, and chloramphenicol. At concentrations </=3.12 mug/ml, 100% of strains of Bacteroides species and Bacteroides fragilis were susceptible to josamycin. At low concentrations (</=0.39 mug/ml), clindamycin was more active than josamycin against the anaerobes. However, at concentrations </=3.12 mug/ml, the activities of josamycin and clindamycin were similar except against the Fusobacterium species, which was quite resistant to josamycin.

Aerobiosis↗
PubMed1976

Comparative activity of immunofluorescent antibody and complement-fixing antibody in cytomegalovirus infection.

Three different tests for detection of antibodies to human cytomegalovirus (CMV), complement fixing with antigen prepared by freeze-thaw disruption (CF-FT) or with antigen prepared by extraction with alkaline glycine buffer (CF-GE) and immunofluorescent staining (FA), were compared in renal transplant recipients and their healthy donors, FA and CF-GE tests yielded positive results at an identical and significantly higher frequency than CF-FT in both donors and recipients. CF-GE and FA performed on donors and recipients predicted all virus shedding post-transplant, whereas CF-FT did not. In the individuals who developed primary infection concurrent with the transplanted kidney, FA developed earlier than other antibodies in about one-half and at the same time in the remainder. In addition, the FA test could be completed more quickly and all sera could be interpreted, which made the FA test more useful than the CF-GE, but both of these tests were clearly superior to CF-FT.

Antibodies, Viral↗
PubMed1976

Evaluation of a temperature-sensitive influenza virus in elderly and chronically ill subjects.

A temperature-sensitive influenza virus, influenza A/Hong Kong/68-ts-1 (E), was administered to 18 elderly subjects and to 18 chronically ill subjects. Clinical reactions were infrequent (n = 3), mild, and afebrile. Vaccine virus was recovered from 5 subjects. Serum-neutralizing antibody responses to A/Hong Kong/68 antigen were detected in 13. Serum hemagglutination inhibiting antibodies were detected in 6 to A/Hong Kong/68 antigen and in 7 to A/England/42/72 antigen. Nasal antibodies were detected in 3. Using any criteria, a total of 17 patients developed evidence of infection, and occurrence of infection was related to concentration of serum antibody before inoculation. Transmission of vaccine virus may have occurred to one of 10 uninoculated subjects. In the presence of a naturally occurring outbreak of influenza A/England/42/72, 15 ts-1 (E) vaccines and 17 of 42 persons who had received parenteral vaccine became ill. Evidence of infection with influenza virus was obtained in 8 of the former and 10 of the latter group.

Adult↗
PubMed1976

Antibody response to influenza vaccination in renal transplant patients: correlation with allograft function.

Thirty renal transplant recipients received 0.5 ml of Influenza Virus Vaccine, Bivalent, USP, intramuscularly. Serum hemagglutination-inhibiting and nasal secretory neutralizing antibodies were measured before and 3 to 4 weeks after vaccination. Creatinine clearance and urinary protein excretion were measured before and weekly for 4 to 8 weeks after vaccination. Ten of 13 patients (77%) with creatinine clearance of greater than or equal to 70 ml/min-1.73m2 (group I) had greater than or equal to a fourfold increase in hemagglutination-inhibiting antibody titers to influenza A or B virus after vaccination, while only six of 17 patients (35%) with creatinine clearance of greater than 70 ml/min-1.73m2 (group II) had a similar increase (chi-square = 5.129; P less than 0.05). Six of 13 patients (46%) in group I had greater than or equal to a fourfold increase in neutralizing antibody titers to influenza A or B virus after vaccination, whereas none in group II had a similar increase (chi-square = 7.135; P less than 0.01). There were no adverse effects on the allografts. Only minor side effects were noted in a few patients. Because of its safety and antigenicity, influenza vaccination should be offered to renal transplant recipients particularly during threats of epidemic outbreaks.

Adolescent↗