Successful aging calls for more than drugs.
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Biomedical subjects
Publications and source records attributed to S Gravenstein.
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BACKGROUND: Large outbreaks of influenza A and B may occur in nursing homes despite high resident vaccination rates, even when the vaccine strain is matched to the circulating strain. This study reports the occurrence of separate influenza A and B outbreaks in a nursing home where more than 85% of residents were vaccinated. METHODS: Prospective surveillance was used to identify symptomatic residents in a rural Wisconsin nursing home with 680 residents. Viral cultures were obtained from all consenting residents identified with new respiratory symptoms even in the absence of temperature elevation. A "case" refers to a resident with a respiratory illness and an influenza isolate. RESULTS: During the 1992-93 season, 86% of 670 total residents were vaccinated, 104 (15.5%) were cases with influenza B. During the 1993-94 season, 89% of 690 total residents were vaccinated, 68 (9.8%) were cases with influenza A. The antigenic matches between vaccine and epidemic strains were characterized as "identical or minimal difference" by the Centers for Disease Control and Prevention. CONCLUSIONS: There is still a need to protect residents from infectious secretions and for contingency plans to permit the rapid use of antiviral agents. Future efforts are needed to develop vaccines that provide greater protection and to improve staff vaccination rates.
To determine whether a chronic stressor (caregiving for a spouse with a progressive dementia) is associated with an impaired immune response to influenza virus vaccination, we compared 32 caregivers' vaccine responses with those of 32 sex-, age-, and socioeconomically matched control subjects. Caregivers showed a poorer antibody response following vaccination relative to control subjects as assessed by two independent methods, ELISA and hemagglutination inhibition. Caregivers also had lower levels of in vitro virus-specific-induced interleukin 2 levels and interleukin 1beta; interleukin 6 did not differ between groups. These data demonstrate that down-regulation of the immune response to influenza virus vaccination is associated with a chronic stressor in the elderly. These results could have implications for vulnerability to infection among older adults.
OBJECTIVE: To determine factors that might account for a significantly lower attack rate in a newly constructed nursing building during an epidemic of type A influenza. SETTING: A four-building, long-term care facility for veterans and their spouses, with an average daily census of 690. DESIGN: Prospective surveillance with retrospective analysis. PARTICIPANTS: Symptomatic residents submitting to viral culture. MEASUREMENTS: Number of respiratory illnesses and influenza cultures in consenting symptomatic residents. Building characteristics. RESULTS: An influenza A (H3N2) outbreak was culture-confirmed in 68 nursing home residents. Influenza A was isolated in 3/184 (2%) residents in Building A, 31/196 (16%) in Building B, 18/194 (9%) in Building C, and 16/116 (14%) in Building D. Denominators are average daily census during the outbreak. Building A had significantly fewer culture-confirmed cases than the other buildings (P < .001). Fewer residents in Building A, 47% compared with 61% in Buildings B, C, and D, were participants in a formal study of influenza. Eight of 15 respiratory illnesses identified during the outbreak that were not cultured occurred in Building A. These factors could not account for the difference in attack rates. Building A has a unique ventilation system, more square feet of public space per resident, and does not contain office space that serves the entire four-building facility. CONCLUSION: Our retrospective observation suggests that architectural design may influence the attack rate of influenza A in nursing homes.
OBJECTIVE: To describe the epidemiology of and clinical findings associated with a rhinovirus outbreak that occurred among institutionalized elderly persons. DESIGN: Retrospective review of medical records and nursing surveillance reports. SETTING: A 685-bed, long-term care facility for veterans and their spouses. PATIENTS: 33 persons from whom rhinovirus was cultured. MEASUREMENTS: Throat and nasopharyngeal virus culture; review of medical records to determine underlying diseases, signs and symptoms of respiratory illness, illness duration, and interventions during illness; and review of nursing surveillance reports to determine room locations of ill persons. RESULTS: Between 14 August and 2 September 1993, the number of respiratory illnesses increased. Throat and nasopharyngeal virus cultures were taken from 67 ill residents; 33 cultures yielded rhinovirus, and no other respiratory virus was isolated. Geographic clustering of persons infected with rhinovirus was observed. Of those persons with rhinovirus infections, 100% had upper respiratory symptoms, 34% had gastrointestinal symptoms, 71% had systemic symptoms, 66% had lower respiratory symptoms (including productive cough), and 52% had new abnormalities on lung auscultation. The 17 persons with rhinovirus infection who had chronic obstructive pulmonary disease had more severe illnesses: Five (29%) required glucocorticoid or bronchodilator therapy for illness-associated bronchospasm; 2 required transfer out of the facility; 1 developed a radiographically documented infiltrate; and 1 died of respiratory failure. CONCLUSIONS: Rhinovirus may cause epidemic, clinically important respiratory illness in nursing homes residents. A large proportion of residents may become ill, and infection may be severe in persons with underlying lung disease.
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We have evaluated the prevalence of selected autoantibodies commonly utilized in rheumatologic practice in different elderly subpopulations grouped according to their clinical status. RF, ANA, double-stranded DNA antibodies, and antibodies to extractable nuclear antigens (ENA) were measured in the serum of all participants using standardized laboratory assays. One hundred and fifty-nine elderly subjects were enrolled, of whom 63 were classified as successfully aging elderly, 62 were ambulatory chronically ill residents of a nursing or Veterans home and 34 were patients attending an RA clinic. Prevalence of autoantibodies were compared to healthy adult blood donors. There was no statistically significant increase in autoantibodies in successfully aging elderly compared to healthy young controls. RF, ANA and ENA antibodies were significantly increased in only the chronically ill and RA sufferers. Antibodies to nDNA were absent in all groups. We conclude that autoantibodies commonly utilized in rheumatological practice are not globally non-specifically increased as a result of aging, but increase in prevalence in chronically ill elderly. Therefore assessment of health status is necessary to evaluate the clinical significance of these autoantibodies in the elderly.
OBJECTIVE: To compare the efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. DESIGN: A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. SETTING: Fourteen Wisconsin nursing homes. PARTICIPANTS: Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. INTERVENTIONS: Participants received, by intramuscular injection, 0.5 mL of a trivalent influenza vaccine containing 15 micrograms each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mL of an influenza vaccine containing the same antigens conjugated to diphtheria toxoid (HA-D). MEASUREMENTS: Blood was obtained pre- and 1 month post-vaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. RESULTS: 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). CONCLUSIONS: HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HA-D's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers.
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Interleukin-6 (IL-6) is a multifunctional cytokine that is proving to be a major contributor to the acute phase inflammatory response. IL-6 expression is normally low and serum levels are usually nondetectable in the absence of inflammation. With advancing age, however, serum levels become detectable and it is proposed that this reflects an age-associated loss in the normal regulation of gene expression for this molecule. There is also speculation that IL-6 may contribute to the pathogenesis of several diseases that are common in late-life including lymphoma, osteoporosis, and Alzheimer's disease. In this report we demonstrate that plasma levels of IL-6 rise with advancing age in well-selected healthy elderly people and comparably in old rhesus monkeys. That this change reflects a primary aging process is suggested by our findings in C57BL/6 mice in which the age-associated increase in the in vitro synthesis of IL-6 is largely prevented by life span-extending dietary restriction.
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Outbreaks of influenza A (H3N2, A/Shanghai/11/87-like) occurred in two partially (60% and 79%) vaccinated nursing home populations in January 1988. A retrospective cohort study using chart review was designed to assess the effectiveness of influenza vaccination and amantadine prophylaxis (100 mg per day) in controlling the outbreaks and to determine the amantadine susceptibility of influenza viruses isolated from case-patients. The point estimate of vaccine efficacy in preventing influenza-like illness was -33% (95% confidence interval -115% to 18%). However, 9% of vaccinated case-patients died within 14 days after onset of influenza-like illness compared with 26% of unvaccinated case-patients (relative risk = 0.4, 95% confidence interval 0.1-1.0). There was no significant difference in illness severity among case-patients who became ill before amantadine prophylaxis was started (n = 84) compared with those who became ill while taking amantadine (n = 34). Four virus isolates obtained before amantadine prophylaxis was started demonstrated 52-68% inhibition by 1 microgram/ml of amantadine; by comparison, six isolates (resistant viruses) obtained from residents who became ill while taking amantadine demonstrated 1-18% inhibition. The resistant viruses had four different RNA sequences in the gene coding for the M2 protein transmembrane region. Three resistant viruses with identical RNA sequences were isolated from residents living in contiguous rooms who had onset of signs and symptoms during a 6-day interval. Further studies are needed to determine how frequently and under what circumstances resistant viruses occur when antiviral agents are used to control institutional influenza A outbreaks. Strategies for antiviral agent administration that limit the emergence and transmission of resistant virus strains may be needed.
To determine whether immunosuppression would result in retrovirus expression in previously infected rhesus monkeys, chronic high dose methyl prednisolone therapy was administered to two groups of animals for 4 weeks. One group was antibody positive for a type D retrovirus, designated Type D/3/wisc. The second group of animals had no known exposure to Type D/3/wisc and was antibody negative to this virus. The monkeys were evaluated for immunosuppression and retrovirus re-expression following the corticosteroid therapy. Although this treatment induced a marked cellular immunosuppression in all animals, as measured by in vitro assays, in none of the animals was retrovirus viremia or retrovirus-associated disease detected.
Influenza remains a major cause of illness and death in elderly people despite current vaccination programs. One factor is an immunization failure rate in the elderly that may be as high as 50%. To test whether administration of thymosin alpha 1 would result in greater antibody production, we administered it (900 micrograms/m2 subcutaneously twice weekly for eight doses) in conjunction with the 1986 trivalent influenza vaccine. Ninety men (65-99 years old, mean age 77.3 years) were randomized double-blind to receive thymosin alpha 1 or placebo by the same schedule; the sera from 85 of these men were acceptable for analysis. The two groups were similar with respect to underlying disease, medications, and age. No toxicity was observed in either group. Antibody response rate was defined as a four-fold rise in antibody titer over 3-6 weeks following vaccination and was measured by an enzyme-linked immunosorbent assay (ELISA). Analysis was performed on treatment groups and subgroups divided by the mean age: the older group consisted of subjects aged 77 years and older, and the younger group those aged from 65-76 years. Baseline and change in absolute antibody levels were compared by t test and using age as a continuous variable by multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Thymic hormone production declines with age, and recent strategies for enhancing immune function in elderly people include the administration of various thymic preparations. In an effort to develop an animal model for such therapeutic intervention, the current study was undertaken. Fourteen female rhesus monkeys (Macaca mulatta), aged 18-25 years, received a 7-day course of either Thymosin Alpha One (TA1) or placebo, and in vitro and in vivo immunologic analyses were performed. The relative percentage of T-cells and T-cell subsets declined during treatment in both TA1 and placebo groups. Nevertheless, mitogen-induced proliferation and NK-cell function were increased in most monkeys that received TA1, a trend that was apparent but not statistically significant. The antibody response to tetanus toxoid vaccine was not greater in the TA1 treatment group when compared to the placebo group. These findings suggest that TA1 can be safely administered to old monkeys and that such treatment, if undertaken in a larger or more sustained trial, may be associated with demonstrable biologic activity. Further studies are warranted to determine the potential for this or similar agents to reduce the consequences of age-associated immune deficiency.
Fourteen female monkeys (Macaca mulatta) received a trivalent influenza vaccine and antibody response was determined by a change in plasma antibody content (ELISA) before and after vaccine. Lymphocyte cultures were also established from these monkeys and the level of antibody response did not correlate with mitogen-induced lymphocyte blastogenesis or natural killer cell function. In vitro anti-influenza antibody synthesis, however, was found to correlate well with the in vivo response. That is, monkeys who were non-responders, as determined by lack of change in plasma antibody content, were also non-responders in vitro. Accordingly, we believe that vaccine response is not necessarily a measure of immune competence but its measurement may, none the less, have clinical utility. The excellent correlation of in vivo and in vitro response provides predictive value for the in vitro test. Furthermore, because the correlation is good, the in vitro test may be useful as a tool in immunopharmacology and toxicology.
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Bone, brain, and liver radioisotope scans as prognostic indicators were studied in a series of 162 patients with primary bronchogenic carcinoma. One or more scans positive for metastasis reliably predicted death in less than six months. An abnormal bone scan was most significant (P less than .001). Reliability in predicting less than one year's survival in abnormal liver and brain scans was P less than .05 for both. Patients with two normal scans were found to have a 50% six-month survival expectation. Brain scans added little information, as they would have predicted a different prognosis for only three of 114 patients who received them.