Fever in the elderly.

Infections in the elderly, similar to other acute illnesses in this age group, may present in atypical, nonclassical fashions. Fever, the cardinal sign of infection, may be absent or blunted 20%-30% of the time. An absent or blunted fever response may in turn contribute to diagnostic delays in this population, which is already at risk for increased morbidity and mortality due to infection. On the other hand, the presence of a fever in the geriatric patient is more likely to be associated with a serious viral or bacterial infection than is fever in a younger patient. Finally, a diagnosis can be made in the majority of cases of fever of unknown origin (FUO) in the elderly. FUO is often associated with treatable conditions in this age group.

Ethanol impairs major histocompatibility complex (MHC) class II molecule-mediated but not MHC class I molecule-mediated T cell response in alcohol-consuming mice.

The goal of this study was to determine whether alcohol affects alloantigen-induced proliferative and cytolytic activity of T cells in mice, and whether the altered immune response was in part due to a defect of IL-2 activity. The ability of spleen cells from individual alcohol-consuming C57BL/6 mice to generate allo-specific mixed lymphocyte response (MLR) and cytotoxic T lymphocyte (CTL) was compared to that of mice fed on an isocaloric maltose diet and regular diet. Allospecific MLR and CTL were generated by sensitizing spleen cells of C57BL/6 mice against spleen cells from BALB/c mice, and the allo-specific CTL activity was determined by the ability of the CTL to kill 51Cr-labeled P815 mastocytoma target cells. Our results showed that the allo-specific MLR of the responder cells from alcohol-consuming mice was significantly reduced (40% reduction, p<0.0 1), and the addition of exogenous interleukin 2 (IL-2) could not reverse the suppression of MLR induced by ethanol. However, our results clearly showed that ethanol has little suppressive effect on allo-reactive CTL of alcohol-consuming mice as compared to the alloreactivity of the control mice (P>0.05). Finally, we also demonstrated that ethanol did not impair the alloantigen-induced IL-2 production in the mixed lymphocyte cultures (P>0.1).

Management of complicated urinary tract infection in older patients.

Urinary tract infection (UTI) in older persons is a common medical problem that is seen in both the ambulatory and institutional settings. It affects older women and men with a gender prevalence ratio of 2:1, respectively. UTI in older persons can be a complex problem in terms of the approach to diagnosis, treatment, and prevention. In this report the discussion will begin with the unique aspects of UTI in older persons, particularly as they relate to UTI in the younger, general population. The remaining discussion will then focus on three complicated clinical circumstances and conditions of UTI in the geriatric population: non-catheter recurrent UTI, asymptomatic bacteriuria, and catheter-related bacteriuria and UTI.

Effects of exogenous cytokines on the ethanol-mediated suppression of murine thymocyte proliferation.

Although attempts have been made to assess the effect of ethanol on murine thymocyte proliferation, the mechanism which accounts for the immunosuppressive effect of ethanol on the thymocyte proliferation has not been elucidated. Thus, a mouse model was used to determine (1) whether there is a similarity in the effect of ethanol exposure in vitro and in vivo on the proliferative response of thymocytes to phytohemagglutinin (PHA), (2) whether ethanol exposure affects the responsiveness of thymocytes to exogenous interleukin (IL)-1 and IL-2, and (3) whether ethanol affects IL-1 production by peritoneal macrophages. We found that the proliferative response of thymocytes from mice fed on an ethanol-containing diet was significantly inhibited (P < 0.05) compared to that in mice fed on maltose or standard diets. We also observed that low concentrations of ethanol (12.5 mM) appeared to enhance the mitogenic response of thymocytes to PHA, but the response was not significantly greater than that of controls (P > 0.05). Ethanol at higher concentrations (25-100 mM) significantly suppressed the mitogenic response of thymocytes to PHA (P < 0.05) in a dose-dependent manner. Our data also revealed that (1) ethanol did not significantly suppress IL-1 secretion by adherent macrophages stimulated by LPS, and (2) the addition of exogenous IL-1 was insufficient to restore full responsiveness in thymocytes from ethanol-fed mice. Taken together, these results suggest that the suppressive effect of ethanol on thymocyte proliferation is not mediated by insufficient IL-1. Finally, we present novel evidence that addition of exogenous IL-2 completely restores the impaired proliferative response of thymocytes from ethanol-fed mice to control levels. In summary, our results demonstrate that ethanol inhibits thymocyte proliferation in response to PHA, and that the inhibition is not due to insufficient IL-1. We also report that addition of exogenous IL-2 is sufficient to restore full proliferative capacity to thymocytes from ethanol-fed mice.

Fever in the elderly.

Fever in elderly persons is only one clinical presentation that can be used to assist the clinician at suspecting a serious disease, such as an infection. Infections, like all other illnesses in the geriatric patient, may occur with a variety of nonspecific, atypical, nonclassic, and unusual manifestations. The clinician caring for elderly patients should be aware of these nonclassical presentations of infections in this age group. Unexplained change in functional capacity, worsening of mental status, weight loss or failure to thrive, weakness and fatigue, falls, and generalized pain are only some of the clues that may aid the clinician in considering infection in elderly persons. Key concepts of fever in older adults are: Fever generally indicates presence of serious infection, most often caused by bacteria. Fever may be absent in 20%-30% of elderly patients harboring a serious infection. Criteria for fever in elderly patients should also include an elevation of body temperature of at least 2 degrees F from baseline values. FUO in elderly persons is caused by infections (30%-35%), CTD (25%-30%), and malignancies (15%-20%) in the majority of cases.

Approach to fever and infection in the nursing home.

OBJECTIVE: To summarize current information on the scope, epidemiology, clinical manifestations, diagnostic approach, and general management of infectious diseases in nursing home residents, as well as the specific treatment of common infections occurring in the nursing home setting. DESIGN: Survey and literature review of the diagnostic and therapeutic problems of nursing home residents with infections. CONCLUSIONS: Older persons residing in nursing homes as well as other types of long-term care facilities are at increased risk for infections. Moreover, infection is the most frequent reason for patients to be transferred from nursing homes to an acute-care facility. The most common infections that are acquired in nursing homes are urinary tract infection (cystitis pyelonephritis), respiratory infections (pneumonia, bronchitis), and skin/soft tissue infections (infected pressure ulcers, cellulitis). Most serious infections in this setting are caused by bacteria; however, influenza and other respiratory viruses as well as herpes zoster may cause significant morbidity in older nursing home residents. Mycobacterium tuberculosis infects nursing home residents at a higher rate than it infects older community dwellers. Infections in older nursing home residents may manifest clinically, with atypical symptoms and signs, including the absence of fever. Rapid diagnostic evaluation and early therapeutic intervention are essential for minimizing the high mortality and morbidity associated with infections in this older population; most nursing home residents with serious infections should be considered for hospitalization.

Effect of age on fever response to recombinant interleukin-6 in a murine model.

BACKGROUND: A blunted or absent fever response to infection may occur in elderly people. Fever is mediated by endogenously produced molecules of leukocytes. The best studied of these molecules is interleukin-1 (IL-1). However, interleukin-6 (IL-6) is also known to possess the biological properties of pyrogenic cytokines. In this study, we assessed the influence of age on the febrile response to recombinant IL-6 (rIL-6) using a well-defined murine model. METHODS: Balb/c male mice were injected intravenously and intraperitoneally with varying doses of rIL-6. Control mice received pyrogen-free phosphate buffered saline. Temperatures were measured rectally at baseline and at 10-minute intervals for 120 minutes post-injection using a thermistor probe. Stable baseline temperatures were first determined, and post-injection temperatures were recorded every 10 minutes for up to 120 minutes. RESULTS: A dose-response correlation was found between the amount of the injected rIL-6 and the mean temperature changes in both young and old mice. The mean temperature changes for both young and old mice were higher following a 25 ng dose compared to a 12.5 ng dose of rIL-6 injected intravenously, and, likewise, following a 500 ng dose compared to a 250 ng dose of rIL-6 injected intraperitoneally. A significant delay in the peak temperature response was seen for both young and old mice when comparing intraperitoneal injections to intravenous injections. However, control mice showed no changes. CONCLUSIONS: Our findings confirm that IL-6 has a role in the pathogenesis of fever and that aging alters the febrile response to rIL-6.

Infection control in long-term care.

Elderly residents of long-term care facilities are especially vulnerable to certain infectious diseases such as pneumonia, urinary tract infection, and skin or soft tissue infections. As part of quality of care, the detection, control, and prevention of infections in long-term care facilities through an organized infection control program is a requirement of federal, state, and professional regulatory agencies. Implementation of the major components of an infection control program requires a cooperative interdisciplinary effort among the facility administration, medical director, infection control committee, infection control practitioner, staff, and local health department.

Treatment of infections in elderly patients.

Infections are common in elderly persons. The clinical manifestations of infection may be atypical or absent in the elderly. The microbial cause for many common infections may be more diverse in elderly patients, and obtaining diagnostic clinical specimens often is more difficult. Aging is associated with changes in pharmacokinetics and a higher rate of adverse drug reactions. These factors impact on the approach to treating infections in the elderly.

Interrelationship of fever, immune response and aging in mice.

Fever is the cardinal manifestation of infection and may be blunted in certain infected elderly individuals. It is known that elevated body temperature enhances both the inflammation response and immune function, resulting in increased host resistance to infection. Recently, it has been suggested that the elevation of body temperature and the activation of lymphocytes by IL-1 are interrelated host effects. However, the question of whether fever response in vivo is closely correlated to cell-mediated immune parameters is unknown. In this study, a well-defined murine model was used to study the relationships between aging, fever and cell-mediated immune response. Thus, measurements of rectal temperature changes were made in individual young (4-6 months) and old (26-27 months) BALB/c mice to determine their ability to respond to endogenous pyrogen (recombinant IL-1). Splenic cells from these animals were used to assess T- and B-cell proliferation, production of interleukin 1 (IL-1) and IL-2. The results revealed that the proliferative capacity and the IL-1 and IL-2 producing capacity of splenic cells from old mice were markedly decreased. However, aging did not significantly affect the mean febrile responses in old mice following rIL-1 injections. Finally, there was no significant correlation between in vivo fever responses and the immune parameters measured in vitro in both young and old mice.

Infections of the bone, joint, and bursa.

Infections of the skeletal system, specifically bone, joint, and bursa, cause major morbidity as well as substantial number of deaths in older patients. In this article, the discussion focuses on the cause, pathogenesis, microbial causes, diagnosis, treatment, and available preventive interventions of septic arthritis, prosthetic joint infection, setic bursitis, and osteomyelitis in elderly patients.

Mechanism of the impaired T-cell proliferation in adult rats exposed to alcohol in utero.

Although attempts have been made to assess the effect of ethanol on the immune responses in individuals with fetal alcohol syndrome, there is no consensus as to the effect of ethanol on the immune system. Evidence that fetal alcohol-exposed (FAE) humans and animals have diminished proliferative response of T-cells to mitogenic lectins is well established. However, little is known about the mechanism of a toxic effect of ethanol on T-cell growth. Thus, a rat model was used to delineate the mode of ethanol action on T-cell proliferation. We found that the diminished T-cell proliferation in young adult FAE rats was due to a decreased responsiveness to interleukin 2 (IL2), but not to an impaired production of IL2 and expression of IL2 receptors (IL2R). Furthermore, the decreased proliferative response did not result from the presence of an excessive suppressor T-cell activity. Measurements of [Ca+2]i and T-cell proliferation were concurrently performed in batches of cells from the same animals. It was demonstrated that an increase in [Ca+2]i induced by Concanavalin A (Con A) in T-cells from FAE rats was not impaired, although the T-cell proliferation induced by Con A was significantly diminished. The results of the IL2-binding study showed that the Kd values and the number of both high- and low-affinity IL2R binding sites on the T-cells of FAE rats were comparable to those of pair-, or chow-fed rats. Finally, the results of the kinetics and rate of the internalization of IL2 showed that (1) the amount of the internalized IL2 was significantly reduced in T-cells from FAE rats, and (2) the half-time (t1/2) for dissociation of IL2 from the receptors in the T-cells from FAE rats was also greater than that of the control rats. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2-IL2R interaction.

Antibiotic therapy: what to consider when treating geriatric patients.

The epidemiology, etiology, clinical manifestations, diagnostic approach, and therapeutic choices may be quite different for infections that occur in elderly patients compared with those that occur in younger adults. Given these variables, it is essential for clinicians who care for older patients to understand how to prescribe antibiotics appropriately for this population. This article examines the unique characteristics of infections in the elderly as well as provides recommendations on the use of specific antibiotic agents commonly used to treat infections in geriatric patients.

Impaired cytosolic free calcium response in splenic T-cells from mice fed with ethanol-containing diet.

Calcium-dependent signal transduction pathways of T-cell proliferation have been extensively studied in the past years. However, little is known about effects of ethanol on the calcium-dependent signal transduction pathway in T-cell proliferation. Thus, a murine model was used to determine effects of ethanol in vivo on T-cell proliferation and the intracellular free calcium concentration [Ca2+]i in response to Concanavalin A (Con A) and recombinant IL2 (rIL2) in T-cells. Splenic cells from young C57BL/6 mice, that had been fed on 3 different diets (ethanol-, maltose substitute- and standard liquid-diet) for 7-8 weeks were tested for their proliferative responses to Con A and rIL2. Concurrently, measurement was also made of [Ca2+]i in the nylon-wool-enriched resting T-cells induced by Con A and in Con-A-activated blast T-cells induced by rIL2. Our results showed that [Ca2+]i increases were seen in the splenic T-cells from three different groups of mice following Con A, but not rIL2 stimulation. However, this increase was much smaller in the splenic T-cells from ethanol-fed mice as compared to mice on maltose- or standard-diet. Furthermore, we also demonstrated that the impaired [Ca2+]i increase was seen in the T-cells of the same ethanol-fed mice having decreased the proliferative response to Con A. This reduced proliferation did not result from the presence of excessive suppressor T-cell activity. Finally, we also demonstrated that both the number of IL2 binding sites/cell and the Kd values of the low- and high-affinity IL2R on the T-cells from ethanol-fed mice were unaltered. Because evidence indicates that (1) a normal level of [Ca2+]i increase is a prerequisite for the production of IL2 by mitogen-stimulated T-cells, and (2) T-cells from ethanol-fed mice have normal capacities to produce IL2 that is the crucial growth factor controlling T-cells to progress through the cell cycle, these lines of evidence taken together with the results of this study suggest that the impairment in [Ca2+]i increases in T-cells from ethanol-fed mice may not be the primary factor contributing to the diminished T-cell proliferation in the same mice.

Actions of alcohol on immunity and neoplasia in fetal alcohol exposed and adult rats.

Alterations of immune function can result not only from alcohol consumption by the adult human or animal, but also from fetal alcohol exposure (FAE). We have demonstrated long-lasting effects of FAE on T cell function and effects of adult ethanol (EtOH) consumption on tumorigenesis. Here, we present recent data that demonstrate that 1) FAE alters the biphasic pattern of thymocyte activation during peripubertal development probably due to effects other than the CD3 pathway; and 2) the long-lasting impaired proliferative response of splenocytes from FAE rats is not due to loss of their ability to express interleukin-2 receptors (IL2R), thus reflecting interference with events following the IL2-IL2R interaction. We also provide direct evidence that acute in vivo administration of EtOH to adult Fisher 344 rats can suppress blood natural killer (NK) cytotoxicity and that such suppression mediates the observed enhanced metastatic growth of a syngeneic mammary tumor.

The equivalency of infrared tympanic membrane thermometry with standard thermometry in nursing home residents.

OBJECTIVE: To compare the equivalence of infrared tympanic membrane (TM) measure of body temperature with standard electronic oral (PO) and rectal (R) measures in a nursing home population. DESIGN: Randomized repeated-measurement design. METHODS: For the study, 82 randomly selected residents (mean age 79 +/- 10 years) of the Nursing Home Care Unit of the VAMC West Los Angeles had PO, R, and TM temperatures measured before arising (6-8 am). An otoscopic exam and the age, sex, presence of neurologic disease, and compliance with thermometry was noted. Also, repeated measures of PO and TM temperatures were performed three times to assess variability. The Pearson's correlation coefficient was determined for PO versus R and for TM versus R temperatures. Stepwise regression analysis was performed with the dependent variable of R temperature and the independent variables of the mean TM temperature, age, sex, presence of neurologic disease, position of the resident, and extent of ear canal occlusion. RESULTS: The correlation of TM versus R (r = .39, P = .004) was better, though not significantly, than of PO versus R (r = .28, P = .04). TM had less variability than PO (pooled standard deviation .38 vs .45 degrees F, respectively) and TM was implemented successfully more often than PO or R (96% vs 81% vs 81%). CONCLUSION: Therefore, TM was at least equivalent or better than PO measures of temperature in this population. The efficacy of fever detection and the use and durability of long-term use by nursing staff needs to be studied.

Infections in elderly persons. An altered clinical presentation.

The high prevalence, morbidity, and mortality of infectious diseases in the geriatric population mandates that clinicians caring for older patients become better acquainted and familiar with the special and unique characteristics and features of this common clinical problem. Only through such awareness and understanding will clinical outcomes, functional capacity, and quality of life be improved in the elderly population.

Platelet microbicidal protein enhances antibiotic-induced killing of and postantibiotic effect in Staphylococcus aureus.

The interaction of bacteria with platelets at the cardiac valve surface represents a critical event in the induction of infective endocarditis. Platelets are thought to modulate induction or propagation of endocarditis via secretion of alpha-granule-derived platelet microbicidal protein (PMP) (a low-molecular-mass, cationic, heat-stable protein distinct from lysozyme). We studied representative PMP-susceptible and PMP-resistant Staphylococcus aureus isolates to determine their in vitro bacteriostatic and bactericidal susceptibilities to combinations of PMP plus antistaphylococcal antibiotics. PMP plus oxacillin exerted a synergistic bactericidal effect, in contrast to either agent alone, regardless of the intrinsic PMP susceptibility of the isolate tested. Exposure of S. aureus to PMP alone resulted in residual postexposure growth-inhibitory effects lasting from 0.9 to 1.8 h. Sequential exposure of S. aureus isolates to PMP for 30 min followed by exposure to either oxacillin or vancomycin (each at 10x the MIC for 120 min) resulted in a significant extension of the postantibiotic-effect duration compared with antibiotic exposure alone (P less than or equal to 0.05). Collectively, these findings indicate that PMP both enhances antibiotic-induced killing of S. aureus and increases the postantibiotic-effect duration in S. aureus.

Characterization of Staphylococcus aureus-platelet binding by quantitative flow cytometric analysis.

Quantitative analyses of Staphylococcus aureus binding to platelets were done using flow cytometry after bacterial exposure to the following treatments: proteases (trypsin, protease K), antibiotics (oxacillin, gentamicin), surface carbohydrate modifiers (sodium periodate, anticapsular antibody), or platelet microbicidal protein. In separate studies, platelets were exposed to a monoclonal antibody to their Fc receptor (Fc gamma RII) before binding was quantified. The percentage of bacteria bound to platelets varied significantly among strains (22.1% +/- 3.8% to 76.4 +/- 3.2%). For all isolates, binding to platelets was rapid, saturable, and reversible, suggesting a receptor-ligand interaction. The following modifiers significantly reduced binding: platelet microbicidal protein (by 32.1% +/- 5.2%; P less than .001), homologous (but not heterologous) anticapsular antibody (by 17.7% +/- 1.9%; P less than .05), sodium periodate (by 36.3% +/- 4.3%; P less than .005), and anti-platelet Fc monoclonal antibody (by 41.5% +/- 4.4%; P less than .002). Collectively, these data suggest that the mechanism(s) involved in S. aureus-platelet binding are complex and multimodal, involving carbohydrate-rich and platelet microbicidal protein-susceptible S. aureus surface ligands as well as the platelet Fc receptor.