NF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases.

Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system.

Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing.

Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, TNF-α, CD206, Arginase 1), and ELISA (TNF-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that TNF-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with IL4 stimulation in aged macrophages, but to a lesser extend than those from younger animals. TNF-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. These age-related changes in macrophage polarization may explain in part the attenuated response to adverse stimuli and delay in processes such as fracture healing seen in the elderly. LAY SUMMARY: Bone healing is a complex process that involves both biological and mechanical factors. Macrophages are key cells that regulate the events involved in bone healing, especially the initial inflammatory phase. In this biological cascade of events, macrophages present as different functional phenotypes including uncommitted (M0), pro-inflammatory (M1), and anti-inflammatory (M2), a process called macrophage polarization. A clear understanding of the effects of aging on macrophage polarization is critical to modulating adverse events such as fractures, atraumatic bone loss, and tissue regeneration in an aging population.

Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways.

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

Polypeptide N-acetylgalactosaminyl transferase 3 independently predicts high-grade tumours and poor prognosis in patients with renal cell carcinomas.

BACKGROUND: The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs). METHODS: Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC. RESULTS: Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low ß-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates. CONCLUSION: N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC.

Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.

[Reduction of medical resources utilization by influenza vaccination for hospitalized elderly patients].

In order to evaluate the economic efficacy of influenza vaccination for the elderly inpatients, we have investigated the health insurance fee of elderly inpatients in Japan. It was revealed that the health insurance fee varied by patients largely, ranging from 7,000 yen to 90,000 yen. Primary reason of this variation was due to the existence of the same effective drugs with variant prices and there were no rules concerning the period of drug medication. Thus, it was found that it would be improper to use the medication fee as a measure in evaluating the effects of influenza vaccinations. In this study, we used the length of days of testing and medication such as oral antibiotics, blood cell count, etc. as a measure to evaluate the effect of influenza vaccination. We compared these measures among elderly hospitalized patients with influenza vaccination or without influenza vaccination by ADL. Mean length of days of oral antibiotics was 2.64 (+/- 6.40) days for those with vaccination, and 3.92 (+/- 7.31) days for those without vaccination. Mean length of days of injection antibiotics was 2.52 (+/- 5.53) days for those with vaccination, and 8.82 (+/- 15.1) days for those without vaccination. Mean length of days of cells blood counter was 2.63 (+/- 2.22) days for those with vaccination, and 4.44 (+/- 3.20) days for those without vaccination. Mean length of days of chest X-ray was 1.30 (+/- 2.07) days for those with vaccination, and 2.56 (+/- 3.49) days for those without vaccination. These results suggest that influenza vaccination reduces medical utilization of resources. It was also revealed that influenza vaccination is most effective when elderly patients who are bed-bound are vaccinated.

[Amantadine usage for influenza A during an influenza outbreak in a nursing home].

An outbreak of an influenza like illness was found in a nursing home in Fukuoka in January, 1999. Results of hemagglutinin inhibition tests with paired sera of patients and rapid diagnosis kit for influenza A indicated that an influenza A (H3N2) outbreak had occurred. A total of 15 patients with influenza like illness from one residential area of the nursing home were administered amantadine, 100 mg per day for five days. Clinical records of 264 residents were surveyed retrospectively from the tenth to the thirty-first of January, 1999. Influenza like illness was found in 112 residents (42.4%). The incidence of influenza like illness differed by residential area, ranging from 27.6% to 54.0%. The mean duration of fever was 3.6 days among patients administered amantadine. The mean duration was 4.4 days for patients not administered amantadine. The incidence of influenza like illness decreased rapidly after amantadine administration in the residential area where amantadine administration was done. These results suggest that amantadine is effective in mitigating influenza symptoms in the elderly. Amantadine may be useful for diminishing the influence of influenza A outbreaks in nursing homes.

[The clinical feature of febrile episodes].

Institutionalized elderly patients are at risk of nosocomial infection because of their compromised status by aging. To clarify the relationship between fever and disease in elderly patients, we analyzed 1,105 febrile episodes, the etiology of which were already diagnosed, of 443 patients (136 men, 307 women). All patients who were 65 years of age or older and who had been admitted to the hospital for more than 7 days had fevers above 37.5 degrees C recorded. The etiologies of the 1,105 febrille episodes were respiratory tract infection in 381 (34.5%), urinary tract infection in 263 (23.8%), other diseases in 164 (14.8%) and in 297 (26.9%) unknown. The episodes were categorized into two groups by the degree of initial fever: group A, 559 episodes (50.6%) of 37.5-38.0 degrees C and group B, 546 episodes (49.4%) of above 38.0 degrees C. Of the episodes, 41.0% were one-day fevers, 21.4% two-day fevers, and 14.0% three-day fevers. The frequency of two-or-more-day fevers was significantly higher in group B (69.0%) than in group A (49.2%) (p < 0.001). In group B, respiratory tract infection (44.3%) was more frequent than urinary tract infection (16.1%) (p < 0.001). Of the respiratory tract infections, 63.5% were in group B and, in contrast, 66.5% of the urinary tract infections were in group A. The white blood cell count and C-reacting protein levels were significantly higher in group B than in group A (p < 0.001). The degree of initial fever is an important predictive marker of severity of disease in elderly patients.

[The efficacy of influenza vaccine among geriatric inpatients].

To investigate the efficacy of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titer for the three types of influenza viruses were measured and the influenza infection rate was determined serologically in geriatric inpatients. Influenza vaccination was done for inpatients. For patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once or twice, and the number of injections were determined randomly. Influenza vaccine was injected twice to those had not received influenza vaccine in the previous year. Serum samples were collected from 166 vaccinated and 104 unvaccinated patients before and after 1996/1997 influenza season. In the vaccinees who had been vaccinated the previous year, 56 patients were injected once and 58 patient were injected twice. Fifty-two patients had not been vaccinated the previous year. Serologically diagnosed influenza infection rate in the 104 unvaccinated patients was 16.3% for influenza A/H3N2 and 8.7% for influenza B. The infection rate was 3.0% for influenza A/H3N2 and 0.6% for influenza B in the 166 vaccinated patients. The infection rates were significantly lower in the vaccinees than in the unvaccinated patients (p < 0.001 with A/H3N2 and p < 0.01 with B). There was no significant difference in the infection rate among the three vaccinated groups. These results suggest that the influenza vaccination had significant protective efficacy for influenza infection in the elderly. Prior vaccination did not diminish the efficacy of the influenza vaccine. The efficacy of a single influenza vaccine injection was equivalent to that of two injection.

[Efficacy of influenza vaccine among geriatric inpatients: effect of previous vaccination and antibody induction by single and twice injections].

To investigate the effect of previous influenza vaccination and the difference in antibody induction by single and twice injection of influenza vaccine in the elderly, hemagglutination inhibition (HI) antibody titers of the three types of influenza viruses were measured. Influenza vaccination was done for 217 inpatients. For the patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once to 77 patients and twice to another 70 patients. Influenza vaccine was injected twice to 70 patients who had not received influenza vaccine in the previous years. The influenza vaccine induced an increase in HI titer in almost all patients. The geometric mean of the HI titer and the frequency of patients with HI titers over 128x were similar after vaccination in the groups of patients who were injected twice, irrespective of whether or not influenza vaccination was given in the year prior to the study. The geometric means of the HI titers for influenzas A/H3N2 and B and the frequency of HI titers over 128x for influenza A/H3N2 after vaccination were lower in the patients who received vaccine once than in the patients vaccinated twice. These results suggest that prior vaccination does not diminish antibody response to influenza vaccine significantly in the elderly when influenza vaccine is injected twice. Although single injection is inferior to twice injection in antibody induction with some vaccine virus strains, induction of HI titers over 128x is found in more than 70% of elderly. Single injection of influenza vaccine may be practically effective and useful for protection of influenza infection in the elderly.

[Cost of medication for influenza infected elderly inpatients].

Influenza vaccine is recommended for the elderly, a high-risk group for influenza infection. Unlike in many developed countries, the rate of influenza vaccination is extremely low in Japan. One of the primary reasons for this low level of vaccination use may be insufficient study on the cost-effectiveness of influenza vaccination in Japan. We determined the cost of medical tests and medications for inpatients with influenza in a referred hospital. We compared the medical costs by (1) level of daily life activity, (2) presence of pneumonia, and (3) living/dead status, 9 months after the infection. In addition, we set up a control group of patients for comparison of their medical costs to those of the influenza patients. Mean costs were 37,279 (+/- 26,784) yen for patients, and 2,361 (+/- 4,893) yen for controls. Mean costs were 32,424 (+/- 30,935) yen for inpatients without limitations to activity, 44,075 (+/- 20,937) yen for bed-bound inpatients, 44,614 (+/- 28,609) yen for inpatients with pneumonia, 27,009 (+/- 22,783) yen for inpatients without pneumonia, 57,624 (+/- 21,041) yen for inpatients who died within 9 months of the onset of influenza, and 16,934 (+/- 11,920) yen for inpatients who were alive 9 month after influenza infection.

[Evaluation of a rapid enzyme immunoassay for detection of influenza A virus among adult and elderly patients].

Directigen Flu A, an enzyme immunoassay membrane test for the detection of influenza A virus, was compared with serum hemagglutinine inhibition assay in adult and elderly patients. Throat specimens were collected by vigorous swabbing from febrile patients who were suspect for influenza by clinical symptoms and tested with Directigen Flu A. Serum samples were collected from the patients at onset of illness and two to eleven weeks later and tested for antibody titer to influenza A/H1N1, A/H3N2, and B. A total of 57 patients were involved in this study; 32 under 59 years of age and 25 over 60 years of age. Influenza was diagnosed in 42 patients by HI titer elevation (73.7%). Directigen Flu A was positive in 25 patients. Results of Directigen Flu A and HI test agreed in 40 patients. Sensitivity and specificity of Directigen Flu A were 59.5% (25/42) and 100% (15/15), respectively. There was no significant difference in sensitivity between the two age groups. These results indicate the potential usefulness of Directigen Flu A in the surveillance of influenza A infection in the geriatric population. Directigen Flu A gives results within 15 minutes without expensive equipment. Use of Directigen Flu permits the timely administration of antiviral therapy and infection control among hospitalized and institutionalized geriatric patients.

[Antibody response to a single injection of influenza vaccine among geriatric inpatients vaccinated annually].

To determine the efficacy of a single influenza vaccine administration in the elderly receiving annual influenza vaccination, antibody response to influenza vaccine was compared between once and twice injections in a geriatric cohort. Influenza vaccination had been done for 69 inpatients in the year prior to the study, and was administered twice for 34 of them and once for the other 35 during the study period. Influenza vaccine was injected twice to 77 inpatients who had not received influenza vaccine in the year prior to the study. Hemoagglutination inhibition (HI) antibody titer for influenza A/H1N1, A/H3N2, and B was measured before vaccination, after the first vaccination, after the second vaccination, and after the epidemic period, September 1995 to April 1996. HI antibody titer prior to vaccination was significantly higher in the patients who had received influenza vaccination the previous year. The influenza vaccine induced an increase in HI titer in almost all subjects, and the geometric mean of the HI titer after vaccination in the patients who received vaccine once was comparable to that of the patients injected vaccine twice. The number of patients with HI titers of over 128x increased, and the frequency ranged from 60.0% to 97.1% for the influenza viruses of the three subtypes. The frequency of HI titers over 128x was not significantly different among the three groups. The second vaccination did not increase the number of patients with HI titers over 128x when compared with the number after the first injection in the patients who had received influenza vaccine the previous year. These results suggest that prior vaccination does not diminish the antibody response to influenza vaccine in the elderly. The efficacy of a single influenza vaccination is comparable to that achieved by twice injections in the elderly receiving annual influenza vaccination.

[Febrile episodes in elderly inpatients--a one year survey to determine the causes of fever in hospital].

To determine the cause of nosocomial infections, all febrile episodes of hospitalized elderly patients aged 65 and older at a hospital in Fukuoka City were categorized between April 15 1994 and April 14 1995. A febrile episode was a temperature above 37.5 degrees C after 7 consecutive days of normal body temperature (below 37.5 degrees C). Various clinical tests including blood examination, urinalysis, chest radiography and bacterial culture were done on the first and 7th day of the fever. A total of 1105 episodes in 443 patients (male 136, female 307) fulfilled this criteria for fever. The fevers were mainly due to respiratory tract (381 cases, 34.5%) and urinary tract infections (263 cases, 23.8%). There were 135 infections (12.2%) of other kinds and 297 cases (26.9%) that were classified as unknown. Approximately 70% of the febrile episodes were caused nosocomial infections, suggesting increased risk of infection in the hospitalized elderly and the importance of early detection of febrile changes in elderly inpatients.

[Impact of influenza epidemics and efficacy of vaccination among geriatric inpatients].

To determine the impact of influenza epidemics among geriatric inpatients and to monitor the clinical efficacy of influenza vaccination, the influenza infection rate in non-vaccinated inpatients was determined serologically and the incidence of febrile episodes and death were compared between the vaccinees and non-vaccinees hospitalized in the referred hospital from January through September, 1995. Three influenza subtypes, influenza A/H1N1, A/H3N2, and B, were endemic simultaneously from January to March in 1995. The pattern of incidence of febrile episodes varied for each ward. A total of 123 non-vaccinated inpatients were tested for elevation of serum hemagglutination inhibition titer to the three subtypes of influenza virus. Of these, 58 (47.2%) patients were infected with at least one of the influenza viruses during the epidemic of 1995. No patient with pre-existing HI titer over 128X was infected with any of three types of influenza, indicating that HI titer over 128X is the protective level. The febrile episode frequency was significantly higher in the non-vaccinees than in the vaccinees (49.6% vs. 32.6%), but it was quite comparable in the two groups after the influenza epidemic (34.9% vs. 35.8%). The number of observed deaths from January to September of 1995 was 4 (4.9%) in the vaccinee group and 12 (9.8%) in the non-vaccinee group. These results suggest that influenza epidemics have a striking impact on geriatric inpatients and that influenza vaccination has significant efficacy for the reduction of harmful events associated with influenza infection.

Comparison of HCV RNA levels by branched DNA probe assay and by competitive polymerase chain reaction to predict effectiveness of interferon treatment for patients with chronic hepatitis C virus.

To compare hepatitis C virus (HCV) RNA levels determined by branched DNA probe assay and by competitive polymerase chain reaction (PCR) as predictive markers of the response to interferon for treatment of patients with chronic HCV infection, we studied data on 140 patients treated for six months with natural interferon-alpha. Serum samples were tested for HCV RNA by PCR. HCV RNA was grouped into four genotypes by PCR with type-specific primers, and HCV RNA level was measured by branched DNA probe assay and by competitive PCR. HCV RNA was detected in all patients prior to initiation of the treatment. A complete response, sustained elimination of HCV RNA, occurred in 51 patients (36.4%). With multiple logistic regression analysis assessment, when using competitive PCR, a low level of HCV RNA (P < 0.0001), younger age (P = 0.0054) and genotype 2a and 2b (P < 0.0158) were significant predictive markers for a complete response to interferon treatment. When using branched DNA probe assay, a low level of HCV RNA (P < 0.0001) and age (P = 0.0089) were predictive markers, but genotype was not. The branched DNA probe assay had a narrower linear range for quantitation of HCV RNA level than competitive PCR. In conclusion, HCV RNA level determined by branched DNA probe assay proved to be useful for prediction of effects of interferon and it is cost effective as a marker of complete response to interferon treatment for patients with chronic HCV infection.

[Effect of the prior influenza vaccination on serum antibody titer induction by subsequent inactivated influenza vaccine in the elderly].

In order to investigate the effects of prior influenza vaccination on subaequent annual influenza vaccination in the geriatric population, we analyzed serum hemagglutinine inhibition antibody tirers (HI titer) before and after vaccination with inactivated influenza vaccine in elderly inpatients. A total of 163 inpatients of 60 years or older were enrolled with informed consent. They were classified by vaccination status in the previous year, 53 patients had inactivated vaccine (inactivated). 52 patients had genetically assorted cold-adapted influenza live attenuated vaccine (cold-adapted), and 53 had no influenza vaccine history during the past year. The HI titer was higher in the inactivated group than in the cold-adapted and non-vaccinated groups, suggesting residual immunological effects of inactivated influenza vaccine from the previous year vaccination. The HI titer after the inactivated vaccine in 1993 was higher in both the inactivated and cold-adapted groups than in the non-vaccinated group. The number of patients with HI titers of 2(7) or higher, which is the putative protective HI titer level for influenza infection, was significantly higher in both the inactivated and cold-adapted groups than the non-vaccinated group. These results suggest that continuous annual influenza vaccination does not impair the effects of vaccination, and may actively promote elevated HI titers.

[A case of an elderly patient with dementia and gait disturbance associated with influenza].

We report a case of progressive dementia and prolonged gait disturbance correlated with influenza A/H3N2 infection in 91-year-old female patient, admitted because of in ability to take care of herself due to aging and cerebral infarction. At admission, conversation and comprehension were not significantly impaired, and she was able to walk by herself. Flu symptoms such as high grade fever, chills, arthralgia, and cough appeared after a short stay at home. Influenza A/ H3N2 was confirmed serologically. Delirium occurred on the sixth day after influenza onset, persisted for three weeks, followed by recovery. Dementia symptoms such as memory defects and disorientation continued and did not improve. Due to this febrile episode, she was unable to walk unassisted. The results of computed tomography performed before and after the influenza episode were unremarkable for additional cellebro-vascular events during the observed period. Influenza infection may be an important risk factor for reducing the quality of life in the elderly. In geriatric cases, influenza should not be treated as a mere transient illness, but rather one which has important consequences for the elderly population, including the possibility of life threatening complications.

[Clinical significance of peak body temperature, white blood cell count, and C-reactive protein level in febrile episodes among geriatric inpatients].

To investigate the clinical implication of peak body temperature, peripheral blood white blood cell (WBC) count, and serum C-reactive protein (CRP) level in febrile symptoms among geriatric hospitalized patients, they were analyzed in 968 febrile episodes obtained from 433 hospitalized patients in the referred hospital. Episodes of one day duration were most frequent (41.6%). WBC count was elevated over 8000/microliters in 475 episodes (49.1%) and CRP exceeded 1.0 mg/dl in 770 episodes (79.5%). Frequency of WBC elevation decreased and frequency of CRP elevation increased according to the time course. The mean value of CRP increased significantly according to the time course. The frequency of WBC count increase and CRP elevation and their averages correlated to the peak body temperature. The peak body temperature displayed the most striking correlation to the length of febrile episodes among three clinical indicators, peak body temperature, WBC count, and CRP level. These results indicate that the elevation of WBC count and/or CRP level is frequent in geriatric patients with febrile symptoms. Peak body temperature may serve as a clinical indicator of the severy of the febrile disease occurring in geriatric patients.

[Serum albumin level as a predictor of incidence of febrile episodes and mortality in hospitalized geriatric patients].

To investigate the relationship between serum albumin level and incidence of febrile episodes and mortality in the elderly, we studied 748 patients hospitalized for over one year. The subjects included 123 males and 355 females with a mean age 81.2 years. The average serum albumin level was 3.79 g/dl and levels of serum albumin decreased with advancing age. The incidence of febrile episodes was 1.8 per year in patients with serum albumin levels over 4.1 g/dl, increasing with decline of serum albumin levels. The incidence of febrile episodes was 5.3 per year in patients with serum albumin levels under 3.0 g/dl. Patients with serum albumin levels under 3.0 g/dl displayed a high incidence of febrile episodes irrespective of age. Age adjusted in-hospital mortality was 40.4% during the observed period in patients with serum albumin levels under 3.0 g/dl, significantly higher than that of the patients with serum albumin levels over 3.1 g/dl. Relative risk of febrile episode and mortality calculated using the patients with serum albumin levels over 4.1 g/dl as a control was 2.9 and 2.1, respectively, in the patients with serum albumin levels under 3.0 g/dl. These results indicate that serum albumin level is a simple, but strong, predictor of susceptibility of febrile episode and death. Patients with serum albumin levels under 3.0 g/dl may constitute a high risk group for febrile episode and death.