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Rationale: The effects of telemedicine on adherence in patients with obstructive sleep apnea with long-term continuous positive airway pressure (CPAP) use have never been investigated.Objectives: T...

Background Our previous study showed that height is inversely associated with the risk of stroke in middle-aged Japanese men, particularly in those with a low body mass index (BMI). Since height is regarded as a surrogate maker of childhood social and physical condition, while BMI may reflect primarily on the current physical condition, a detailed analysis of those with a lower BMI may elucidate the effects of childhood conditions. On the other hand, dyslipidemia is recognized as a prominent risk factor for cardiovascular disease. However, no studies have reported on the association between height and dyslipidemia accounting for BMI status. Methods We conducted a hospital-based general population cross-sectional study of 3016 Japanese men aged 30–59 years. Dyslipidemia is defined by the Japan Atherosclerosis Society (JAS) Guidelines as follows: triglycerides (TG) ≥ 150 mg/dL and/or low-density lipoprotein-cholesterol (LDL) ≥ 140 mg/dL, and/or high-density lipoprotein-cholesterol (HDL)

A positive association between white blood cell count and carotid atherosclerosis has been reported. Our previous study also found an inverse association between height and carotid atherosclerosis in overweight but not non-overweight men. However, no studies have reported on the association between high white blood cell (WBC) count and height accounting for body mass index (BMI) status. We conducted a hospital-based general population cross-sectional study of 3016 Japanese men aged 30–59 years undergoing general health check-ups between April 2013 and March 2014. High WBC count was defined as the highest tertiles of WBC count among total subjects. Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for subjects with a BMI ≥ 23 kg/m2. The classical cardiovascular risk factors adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) of high WBC count for an increment of one standard deviation (SD) in height (5.7 cm) were 0.91 (0.83–0.99) for total subjects, 1.00 (0.86–1.15) for subjects with a BMI

Several studies have reported the association between sleep apnea syndrome and insulin resistance. Being overweight is known risk factor both for sleep apnea syndrome and insulin resistance. However, no studies have reported on the association between serum triglyceride levels in relation to high-density lipoprotein cholesterol (TG-HDL) ratios (a marker of insulin resistance) and sleep apnea syndrome accounting for body mass index (BMI) status. Subjects for the present cross-sectional study consisted of 1,528 men aged 30–69 years undergoing pulse oximetry at a sleep disorders clinic for sleep apnea syndrome. Sleep apnea syndrome was diagnosed as a 3 % oxygen desaturation index (ODI) of ≥15 events/h. Among study participants, 241 men were diagnosed with sleep apnea syndrome. Independent of classical cardiovascular risk factors, TG-HDL was significantly positively associated with sleep apnea syndrome in participants with a BMI

The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of nonfunctional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a two-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4+ cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0-4.3% for serotype 4 and 26.7-42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3-86.2% for serotype 4 and 63.3-96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy., Vaccine, 26(38), pp.4962-4968; 2008

Objectives. The present study was designed to determine whether adjuvant chemotherapy with paclitaxel (TXL) and carboplatin (CBDCA) after surgical resection is feasible in Japanese patients with non-small cell lung cancer (NSCLC) in a multiinstitutional trial. Methods. From August 2005 to March 2006, 34 patients received the following regimen: TXL (175 mg/m2) and CBDCA (AUC = 5) on day 1, every 3 weeks. The primary endpoint of this trial was the completion rate of four cycles. Results. The completion rate of four cycles was 79.4% [90% confidence interval (CI), 67.5%-91.3%]. Perfect completion rate of four cycles on schedule and full doses without delay was 50% (90% CI, 34.9%-65.1%). The reasons for incomplete cycles were hypersensitivity to TXL infusion during the first cycle in 3 patients, patients refusal in 2, and anemia and cerebral infarction in 1 patient each. As a consequence of delay and/or dose reductions, the relative dose intensity of TXL and CBDCA was 86.2% and 85.8%, respectively. Conclusion. Doublet chemotherapy with TXL and CBDCA in the planned doses and schedule was found to be a feasible treatment for Japanese patients following surgical resection for NSCLC.

Background: A high frequency of drug-resistant pneumococci has been reported in Asian countries. Few data on the drug-resistance or serotype of pneumococcal strains responsible for community-acquired pneumonia (CAP), however, are available for the past two decades in Japan. Methodology: Susceptibility to antibiotics and the genotype of antibiotic-resistant genes and serotypes of Streptococcus pneumoniae isolates from 114 adult patients with CAP were examined in a nationwide study in Japan between 2001 and 2003. Results: Most of the cases were non-bacteraemic pneumonia and the case fatality rate was 4.4%. The most frequent genotype of the pbp gene was pbp1a + 2x + 2b (gPRSP; 36.8%) followed by pbp 2x (28.1%) and of the macrolide-resistant gene, it was ermB (50.0%). The most common serotype was 19F (29.1%), followed by serotype 23F (13.2%), 6B (12.3%) and 3 (11.4%). The coverage of serotypes of isolates by a 23-valent pneumococcal polysaccharide vaccine (PPV) would be 82.5% in these patients with CAP. Most of strains with serotypes 19F and 23F were gPRSP. A cluster of serotype 3 strains associated with the pbp 2x and ermB gene was also noted. Conclusion: A high frequency of altered pbp gene mutations or of macrolide-related genes and a high serotype coverage by the 23-valent PPV found in our study of pneumococcal pneumonia facilitates attempts to increase the coverage rate of the 23-valent PPV in adults older than 65 years in Japan.

Neutrophil infiltration is the first step in eradication of bacterial infection, but neutrophils rapidly die after killing bacteria. Subsequent accumulation of macrophage lineage cells, such as alveolar macrophages (AMs), is essential to remove dying neutrophils, which are a source of injurious substances. Macrophage lineage cells can promote tissue repair, by producing potential growth factors including hepatocyte growth factor (HGF). However, it remains elusive which factor activates macrophage in these processes. Intratracheal instillation of Pseudomonas aeruginosa caused neutrophil infiltration in the airspace; subsequently, the numbers of total AMs and neutrophil ingested AMs were increased. Bronchoalveolar lavage (BAL) fluid levels of monocyte chemoattractant protein (MCP)-1/CC chemokine ligand-2 (CCL2), a potent macrophage-activating factor, were increased before the increases in the number of AM ingesting neutrophils and HGF levels in BAL fluid. Immunoreactive MCP-1 proteins were detected in alveolar type II epithelial cells and AMs only after P. aeruginosa infection. The administration of anti-MCP-1/CCL2 Abs reduced the increases in the number of AM-ingesting neutrophils and HGF levels in BAL fluid, and eventually aggravated lung tissue injury. In contrast, the administration of MCP-1/CCL2 enhanced the increases in the number of AM ingesting neutrophils and HGF levels in BAL fluid, and eventually attenuated lung tissue injury. Furthermore, MCP-1/CCL2 enhanced the ingestion of apoptotic neutrophils and HGF production by a mouse macrophage cell line, RAW 267.4, in a dose-dependent manner. Collectively, MCP-1/CCL2 has a crucial role in the resolution and repair processes of acute bacterial pneumonia by enhancing the removal of dying neutrophils and HGF production by AMs

Type-specific immunoglobulin G (IgG) to pneumococcal capsular polysaccharide (CPS) and opsonic activity against Streptococcus pneumoniae were evaluated in serum samples from 36 Ugandan adults with community-acquired pneumonia and 58 asymptomatic Ugandan adults with or without human immunodeficiency virus type 1 (HIV-1) infection. The levels of serum IgG to CPS were significantly higher in HIV-1-infected subjects than in HIV-uninfected subjects. Serum samples from HIV-1-infected subjects that had lower IgG titers demonstrated higher opsonic activity against type 3 (titers of 7) and type 9 (titers of 7-11) pneumococcal strains. Plasma HIV-1 load also correlated inversely with serum opsonic activity against these strains, and peripheral blood CD4+ lymphocyte numbers also tended to correlate with serum opsonic activity in asymptomatic HIV-1-infected adults. Our findings suggest that the opsonic activity of type-specific IgG is impaired in the serum of HIV-1-infected African adults, which may expose them to a serious risk of invasive pneumococcal infections.

A 14-member macrolide was found to inhibit interleukin-8 (IL-8) synthesis in lipopolysaccharide-stimulated neutrophils but did not accelerate apoptosis in activated neutrophils. These data suggest that 14-member macrolides achieve clinical efficacy for chronic airway diseases partly by suppressing IL-8 production by activated neutrophils, but not by enhancing apoptosis in these cells.

We investigated the efficacy of infection control measures against nosocomial pneumonia in geriatric wards. Cases with nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995. The study period was divided into four annual periods (periods 1, 2, 3 and 4). Period 1, January to December 1991, was applied as the cotrol. We investigated patients with nosocomial pneumonias in geriatric wards (190 beds) of AINO Memorial Hospital, affiliated with Nagasaki University. During the study period, nosocomial pneumonia significantly diminished. (period 1 vs periods 2, 3 and 4, p < 0.05, p < 0.05, p < 0.05, respectively). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa. During the four periods, a significant reduction in cases with MRSA- and P. aeruginosa-induced nosocomial pneumonia was observed (MRSA: period 1 vs periods 2, 3 and 4, p < 0.05, p < 0.05, p < 0.01, respectively; P. aeruginosa: period 1 vs period 3, p < 0.01, period 2 vs periods 3 and 4, p < 0.01, p < 0.05, respectively). On the other hand, the improvement of decubitus ulcers was associated with a significant reduction in nosocomial pneumonia (period 1 vs. periods 2 and 3, p < 0.05 and p < 0.05, respectively). In conclusion, stringent infection control programs, including a cleaning in the upper airways by povidone iodine, are necessary in geriatric wards to reduce and prevent nosocomial pneumonia.

Objectives (1) To investigate the efficacy of infection control measures against methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in geriatric wards. (2) To identify predisposing risk factors for MRSA bacteremia. Methods Cases with nosocomial bacteremias were retrospectively analyzed between January 1991 and March 1995. The study period was divided into four annual periods and the period 1, January to December 1991, was applied as the control. Materials We investigated patients with nosocomial bacteremias in geriatric wards (190 beds) of AINO Memorial Hospital, affiliated with Nagasaki University. Results A significant reduction in cases with MRSA-induced nosocomial bacteremia was observed after the introduction of a stringent infection control and prevention program (period 1 vs. periods 2, 3, and 4: p

CXCR4, a coreceptor for T cell (T)-tropic HIV-1, is preferentially expressed on naive T cells, whereas CCR5, a coreceptor for macrophage (M)-tropic HIV-1, is preferentially expressed on previously activated memory T cells and the Th1 subset of CD4+ T cells. CCR4 is preferentially expressed on the Th2 subset of CD4+ T cells. A cross-sectional flow cytometry study was conducted to evaluate the expression of CXCR4, CCR5, and CCR4 on the peripheral blood CD4+ T cells from African HIV-1-infected and uninfected Ugandan adults. The plasma viral load in HIV-1-infected individuals was also examined. Upregulation of CCR4 and CCR5 expression but no decrease in CXCR4 expression on CD4+ T cells were obtained in peripheral blood from African adults with progression of the disease. Plasma HIV-1 viremia significantly and inversely correlated with the peripheral CD4+ T cell count but did not correlate with the degree of CCR4 and CCR5 expression on the peripheral CD4+ T cells in HIV-1-infected individuals. Our present data suggest an increase in percentage of activated memory CD4+ T cells in the advanced stage of HIV-1 infection among African adults. There was no evidence of a Th1 to Th2 shift in terms of chemokine receptor expression profile with advancing disease in the peripheral blood of these subjects.

A 28-year-old woman with community-acquired pneumonia was treated with sulbactam/ampicillin and clarithromycin, but failed to show any improvement after 4 days. The antibiotic regimen was changed to pazufloxacin and rapid clinical improvement was seen. Mycoplasma pneumoniae was identified as the causative agent, and adenine (A) to guanine (G) mutation at position 2063 in domain V of the 23S rRNA was noted in the isolate. The minimum inhibitory concentration of macrolide antibiotics, including clarithromycin, of this isolate was greatly elevated.

We studied the clinical aspects of 25 patients (17 male, 8 female, median age 79.4 y.o.) whom MRSA was colonized in sputum from 1989 January to 1994 December. Main underlying diseases were 16 chronic bronchitis and 15 Cerebrovascular damage. Nineteen cases (76%) had catheters, for example 15 urinary tract catheters and 8 nasogastric tube. Twenty-two cases (88%) used previous antimicrobial agent. Fifteen cases (60%) were dead during previous period, and that 14 cases were dead because of respiratory failure within a year after MRSA was colonized in sputum. Nine cases (36%) were able to remove MRSA in sputum, but mortality rate was not different whether MRSA disappear or continue, MIC50 against MRSA (19 strains) were minocycline 12.5 micrograms/ml, arbekacin 6.25 micrograms/ml, vancomycin 0.78 microgram/ml and 16 cases (84.2%) were coagulase type II.

In the early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in our geriatric wards, including 190 beds, MRSA infection was prevalent. In the early 1980's in our geriatric wards minocycline was one of the most sensitive antibiotics to MRSA isolated in our wards and used frequently against MRSA pneumonias and bacteremia. In the late 1980's resistant strains of MRSA to minocycline rapidly increased because vancomycin was not allowed to introduced for treatment of MRSA before 1991 in Japan. At the same period the predominant coagulase type changed from type II to type VII. To decrease minocycline-resistant strains to MRSA after 1987, use of minocycline was limited. Moreover since Oct. 1991 to decrease nosocomial infections some active preventive measures against hospital infection, including limited use of 2nd and 3rd cephems, were taken. In this study changing patterns of coagulase type of Staphylococcus aureus were discussed. At least 4 years was needed to find out that the predominant coagulase type changed from type VII to type II again in 1991. In this study about 22 antimicrobial agents MICs of 313 strains of Staphylococcus aureus isolated between March 1992 and June 1993 were determined and compared with the data of MICs before introduction of preventive measures. The pattern of susceptibility to MINO was in part improved. Thus the some sensitive strains of S. aureus were observed again in our geriatric wards. Interestingly indeed it took approximately 5 years to find out the emergence of sensitive strains to MINO since limitation of use of MINO in 1987.

BackgroundInfluenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting.MethodsA prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records.ResultsBetween December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures.ConclusionThe test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.

We studied the clinical aspects of 18 patients from whom MRSA was detected from the stool and compared with 9 enterocolitis cases (7 male, 2 female, median age 72.4 y.o.) with 9 colonization cases (5 male, 4 female, median age 70.2 y.o.) from 1991 June to 1995 May. Cases of postoperative, use of anti-peptic ulcer drugs and administration of antibiotics for enterocolitis were more than that of colonization. On the other hand, eatable patients in the colonization group who could take food orally were more in number. Many patients of both enterocolitis and colonization were colonized in the respiratory tract. Drug sensitivity of MRSA in both cases were almost the same and the coagulase type were all that of II. Three courses on how MRSA enterocolitis occurs is considered. At first, colonization in the respiratory tract, second, proliferation of MRSA in the higher pH gastric juices as a result of gastrectomy or use of anti-peptic ulcer drugs, and third, selection of MRSA after administration of antibiotics.

In early 1980's methicillin-resistant Staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the A geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. After introduction of preventive measures of hospital infection in geriatric ward (190 beds) nosocomial bacteremia and pneumonia were markedly decreased in comparison to the episode number before introduction of prevention. However several patients with MRSA colonization were observed every month. The aim of this clinical study was to clear how frequent MRSA was isolated from the gastric juice and stool. Any MRSA was not observed in 63 cultured stool, but just one MRSA was isolated in patients with MRSA colonization. On the other hand gram-negative organisms, which were E. coli, P. aeruginosa, P. mirabilis etc., were frequently observed in cultured stool. In conclusion, we considered frequency of MRSA colonization in gastrointestinal space was not so high but rather very low.

In this clinical study we tried to find out the clinical significance of positive blood cultures between Jan. 1984 and Dec. 1989 in the Nagasaki Rosai Hospital. In this period the association between the isolated bacteria from blood cultures (398 specimens: 17.9%) and clinical background were evaluated. Each year the positive cultures were seen in about 18-20%. The distribution of bacteria showed increase percentage of the gram-positive organisms such as coagulase-negative Staphylococcus. Gram-negative organisms in included P. aeruginosa, A. calcoaceticus and E. coli. A. calcoaceticus was frequently found from the dept. of neurosurgery. Fungus, mostly Candida, was isolated in about 10-20%. The specimens were provided from department of internal medicine (62.9%) and neurosurgery (22.8%). An analysis of 213 episodes of 188 bacteremic cases was made. The onset of bacteremia had two peaks, 24 h or 1 month, after admission. The primary infected sites were the urinary tract (26.7%), respiratory system (14.5%) and central nervous system (6.1%). The central venous catheter was an important infected site. The major underlying diseases included acute cerebrovascular diseases, cardiac failure due to valvular heart diseases or acute myocardial infarction and/or iatrogenic immunocompromised state. The major complications were disseminated intravascular coagulation (DIC) (24.4%) and multiple organ failure (MOF) (8.9%). Half of the DIC episodes was caused by gram-positive cocci such as CNS, E. faecalis and MRSA. 68.4% of MOF episodes was associated with gram-negative bacteria. While the remainder was caused by gram-positive cocci including CNS and MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)

A 38-year-old male with Kartagener's syndrome (KS) was admitted to our department for evaluation of recurrent pneumonia. Before admission the patient was diagnosed as having pneumonia in another hospital and received ofloxacin (300 mg/day). Fever and production of purulent sputum decreased initially but again increased in the middle of April. On admission the films of both X-ray and CT scan of the chest revealed several air-fluid levels and infiltrative shadows on the left lower lung field. The patient was diagnosed as lung abscess using bronchofiberscopy. Gram staining of the intrabronchial specimens revealed many Gram-positive cocci and neutrophils including phagocytosed bacteria. A new carbapenem (L-627, 600 mg/day), was started intravenously. After the therapy Streptococcus pneumoniae were eradicated soon from the sputum. At the same time the above symptoms including dyspnea on exertion subsided, and the findings of the chest X-ray and CT scan were also improved. Regarding KS the electron micrograph of the cilia showed the absence of the outer-dynein arms. While by both the saccharin test and the sputum cytology impaired mucociliary clearance was found. Lung abscess infrequently accompany KS. There are reports of respiratory infections in KS, but to our knowledge no report of lung abscess was found in KS. We present this case report describing lung abscess in KS.

A 67-year-old woman, suffering from continuous hemoptysis, was admitted to our hospital where she was managed with mechanical ventilation. Computed tomography of the chest demonstrated bilateral massive alveolar hemorrhage without evidence of infectious disease. She was diagnosed with anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated diffuse alveolar hemorrhage because a high titer of MPO-ANCA was found in the serum. Plasmapheresis as well as methylprednisolone pulse therapy were initiated, followed by intravenous administration of cyclophosphamide. Tacrolimus was employed for the maintenance therapy, and the oral prednisolone dosage could successfully be tapered without recurrence, along with the decrement of the titer of MPO-ANCA.

We investigated the efficacy of disinfection of the upper airway using povidone-iodine against nosocomial pneumonia in geriatric wards. Cases of nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995 in geriatric wards (190 beds). Moreover, the relationship concerning methicillin-resistant Staphylococcus aureus (MRSA) isolates between patient and environment was investigated using pulsed-field gel electrophoresis (PFGE) with the SmaI restriction enzyme. The incidence of nosocomial pneumonia decreased significantly (p < 0.05). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa, which significantly decreased. PFGE studies showed that the patterns of MRSA isolates show a strong association between patient and environment. Our study indicates that disinfection of the upper airways by povidone-iodine is very important in the prevention of nosocomial pneumonia in geriatric wards.

Exercise or acute stress can exert significant effects on immune system as well as cardiovascular and respiratory systems through catecholamines. In this study, we investigated effects of norepinephrine (NE), a catecholamine neurotransmitter on human immunodeficiency virus type-1 (HIV-1) infection. NE inhibited in vitro HIV-1 infection of peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo HIV-1 replication in patients' PBMC. In transient expression assays, NE downregulated HIV-1 long terminal repeat, but site-directed mutagenesis on NF-kappaB-binding sites or cotreatment with H89 (a protein kinase A inhibitor) abrogated the NE-mediated effect. Gel-shift assays showed suppression of NF-kappaB activity in NE-treated cells. NE increased cytoplasmic levels of IkappaB-alpha, a natural inhibitor of NF-kappaB. Thus, NE apparently inhibits HIV-1 infection, at least in part through NF-kappaB inactivation.

An inflammation of the airway of patients with diffuse panbronchiolitis (DPB), is characterized by dense neutrophil infiltration. Resolution of the inflammation can be achieved by the removal of apoptotic neutrophils by human alveolar macrophages (AM) without liberating neutrophil proteases in the airway. To understand clinical efficacy for the treatment of DPB by 14- or 15-member macrolides, their effects on the phagocytosis of apoptotic neutrophils by AM were examined. Treatment of AM with erythromycin (ERY) or clarithromycin at clinically achievable levels significantly increased the levels of phagocytosis of apoptotic neutrophils. A serum factor was not essential for the enhancement by these 14-member macrolides. Of the antibiotics tested, these effects were specific for the 14-member macrolides and a 15-member macrolide, azithromycin, but not for the 16-member macrolides, clindamycin or β-lactam antibiotics. The enhanced phagocytosis of apoptotic neutrophils by ERY had no effect on the levels of interleukin-8 or tumor necrosis factor alpha production by lipopolysaccharide-stimulated AM after phagocytosis of the apoptotic neutrophils. The increased phagocytosis of apoptotic neutrophils by ERY was also found to be phosphatidylserine receptor-dependent for AM. These data indicate a novel anti-inflammatory action of 14-member and 15-member macrolides, and suggest that such antibiotics achieve clinical efficacy for patients with DPB, in part, through enhancing the nonphlogistic phagocytosis of apoptotic neutrophils by AM.

Hepatocyte growth factor (HGF) is postulated to play an important role in the repair of pulmonary epithelium in acute lung injury. To evaluate the role of HGF in bacterial pneumonia, the kinetics of HGF production and the cellular sources of HGF have been examined in the lungs of mice that had been intratracheally challenged with Pseudomonas aeruginosa . Neutrophil accumulation in the airway occurred immediately, reached a peak at 36 h, and then progressively declined by 14 d after infection. We found a biphasic pattern of HGF messenger RNA expression and protein synthesis in the lung after bacterial infection. The first peak for HGF production was found at 6 h after infection, and the primary source of HGF was shown to be bronchial epithelial cells. Interestingly, the second peak for HGF production, which was found around 48 to 72 h after infection, was closely associated with the increase in the percentage of alveolar macrophages (AMs) that became positive for myeloperoxidase, indicating phagocytosis of apoptotic neutrophils. The cellular source of the second peak was found to be AMs. Further, murine AMs which phagocytosed apoptotic neutrophils induced higher levels of HGF production in vitro . These results strongly indicate a novel mechanism of HGF production by AMs, which are phagocytosing apoptotic neutrophils, and the pivotal role of AMs in the healing and repair of damaged pulmonary epithelium through the production of HGF.

In the early 1980's methicillin-resistant staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the A geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. About a year before introduction of prevention of hospital infection in the geriatric ward (190 beds) of A hospital 193 episodes of nosocomial bacteremia were observed. However a year after introduction of preventive measures episodes of nosocomial bacteremia were decreased to less than a half (45.6%) in comparison to the number before introduction of prevention. As a causative organism gram-positive bacteria including MRSA were markedly decreased. Major portals of entry of bacteremia (74.9%) were urinary-tract system, intravenous hyperalimentation (IVH) catheter, and pressure sores. MRSA-positive pressure sores were decreased to 20.4% of those before prevention. On the other hand 87 episodes of nosocomial pneumonia were observed before prevention. However a year after introduction of preventive measures episodes of nosocomial pneumonia were decreased to less than a half (44.8%) in comparison to the number before introduction of prevention. After prevention MRSA and mixed infection of P. aeruginosa and MRSA were markedly decreased. The decrease of bacteremia and nosocomial pneumonia were caused by cleaning hands, the preventive measures for decrease and improvement of pressure sores, cleaning the upper respiratory tract for prevention of lower respiratory-tract infection cleaning floors and education of the staff, etc.