山口 泰弘

AIM: Older adults at the end-of-life stage receiving home visits from physicians often experience symptoms such as dyspnea, pain and fatigue, among others. This study aimed to investigate the practices and opinions of physicians providing home visits regarding palliative care for older adults with respiratory symptoms due to non-malignant diseases in Japan. METHODS: A nationwide questionnaire survey on home palliative care for non-cancer chronic respiratory diseases was sent to 2988 home-care physicians in 2020 through postal mail and/or email. The questions focused on their background, their use of rating scales to evaluate the intensity of dyspnea, and their practices and opinions regarding home palliative care for respiratory diseases or symptoms. RESULTS: Valid responses were collected from 592 physicians (19.8%). A total of 251 participants (43.1%) used a rating scale to evaluate the intensity of dyspnea. While 87.8%, 86.6%, 67.3%, and 60.0% of physicians considered pulmonary rehabilitation, morphine, sedative medications, and non-invasive positive pressure ventilation (NPPV), respectively, as effective in relieving respiratory distress, 73.0%, 66.9%, 57.3%, and 55.2% of those physicians, respectively, used each modality to relieve respiratory distress. Frequently involved physicians in the aforementioned care prescribed morphine or sedative medications and used NPPV more frequently. CONCLUSIONS: This study found a discrepancy between the proportion of physicians who considered palliative care as effective and those who prescribed it. Geriatr Gerontol Int 2022; 22: 943-949.

BACKGROUND: We developed a novel training program for health care professionals that incorporated shared decision making (SDM) skills training into an advance care planning (ACP) training course, the first in Japan. This study aimed to assess the training program's impact on health care professionals' knowledge, skill, attitudes, and confidence to initiate ACP. METHODS: Using the novel Japanese educational program, we evaluated the effect of 8-month programs conducted eight community training sites of professionals who can practice ACP in a local area in Aichi Prefecture (the Aichi ACP Project). SDM skills training was provided during the workshops conducted in the ACP training course, and the participants' satisfaction and understanding of the training were assessed. After the completion of two workshops, information on SDM skill results from the training and submitted assignments were collected anonymously from the training sites. RESULT: A total of 404 participants completed all education programs. After the first workshop, at least 95% of trainees stated that they were satisfied with the training and that it was useful for ACP practice. The evaluation of the results between the first and second workshops indicated improvement in SDM skills on some items of the SDM measures. In the second workshop, at least 90% of participants submitted implementation reports, and after the second workshop, a survey of confidence in ACP practice was administered, with responses indicating improvement. There were high levels of interest in education related to the ACP practices of oneself and others. CONCLUSIONS: This educational program can be an effective for developing professionals who can practice ACP with SDM skills.

PURPOSE: Severe cardiac dysfunction can manifest with diurnal breathing irregularity. However, it remains to be clarified whether or not diurnal breathing irregularity is observed in patients with heart diseases, including relatively mild chronic heart failure (CHF), compared to those without heart diseases. METHODS: In this cross-sectional study, consecutive inpatients who were admitted for evaluation of sleep-disordered breathing were enrolled. We extracted 3.5 min of stable respiratory signals before sleep onset using polysomnography, analyzed the airflow data using fast Fourier transform, and quantified breathing irregularities using Shannon entropy S. RESULTS: A total of 162 subjects were evaluated. Among these, 39 subjects had heart diseases, including ischemic heart disease (IHD), atrial fibrillation (Af), CHF, and a history of aortic dissection. The values of Shannon entropy S of airflow signals in subjects with heart diseases were significantly higher than in those without heart diseases (p < 0.001). After excluding CHF, the Shannon entropy S was also significantly higher in subjects with heart diseases than in those without heart diseases (p < 0.001). The values of Shannon entropy S were significantly correlated with plasma brain natriuretic peptide levels (r = 0.443, p < 0.001). Although the values were also significantly correlated with body mass index, the presence of heart diseases was independently associated with breathing irregularity in the multiple logistic analysis. Matching analysis revealed consistent differences between subjects with heart diseases and without heart diseases. CONCLUSION: Breathing irregularity was observed before sleep onset in subjects with heart diseases who underwent polysomnography to diagnose sleep-disordered breathing.

A previous pooled analysis demonstrated significant relief of breathlessness following opioid administration in patients with chronic obstructive pulmonary disease. However, in clinical practice, it is important to know the characteristics of patients responding to opioids, the best prescription methods, and the evaluation measures that can sufficiently reflect these effects. Thus, we performed a systematic review of systemic opioids for non-cancer chronic respiratory diseases. Fifteen randomized controlled studies (RCTs), four non-randomized studies, two observational studies, and five retrospective studies were included. Recent RCTs suggested that regular oral opioid use would decrease the worst breathlessness in patients with a modified Medical Research Council score ≥ 3 by a degree of 1.0 or less on a scale of 1-10. Ergometer or treadmill tests indicated mostly consistent significant acute effects of morphine or codeine. In two non-randomized studies, about 60% of patients responded to opioids and showed definite improvement in symptoms and quality of life. Furthermore, titration of opioids in these studies suggested that a major proportion of these responders had benefits after administration of approximately 10 mg/day of morphine. However, more studies are needed to clarify the prescription method to reduce withdrawal due to adverse effects, which would lead to significant improvements in overall well-being.

A 70-year-old woman with bilateral pleural effusion and respiratory failure was admitted to our hospital. Nephrotic syndrome due to minimal change disease had been diagnosed four months before admission. Because blood tests and a pleural fluid analysis did not reveal the etiology of her condition, we performed a video-assisted thoracoscopic pleural biopsy. No specific thoracoscopic findings were noted. The pathological findings revealed an increase in immunoglobulin G4 (IgG4)-positive cells; IgG4-related pleuritis was diagnosed. Her pleuritis improved with oral corticosteroid therapy. A further investigation was performed on previous kidney samples; however, the etiology of the nephrotic syndrome was not IgG4-related disease but minimal change disease.

BACKGROUND: Poor oral health conditions are known to affect frailty in the older adults. Diabetes is a risk factor for both poor oral health and frailty, therefore, oral health status may affect frailty in diabetic patients more than in the general population. The purpose of this study was to evaluate the influence of oral health and other factors on frailty and the relationship among oral health, diabetes and frailty in older adult patients with type 2 diabetes. METHODS: Patients with type 2 diabetes aged 75 years or older were included in this cross-sectional study. Eligible patients were surveyed by questionnaire for frailty, oral health status, and cognitive and living functions. Factors influencing pre-frailty, frailty, and individual frailty screening index (FSI) classes were evaluated. RESULTS: Of the 111 patients analyzed, 66 cases (59.5%) were categorized as robust, 33 cases (29.7%) as pre-frailty, and 12 cases (10.8%) as frailty. The oral frailty index, the cognitive and living functions score, and BMI were found to be factors influencing pre-frailty or frailty. In the evaluation of individual FSI classes, BMI had an influence on those with a FSI ≤2. The cognitive and living functions score was a factor influencing those with FSI ≤3. The oral frailty index was found to have a significant influence on all FSI classes. CONCLUSIONS: Poor oral health has an influence on frailty in patients with type 2 diabetes aged ≥75. In this patient population, as frailty progresses, the impact of oral health on frailty may increase. TRIAL REGISTRATION: This study was retrospectively registered in UMIN-CTR ( UMIN000044227 ).

BACKGROUND: In Japan, the number of older people with various health problems and difficulties in living is increasing. In order to practice patient-centered care for them, not only medical professionals but also multidisciplinary teams including care professionals and patients need to practice shared decision making (SDM) in the context of long-term care. For this reason, a measure of SDM in consultations with healthcare professionals (HCPs) other than physicians is needed. Therefore, this study aimed at adapting the patient and physician versions of the 9-item Shared Decision Making Questionnaire (SDM-Q-9, SDM-Q-Doc) for consultations with HCPs other than physicians in Japan. METHODS: A pair of SDM measures that can be used by HCPs other than physicians, "Care SDM-Questionnaire for care receivers (SDM-C-patient)" and "Care SDM-Questionnaire for care providers (SDM-C-provider)" were prepared based on the Japanese versions of the SDM-Q-9 and SDM-Q-Doc. The internal consistency and conceptual structure of these measures were tested by secondary analysis of data from 496 participants from a workshop on SDM for different HCPs. Measurement invariance were tested by multigroup confirmatory factor analysis (CFA) for the patient (SDM-C-patient and SDM-Q-9) and provider (SDM-C-provider vs. SDM-Q-Doc) versions. RESULTS: Both the Japanese SDM-C-patient and SDM-C-provider demonstrated high internal consistencies (Cronbach's α coefficient was 0.90 and McDonald's ω coefficient was 0.90 for both measures). CFA showed one-factor structures for both measures and original measures for physicians. Moreover, multigroup CFA showed configural and metric invariance between the novel care measures and original physician's measures. CONCLUSIONS: Thus, the novel SDM measures for care providers in Japan as well as the original physician's measures could be used in training setting. As these measures were tested only in a training setting, their reliability and validity as new measures for care should be tested in a clinical setting in future.

Immunoglobulin G4 (IgG4)-related disease is established as a new clinical entity, characterized by high levels of plasma IgG4 and IgG4-positive plasma cell infiltration. However, the elevation of plasma IgG4 and infiltration of IgG4-positive cells have been observed in other diseases, including malignancy. We experienced a case of prominent IgG4-positive lymphadenopathy, which was diagnosed as a reactive lesion in response to lung cancer. The cancerous lesion was so small in size that it was difficult to reveal the coexisting lung cancer. Surgical lymph node biopsy and endobronchial ultrasound-guided transbronchial needle aspiration did not reveal lymph node metastasis of cancer. Mediastinal lymph node dissection finally revealed it. After the right upper lobectomy, the patient underwent postoperative chemotherapy and remains cancer-free after 1 year. Our case suggests that close examination and careful follow-up are necessary when IgG4-positive lymphadenopathy is observed.

Lung cancers with anaplastic lymphoma kinase (ALK) rearrangements are highly sensitive to treatment with ALK tyrosine kinase inhibitors (TKIs). Due to the very low rate of patients with squamous cell carcinoma enrolled in clinical trials, the efficacy of ALK inhibitors in patients with ALK-rearranged squamous cell carcinoma in the lung remains unclear. Herein, we present the case of a 70-year-old female patient with squamous cell lung cancer harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. The patient was treated with the ALK-TKI alectinib as first-line regimen and achieved a dramatic response without severe adverse events, demonstrating alectinib as a therapeutic option for patients with ALK-positive squamous cell carcinoma.

A 52-year-old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death-ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration.

In 2020, the COVID-19 pandemic has had unprecedented impacts on various aspects of the world. Each academic society has published a guide and/or guidelines on how to cope with COVID-19 separately. As the one and only nationwide association of academic societies that represent medical science in Japan, JMSF has decided to publish the expert opinion to help patients and care providers find specifically what they want. This expert opinion is a summary of recommendations by many academic societies and will be updated when necessary. Patients that each academic society targets differ even though they suffer from the same COVID-19, and recommendations can be different in a context-dependent manner. Readers are supposed to be flexible and adjustable when they use this expert opinion.

Since the end of 2019, a life-threatening infectious disease (coronavirus disease 2019: COVID-19) has spread globally, and numerous victims have been reported. In particular, older persons tend to suffer more severely when infected with a novel coronavirus (SARS-CoV-2) and have higher case mortality rates; additionally, outbreaks frequently occur in hospitals and long-term care facilities where most of the residents are older persons. Unfortunately, it has been stated that the COVID-19 pandemic has caused a medical collapse in some countries, resulting in the depletion of medical resources, such as ventilators, and triage based on chronological age. Furthermore, as some COVID-19 cases show a rapid deterioration of clinical symptoms and accordingly, the medical and long-term care staff cannot always confirm the patient's values and wishes in time, we are very concerned as to whether older patients are receiving the medical and long-term care services that they wish for. It was once again recognized that it is vital to implement advance care planning as early as possible before suffering from COVID-19. To this end, in August 2020, the Japan Geriatrics Society announced ethical recommendations for medical and long-term care for older persons and emphasized the importance of conducting advance care planning at earlier stages. Geriatr Gerontol Int 2020; 20: 1112-1119.

Cryptogenic organizing pneumonia (COP) usually responds well to steroid therapy; however, recurrence is commonly observed when the steroid dose is tapered. A 74-year-old man suspected of having steroid-resistant COP presented to our hospital. Chest computed tomography (CT) revealed new consolidations of the left inferior lobe despite administration of a moderate dose of oral steroids. Repeated transbronchial lung biopsy showed pulmonary cryptococcosis. The left interior consolidations shrank gradually after antifungal therapy was initiated. Immunocompromised patients with pulmonary cryptococcosis show various CT findings, and consolidation is frequently observed. Superimposed pulmonary cryptococcosis infection should be considered in cases of steroid-refractory COP.

Chronic obstructive pulmonary disease (COPD) often accompanies type 2 diabetes mellitus (T2DM). However, background factors affecting these diseases in the elderly remain unclear. Eligible patients with T2DM were divided into two age groups-non-elderly (<65 years) and elderly (≥65 years); COPD, ratio of forced expiratory volume in one second to forced expiratory volume (FEV1/FVC ratio), and percent predicted forced expiratory volume in one second (FEV1% predicted) were examined, and factors related to reduced respiratory function according to age group were evaluated. In total, 371 patients with T2DM were analysed. COPD was found in 9 patients (5.3%) in the non-elderly group and 45 (22.5%) in the elderly group. In the elderly, male sex, low body mass index (BMI), insulin therapy, and high C-peptide immunoreactivity levels were factors related to COPD. In the non-elderly, age, female sex, high BMI were factors related to decreased FEV1% predicted. Female sex was factor related to decreased FEV1% predicted in both age groups. Low BMI was a factor related to reduced respiratory function in elderly patients and high BMI was a factor related to reduced respiratory function in non-elderly patients. Thus, BMI needs to be managed according to the age and general condition of T2DM patients.

PURPOSE: In patients with overlap syndrome (OVS), the pathophysiologies of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease can interact with one another. Focusing on low arousal threshold, the authors evaluated polysomnographic features of OVS patients. METHODS: This retrospective, multicenter study was conducted at three hospitals in Japan. Patients aged ≥ 60 years who underwent polysomnography and pulmonary function testing were reviewed. Severity of airflow limitation (AFL) was classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Low arousal threshold was predicted based on the following polysomnography features: lower apnea-hypopnea index (AHI); higher nadir oxygen saturation, and larger hypopnea fraction of total respiratory events. These features were compared among patients with only OSA (n = 126), OVS with mild AFL (n = 16), and OVS with moderate/severe AFL (n = 22). RESULTS: A low arousal threshold was more frequently exhibited by OVS patients with moderate/severe AFL than by those with OSA only (p = 0.016) and OVS with mild AFL (p = 0.026). As forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) decreased in OVS patients, the mean length of apnea decreased (r = 0.388, p = 0.016), hypopnea fractions increased (r = - 0.337, p = 0.039), and AHI decreased (r = 0.424, p = 0.008). FEV1/FVC contributed to low arousal threshold independent of age, sex, smoking history, hospital, or body mass index in all subjects (OR 0.946 [95% CI 0.909-0.984]) and in OVS patients (OR 0.799 [95% CI 0.679-0.940]). CONCLUSIONS: This study first described peculiar polysomnographic features in OVS patients with moderate/severe AFL, suggesting a high prevalence of low arousal threshold.

We report the case of an 82-year-old woman who developed pneumothorax during treatment for nontuberculous mycobacterium (NTM). In year X, she was diagnosed with NTM at another hospital after abnormalities were pointed out on a chest X-ray. She received no treatment for NTM at that time. Antibiotic treatment was introduced at the department of respiratory medicine in our hospital in year X+15. The regimen was composed of clarithromycin (800 mg/day), ethambutol (750 mg/day) and rifampicin (600 mg/day) however, treatment with the three-drug antibiotic regimen was canceled at her request and changed to erythromycin. She was then referred to our department. However, right-side cavity wall thickening was detected on chest CT in year X+17. We resumed clarithromycin (600 mg/day), ethambutol (750 mg/day) and rifampicin (450 mg/day). On the 43rd day after treatment with three types of antibiotics, she felt dyspnea and she was admitted to the hospital and was diagnosed with right-side pneumothorax. The pneumothorax was thought to have been caused by a break in the adhesion of the cavity wall. The visceral pleura was weakened by the exacerbation of NTM and the thickness of the cavity wall was improved after the resumption of antibiotic therapy. This report is considered to be an important case in which pneumothorax developed as a complication in an elderly patient during treatment for NTM.

Vitamin D insufficiency is increasingly recognized as a prevalent problem worldwide, especially in patients with a chronic lung disease. Chronic obstructive pulmonary disease (COPD) is a type of chronic inflammatory lung disease. Previous clinical studies have shown that COPD leads to low vitamin D levels, which further increase the severity of COPD. Vitamin D homeostasis represents one of the most important factors that potentially determine the severity of COPD. Nonetheless, the mechanisms underlying the anti-inflammatory effects of vitamin D receptor (VDR) in lung tissues are still unclear. To investigate the anti-inflammatory effects of VDR, we generated transgenic mice that show lung-specific VDR overexpression under the control of the surfactant protein C promoter (TG mice). The TG mice were used to study the expression patterns of proinflammatory cytokines using real-time polymerase chain reaction and immunohistochemistry. The TG mice had lower levels of T helper 1 (Th1)-related cytokines than wild-type (WT) mice did. No significant differences in the expression of Th2 cytokines were observed between TG and WT mice. This study is the first to achieve lung-specific overexpression of VDR in TG mice: an interesting animal model useful for studying the relation between airway cell inflammation and vitamin D signaling. VDR expression is an important factor that influences anti-inflammatory responses in lung tissues. Our results show the crucial role of VDR in anti-inflammatory effects in lungs; these data are potentially useful for the treatment or prevention of COPD.

AIM: To promote advance directives, it is crucial to understand how many older persons have wishes related to end-of-life care. Additionally, it is important to understand how cognitive function or mood affect these wishes. METHODS: For the interview-based survey, 99 inpatients aged 75 years or older were enrolled after excluding patients with a Mini-Mental State Examination score of 20 or less. For the questionnaire-based survey, 99 outpatients aged 75 years or older without dementia were enrolled. Both surveys comprised the same items on older patients' wishes related to artificial nutrition and hydration (ANH) during end-of-life care. RESULTS: Of the total enrolled patients, 76.8% participated in the interviews. Of these, 50.0% were against ANH during their end-of-life care, including the patients who were definitely against ANH (26.3%). In contrast, just 5.3% wished to receive ANH. In the questionnaire survey, 65.6% of the respondents were against ANH, and 4.9% wished to receive ANH. Aging and Mini-Mental State Examination scores of less than 24 were significantly associated with a higher tendency to decline from participating in the interview. However, the distribution of the interview answers was not associated with age, Mini-Mental State Examination or Geriatric Depression Scale scores. Of the interviewed patients, 84.2% agreed to their responses being preserved in their medical records. CONCLUSIONS: Although the majority of the elderly patients were against ANH during end-of-life care, many patients did not have definite wishes in Japan. The percentage of those who were against ANH was not associated with cognitive function or depressive state. Geriatr Gerontol Int 2016; 16: 1204-1210.

BACKGROUND/AIM: Defensins comprise a family of mammalian cationic antimicrobial peptides. We investigated the anticancer effects of human β-defensin-3 (hBD3) and its mouse homolog, Defb14, on lung cancer cells. MATERIALS AND METHODS: We stained lung cancer cells cultured after treatment with the defensin peptide using propidium iodide and Hoechst 33342. In vivo, Defb14 peptide or vehicle was continuously infused near subcutaneous Lewis lung carcinoma cell tumor in mice. After 9-day infusion, the weights of excised tumors were determined. RESULTS: A 10-min treatment with hBD3 (70 μg/ml) induced propidium iodide uptake in lung cancer cells. The anticancer activity of hBD3 was significantly more potent than the activity of other defensin isoforms. Continuous infusion of Defb14 peptide showed significant tumor-growth suppression in Lewis lung carcinoma cells in mice. CONCLUSION: Our study demonstrated the suppression of tumor growth by Defb14 peptide in an animal model.

PURPOSE: We investigated the relationships among nocturnal polyuria, sleep apnea and body fluid volume to elucidate the pathophysiology of nocturia in sleep apnea syndrome. MATERIALS AND METHODS: We enrolled 104 consecutive patients who underwent polysomnography for suspected sleep apnea syndrome. Self-assessed symptom questionnaires were administered to evaluate sleep disorder and lower urinary tract symptoms, including nocturia. Voiding frequency and voided volume were recorded using a 24-hour frequency-volume chart. Body fluid composition was estimated in the morning and at night using bioelectric impedance analysis. Frequency-volume chart data were analyzed in 22 patients after continuous positive airway pressure therapy. RESULTS: Patients with nocturnal polyuria showed a higher apnea-hypopnea index (33.9 vs 24.2, p = 0.03) and a larger circadian change in extracellular fluid adjusted to lean body mass (0.22 vs -0.19, p = 0.019) than those without nocturnal polyuria. These relations were more evident in patients 65 years old or older than in those 64 years or younger. A multivariate linear regression model showed an independent relationship of nocturnal polyuria with the apnea-hypopnea index and the circadian change in extracellular fluid adjusted to lean body mass (p = 0.0012 and 0.022, respectively). Continuous positive airway pressure therapy significantly improved nocturnal polyuria and nocturia only in patients with nocturnal polyuria. CONCLUSIONS: This study identified sleep apnea and the circadian change in extracellular fluid as independent factors for nocturnal polyuria.

BACKGROUND: Some patients with obstructive sleep apnea syndrome remove the CPAP device during sleep, although they start CPAP at bedtime. We hypothesized that body position changes and oxygen desaturations may be associated with patient removal of the CPAP device. METHODS: We consecutively enrolled 36 poor CPAP adherers and 25 good CPAP adherers. Body positions and oxygen desaturations were evaluated when these subjects used CPAP during sleep for 2 nights, permitting the removal of the CPAP device during the recording. RESULTS: Twelve poor CPAP adherers exhibited subject removal of the CPAP device within 4 h from the start of body position recording. The frequency of body position changes was significantly higher within 15 min before the CPAP removal than during other periods when CPAP was used. At the same time, oxygen desaturations were significantly more frequent within 15 min before CPAP removal than during other periods when CPAP was used. In addition, the majority (66.7%) of the CPAP removal events were followed by a change from a supine position to a non-supine position within 5 min. The number of body position changes during the first 4-h recording was significantly higher in the poor CPAP adherers who had removed their CPAP device compared with the poor CPAP adherers who had not removed their device. However, the number of body position changes or oxygen desaturation index under CPAP during the first 4-h recording was not significantly different between the poor CPAP adherers and good CPAP adherers. CONCLUSIONS: Our findings are the first to indicate associations among CPAP removal, body position changes, and oxygen desaturations during sleep in poor CPAP adherers. However, our findings also indicated that most good CPAP adherers make frequent body position changes without removal of CPAP device, suggesting that patients can adapt to the discomfort of CPAP therapy at the time of body position changes.

OBJECTIVES: Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD). DLB is characterised by intracytoplasmic inclusions called Lewy bodies that are often seen in the brainstem. Because modulation of the respiratory rhythm is one of the most important functions of the brainstem, patients with DLB may exhibit dysrhythmic breathing. This hypothesis has not yet been systematically studied. Therefore, we evaluated the association between DLB and dysrhythmic breathing. DESIGN: In this cross-sectional study consecutive inpatients who were admitted for the evaluation of progressive cognitive impairment were enrolled. We assessed breathing irregularity using polysomnographic recordings on bed rest with closed eyes, without reference to the clinical differentiation among DLB, AD and having no dementia. SETTING: Single centre in Japan. PARTICIPANTS: 14 patients with DLB , 21 with AD and 12 without dementia were enrolled in this study. PRIMARY OUTCOME MEASURES: The coefficient of variation (CV) of the breath-to-breath time was calculated. We also examined the amplitude spectrum A(f) obtained using the fast Fourier transform and Shannon entropy S of A(f) in patients with DLB compared with patients with AD and patients without dementia. RESULTS: The values of CV and entropy S were significantly higher in patients with DLB than in patients with AD and patients without dementia. No significant differences were observed between patients with AD and patients without dementia. CONCLUSIONS: Patients with DLB exhibit dysrhythmic breathing compared with patients with AD and patients without dementia. Dysrhythmic breathing is a new clinical feature of DLB and the spectral analysis of breathing patterns can be clinically useful for the diagnostic differentiation of DLB from AD.

Acute exogenous lipoid pneumonia is an uncommon condition caused by aspiration of oil-based substances, occurring mainly in children. Here, we report the case of an 83-year-old patient with Alzheimer's disease who presented with coughing and hypoxia. The diagnosis of acute exogenous lipoid pneumonia caused by accidental kerosene ingestion was made on the basis of the patient's clinical history, and typical radiological and cytological findings. The patient's cognitive impairment and an unsafe environment, in which the patient's 91-year-old husband stored kerosene in an old shochu bottle, were responsible for the accidental ingestion. Acute exogenous lipoid pneumonia should be considered in the differential diagnosis for acute respiratory disorders in the rapidly aging population.

BACKGROUND: Although dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD), the clinical diagnosis is frequently difficult. Because both REM sleep behavior disorders and Parkinson's disease also have alpha-synucleinopathy similar to DLB, and show an increase in periodic limb movements (PLM), we evaluated the association between DLB and PLM, which may serve as an additional information to differentiate AD and DLB. METHODS: Overnight polysomnographic recordings were performed for the inpatients in our hospital who were suspected to have dementia. The quality of sleep, oxygen-desaturation index and periodic limb movements were compared among the patients clinically diagnosed with DLB, AD or as having no dementia. RESULTS: Nine DLB patients, twelve AD patients and ten non-demented patients were enrolled in the study. The number of PLM during sleep per hour of total sleep time (PLMS index) was significantly higher in the DLB patients than the AD patients or the non-demented patients. No significant differences were found between the AD patients and the non-demented patients. To differentiate DLB from AD, a PLMS index of more than 15.0 had a sensitivity of 88.9% and a specificity of 83.3%. CONCLUSIONS: The DLB patients exhibited a higher PLMS index than the AD patients, and this index could be clinically useful for the diagnostic differentiation of DLB from AD.

Defensins comprise a family of cationic antimicrobial peptides containing a specific six-cysteine motif. Their contribution to the host defense against microbial invasion and the control of normal flora have been previously described. Some of the β-defensin isoforms are predominantly expressed in the epididymis and showed a region-specific expression pattern in the epididymis, which thus suggested that these isoforms may possess epididymis-specific functions in addition to antimicrobial activities. A sequence variant of the β-defensin 126 gene has been shown to be associated with reductions in the human sperm function, thus supporting this hypothesis. Furthermore, defensins have the capacity to chemoattract immune cells and induce the secretion of inflammatory cytokines. Mice expressing human neutrophil α-defensin showed more severe lung injuries after the aspiration of acidic contents than did control mice. Recent investigations regarding copy number variations of human defensin genes also suggest the significance of defensin in the pathogenesis or the worsening of chronic obstructive pulmonary diseases, sepsis and psoriasis.

Homozygous mutant klotho (KL(-/-)) mice exhibit various characteristics resembling those of human aging, including emphysema. However, age-related changes of lungs have not been fully elucidated. Here, we investigated the structural, functional, biochemical, and cell kinetic alterations of lungs in KL(-/-) mice at 2-12 weeks of age. Homogeneous airspace enlargement and decreased lung elastic recoil were observed in KL(-/-) mice with aging. The apoptotic cells in airway walls in KL(-/-) mice were approximately 6 times greater than those in wild-type (KL(+/+)) mice at 2 weeks of age. However, lipid peroxidation and elastase activity of lungs were not increased in KL(-/-) mice. Western blotting suggested that protein levels of epidermal growth factor (EGF) and phosphorylated extracellular signal-regulated kinase were decreased in KL(-/-) mice. These data suggest that significantly increased apoptosis of airway cells via inhibition of the EGF-dependent pathway may be involved in the development of the aging lungs in KL(-/-) mice.

We report an 82-year old man prescribed paroxetine who had hyponatremia and in whom the syndrome of inappropriate secretion of antidiuretic hormone was diagnosed. He had taken sulpiride for depressed mental status. However, he showed parkinsonism, which was an adverse effect from the treatment of sulpiride. Therefore sulpiride was changed to selective serotonin reuptake inhibitor, paroxetine 10mg daily. His depressed mental status deteriorated after paroxetine treatment started. His depression had not lessened after 12 days, and the dosage was increased to 20mg daily. On the 15th day after starting paroxetine, routine laboratory tests showed that his serum sodium level was 126 mEq/l. We recognized that his confusion and loss of appetite were symptoms of hyponatremia, rather than of worsening depression. Laboratory data revealed hyponatremia, low serum osmolarity (242 mOsm/kg) with a relatively high level of serum antidiuretic hormone, and concentrated urine (439 mOsm/kg). We diagnosed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), associated with paroxetine. The dosage of paroxetine was reduced gradually and the serum sodium level returned to normal on day 2 after medication ceased completely. Paroxetine produces fewer adverse effects than other types of antidepressants. However, its use can be associated with inappropriate secretion of antidiuretic hormone in the body and may lead to SIADH, which is characterized by hyponatremia, a potentially fatal condition that is typically asymptomatic until it becomes severe. SIADH is more likely in some populations, including the elderly. Serum sodium levels should be monitored closely, especially in elderly patients.

Background and purpose: Obstructive sleep apnea syndrome (OSAS) is recognized as one of the risk factors of hypertension and cardiovascular disorders. In the current study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating adrenomedullin (ADM) levels in untreated OSAS patients compared to an age-matched control group. We further hypothesized that oxygen administration treatment may decrease OSAS-induced hypoxic stress and ADM levels. Methods: We examined short-term and long-term oxygen administration effects on circulating ADM in 41 OSAS patients. Results: The circulating levels of ADM in untreated OSAS patients were significantly greater than those in the controls. We did not observe a significant effect inU:/AP/DTD501/SLEEP/896 2 weeks of oxygen administration on the circulating ADM in the patients, but we observed a significant effect in long-term oxygen administration for more than 3 months on plasma ADM levels. Long-term oxygen therapy decreased both the magnitude of arterial oxygen desaturation and plasma ADM levels in patients but did not decrease blood pressure. Conclusions: These observations suggest that long-term oxygen therapy could reduce OSAS-induced nocturnal hypoxemia and plasma ADM levels in patients with OSAS. (c) 2007 Elsevier B.V. All rights reserved.

We report a 77-year-old woman with Group B streptococcal bacteremia, subcutaneous abscess and reactive polyarthritis. Two years previously she suffered from atrial fibrillation and osteoarthritis of the knee. After she was admitted for treatment of the knee joint with hyaluronate sodium, she complained of pain in the left shoulder and both knees. Pyogenic arthritis was suspected and administration of cefazolin was started immediately after blood culture. One set of blood cultures showed Group B streptococcus. Therefore the antibiotic was changed to ampicillin. To investigate the cause of polyarthritis, enhanced CT of the left shoulder and both knees was performed and demonstrated fluid collection with marginal enhancement, suggesting a bacterial abscess. However, findings of arthrocentesis and synovial fluid culture were incompatible with bacterial arthritis. A subcutaneous abscess, which appeared at 5 days after admission to the hospital, was not connected to the synovial fluid, suggesting reactive arthritis was the main cause of her polyarthritis. We performed drainage surgery and one week later, the clinical symptoms and inflammatory findings mostly disappeared. Several microbes are able to cause reactive arthritis, however, cases with Group B streptococcus are very rare. Group B streptococcus infection should be taken into consideration not only in patients with diabetes and cerebrovascular disease but also in elderly patients.

BACKGROUND AND OBJECTIVE: Acid-induced lung injury from aspiration is one of the most important causes of ARDS. Calcitonin gene-related peptide (CGRP) is a neuropeptide that has various biological actions. The current study investigated whether CGRP might have pathophysiological roles in acid-induced lung injury. METHODS: The investigations employed CGRP gene-disrupted mice--mutant mice (CGRP(-/-)) and their littermate controls (CGRP(+/+)). Anaesthetized and mechanically ventilated mice received 2 mL/kg HCl (pH = 1.5) intratracheally. Lung wet-to-dry weight ratios were calculated to assess pulmonary oedema, total and differential cell counts of the BALF were determined, and measurements of myeloperoxidase activity were performed. RESULTS: Acid-induced lung injury was characterized by an increase in lung permeability and respiratory failure. Disruption of the CGRP gene significantly attenuated acid-induced injury, oedema and respiratory failure. CONCLUSIONS: This study suggests that CGRP is involved in the pathogenesis of acute lung injury caused by acid aspiration and CGRP mutant mice may provide an appropriate model to study molecular mechanisms in this context.

We report a 94-year-old woman, who underwent percutaneous endoscopic Jejunostomy (PEJ) tube feeding for enteral nutrition, developed the intussusception of the small intestine. She suffered from nontuberculous mycobacterium (NTM), and her lung inflammation deteriorated due to aspiration pneumonia and malnutrition. Because of old age, dysphagia, esophageal hiatus hernia, gastro-esophageal reflux and her bedridden condition due to severe osteoporosis, oral nutritional supplementation is nearly impossible. To reduce the aspiration risk, we chose PEJ instead of percutaneous endoscopic gastrostomy (PEG) as the route of tube feeding. Six months after the placement of a PEJ tube, aspiration pneumonia was diagnosed and she was readmitted to our hospital. During hospitalization, she had sudden diarrhea, vomiting, and lower abdominal pain. Abdominal CT scan and radiographs using contrast medium showed small intestinal intussusception related to the PEJ tube. We observed the clinical course without performing surgery, pulling it back towards the stomach and placing an ileus tube, because the small intestine was not completely obstructed. Two months later, although she suffered from aspiration pneumonia once more, she remained in a stable condition without further intervention so that she could move to aother hospital. Recently PEJ has been expected to prevent aspiration pneumonia, but we believe that it can be a risk factor for intussusception. Although the PEJ can be a good parenteral nutrition route for frail elderly with dysphagia, we need to consider possible complications including intussusception.

Defensins comprise a family of cationic antimicrobial peptides characterized by conserved cysteine residues. They are produced in various organs including skeletal muscle and are identified as key elements in the host defense system as potent effectors. At the same time, defensins have potential roles in the regulation of inflammation and, furthermore, can exert cytotoxic effects on several mammalian cells. Here, we developed transgenic mice overexpressing mouse beta-defensin-6 to explore the pathophysiological roles of the defensin family as a novel mediator of inflammatory tissue injury. Unexpectedly, the transgenic mice showed short lifespan, poor growth, and progressive myofiber degeneration with functional muscle impairment, predominant centronucleated myofibers, and elevated serum creatine kinase activity, as seen in human muscular dystrophy. Furthermore, some of the transgenic myofibers showed IkappaBalpha accumulation, which would be related to the myofiber apoptosis of limb-girdle muscular dystrophy type 2A. The present findings may unravel a concealed linkage between the innate immune system and the pathophysiology of degenerative diseases.

Adrenomedullin (ADM), a newly identified vasodilating peptide, is reported to be expressed in lungs and have a bronchodilating effect. We hypothesized whether ADM could be involved in the pathogenesis of bronchial asthma. We examined the role of ADM in airway responsiveness using heterozygous ADM-deficient mice (AM+/-) and their littermate control (AM+/+). Here, we show that airway responsiveness is enhanced in ADM mutant mice after sensitization and challenge with ovalbumin (OVA). The immunoreactive ADM level in the lung tissue after methacholine challenge was significantly greater in the wild-type mice than that in the mutant. However, the impairment of ADM gene function did not affect immunoglobulins (OVA-specific IgE and IgG1), T helper 1 and 2 cytokines, and leukotrenes. Thus the conventional mechanism of allergen-induced airway responsiveness is not relevant to this model. Furthermore, morphometric analysis revealed that eosinophilia and airway hypersecretion were similarly found in both the OVA-treated ADM mutant mice and the OVA-treated wild-type mice. On the other hand, the area of the airway smooth muscle layer of the OVA-treated mutant mice was significantly greater than that of the OVA-treated wild-type mice. These results suggest that ADM gene disruption may be associated with airway smooth muscle hyperplasia as well as enhanced airway hyperresponsiveness. ADM mutant mice might provide novel insights to study the pathophysiological role of ADM in vivo.

An 81-year-old woman was admitted due to exacerbation of chronic back pain from a vertebral osteoporosis fracture. The lumbar MRI examination revealed compression fracture of Th12 and L1 bones. Initial treatment with roxoprofen, calcitonin, bupurenorfin, and morphine did not achieve pain reduction in the patient. Because her geriatric depression scale score was low, we next tried to treat the pain using an antidepressant. Although the pain was improved by amitriptyline, the side effects of dry mouth and urinary incontinence were occurred. Milnacipran, a serotonin and norepinephrine reuptake inhibitor (SNRI), was then tried for the treatment of the chronic pain instead of amitriptyline, but the pain was increased. Then, she was given amitriptyline again for treatment of the chronic back pain instead of SNRI. The second-time amitriptyline treatment was effective to reduce the pain, with minimal side-effects. Because chronic pain due to osteoporosis is often difficult to treat in elderly patients, the classic antidepressant, amitriptyline, may help pain control by narcotics and anti-inflammatory agents in some elderly patients.

We report an elderly case with nontuberculous mycobacteria (NTM). Four years after left lung upper lobectomy due to lung cancer by the video-assisted thoracic surgery (VATS), an 81 year-old patient complained of general fatigue and appetite loss. Although he did not exhibit fever or respiratory tract symptoms, a Chest X ray film revealed unilateral massive pleural effusion in the left lung. NTM (Runyon classification type II) was grown in the sputum culture. Neither mycobacterium tuberculosis DNA nor M. avium-intracellulare complex DNA was detected by polymerase chain reaction. The pleural effusion adenosine deaminase (ADA) activity was 127.6U/l. NTM was considered as the most probable diagnosis. After admission his condition and appetite improved. Chest computed tomography (CT) scan showed reduction of left pleural effusion, but another pulmonary nodule lesions were sustained. Although the abnormal findings on chest CT did not totally resolve, we did not prescribe antituberculosis drugs, based on the comprehensive assessment of his NTM disease state. The pathogenesis and diagnosis of HTM in elderly cases was discussed.