Antimicrobial peptides, including β-defensins, are thought to be effective agents against opportunistic infections. In humans, three β-defensins have been identified. The first human β-defensin, hBD-1, is predominantly expressed in epithelia of the urogenital tract and has been reported to be constitutive. The second and third human β-defensins, hBD-2 and hBD-3, were isolated from psoriatic skin and found to be predominantly expressed in skin and respiratory tract. Of note, the hBD-2 gene expression is inducible by various proinflammatory agents such as TNF-α, IL-1β, IL-8, LPS, bacteria, and yeasts. It has been shown that LPS-induced expression of hBD-2 in human tracheobronchial epithelial cells requires CD14, which may complex with Toll-like receptors (TLRs)to ultimately activate NF-κB. In addition, β-defensins have been recently reported to promote immune responses by recruiting dendritic and T cells. Defensins may play a key role in the mechanism of host defense and innate immunity. These defensins, including hBD-2, might provide a new therapeutic approach to infectious diseases.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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Aspiration of oral secretions and their bacteria, especially gram-negative bacilli, is increasingly being recognized as an important factor in pneumonia. We investigated whether oral care reduces the frequency of pneumonia in the institutionalized elderly. Nurses or caregivers cleaned patients' teeth with toothbrushes after each meal, and scrubbed the oropharynx with an applicator with povidone iodine (1%) every day. Dentists or dental hygienists gave professional care once a week. During follow up, pneumonia decreased significantly in patients with oral care. Oral care was of benefit for both edentate as well as dentate subjects, although periodontal diseases might cause pneumonia. We suggest that oral care may be useful in preventing pneumonia in institutionalized elderly, irrespective of dentate or edentate status.

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Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients either receiving or not receiving inhaled corticosteroids, and in nonsmoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids and similar in asthmatic patients receiving inhaled corticosteroids and nonsmoking healthy control subjects (Am J Respir Crit Care Med 1997; 156: 1140-1143). All patients with inhaled corticosteroid treatment had reductions in exhaled CO concentration and eosinophil cell counts in sputum that were accompanied by an amelioration of airway obstruction. These results showed that detection of exhaled CO could be a simple noninvasive tool for monitoring airway inflammation and acute exacerbation of asthma.

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[in Japanese]

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The pathogenesis of idiopathic Parkinson's disease (PD) remains to be elucidated. The discovery of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) suggests that neurotoxins in the human brain may cause selective depletion of striatal dopamine neurons, a hallmark of PD. An endogenous isoquinoline, N-methyl (R) salsolinol is a most promising neurotoxin candidate, and it was proved to be selectively toxic to dopamine neurons in the rat brain by in vivo experiments. The level of N-methyl (R) salsolinol in the cerebrospinal fluid obtained from PD patients was significantly higher than control. N-Methyl (R) salsolinol is synthesized by 2 enzymatic reactions from dopamine; condensation of dopamine with acetaldehyde into (R) salsolinol by (R) salsolinol synthase and N-methylation of (R) salsolinol by neutral (R) salsolinol N-methyltransferase. The second enzyme, which catabolizes the N-methylation of (R) salsolinol, was found to determine the level of the neurotoxin in the brain. The activity of neutral (R) salsolinol N-methyltransferase was examined using lymphocytes prepared from PD patients, normal controls and diseased controls as enzyme source. A significant increase in the activity was confirmed in lymphocytes from PD cases compared to normal- and diseased-control. Studies to clarify the enviromental and genetic factors determining the activity of the enzyme are now under the way.
The cytotoxicity of N-methyl (R) salsolinol was examined using a cultured cell model. N-Methyl (R) salsolinol was found to induce apoptotic cell death in a dose-dependent way. The mechanism of apoptosis was clarified to be mediated by collapse in mitochondrial membrane potential, activation of caspase 3 and fragmentation of nuclear DNA. In addition, propargylamines protected the cells from apoptosis. It was suggested that N-methyl (R) salsolinol and propargylamines have specific binding sites in mitochondria which regulate the death signal transduction. Propargylamines might be applicable as neuroprotective drugs, which can be orally administrated to PD patients.

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We have identified that familial amyloid polyneuropathy with middle age onset results from missense mutations of the transthyretin gene. In the present study, we investigated molecular abnormalities of transthyretin in elderly patients with cardiac amyloidosis or amyloid polyneuropathy, using DNA sequencing and protein sequencing. We detected 5 cases of transthyretin-related cardiac amyloidosis using immunohistochemical techniques. All of them had late-onset, mild or no peripheral neuropathy or autonomic dysfunctions, and no family history. Three had transthyretin Met30 and two transthyretin Ile50. We also found 15 patients with transthyretin-related amyloid polyneuropathy. All of them had late-onset and no contributory family history. Twelve had transthyretin Met30, two transthyretin Ile50, and one transthyretin Ser109. Clinical manifestations and sequencing procedures of six representative patients were also presented. Molecular investigation of transthyretin is needed for elderly patients with etiology-unknown cardiac amyloidosis or amyloid polyneuropathy even if there is no family history of amyloidosis.

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To clarify the influence of elevated serum lipoprotein (a) (Lp (a)) concentration on ischemic heart disease (IHD) and the perforating artery occlusion type of cerebral infarction (CI) in elderly patients with type 2 diabetes, we measured the serum levels of Lp(a) of type 2 diabetic patients (n=158, 81 men and 77 women). The group was followed up prospectively for 4 years and the incidence of IHD or CI was monitored. The diagnosis of CI was confirmed by computed tomography and that of IHD, which includes myocardial infarction and angina pectoris, was diagnosed by electrocardiogram and blood chemistry examination. Lp (a) concentrations of 20mg/dl or more were identified as elevated Lp (a) levels and Lp (a) concentrations of less than 20mg/dl were identified as normal Lp (a) levels. A Kaplan-Meier survival analysis (log-rank test) assessed the time to event rate stratified by an Lp (a) cutoff point of 20mg/dl. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis. The probability of IHD events was significantly higher in the elevated Lp (a) group than in the normal Lp (a) group without a history of IHD but was similar in the two groups for those patients with a history of IHD. There was no significant difference between the elevated Lp (a) group and the normal Lp (a) group with regard to CI events in patients without a history of CI and with a history of CI. On multiple logistic regression analysis, Lp (a), hyperlipidemia and a history of IHD were significant predictors of IHD and hypertension, hyperlipidemia and a history of CI were significant predictors of CI.
These results show that elevated serum Lp (a) concentrations is an independent risk factor for IHD, but not for the perforating artery occlusion type of CI in type 2 elderly diabetic patients.

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Patients receiving operative treatment for fracture are good candidate for critical path management. Recently, we have developed a Short Program (SP) for post-operative rehabilitation of hip fractures. The purpose of this study was to evaluate the effectiveness, the safety and the cost efficiency of this SP, by comparing it with the former Long Program (LP) in terms of choosing the better program for the critical path. The enrolled patients were over 65 years old, had been able to walk by themselves with or without canes, were free from neurological diseases like hemiplegia and Parkinson's disease, and without pathological fractures. We enrolled 101 patients (mean age: 83.1) for the LP and 143 patients (mean age: 82.8) for the SP. The operative procedure for these patients was internal fixation with a sliding hip screw or prosthetic replacement for a femoral head. Length of hospitalization, the rate of recovering walking ability, medical expenses during hospitalization, and the types and incidence of complications were investigated to determine differences between the SP and the LP. Length of hospitalization was significantly shorter in SP patients (p<0.01). The ratio of recovering walking ability was equal in both programs, while that among the patients with dementia was lower in the SP group. Medical expenses were significantly less in SP (p<0.01). The SP had fever complications than the LP group (p<0.05). As a result, the SP was superior to the LP in terms of effectiveness, safety and cost efficiency, thus it was considered to be suitable for critical path management of hip fracture cases. However, because recovery of walking ability was harder for patients over 85 years old with the SP than with the LP, a modified program is necessary for such older patients.

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Effects of inhaled anticholinergic drug on the physiological function of the respiratory system and quality of life (QOL) in elderly patients with chronic obstructive pulmonary disease (COPD) have not been fully elucidated. We examined the pulmonary function, static respiratory pressures, and ventilation during exercise, before and after inhalation of oxitropium bromide (OTB) in 12 male patients with COPD (mean age 82.1±0.6 years). QOL was measured with a St George's Respiratory Questionnaire (SGRQ) in the patients. Forced expiratory volume in one second was increased by the inhalation of OTB in the patients, whereas the ratio of residual volume to total lung capacity was decreased by the inhalation. Maximum inspiratory pressure was significantly increased after the administration of OTB. Dyspnea sensation during exercise measured on the Borg scale was reduced by the inhalation of OTB. The scores of SGRQ were improved by one-month treatment with OTB. These results suggest that the treatment with OTB are effective for both physiological function and several aspects of QOL in elderly patients with COPD.

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In April 1999, 75 elderly patients (mean age: 79 years old) with low back pain and/or knee pain visited an acupuncture and physical therapy unit in a geriatric hospital. A cross-sectional study was carried out in order to evaluate the effects of acupuncture therapy on low back pain and/or knee pain in elderly patients. Among them, 60 patients answered that their pain diminished following their therapy. The proportion of patients who were treated with acupuncture therapy were higher in these 60 patients than the other 15 patients (55.5% vs. 26.7%, p=0.05). The result suggests that acupuncture therapy may be able to relieve low back pain and/or knee pain in elderly patients. However, 46% of the patients with acupuncture therapy were also treated with other types of physical therapy. Further studies should be recommended to confirm the effects of acupuncture therapy on low back pain and/or knee pain.

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To clarify the present status and problems in medical care for the elderly with dementia, 103 cases were studied according to the descriptive records obtained at a public counselling facility for dementia, based on interviews with patients' families. Their records were analysed based on their background, severity of dementia (clinical dementia rating: CDR), and counselling content. There were 75 demented patients with a CDR score of 1 or more, and 50 of them were women aged 54 to 90, while the remaining 25 men were aged 55 to 88. The consultation content was clustered into 5 codes: code 1, evaluation of dementia and/or dementia-related symptoms including psychiatric symptoms and behavioral disturbance; code 2, methods to manage patients; code 3, methods to take a patient to a medical institution; code 4, questions regarding medical treatment and drugs prescribed at present; code 5, information on the welfare resources provided. In most of the 75 patients, the degree of dementia deteriorated insiduously without any physical symptoms. The key person and/or caregiver was usually an elderly spouse, and the family noticed dementia only after cognitive impairment progressed with or without troublesome symptoms. Hallucination was a common troublesome symptom. Concerning consultation content, codes 1, 2, and 3 were common, while 13 cases had dissatisfaction with their medical treatment. Therefore, it was necessary to explain the significance of early diagnosis of dementia to families and their caregivers. There were also many families who felt strain and wondered about what hospital or department to take the patient to. In addition, it seemed that explanation on the clinical course and adverse drug reactions, advice for the correspondence with psychiatric symptoms and abnormal behaviour, and information services concerning utilization of social resources was not yet sufficient.

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The aim of this study was to examine the frequency and number of falling accidents in the the elderly population and to investigate the characteristics of the accidents. The investigation was performed in 58 Tokyo metropolitan townships for a one-year period from September 1st, 1997, and the 517 cases, in which persons were over 65 years old, fell down were studied (136 men, 381 women).
The yearly accident frequency for 1, 000 elderly over 65 population was 4.13 cases for men and 7.88 cases for women, being 1.9 times higher in women. Also the number of accidents in each township was significantly correlated to the population of the elderly over 65 (men r=0.674, women r=0.846, p<0.001).
The analysis by age showed the percentage of accidents in single-family housing among the oldest-old population was significantly higher than the young-old population (p<0.05) for both men and women. According to logistic regression analysis results, injured body part and the form of dwelling house were significantly correlated as risk factors of fracture (p<0.05). The odds ratio of injured body part was 7.559 (95% CI 4.926-11.598), and that of the form of dwelling house was 1.660 (95% CI 1.067-2.584), showing that injury of limbs and the accidents in single-family housing would increase risk of fracture.
Promoting preventative measures for falling accidents in single-family housing appears important in the prevention of falling accidents among the metropolitan elderly.

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Gliomatosis cerebri is a rare form of glioma, which diffusely extends to both cerebral hemispheres. Because it sometimes fails to show severe neurological symptoms in spite of diffuse invasion, the antemortem diagnosis is difficult. We report a case of a 77-year-old woman, who was admitted with progressive left hemiparesis and dysarthralgia. Plain CT scan of the brain showed almost no abnormal findings. MRI T2-weighed image revealed widespread and nearly symmetrical extension of a high intensity area from the corpus callosum to the deep white matter of both cerebral hemispheres. Open biopsy of the brain showed glioblastoma multiforme, which finally confirmed the clinical diagnosis of gliomatosis cerebri. We also review the classic and recent literatures.

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We describe an elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84-year-old man, who had a 10-year history of episodic edema, was treated with proscillaridin and verapamil hydrochloride at another hospital. He had experienced a poor appetite and general malaise 2 months previously, and exertional dyspnea 10 days previously. On admission, he had jugular venous dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart sound originating from the right ventricle and systolic murmur of tricuspid regurgitation were heard. An admission electrocardiogram showed an atrial standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram disclosed idiopathic dilatation of the right atrium and secondary tricuspid regurgitation. He was given a diagnosis of right-sided heart failure due to idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which was suspected to derive from the side effects of proscillaridin and verapamil hydrochloride. Thus, these agents were withheld. In addition, the patient reduced sodium intake and was treated with diuretics and beta-adrenergic agonist. Thereafter, right-sided heart failure markedly improved. At the time of the last follow-up 16 months after discharge, he felt well.

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A 76-year-old woman was admitted with a one-month history of low grade fever and dizziness. She had a palpable right supraclavicular lymph node. Abdominal ultrasonography showed swollen lymph nodes around the abdominal aorta. A specimen from the right supraclavicular lymph node showed malignant lymphoma (diffuse large B cell type). We started chemotherapy according to the low-dose THP-COP protocol (pirarubicin, cyclophosphamide, vincristine and prednisolone) on the 31st hospital day. Since no adverse effects were detected after two low-dose cycles, the patient received a third course with standard doses on the 87th hospital day. The total dose of pirarubicin was 72mg/m². Two days after the third course started, she suffered from dyspnea caused by congestive heart failure. A chest X-ray showed advanced cardiomegaly, severe congestion and bilateral pleural effusion. These conditions improved with transvenous administration of diuretics, a vasodilator and phosphodiesterase inhibitor. In this case, congestive heart failure developed even though the total dose of pirarubicin was lower than in previous reports of this complication. When the THP-COP protocol is indicated in elderly patients, cardiotoxicity should be monitored even if the total dose of pirarubicin is very low.

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We report two cases of cerebral infarction in which swallowing function improved following swallowing rehabilitation. Patient 1 was an 82-year-old man, who was admitted due to rheumatoid arthritis and multiple cerebral infarction, suffering from aspiration pneumonia. The abnormality of swallowing was assessed by the water swallowing test and videofluorography. It has been reported that videofluorography is useful in the diagnosis of aspiration. Three weeks after the start of swallowing rehabilitation, the serum level of inflammatory markers and the chest X-ray had returned to normal. His score on the water swallowing test had improved. Patient 2 was a 62-year-old man, who was admitted with severe hemiplegia, dysphagia and dysarthria. One month after the swallowing rehabilitation, videofluorography showed that the magnitude of aspiration into the trachea had decreased and the pooling of barium in the piriform sinus had disappeared. The patient could begin taking a little food by mouth. These results suggest that swallowing rehabilitation will be affect the clinical improvement of swallowing function and help preventing aspiration pneumonia in our hospital.

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An 88-year-old woman was first referred to an eye clinic in mid-May 2000 because of limitation of ocular movement. A right orbital tumor was recognized on orbital CT scans and she was referred to our hospital. A chest X-ray film showed an abnormal mass in the right middle lung field, so she was admitted for further investigations. Adenocarcinoma was diagnosed by transbronchial lung biopsy. The right orbital tumor was thought to be a metastasis from the lung cancer. She received radiation therapy for the metastatic orbital tumor. However, two months after the onset of symptoms, she died due to progressive systemic metastasis.
In summary, we report an elderly lung cancer patient whose initial symptoms were related to orbital metastasis.

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