[in Japanese]

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[in Japanese]

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The cause of the high asthma mortality in the elderly is not exactly known. We measured intrabronchial pressures in elderly asthma patients who had long-standing asthma and compared them with those in newly-diagnosed asthma and young healthy volunteers. In elderly asthmatics, at baseline conditions, both central and peripheral airway resistances were significantly higher compared with those in the other groups, which may partly explain the high asthma mortality in the elderly. We report a case of severe acute asthma associated with disturbed consciousness, in which asthma-induced cerebral swelling was considered to be accompanied by neuronal damage, after examination of cerebrospinal fluid. Inhaled steroid is essential for the treatment of moderate to severe asthma. However, approximately 40% of the elderly patients in this category did not use inhaled steroid. Physicians should strongly recommend the use of inhaled steroid to prevent asthma death in elderly asthma patients.

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Allogeneic hematopoietic stem cell transplantation after conditioning regimen with high dose cytostatic drugs and total body irradiation may induce severe transplantation related complications especially in older adults. Recently, several reports showed successful engraftment in older patients with hematological and non hematological malignancies after reduced doses of cytostatic drugs. So called mini-transplantation (nonmyeloablative hematopoietic stem cell transplantation) might be able to induce graft-versus-leukemia/tumor effect (GVL/T) without severe transplantation related complications. Older patients and patients with reduced performance status induced by prior infectious and organ complications might benefit from this mini-transplantation strategy.

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[in Japanese]

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[in Japanese]

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Recently, some Alzheimer-associated genes have been found: amyloid β protein precursor (APP), apolipoprotein E (apoE), presenilin 1 (PS-1), and presenilin 2 (PS-2). First, we failed to discover other susceptibility genes of familial Alzheimer's disease (FAD). However, we dislosed a novel mutation, Asp678Asn (D678N), in the APP gene in a pedigree of early-onset Japanese FAD. The alteration in the aggregation properties of mutant Aβ may be involved in the pathogenesis of FAD with D678N APP mutation.
Many reports have established that apoE genotype distribution for the ε4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheier's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) α gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p<0.05). Polymorphism of the ERα gene may be a genetic risk factor for SAD.

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[in Japanese]

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[in Japanese]

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It is controversial whether pulmonary rehabilitation is effective in patients with chronic obstructive pulmonary disease (COPD). To test the effect of pulmonary rehabilitation, 7 patients with COPD (aged 76.0±2.6 years) were enrolled in pulmonary rehabilitation program for 6 weeks. The program consisted of relaxation, pursed lip breathing, diaphragmatic breathing, panic control, muscle stretch gymnastics, and exercise training. The distance of the 6-minute walking test increased significantly from 246.4±38.0 (m) to 304.3±28.4 (m) (p<0.05). The minimum SpO₂ during the 6-minute walking test increased from 86.0±2.8 (%) to 90.1±1.3 (%) and dyspnea as measured with Borg scale decreased from 5.6±1.1 to 4.6±0.5, although they were not significantly different. These results suggest that pulmonary rehabilitation might improve exercise tolerance in elderly patients with COPD.

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In order to examine the relationship between depressive symptoms and the lipid metabolism in the elderly with hypertension, we recruited 311 outpatients aged 65 or older with hypertension and defined depression as patients with 6 or more symptoms on Geriatric Depression Scale short form. We further classified depressed patients into three groups: mild depressed with 6-7 symptoms, moderate depressed with 8-10 symptoms and severe depressed with 11 or more symptoms. Serum total cholesterol, serum HDL cholesterol and serum LDL cholesterol levels were significantly higher in female depressed patients than those in nondepressed patients (TC, 194.6±30.1 vs 208.0±32.8 p<0.01; HDL, 67.3±19.3 vs 72.3±16.2 p<0.01; LDL, 107.6±26.5 vs 116.0±29.1 p<0.05). In male patients, serum lipids were not significantly associated with depressive symptoms but depressed patients were significantly older than nondepressed patients (75.3±6.2 vs 78.0±5.9 p<0.05). Concerning the analysis of the severity of depression, serum total cholesterol and serum LDL cholesterol levels were significantly higher in mildly depressed patients than nondepressed patients in females and the same tendency was seen in male patients. No linear associations were shown between the severity of depression and serum lipids. We concluded that hyperlipidemia may be associated with depressive symptoms in elder patients with hypertension and that it might be related the severity of depression. We need to further investigate the relationship between depression and lipid metabolism in larger population samples.

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To clarify the clinical features and to select optimal treatment of hepatocellular carcinoma (HCC) in the elderly, 163 patients were divided into the following three groups and retrospectively evaluated: Group O (≥70 years of age, 47 cases), Group IM (<70 and ≥60 years, 70 cases) and Group Y (<60 years, 46 cases).
There were fewer HBsAg-positive cases and those in clinical stage III in Group O than in Group Y (p<0.05). Although the percentage of women and small HCCs in Group O were somewhat higher than those in other groups, there were no significant differences among the three groups with regard to sex, size of nodule and time after blood transfusion. Most of the alcohol-abuser were in Group Y (p<0.05). Some active treatment was possible in 76.6% of the elderly individuals, in 87.1% of the patients of Group IM, and in 78.3% of the Group Y, while few underwent hepatic resections (Group O, 4.3% vs. Group IM, 8.5% vs. Group Y, 8.6%) or PMCT (4.3% vs. 11.4% vs. 8.6%). The allocation of other therapeutic modalities in the three groups were also statistically identical. The prevalence of concomitant diseases was significantly higher in the elderly patients (53%) than in their younger counterparts (Group IM; 30%, Group Y; 28.2%) (p<0.05). Although the reasons for the paucity of treatment in Group IM and Y (9 and 10 cases) were liver-associated factors (i.e., advanced clinical stage or tumor size), attempts to apply therapeutic measures were abandoned in 11 cases in Group O because of their advanced age (2 cases) or heart failure (1 case). The 5-year survival rate was higher in Group O (55%) than those in Group IM (32%) and Y (26%) (p<0.01).
These results suggest that because of the higher incidence of concomitant diseases, less invasive therapeutic modalities, such as PEI/PMCT, should be recommended for elderly patients with HCC.

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The reliability of overnight (sleep) urine (SU) and 2nd morning urine (2MU) were compared with that of 24-hour urine (24U) for the evaluation of bone resorption markers. A total of 50 women were subjected to the study and were divided into two groups according to their lumbar bone mineral density, namely 25 females with normal BMD (mean age 47) and 25 women with low BMD (mean age 78). Calcium (Ca), collagen degradation products crosslaps (CTx), pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) were measured in 24U, SU and 2MU and corrected for urine volume with creatinine (Cr) and osmolality (Osm). Among these four components, the corrected values tended to be higher in SU than 2MU, regardless of the method of correction and BMD level. Ca, CTx, Pyr and D-Pyr concentrations in spot urine were always significantly correlated with total excretion/body weight (Kg) regardless of the method of correction and BMD level. In low BMD subjects, Ca, CTx and D-Pyr concentrations corrected by Osm with further correction by body weight as an index of body size in the SU were significantly correlated with BMD. The SU may be a sensitive indicator of augmented nighttime bone resorption replacing 24U especially on correction by Osm to eliminate the influence of sodium intake as an extraskeletal factor. In 51 women with normal BMD (A) with a mean age of 56, 16 with osteopenia (B) with a mean age of 64 and 35 with osteoporosis (C) with a mean age of 71, correlation coefficients were calculated between lumbar BMD and Ca/Osm, Ca/Osm/Kg, Ca/Cr and Ca/Cr/Kg in SU. Although no significant difference of mean urine Ca values were found between A and B groups, Ca values in C were significantly higher than that of A regardless of the correction method. The mean value of Ca/Osm/Kg in C was significantly higher than that of B. Ca/Osm/Kg showed a significant negative correlation with BMD in C. On examination of the correlation between % change of BMD in 23 women with a mean age of 59 and Ca concentration in SU corrected by urine volume and body weight, Ca/Osm was -0.427 (p=0.0419), Ca/Osm/Kg-0.450 (p=0.0313), Ca/Cr-0.400 (p=0.058) and Ca/Cr/Kg-0.420 (p=0.0462), suggesting the usefulness of Ca/Osm/Kg as an indicator of low BMD in screening.

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The purpose of this study was to assess the relationship between experiences of falls or fear of falling and functional fitness in the elderly. A total of 41 women, aged 66-88, who visited Fall Prevention Clinic in Tokyo Metropolitan Geriatric Hospital, underwent an interview and functional assessment. We used a questionnaire about falls, fear of falling, activity restriction, and twelve variables were used to assess functional fitness. Data were collected from June 2000 to November 2001. The subjects were classified into four subgroups: the faller group (n=29) were subjects who had at least one or more experiences of falling accidents in the past one year; the non-faller group (n=12) were subjects who did not have any falling accidents in the past one year; the activity restricted group (n=12) were subjects who were restricted from going out because of fear of falling; the activity non-restricted group (n=23) consisted of subjects who did not have any restriction concerning going out because of fear of falling. The results were:
1) Among all subjects, 85.4% had fear of falling. Among the subjects who had fear of falling, 34.3% had restricted outdoor activities due to the fear of falling.
2) Where 86.2% of the faller group responded that they had fear of falling, 83.3% of the non-faller group also responded as having fear of falling. Of the faller group, 44.0% had some restriction concerning going out because of fear of falling. In the non-faller group, 10.0% of them showed some restriction concerning going out because of fear of falling. The rate of activity restriction in the faller group was significantly higher (p<0.05) than in the non-faller group.
3) The faller group had significantly reduced LNG with eyes open and closed, one-leg balance with eyes open, tandem walking, grip strength, and leg extension than the non-faller group.
4) The activity-restricted group exhibited significantly reduced one-leg balance with eyes open, Up & Go test, grip strength, and leg extension than the activity non-restricted group.
In conclusion, lower leg strength and walking ability as well as history of falls are significant predictors of activity restriction in elderly women related to fear of falling.

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MRI and bone scintigraphy of a 64-year-old woman admitted with severe lumbago showed multiple metastatic bone cancer mainly on vertebrae, and breast cancer was found by mammography. After enucleation was performed, treatment with tegafur, tamoxifen and oral bisphosphonate/etidronate was started. Because symptoms associated with bone metastasis worsened, we began to administer 30mg of pamidronate intravenously every 4 weeks. Since that time the extent of metastasis has been inhibited, resulting in ameliorated lumbodynia and improved quality of life.

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A 60 year-old man who has suffered dysarthria since 1999. He had noticed twitching of right upper extremity and orbicularis oris muscle since August 2000. The bulbar type of amyotrophic lateral sclerosis was diagnosed. He was admitted for evaluation of sleep disorder with respiratory distress on November 20, 2000. Arterial blood gas analysis on admission showed marked hypercapnea (PaCO₂:51.6Torr). Nocturnal hypoxia index, which was calculated using the nocturnal oximetry monitoring, was elevated. Non-invasive positive pressure ventilation started during sleep at night, although it was earlier than to start for mechanical ventilation. After one week, both hypercapnea and his nocturnal hypoxia index, together with symptoms, improved markedly.
Respiratory insufficiency due to progressive fatigue of respiratory muscles, such as diaphragm and intercostal muscles, is a major cause of death in amyotrophic lateral sclerosis. In general mechanical ventilation is introduced when marked hypercapnea and dyspnea become clinically overt. However, the exact time to introduce noninvasive methods of ventilatory support for amyotrophic lateral sclerosis has not been established.
Based on the observation in this patient, we would suggest that earlier introduction of non-invasive mechanical support for ventilation (nocturnal hypoxia index>70) would be useful to improve the symptoms and to prolong the life of patients with ALS. The nocturnal hypoxia index is useful to decide the time of the introduction of non-invasive mechanical support for ventilation.

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An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experiened the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease.

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The patient was a 68-year-old man with a 1-year history of delusions related to well-formed and detailed visual hallucinations. Bromperidol 12mg was prescribed to treat his symptoms. After a diagnosis of dementia of Alzheimer's type was suspected, the patient received donepezil hydrochloride 5mg. One week later, the patient's Parkinsonism deteriorated. One month later, the patient developed radical edema of the eyelids and the anterior neck, hypoproteinemia, and severe anteflexion of the body. One and a half months later, the patient developed malignant syndrome. His medication was discontinued and parenteral nutrition was started. The patient recovered from his malignant syndrome. However, 1 month later, his Parkinsonism had not improved. The patient received levodopa to treat his Parkinsonism and his symptoms subsequently improved. The hallucinations and systematized delusions returned. The patient's cognitive impairment deteriorated on one side.
The aggravation of extrapyramidal symptoms and the development of malignant syndrome were believed to have been caused by the combination of bromperidol and donepezil hydrochloride and poor nutrition. Caution should be exercised when prescribing an antipsychotic drugs with donepezil hydrochloride.

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An 82-year-old woman was diagnosed with hypertension at the age of 50 and had been treated with antihypertensive agents. Proteinuria was detected at age 60 and her renal function subsequently deteriorated. Hemodialysis was started on February 14, 2000. She fell out of the bed and hit her neck in the early morning on February 15.
Neck X-ray tomography revealed Anderson type III dens fracture. Since she had several complicating conditions including angina pectoris and arrhythmia, she was treated by external fixation using a halo-vest. The neck pain improved gradually. During her clinical course, she experienced delirium due to immobilization. However, bone union was complete 5 months later.
Physicians should be aware of the possibility that even minor injury can cause dens fracture in elderly patients. Conservative management of type III dense fracture should be considered for elderly patients with a compromised condition.

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