The authors studied the relationship between aging and exocrine pancreatic function by the secretin test which was recently standardized by the Japanese Society of Gastroenterology. Pancreatic juice was collected at 10min intervals for 60 minutes after a bolus intravenous injection of secretin (Secrepan, Eisai Co., Ltd., 100U/body) through a quadruple-lumen doudenal tube equipped with double balloons. Exocrine pancreatic function was evaluated by three parameters: secretory volume, maximal bicarbonate concentration or bicarbonate output, and enzyme (amylase and lipase) output. Control subjects consisted of 65 outpatients presenting with mild vague abdominal symptoms who fulfilled the following three criteria: 1) good general condition with no known diseases; 2) no abnormality in the liver, bile duct, pancreas, kidney and metabolism judged from blood chemistry, urine and stool analysis, upper GI series, abdominal ultrasonography (US), and endoscopic retrograde cholangiopancreatography (ERCP); 3) alcohol consumption <25g/day. Control subjects were divided into three groups: 15 subjects below 40 years of age (group A), 32 subjects from 40 to 65 years (group B), and 18 subjects of 65 years and above (group C). Nineteen patient with chronic pancreatitis were also studied. The group C showed significantly lower values in secretory volume, bicarbonate output, and enzyme output than group A and B. Enzyme output showed a gradual decrease with aging. However, secretory volume and bicarbonate output showed a gentle convex curve with a peak around age 40 and a rather steep down-slope after late 50s. The degree of the decrease was significantly more marked in volume and bicarbonate output than in enzyme output in group C. Abnormally low values in more than two parameters were found in 10 of the 18 subjects of group C. No distinctive features which permitted distinguishing exocrine pancreatic dysfunction in group C from that in 19 patients with chronic pancreatitis were found. Exocrine pancreatic function (both duct-cell function and acinar-cell function) significantly decreased in the elderly. The age-associated decrease shows a different pattern between duct-cell and acinar-cell function. The degree of duct-cell dysfunction was significantly higher than that of acinar-cell dysfunction in the elderly. In the elderly, exocrine pancreatic function tests are unreliable in making a diagnosis of chronic pancreatitis, so that clinical symptoms and findings and findings of imaging tests (US, CT and ERCP) should be taken into consideration for the correct diagnosis.

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The authors investigated the relationship between morphological changes and functional changes of the stomach with ageing, especially in term of change of gastric emptying in 92 healthy subjects. We checked the difference in chronological age and the stomach age in these subjects (in order to assess these subjects). The morphological change was evaluated by extent of atrophic gastritis in endoscopical atrophic border and histological findings of biopsy specimens, and the functional change was evaluated by maximal acid output in gastric secretion. Atrophic gastritis was expanded and maximal acid output was significantly reduced with ageing. From these results we confirmed that there was no difference between the chronological age and the stomach age and the quality of these subjects was very good. Gastric emptying was investigated by the acetaminophen method. In spite of ageing, gastric emptying was almost constant in these healthy subjects.

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To evaluate the efficacy of the single dose chemoprophylaxis of recurrent urinary tract infection (UTI) in the elderly, 20 female inpatients (mean age 81.4) who had one or more culture documented UTIs in the past 12 months were studied. They were randomly assigned to be treated for 6 months either with chemoprophylaxis (200mg of norfloxacin) or conventional therapy (without any antimicrobials except when overt UTI occurred). After a 4 months of washout period, the protocols were exchanged with each other and next 6 months of trial was carried out. All cases were followed at least 4 months after the discontinuance of the chemoprophylaxis. The difference of efficacy between the two modalities was evaluated by periodical examinations of urine cultures, urinalysis and inflammatory markers. During chemo-prophylaxis, the frequency of the symptomatic UTI (bacteriuria>10⁴/ml, pyuria>5/HPF, CRP>+) was 0.267/patient·year which was significantly lower than during convertional therapy (2.97/patient·year, p<0.01). This prophylactic effect remained 4 months after the discontinuance of the drug. On the other hand, bacteriuria was persistent in more than half of patients with chemoprophylaxis. Minimal inhibitory concentration of norfloxacin for separated bacteria revealed that the resistant species steeply increased from 4 to 6 months after the beginning of chemoprophylaxia. These species disappeared 4 months after the drug was discontinued. Optimal durations of chemoprophylaxis and drug-holidays were discussed.

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The effects of aging on the diastolic and systolic functions of the left ventricle were studied by echocardiography as follows. (1). Maximum velocity of circumferential fiber lengthening (negative peak Vcf) and shortening (peak Vcf) was assessed by digital M-mode echocardiography in 20 healthy young subjects and 26 healthy elderly subjects. The mean value of negative peak Vcf (-circ/sec) was -3.87±0.85 in the 20's. -4.48±1.14 in the 30's, -3.71±1.21 in the 40's, -2.70±0.90 in the 60's, -2.57±0.64 in the 70's, -2.33±0.77 in the 80's and -2.57±0.65 in the 90's showing significant difference among young and elderly groups (p<0.05-p<0.005). The mean value of peak Vcf showed no significant difference among young and elderly groups except for the group in the 30's which showed significant (p<0.05) difference between other groups. (2). Indices of the left ventricular systolic and diastolic functions were calculated by standard M-mode echocardiographic technique in 227 healthy subjects from 5 to 94 years in age by dividing them into 3 young groups and 4 elderly groups. As for the left ventricular internal diameters a tendency of increase was observed in the enddiastolic diameter of the left ventricle in accordance with ageing. Fractional shortening of the left ventricular diameter which ranged from 36.2% to 36.7% in the 3 young groups and 36.9 to 40.3% in the 4 elderly groups and cardiac output showed no age dependent decrease. The E-F slope of the mitral valve showed marked age-dependent decrease, i.e. 93.6mm/sec-108.7mm/sec in the 3 young groups and 39.5-30.7mm/sec in the 4 elderly groups. Current data distinguished the age dependent deterioration of the diastolic function from the preserved systolic function of the left ventricle. This fact seemed attributable to the increased stiffness of the left ventricular wall.

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Recent positron or single photon emission computed tomographic studies have demonstrated that the impairment of regional hemodynamics or metabolism in cerebrovascular disease is not limited to the focal lesion, but also involves more remote areas. The present study evaluated cerebral blood flow in areas remote from the primary lesion in patients with subcortical cerebrovascular disease, and assessed correlations with the clinical features. Twenty patients aged 61∼89 (mean, 74.7±6.7 years) were divided into the L group (lacunar infarction in deep penetrating arterial territory, n=7), the NL group (non-lacunar subcortical infarction caused by main trunk occlusion or severe stenosis, n=6), and the H group (putaminal or thalamic hemorrhage, n=7). Ipsilateral cortical and contralateral cerebellar blood flow were assessed using single photon emission computed tomography with ¹²³I-IMP. Although only some patients of the L group showed a mild reduction of ispilateral cortical blood flow, most of the patients in the NL and H groups showed a moderate or severe flow reduction. The cortical blood flow reduction was suggested to be caused by several mechanisms, including brain edema, a decreased perfusion pressure associated with disease of large arteries, partial cortical neuronal damage, and deactivation. The degree of the flow reduction was considered to depend on the relative contribution of each of these factors. Contralateral cerebellar blood flow reduction, i.e., crossed cerebellar diaschisis, was observed more frequently and prominently in the NL and H groups than in the L group. Transneuronal depression through corticopontocerebellar pathways was suggested to be involved in the development of this phenomenon, since it was noted in patients with lesions involving the internal capsule or corona radiata. Neuropsychological impairment like aphasia or agnosia was associated with ipsilateral cortical blood flow reduction, and motor deficits seemed to be associated with ipsilateral cortical or contralateral cerebellar blood flow reduction. However, no correlation between cerebellar ataxia and contralateral cerebellar blood flow reduction was demonstrated. Thus, functional abnormalities affecting remote areas should be considered in patients with subcortical lesions.

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Percutaneous endoscopic gastrostomy (PEG) was performed in 32 patients with nasogastric feeding (NGF) or total parenteral nutrition (TPN), who were unable to swallow. Our cases of PEG included 10 with dementia, 8 with cerebral infarction, 8 with cerebral bleeding, 3 with gastric cancer, and others. TPN was performed after PEG for a short time. Because of the combination of TPN and PEG, there was no mortality or major complication related to the procedure. Minor complications included subcutaneous abscess and TPN catheter fever. PEG can be safely and rapidly performed. Furthermore, painless life, better cosmetic features and physical condition can be obtained with this procedure. The majority of the patients are able to return home after PEG. PEG can improve the quality of life of the patients who cannot swallow but have an intact gut.

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To evaluate the significance of parasympathetic nerve activity in essential hypertension, we measured the coefficients of variation of RR intervals (CV_RR) on electrocardiogram and examined the relationships between CV_RR and aging, hemodynamics and sympathoadrenomedullary function in normotensive subjects (NT) and in patients with essential hypertension (EHT). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA), plasma adrenaline concentration (pAd) and CV_RR resting in a supine position were simultaneously measured in 37 NT (33.8±2.0 years) and 47 mild-to-moderate EHT (51.3±1.5 years). In both NT and EHT, significantly negative correlations between CV_RR and age (NT: r=-0.54, p<0.001, EHT: r=-0.41, p<0.005) were observed, however, CV_RR correlated with neither MAP, HR nor pAd. CV_RR tended to correlate negatively with pNA (r=-0.27, p<0.1) in NT, unlike in EHT. The mean value of CV_RR in EHT (n=10, age: 38.3±1.6 years, CV_RR: 3.61±0.37%) was significantly (p<0.005) lower than in age-matched NT (n=10, age: 38.3±2.5 years, CV_RR: 5.76±0.45%). These results indicate that the parasympathetic tone suggested by CV_RR may be related to aging and sympathetic nerve activity, and that parasympathetic function might be impaired in EHT.

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The diurnal changes in postheparin lipolytic activity (PHLA) were studied as one aspect of its physiological changes in eight healthy volunteers in a fasting state. Serum lipids and PHLA in obese males were measured to determine the etiology of obesity-associated hypertriglyceridemia with respect to triglyceride (TG) catabolism. In the healthy nonobese volunteers, the lipoprotein lipase (LPL) activity did not show any diurnal changes, but decreased with time during fasting. The hepatic triglyceride lipase (HTGL) activity underwent diurnal changes, and was high in the morning and low at night. Perceiving the metabolic difference between young obese individuals (obese since childhood) and middle-aged obese individuals (obese since adulthood), PHLA and serum lipids were simultaneously determined and examined from the aspect of TG catabolism in a young male group aged 17-27 and an older male group aged 35-62. The lower-age group consisted of 15 normal-weight men and 25 obese men with 11 years (mean) of a history of obesity. The higher-age group consisted of 15 normal-weight men and 25 obese men with 12 years of a history of obesity. No differences were found in total cholesterol and LDL-cholesterol between the normal-weight and obese individuals of both groups. However, HDL-cholesterol was significantly decreased, only in the obese individuals of the higher age group, compared to the normal-weight individuals of this group. Serum TG and insulin were significantly higher in the obese individuals than normal-weight individuals of both groups. In the obese individuals in both groups, a positive correlation was demonstrated between serum TG and insulin. This suggested the increased production of TG in association with hypertriglyceridemia. In addition, TG positively correlated with LPL and HTGL activities in young obese individuals, while a negative correlation was demonstrated only between TG and LPL activity in older obese individuals. These results indicated an age-related difference in TG catabolism in obese individuals with obesity-associated hypertriglyceridemia.

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In 53 elderly participants aged more than 60 the thoracic aorta and bilateral carotid arteries were observed with noninvasive techniques, MRI and ultrasonography, in order to elucidate the relationship between hypercholesterolemia and atherosclerosis in the elderly. Hypercholesterolemic subjects were classified as group H (serum total cholesterol (TC)>220mg/dl), group H-I (220mg/dl<TC<250mg/dl) and group H-II (TC≥250mg/dl). Atherosclerotic changes of the thoracic aorta were observed in 46% of group H, 27% of group H-I, 60% of group H-II and 37% of normolipidemic subjects (group NL). Carotid atherosclerotic changes were observed in 19% of group H, 9% of group H-I, 27% of group H-II and 18% of group NL. In group H-I, the percentages of atherosclerotic changes in both thoracic aorta and carotid arteries were lower than those in group NL. However, atherosclerotic changes of thoracic aorta and carotid arteries were detected in 43% and 29% of the subjects showing higher apo B/Apo Al ratio than 1.0 among group H-I+NL (TC<250mg/dl). These changes occurred in 32% and 13% of the subjects showing lower apo B/Apo Al ratio than 1.0 among the same groups. Namely, atherosclerotic changes of the thoracic aorta and carotid arteries were observed more frequently in the subjects showing a higher apo B/Apo Al ratio than 1.0 even if their serum cholesterol values were not higher than 250mg/dl. We should use not only the serum cholesterol value but also the apo B/Apo Al ratio as an indicator to evaluate the roles of lipids in the development of atherosclerosis.

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Pulse wave velocity (PWV) of the aorta was measured in 40 patients with diabetes mellitus, in order to study the relation between PWV and diabetic angiopathy. The PWV was significantly faster in diabetic patients on oral hypoglycemic agents than in those on diet alone or on insulin. The PWV correlated significantly and positively with age, systolic blood pressure and urinary albumin index. The PWV significantly faster in diabetics with microalbuminuria than in those without this findings. It was concluded that PWV in addition to known risk factors such as elevated blood pressure, atherogenic abnormalities of plasma lipids and lipoproteins, and elevated blood glucose, may be a reliable index of diabetic micro- and macroangiopathy.

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To study the relationship between serum uric acid, lipid fractions, and coagulation factor VII (FVII) in the elderly, we measured FVII coagulation activity (FVIIc). FVII antigen (FVIIag), in 138 normal subjects without alcohol intake ranging in age from 60 to 98 years. We also measured blood lipid fractions including apolipoprotein A-I, A-II, B, E, and serum cholinesterase activity (ChE). Serum uric acid levels significantly correlated with FVIIc (p<0.01) and FVIIag levels (p<0.05) as well as with tryglycerides, VLDL, LDL, total cholesterol, and ChE in elderly men, but not in women. However, multiple regression analysis showed these correlations in elderly men were not significant, after excluding the effect of triglycerides and VLDL. These results also suggest that elevation of uric acid may be a coronary risk factor in elderly men through high FVII levels.

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Elderly patients (aged ≥65 years) with non-Hodgkin's lymphoma were treated either with CHOP or COP-BLAM therapy, and the effectiveness and reverse effects of COP-BLAM therapy were compared with those of CHOP therapy. Thirty-three patients (aged ≥65 years) with previously untreated non-Hodgkin's lymphoma were entered either on CHOP or COP-BLAM regimen between September, 1979 and February 1990. To CHOP therapy was performed in 15 patients (median age; 70 years). Eight of them had diffuse large cell type lymphoma (large), five had diffuse medium-sized cell type (medium) and two had diffuse mixed cell type (mixed). As to clinical stage, there were patients in stage II, 4 in stage III and 9 in stage IV in CHOP group. Of 18 patients (median age; 68 years), who were treated with COP-BLAM therapy, 8 had of large lymphoma and 10 medium lymphomas in histopathological classification. In terms of clinical stage, there were 5 patients in stage II, 4 in stage III and 9 in stage IV. CHOP therapy and COP-BLAM therapy were performed according to the method reported by McKelvey et al, and by Laurence et al., respectively, using the full doses of drugs without consideration the age. Complete remission (CR) was achieved in seven (46.7%) of 15 patients treated with CHOP therapy. In this group, five (38.5%) of 13 patients in advanced stages (stage III or IV) entered CR. Of 18 patients subjected to COP-BLAM therapy, 15 (83.3%) achieved CR. Among 13 patients in advanced stage treated with COP-BLAM therapy, CR was achieved in 11 (84.6%). No significant difference in CR rate was found concerning the presence or absence of a bulky mass (larger than 8cm in diameter), bone marrow infiltration or B symptoms, and serum LDH levels (cutoff point; 400U/L) at a risk rate of 5%. As to adverse effects, we observed leukopenia (<1, 000/μL) in 26.7% of patients treated with CHOP and in 22.2% of patients treated with COP-BLAM, and thrombocytopenia (<5×104/μL) in 20.0% and 11.1% respectively. Other various adverse effects including nausea, vomiting, alopecia and peripheral neuropathy were observed. In elderly patients with non-Hodgkin's lymphoma COP-BLAM therapy demonstrated a higher CR rate with similar extent of adverse effects compared with CHOP therapy.

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A retrospective analysis of 312 stroke patients (200 men, 112 women; average age 65) admitted to Yamaguchi Rehabilitation Hospital during the past three years showed the following results. 1) After an average period of stay of 244 days 225 patients were discharged to home, general hospitals, extended care facilities, or nursing homes. 2) The group of patients over 80 years of age at admission had a lower ratio of home returns than in other groups (p<0.01). 3) Patients who returned home had higher scores not only on discharge Barthel index scores but on admission Barthel index scores, compared with other discharged patients (p<0.01). 4) The higher the admission Barthel index score, the shorter the period of stay (p<0.01). Concerning discharge Barthel index scores, patients who stayed over two years had lower scores than patients who stayed less than two years (p<0.01). The results of this analysis suggest the importance of determining goals and programs taking admission Barthel index scores as well as other available factors into consideration for patients with stroke admitted to rehabilitation institutions.

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Gastric xanthomas are single or multiple yellowish-white small nodules or plaques in the gastric mucosa. Microscopically they consist of macrophage-derived foam cells full of lipids. However, because of their benign nature, there are few reports of gastric xanthomas in the literature and their clinical significance still remains unknown. In this study, we studied 131 elderly cases (42 males and 89 females) with the average age of 75.6±12.3 (S. D.) years old who were examined gastroendoscopically. The endoscopic finding of gastric xanthomas was observed in 17 males (40.5%) and in 23 females (25.8%). Gastric xanthomas tended to increase with age, and the frequency was highest in the seventies (40.0%). Of the xanthoma cases, 42.5% had a solitary xanthoma, and 17.5% had more than 5 xanthomas. More than 70% of xanthomas were observed in antral and pyloric regions. There was no difference in serum lipids between the cases with and without xanthomas. Gastric mucosa biopsied from around xanthomas showed moderate to severe atrophic change of gastric glands in most cases (89%). Hyperplasia of gastric-pit epithelia and intestinal metaplasia were also often observed. However, there was no correlation between gastric xanthomas and small round cell infiltration in the gastric mucosa. It was concluded that gastric xanthomas in the elderly arise from the mucosa with atrophic change in most cases, which may have a disturbance of local lipid metabolism, and that the presence of gastric xanthomas may be a marker of the pathological aging change of gastric mucosa.

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A 85-year-old man was admitted to our hospital because of semicomatous status. Laboratory data on admission showed elevation of blood sugar (823mg/dl) and serum osmotic pressure (345mOsm/l), but ketonuria was not detected. Non-ketotic hyperosmolar diabetic coma was diagnosed. The insulin infusion and physiological saline improved the blood sugar level and consciousness within a day. The abdominal ultrasound examination revealed an abscess in the left kidney and right psosas muscle. The same findings were seen by abdominal computed tomography but the possibility of malignant neoplasm of the left kidney could not be ruled out because of a swelling of the left adrenal gland. Pain associated with psoas abscess and low grade fever were observed. Because of his poor general condition, drainage of the abscess was not performed and conservative therapy using antibiotics was administered. Without any improvement of the abscess, he died due to general deterioration four months later. Autopsy findings showed carcinoma of the left renal pelvis and metastasis to the right psoas muscle, left adrenal gland, liver, bilateral lungs and lymph modes. Psoas abscess is a relatively uncommon disease, especially in elderly patients. The etiology of the disease is devided into primary and secondary causes. Most secondary psoas abscess cases are caused by intestinal diseases, and Crohn's disease has been related to the highest incidence. A few cases of psoas abscess caused by colorectal carcinoma have been reported. Ultrasound and computed tomography are useful in diagnosing this disease and drainage of an abscess is necessary for therapy and proving the cause. Cancer metastasis should considered in differential diagnoses, when psoas abscess is seen in elderly patients.

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A 70-year-old man was admitted to our hospital because of fever and progressive dyspnea in December 1989. He was already diagnosed as having erythrocytosis secondary to pulmonary fibrosis 4 years previously and the values of his hematocrit (Ht) were maintained between 44.5 and 62.9% by repeated phlebotomy. Immediately after admission, severe diarrhea developed and the Ht value was 61.5%. Around 1:30 a. m. of the 3rd hospital day, he developed disturbance of consciousness. In addition, the serum levels of LDH, CPK, aldolase, and myoglobin of muscle origin increased markedly and the Ht value showed 78.5%. While the level of consciousness was gradually restored by 600ml phlebotomy and 1, 500ml saline infusion, dysarthria and hemiplegia became evident. The Ht value early in the morning of the 3rd hospital day was reduced to 59.4%. Although cranial CT and MRI performed 74 days and 15 months, respectively, after the onset of the symptoms failed to reveal any abnormal shadow, he was clinically suspected to have cerebral infarction. These findings emphasize that abrupt increase in Ht or blood viscosity is a possible factor triggering cerebral infarction, and adequate control of Ht value is recommended for the prevention of such a condition in the aged.

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A 70-year-old female patient with multiple bilateral pulmonary arteriovenous fistulas was referred to our hospital for its treatment. She had experienced frequent epistaxis and had nasopharyngeal telangiectasia. Her mother, sister and all four children also suffered from epistaxis. We diagnosed this patient as Rendu-Osler- Weber disease combined with multiple bilateral pulmonary arteriovenous fistulas. Her chest roentgenogram revealed 4 arteriovenous fistulas in the left lung and 2 arteriovenous fistulas in the right. On admission arterial blood gas analysis while breathing room air showed a PaO₂ of 39.8 torr and an SaO₂ of 75.4%. The percent of R-L shunt was calculated to be 56.5%. Because of severe hypoxemia, she underwent resection of four large fistulas in segments 3, 4, 5, and 8 of the left lung. Twenty-eight days after the operation, the PaO₂ was 76.4 torr and SaO₂ was 95.7%. There was no sign of enlargement in size of the remaining arteriovenous fistulas.

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