Assessment of human islet isolation with four different collagenases.

BACKGROUND: The isolation of islets from the human pancreas critically depends on the efficiency of the digestive enzymes. Liberase HI had been used as a standard preparation until the issues concerning bovine spongiform encephalopathy. Thus, we must now use other collagenases for clinical islet transplantation, four of which we have evaluated herein. METHODS: The digestion of each of 17 pancreata from brain-dead donors was performed using the following collagenases: Liberase HI (HI; Roche, n = 9); Liberase MTF C/T (MTF; Roche, n = 4); Collagenase NB1 Premium Grade (NB1; Serva, n = 7); or Clzyme Collagenase HA (CI, VitaCyte, n = 4). Islet isolations were based on the Edmonton protocol for HI, whereas our modified islet isolation method was used for the three new enzymes (MTF, NB1, and CI). RESULTS: There were no significant differences in donor age, body mass index, pancreas size, and cold ischemic time among the four groups. The phase I time in the NB1 group was significantly shorter than in the CI group (P = .0014). The prepurification IEQ/g in the HI group was significantly lower than the others (P = .0003 vs MTF, .0007 vs NB1, and .0009 vs CI, respectively). The postpurification IEQ/g in the MTF group was significantly higher than in the HI group (P = .006). The viability in the NB1 group was significantly greater than the HI group (P = .003). CONCLUSION: Three new enzymes (MTF, NB1, and CI) may enable us to obtain higher islet yields than with HI.

[Home anti-cancer therapy with a venous port].

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

Physical activities and energy expenditures of institutionalized Japanese elderly women.

The daily energy expenditure and physical activity index of institutionalized Japanese elderly women were measured. One hundred and thirteen Japanese elderly women (aged 79.5 -/+ 7.0 y) who live in institutions for the elderly and receive meal services participated voluntarily. A dietary survey, energy metabolic study, and time study were carried out over three consecutive days, and the basal metabolic rate (BMR) and energy expenditure by physical activity were measured. The intensity of daily physical activity was based on the physical activity index (PAI: total/basal energy expenditure). The mean BMR was 881 +/- 145 kcal/d (20.9 +/- 3.8 kcal/kg BW). The PAI in individuals ranged from 1.01 to 1.57, the mean value was 1.26 +/- 0.14, and 64% of the subjects examined showed a lower value than 1.3 of PAI. From these values, the mean total energy expenditure was calculated as 1,112 +/- 231 kcal/d (26.2 +/- 5.2 kcal/kg BW).

[Building aging level indices based on ability to perform personal care and household management activities].

Defining aging as deterioration of the ability required for the activities of daily living with increasing age, we developed a formula for estimating the age of aging. In 1994 and 1995, a questionnaire survey was conducted for 11,592 individuals (4,885 men, mean age 61.6, standard deviation 14.6; and 6,677 women, mean age 63.2, standard deviation 14.8) who were members of 7 cohorts (5 community-based cohorts and 2 cohorts of examiners at a health-promotion center). The questionnaire included three groups of questions related to medical treatment, aging-related symptoms, and personal care (ADL; Activities of Daily Living) and household management (IADL: Instrumental ADL). Multiple regression analysis was made by sex and age group (over 65 years old, under 65 years old) using age as a dependent variable and the three question categories as explanatory variables. Using multiple regression analysis by question category, five items were abstracted from each of the three groups, so that a total of 15 items were abstracted from all questions. Five items were then abstracted from the 15 by multiple regression analysis, and the predicted aging age for an individual is estimated using this statistical model from the results of the questionnaire survey. The predicted aging age is significantly associated with age (r = 0.40-0.49, p = 0.0001). The difference between the predicted aging age and age is greater among the older or younger people. The expected predicted aging age is estimated using regression analysis of the predicted aging age on age. Aging level indices by sex and age groups were determined by the difference between the expected predicted aging age and age. We are planning to carry out an epidemiological study on the risk factor for aging using the aging level indices in seven cohorts.

[Assessment of beta-methyl lodophenyl pentadecanoic acid myocardial scintigraphy in patients with chronic pulmonary diseases].

The purpose of this study was to determine whether impaired fatty acid metabolism occurs in the right ventricle of patients with chronic pulmonary diseases (TB sequelae, TB seq.; 8, and chronic pulmonary emphysema. CPE; 14). 123I-BMIPP myocardial scintigraphy was performed on 22 subjects. The RV-BMIPP index (ratio of radioactivity in the right ventricle to that in the upper mediastinum), LV-BMIPP index (ratio of radioactivity in the left ventricle to that in the upper mediastinum), and RVc/LVc (ratio of radioactivity in the right ventricle to that in the left ventricle) were calculated to compare the distribution of radioactivity in the right and left ventricles. We also examined the correlations between these parameters and parameters of blood gas analysis and pulmonary hemodynamics. The RV-BMIPP index. LV-BMIPP index, and RVc/LVc were elevated in the TB seq. and CPE patient groups compared to the control group. The RV-BMIPP and LV-BMIPP indices demonstrated significant, negative correlations with PaO2; also a significant positive correlation was observed between the RV-BMIPP index and mean pulmonary arterial pressure. On the other hand, no significant correlation was found between the LV-BMIPP index and mean pulmonary arterial pressure. In the arm-stretching test under right heart catheterization, the RV-BMIPP and LV-BMIPP indices demonstrated significant, positive correlations with the cardiac index during exercise. These results suggest that hypoxemia accelerates fatty acid metabolism in the myocardium, and that local pressure overloading accelerates fatty acid metabolism in the right ventricle. Anomalies of fatty acid metabolism in the right ventricle may appear in patients with chronic pulmonary disease, and could be an adaptation to hypoxemia and overload, not an impairment.

Disappearance of diurnal rhythm of energy expenditure in genetically diabetic obese rats.

The daily profile of energy expenditures was examined in the new animal model of genetically diabetic obese rats. The diurnal rhythm was observed at 8 weeks of age, with highest and lowest values for energy consumption per hour observed in the dark and light periods, respectively. However, at 24 weeks of age after the manifestation of noninsulin-dependent diabetes mellitus, the rhythm completely disappeared, but it did not in the control rats.

[Assessment of the distribution of renal cortical blood flow by contrast ultrasonography].

The importance of the distribution of intrarenal blood flow in the regulation of various renal functions, such as urine concentration and sodium excretion, has been well recognized. However, there have been no reliable methods to measure local flow in the kidney in vivo. The present study demonstrated the usefulness of contrast ultrasonography combined with injection of sonicated 5% albumin for assessment of the distribution of renal cortical blood flow in eleven mongrel dogs. The left kidney was displayed by tomographic echography, and microbubbles of sonicated albumin were injected into the abdominal aorta above the left renal artery. Video density time curves were generated and fitted to a time-intensity curve. Intrarenal infusion of acetylcholine (4.0 micrograms/kg/min) increased renal blood flow (RBF) from 2.5 +/- 0.3 to 4.6 +/- 1.0 ml/min/g kwt (p < 0.01), and norepinephrine (0.5 microgram/kg/min) decreased RBF from 2.5 +/- 0.3 to 1.2 +/- 0.5 ml/min/g kwt (p < 0.01). There were significant positive correlations between percent change in RBF and peak intensity and area under the curve, which were calculated with a time-intensity curve. Furthermore, the inner/outer renal cortex ratio of peak intensity significantly increased during acetylcholine infusion (0.72 +/- 0.11 vs 0.86 +/- 0.09; p < 0.01), whereas no significant change was observed during norepinephrine infusion. These results suggest that renal contrast ultrasonography may be useful for real-time assessment of the distribution of renal cortical blood flow in vivo.

[Characteristics of medical institutions visited by 30 intractable disease patients receiving financial aid for treatment].

In order to determine the characteristics of medical institutions which patients with 30 intractable diseases visited, we analyzed data of a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee in 1989. Each of 47 prefectural governments in Japan reported information of all patients with 30 intractable diseases who received financial aid for the diseases between April 1988 and March 1989. Information collected about each patient consisted of identification numbers, which included the disease code, sex, age, the code of the municipality where the patient lived, the medical institution which treated the patient, etc. Out of 173,637 patients whose information was reported by prefectural governments, we used data of 159,910 patients whose medical institutions were reported completely. The results can be summarized as follow: 1) Of the 159,910 patients, 8.6 percent visited medical institutions outside of the prefectures where the patients lived. Many patients living in prefectures located close to large cities, such as Tokyo, visited medical institutions in large cities. 2) The proportion of patients who visited hospitals of medical schools was 27.9 percent. 3) Patients who were affected by diseases causing physical disabilities such as SMON and malignant rheumatoid arthritis tended to visit medical institutions located in their neighborhoods and were treated in small hospitals or clinics. Old patients had the same tendency as patients with such diseases. 4) Although the number of patients receiving aid in 1988, whose data we analyzed in the current study, was larger than that in 1984, the proportion of patients visiting medical institutions outside of the prefecture where the patients lived, and the proportion of patients visiting hospitals of medical schools were nearly equal to those in 1984.

[Study of yearly changes in intractable disease patients receiving financial aid for treatment].

Yearly changes of intractable disease patients receiving financial aid for treatment were observed for 24 intractable disease patients from 1983 to 1987. The results obtained were as follows. 1. The number of intractable disease patients receiving financial aid for treatment increased from 1983 to 1987 for 23 of the diseases. Only the number of SMON patients did not increase. 2. Medical care expenditures for these patients also increased since 1983. Greater increases for in-patients than for out-patients were seen for Huntington's chorea and Behcet's disease, while larger increases were seen for out-patients with Parkinson's disease, Scleroderma.dermatomyositis.primary multiple myositis, Buerger's disease, and others. 3. The proportion of national health insurance holders among intractable disease patients was 42.1% as compared with 34.7% among total national patients. The proportion was especially higher for Huntington's chorea (64.6%), Parkinson's disease (64.1%) and SMON (59.4%) patients.

[An epidemiologic study on patients with lung disease, using a data base management system and the histopathologic diagnosis].

A new pathologic data base management system was introduced in the Section of Pathology, Clinical Laboratory, of this hospital for an efficient sorting and searching past data and for the rapid epidemiological study of them. By the use of this system, the incidence and the age and sex distribution of various diseases were studied in a total of 1,264 patients received pathological examination for surgically operated specimens or biopsied materials at the Chest Disease Research Institute Hospital, Kyoto University, from January, 1986 to December, 1988. A gradual increase in the number of frozen section samples of surgically removed organs and of open lung biopsies was noted during this period. Adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma amounted to 42.5%, 32.9%, 12.2%, and 7.5% of primary lung cancers, respectively. The male-to-female ratio of patients with primary lung cancers was 2.9:1 but there was no significant difference in the age distribution among four types of the primary cancers in both sexes. Two hundred and ninety nine (32.6%) patients were diagnosed as non-neoplastic lung diseases: 121 infectious (13.2%), 69 granulomatous (7.5%), 62 pulmonary fibrotic (6.8%) and 47 miscellaneous non-neoplastic (5.1%) diseases.

Long-term effect of energy restriction at different protein levels on several parameters of nutritional assessment.

Experiments were conducted to evaluate long-term effects of energy restricted diets containing different protein levels initiated in adult life on various parameters of nutritional assessment. Rats (male SPF Wistar) were fed 20%-casein diet ad libitum, or 10%-, 20%-, or 40%-casein diets (group 10R, 20R, and 40R, respectively) under energy-restricted conditions, which corresponded to about 60% ad libitum feeding, from 18 to 55 weeks of age. Energy restriction induced a decrease of body-lipid percentage. Although skeleton weight and tail length increased throughout the experimental period in all the groups, these increases were found to be depressed under energy restriction. On the other hand, protein intake level under the energy restriction did influence plasma concentrations of urea and cholesterol, hematocrit, and systolic blood pressure. The group fed the 40%-casein diet tended to be lower in total cholesterol levels at 55 weeks of age, while the group fed 10%-casein diet tended to be lower in hematocrit and higher in systolic blood pressure levels. When mature rats were fed the 60%-energy-restricted diet for a long-term period, those on the 20%- and 40%-casein diets showed somewhat more preferable levels of hematocrit and blood pressure than those on the 10%-casein diet; the 10%-casein diet did not, however, reveal symptoms of malnutrition.

A clinical and manometric correlation for assessment of postoperative continence in imperforate anus.

Functional results after surgical correction of anorectal malformations were assessed on a clinical basis following Kelly score and by manometric study. Forty-six patients, aged 2--17, were personally interviewed and 25 of these 46 had manometric studies to evaluate postoperative continence. The manometric study was also performed on 35 normal children as a control group. Continent patients characteristically had marked high pressure zones as did the normal subjects. On the other hand, in the patients with fair or poor results, the anorectal pressure profile had no marked high pressure zone in the anal canal. The presence of normal anal pressure at rest as well as adequate ano-rectal pressure difference was found to correlate well with continence. In patients with perineoplasty, the ano-rectal reflex correlated well with continence but not in patients treated by abdominoperineal rectoplasty.

A manometric assessment of anorectal pressures and its significance in the diagnosis of Hirschsprung's disease and idiopathic megacolon.

Anorectal manometric studies were performed on nine patients with Hirschsprung's disease and ten patients with idiopathic megacolon for the purpose of differentiation, comparing with those of the normal subjects. The anorectal reflex was absent in all nine of the patients with Hirschsprung's disease while in all of ten patients with idiopathic megacolon rectal distension produced a relaxation in the anal canal like that of the normal subjects. Manometric studies proved to be a reliable and non-invasive technique for the diagnosis of Hirschsprung's disease and were of particular value as simple screening tests in patients with a clinical suggestion of this disease. The manometric studies of the patients with Hirschsprung's disease or idiopathic megacolon in the present series also demonstrated that the pronounced internal sphincter contraction combined with a total absence of reflex relaxation or an inadequate response of the sphincter to rectal distension might be responsible for the obstructive symptoms in these diseases.