To clarify the chief complaints, pancreatograms, pancreatic exocrine function and glucose tolerance at diagnosis and their serial changes in chronic pancreatitis (CP), 112 patients with alcoholic CP, nine with biliary CP and 49 with idiopathic CP were studied. The following conclusions were obtained. Seventy-seven patients with alcoholic CP, nine with biliary CP and 22 with idiopathic CP had presented with recurrent abdominal pain for more than one year before the time of diagnosis. Chief complaints consisted of abdominal pain, diabetes mellitus and others. Proportion of patients with abdominal pain was significantly higher in alcoholic CP than in idiopathic CP. Elderly patients with CP presented with abdominal pain less frequently than non-elderly patients. These findings indicate that chronic pancreatitis should be considered when diagnosing and treating diabetics and the elderly. Patients with alcoholic CP were significantly younger than those with nonalcoholic CP at diagnosis. Sex distribution showed male predominance in alcoholic CP and female predominance in nonalcoholic CP. Calcification in the pancreas was detected more frequently in alcoholic CP than in nonalcoholic CP. The number of patients with CP increased in more recent years. Alcoholic CP showed more severe damage of the pancreas than nonalcoholic CP at the time of diagnosis. No differences between alcoholic CP and nonalcoholic CP were found in the frequency of the progressive changes in pancreatograms. Deteriorative changes in pancreatic exocrine function were not related with etiological category, but improvement was observed frequently in nonalcoholic CP. The deterioration of glucose tolerance was not related with etiological category, drinking habit and pain relief.
To investigate the relief of pain, quality of life and treatment of chronic pancreatitis (CP), 112 patients with alcoholic CP, nine with biliary CP and 49 with idiopathic CP were followed up. Partial or complete relief of pain was obtained in 64 patients with alcoholic CP (66%), nine with biliary CP (100%) and 29 with idiopathic CP (88%). Alcoholic CP showed a significantly lower ratio of pain relief than nonalcoholic CP. A long follow-up period (≥6 years) revealed greater pain relief. Patients with discontinued or decreased intake of alcohol showed a significantly higher ratio of pain relief than those continuing drinking. These findings indicate that factors contributing to pain relief are etiological category of CP, drinking habit after diagnosis and length of the follow-up period. Deterioration in quality of life was observed in 42 patients with alcoholic CP, one with biliary CP and 13 with idiopathic CP. Main causes for the deterioration in quality of life were pain, diabetes and loss of interest in work. Abstinence is important for patients with CP to maintain their quality of life. Endoscopic removal of protein plug contributed to pain relief. Surgical treatment was done in 54 patients with CP. Pain relief was observed in 41 operated patients, and deterioration in the quality of life in 17. Abstinence was important for operated patients as well as nonoperated patients to obtain pain relief and maintain the quality of life. Clinically overt steatorrhea was observed in two patients with CP, which was improved by a large dose of enzyme replacement therapy. Aggravation of diabetes had been observed, and number of patients dependent on insulin therapy increased during the follow-up period. Diabetes must be treated carefully because diabetes is an important factor contributing to the prognosis of CP.
To investigate complications, prognosis and prognostic factors for chronic pancreatitis (CP), 170 patients with CP (112 with alcoholic CP, nine with biliary CP and 49 with idiopathic CP) were followed up. Pancreatic pseudocysts were found in 29 patients with CP, biliary stenosis in 20 patients, and a peptic ulcer in 26 patients. Determination of whether the abdominal pain is caused by acute exacerbation of CP or by the peptic ulcer is important, because abdominal pain due to peptic ulcer is easily relieved by administration of H2-receptor antagonist. Mild liver damage or chronic hepatitis was observed in 26 patients with CP; and liver cirrhosis in nine. Duodenal stenosis was found in two patients. Thirty-nine patients with CP died during the follow-up period. Patients with alcoholic CP were significantly younger than those with nonalcoholic CP at the time of death. Thirteen patients died from malignancy which was the most frequent cause of deaths. Sudden deaths were observed in seven patients. Six patients died from pneumonia which was refractory to the intensive medical treatment. Three patients died from diabetic renal failure and three from heart failure. The observed number of CP was significantly higher than the expected number for the sex-age-matched general population in total deaths and cancer deaths. A similar finding was obtained in alcoholic CP. Alcoholic CP showed poorer prognosis than nonalcoholic CP. Contributing factors to the prognosis were age at the time of diagnosis, diabetes, smoking habit, outcome of pain, years at diagnosis in alcoholic CP, whereas they were age at diagnosis, smoking habit and diabetes in nonalcoholic CP. This indicates that abstinence, quitting smoking, and careful treatment for diabetes are important for improving the prognosis of CP.
Neutrophil function in patients with acute renal failure (ARF) and serum inhibitors of neutrophil chemotaxis associated with ARF were studied. Neutrophil function was examined by measurement of chemotaxis, phagocytosis and superoxide anion generation by neutrophils. Chemotaxis, phagocytosis and superoxide anion generation by neutrophils in ARF patients showed significantly (p<0.01) reduced quantities (84.4±34 counts/field, 320±195 counts/100cells and 0.78±0.21 nmol/min/105cells, respectively) in comparison with normal healthy subjects (117±26.6, 582±132, 1.41±0.25, respectively). Sera from ARF patients were studied before and after hemodialysis. Hemodialysis reduced the inhibition of chemotaxis and phagocytosis of normal neutrophil by sera from ARF patients. When sera of these ARF patients were fractionated by Sephacryl S-300 column chromatography, the specific fractions responsible for reducing chemotaxis were found in the molecular weight range of 2001500 daltons, which were not found in normal healthy subjects. The rate of inhibition of chemotaxis by fractionated inhibitors was reduced approximately 30% by hemodialysis. These findings suggested that hemodialysis for ARF patients contributes to the preservation of neutrophil function.
The effect of endotoxin administration on zinc metabolism was studied in rats. In the endotoxin-treated rats, serum zinc concentration was significantly reduced as compared to saline-treated rats (control group). On the other hand, hepatic zinc concentration was significantly increased after endotoxin administration as compared to the control group. However, the zinc concentrations of the liver cell components showed slightly dissimilarity. In the mitochondria and cytosol, the concentration increased significantly after endotoxin administration as compared to the control group, whereas no change was observed in the microsomes. Furthermore, we have examined whether the increase of the zinc level in the cytosol of the liver is associated with zinc-binding protein metallothioneins (MTs) or not. MTs also increased significantly after endotoxin administration. Furthermore hepatic MTs were analyzed for MT isoforms. In the endotoxin-treated MT-II was the major Iso-MT. Judging from these results and some other published reports, the role of zinc metabolism in endotoxemia is proposed to be as follows. In endotoxemia the serum zinc concentration is reduced and as a result the production of superoxide by polymorphonuclear leukocytes is increased as zinc has an inhibitory effect on it. This free radical helps the host against the organism. On the other hand zinc accumulation in the liver following endotoxin administration increases the activity of the zinc binding-enzyme and also stabilizes the plasma membrane. MTs induced by endotoxin protect the host from the harmful effects of the free radical on the host by its scavenging action.
To determine the relationship between halothane metabolism and hepatic injury following halothane anesthesia, male rats pretreated with phenobarbital for 5 days were fasted for 24 hours, and then exposed to 10% or 100% oxygen, or to 0.7% halothane at 10% or 100% oxygen for 2 hours. In the group of rats exposed to halothane at 10% oxygen, increases of GPT, OCT and free F- ion in the plasma, a decrease of GSH in hepatocytes, and centrilobular-necrosis in hepatic tissue were seen, but not in the groups of rats exposed to 10% oxygen or halothane at 100% oxygen. Furthermore, hepatic tissue PO2 in the group of rats exposed to halothane at 10% oxygen decreased to less than 10mmHg. This value has been reported that reductive metabolism of halothane became dominant rather than oxidative metabolism. These results indicated that hepatic injury following halothane anesthesia in rat closely related to the increase in reductive metabolism of halothane.
Using male rats pretreated with phenobarbital (PB), fasted, and then exposed to 0.7% halothane at 10% or 100% oxygen, the content and activity of hepatic microsomal enzymes were measured. The content of cytochrome b5 and the activity of NADPH-cytochrome P-450 reductase were increased by PB-pretreatment, but not changed by exposure to halothane at 10% or 100% oxygen. Although the content of cytochrome P-450 (P-450) and the activity of aminopyrine demethylation were increased by PB-pretreatment and decreased by exposure to halothane at 10% oxygen, aniline hydroxylation activity was decreased by PB-pretreatment and not changed by exposure to halothane. These results suggested that the subtypes of P-450 which were increased by PB-pretreatment were decreased by exposure to halothane at 10% oxygen. A close relationship may exist between the decreases in content of P-450 and the development of hepatic injury following halothane anesthesia in rat.
To examine the effect of hypoxia on extravascular lung water (EVLW), rats were divided into 3 groups. The first group (G1, n=9) rats as control were allowed to breathe air spontaneously. The second group (G2, n=9) and the third group (G3, n=7) rats were mechanically ventilated for 1 hour with room air and with 10% oxygen in nitrogen, respectively. Subsequently, lungs were removed and EVLW were measured by the improved gravimetric method. Values of EVLW/(blood-free lung dry weight) are 3.64±0.23 (mean±SD) in G1, 3.97±0.29 in G2 and 4.04±0.33 in G3. There were significant differences in values between G1 and G2, and between G1 and G3. Mechanical ventilation increased EVLW. In conclusion, 1 hour hypoxia did not affect EVLW. Hypoxia did not induce hydrostatic pulmonary edema nor permeability edema.
The dynamics of systemic and hepatic circulation of 54 dogs were investigated both during and after anesthesia with halothane plus 60% nitrous oxide (GOF) and halothane plus 60% nitrogen (OF). To examine the effects of nitrous oxide, the systemic and hepatic circulation dynamics of GOF and OF anesthesia were compared at the same halothane concentration (1.5%) and minimum alveolar concentration (1 and 2 MAC) in both procedures. There were no significant differences in the dynamics of GOF and OF at 1.5% halothane concentration. The halothane concentrations of 0.9% and 1.25% were equivalent to 1 MAC of GOF and OF, respectively. The mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI), hepatic arterial blood flow (HABF), portal venous blood flow (PVBF), and total hepatic blood flow (THBF), all decreased dose-dependently after starting inhalation during GOF and OF (1 and 2 MAC). After stopping inhalation, MAP and HABF recovered rapidly, but the recovery of HR was slow and the recovery of CI, PVBF and THBF was poor. GOF of 2 MAC caused remarkable reduction (77.9%) of hepatic oxygen supply. The results indicate that nitrous oxide itself has less effects on hepatic circulation dynamics, and that deep anesthesia of GOF should be avoided since halothane decreases hepatic blood flow dose-dependently.
The pharmacodynamics of non-depolarizing muscle relaxants in chronic renal failure (CRF) was examined in a rat model made by removing three-fourths of the right kidney and total of left kidney. Single dose response curves in the CRF group and control for pancuronium and vecuronium were obtained respectively to investigate the pharmacodynamics of these drugs in CRF. Single dose response curves for both drugs in CRF were significantly shifted to the right compared to those in the control. This means that more non-depolarizing neuro-muscular blocking agents are needed in CRF to obtain the same neuro-muscular block as in the control. The factors changing the pharmacodynamics in CRF are hyperpotassemia, hypercalemia, large distribution volume, metabolic acidosis and possible accumulations of methyl guanidine and guanidine. This study suggested that more non-depolarizing muscle relaxants are necessary in CRF in the initial dose because of the resistance in pharmacodynamics and less in the maintenance dose because of the accumulation in pharmacokinetics.
The effects of the calcium channel entry blocker nimodipine on the brain injury induced by complete global brain ischemia (CGBI) in dogs were studied. Dogs were kept under 18 minutes of CGBI by a method of clamping the ascending aorta combined with a bypass formation between the aorta to the right atrium and the aorta to the femoral vein, and then divided into two groups, control group and nimodipine-treated group (group N). In this study, 10μg/kg of nimodipine was initially administered 15 minutes after CGBI followed by a maintenance doze of 1.0μg/kg/min for 6 hours. In both groups, hemodynamic changes, such as cerebral blood flow (CBF), mean arterial pressure (MAP), and heart rate (HR) were measured for seven hours after CGBI, the neurologic data were recorded for seven days after CGBI and the histological changes were evaluated on the 7 th day after CGBI. The reduced CBF in group N was significantly improved compared to the control group, MAP and HR in group N were lower than in the control group, and the increase in CI in group N was greater than in the control group. Neurologic data also showed no significant difference between the two groups, and the histological examination showed that damage of cerebral cortex and CA3 region of hippocampus in group N was severer than in the control group. In conclusion, nimodipine had no beneficial effects on brain injury induced by 18 minutes of CGBI and the delayed post-ischemic hypoperfusion itself might not necessarily play an important role in brain injury.
In vitro immunoglobulin synthesis in JRA was compared with that in the normal control as a representative marker of B and T cell function, in particular, of helper and suppressor T cell function. Increase in spontaneous IgG synthesis was observed in 4 patients with active JRA. PWM stimulated immunoglobulin synthesis including IgG, IgM and IgA was decreased significantly in JRA as compared to that in normal controls. Functional impairments of T and active phase B cells were observed in JRA in co-culture experiments. This T cell abnormality appears to be due to helper T cell dysfunction and to be specific to this disorder. Suppressor T cell function is significantly decreased in JRA. IgG suppressor T cell function, in particular, correlated significantly with activity of the disease. In JRA, there appears to be an imbalance in immuno-regulatory functions resulting from extensive functional impairments in B, suppressor T and helper T cells. The association in particular of functional impairments of B and suppressor T cells with the activity of JRA, suggests that these cells are involved in the process of remission and exacerbation or etiology of JRA.
Urinary excretion and exhalation of trichloroethylene were examined in rats. After intraperitoneal injection of trichloroethylene (1 m mole per Kg body weight) to Wister female rats, urine and expired air were collected regularly. The concentrations of trichloroethylene in exhaled air were determined by gas chromatography. The urinary metabolites of total trichlorocompounds (trichloroethanol glucronide and trichloroacetic acid) were measured by colorimetry. After the injection of trichloroethylene, the exhalation rate per hour of the vapor in expired air increased rapidly and reached a maximum (7.8%) in with 2 hours, then decreased with a half of 0.7 hours at a rapid phare. The elimination ratio of trichloroethylene to administered trichloroethylene in expired air for 7 hours after the administration of trichloroethylene was 20.7%. The total excretion ratio in urine as metabolites to administered trichloroethylene for 144 hours after administration was 16.96% for total trichloro-compounds. The total excretion ratio of both expired air for 7 hours and urinary metabolites for 144 hours was 37.3% of the trichloroethylene administered. The ratio of amounts of urinary excretion to those of expiratory excretion was 0.8.
The organ distribution and the concentration of trichloroethylene were defermined in mice exposed to trichloroethylene 500ppm. Organ distribution of trichloroethylene was in the descending order of adipose tissue, such as the kidneys, the lung, the liver, the spleen, the heart, the digestiveorgan and brain. The concentration of trichloroethylene in the organ decreased in descending order of the blood>the kidneys>the brain>the heart. Biological half lif in the blood, the lungs and the kidney was within 30 minutes and that in the brain, the stomach and the heart over 2 hours.
To defermine the mutual metabolic inhibition of trichloroethylene and ethanol, experiments were conducted on mice. Mice were injected both solvents at 60 minutes intervals intraperitoneally, and 30 or 45 minutes after the final injection, concentration of both solvents in the blood and organs were determined. Mice were preliminarily administered trichloroethylene intraperitoneally (131mg/Kg) and ethanol (500mg/Kg). The ethanol concentrations in blood, brain and livers of mice administered with trichloroethylene were higher than those in the respective organs of mice without trichloroethylene. When the mice were administered ethanol followed by trichloroethylene the concentration of trichloroethylene in mice given ethanol was higher than that of in mice not given ethanol injection.
Rats were injected trichloro-compounds (TTC) of, 1 m mole/kg body weight and urine taken and stored by various methods. The ration of total trichloro-compound concentration to creatinine in rat urine was not changed after storage at 4°C for 7 days or after kept in the frozen state for 15 days compared with those before storage. The filter paper was dipped in rat urine dried and stored at 5°C, 10°C and 25°C, the total trichloro-compound concenration to hreatinine ratio before and after storage were examined. These finding indicate the rations were not changed after 9 days at 5°C or 10°C and after 6 days at 25°C compared with the ratio before storage.
A close correlation was observed between 3 climatic factors (atmospheric temperature, duration of sunshine and rainfall amounts in July) and the date showing 50% positive rate of hemagglutination inhibition (HI) antibody of Japanese Encephalitis in swine in each prefecture of Japan from 1982 to 1988. The multiple regression equation to estimate the date showing a 50% positive rate of HI antibody in swine from 3 climatic factors was established. A close correlation was obtained between the date showing 50% positive rate of HI antibody in swine and the date showing first outbreak of Japanese encephalitis patient, and the difference in days from the latter to the former was calculated to be 20.6±11.5 days.
Hemagglutination inhibition (HI) reaction of Japanese encephalitis was determined with the sera of inpatients at a hospital in Kurashiki City. The ratio of inpatients having a hemagglutination inhibition (HI) reaction abobe 10 to all patients decreased from 86.8% in 1982 to 67.9% in 1985, indicating that about one third of the patients had trace HI antibody in 1985. The titer of HI antibody in inpatients decreased yearly. The titer obtained in 1984 was significantly lower than that obtained in 1983 and the titer obtained in 1985 was significantly lower than that obtained in 1984. Thus the biological half life of HI titer in the sera of inpatients was 1.8 years.
A novel method was developed to investigate the mechanisms about the transferrin receptor (TfR) expression in human erythroid cells. Human bone marrow smear was reacted with OKT9 monoclonal antibody to measure TfR on a single erythroid cell using K562 cells as an inner control. TfRs detected by OKT9 were visualized by autoradiography. The maturational stage and stainable iron granules (SIGs) of erythroid cells were identified by Wright Giemsa staining method and iron staining method alternately. Using this method, the following results were obtained. TfR was expressed on immature erythroid cells from proerythroblasts to immature RBC, with a decreased number occurring during erythroid maturation, and was absent on mature red cells. Maximal density of TfR occurred at the proerythroblast stage and then decreased progressively during maturation to immature RBC. It is assumed that cell maturation had a suppressive effect on TfR expression. The mean number of TfRs on erythroblasts was obviously higher in iron deficiency, and lower in iron overload. Although stainable iron granules had no manifest correlation with TfR number on each erythroid cell within each patient, there was a negative correlation between the mean number of TfRs and that of SIGs obtained from each donor (r=-0.89). The same correlation was obtained between mean density of TfRs and that of SIGs. These findings indicate that, in the human erythroid cell, cell maturation may be a key regulatory factor than stainable iron granules in TfR expression of erythroid cell. However, when examined in different iron environments, the mean stainable iron granule which may be regarded as one measurable form of iron state clearly correlated negatively with the state of TfR expression.
To determine the influence of intracellular hemoglobin on the expression of transferrin receptors (TfRS) in human eryhtroid cells, a novel method was developed to measure cell morphology, cellular hemoglobin content, and the number of stainable iron granules and TfRs at the single-cell level. The relation between hemoglobin content and cell maturation was confirmed. There were no significant correlations between hemoglobin content and the number of stainable iron granules, or between hemoglobin concentration and the concentration of stainable iron granules. Although the number of TfRs was not related to cellular hemoglobin content, TfR density was negatively related with hemoglobin concentration (r=-0.71). These results suggest that hemoglobin concentration plays an important role in the expression of TfRs in human erythroid cells.
The methods of simultaneous analysis of heavy metals in urine using simultaneous multielement atomic absorption spectrophotometry were examined. Seven elements, Co, Cr, Cu, Mn, Ni, Pb, Cd, important as environmental chemical hazards were examined concerning, analytical method, term and cautionary points for human urine analyses. Analytical method of creatinine in urine was improved with no reexaminations. Standard added method is superior to the working curve method for human urine analyses. Highly precise urine analysis is possible by the standard added method without consideration for deterioration of source of light.
The concentration and distribution of cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), cadmium (Cd) in normal human urine were determined. A total of 334 (264 males and 70 females) human urine samples were taken from normal adult subjects from 20 to 80 years old living in Okayama city, Seto-tyo, and Himeji city. Then the heavy metal concentrations were measured with a flame-less atomic absorption spectrophotometer. Heavy metal concentrations in male urine was in the descending order of Cu (G. M.: 18.87μg/g creatinine)>Ni>Pb>Co>Mn>Cd>Cr (G. M.: 0.440μg/g creatinine). The order of heavy metal concentration in female urine was in the descending order of Cu (G. M.: 22.61μg/g creatinine)>Ni>Co>Mn>Pb>Cd>Cr (G. M.: 0629μg/g creatinine).
Exercise test with a treadmill at 2 constant work loads (2 and 4 METs) and measurement of MIP were carried out in 73 patients before lung resection. 69 patients underwent surgery and postoperative cardio-pulmonary complications developed in 16. During the exercise, expiratory gas analysis was performed. VO2/VE at 4METs seemed to be useful for the evaluation of the exercise performance and was significantly lower in the cases with complications than in those without (P<0.05). MIP was also significantly lower in the cases with complications (P<0.01). The product of FEV1.0 (ml/m2) by VO2/VE (%) at4METs was defined as “Oxygen uptake index” (OUI). Exercise capacity and development of complications were correlated with OUI more closely than FEV1.0 or VO2/VE at 4METs alone. Postoperative complications developed in 15 out of 29 cases with a predicted OUI of V3300 and MIP of V110cmH2O, and not in 39 of 40 cases with a predicted OUI of >3300 and/or MIP of >110cmH2O. Thus, FEV1.0, VO2/VE at 4METs, and MIP reflect the potentiality of volume, quality, and power of respiratory system, respectively. Therefore, these 3 parameters are considered to be essential and actually useful in the evaluation for tolerance of lung resection.
Traditionally, no patients have any limitation in selecting a doctor in Japan. A new public hospital started a special outpatient service for patients referred from private clinics in the are of K-ku of Y city; this is called “the referral system”. Medical records of referred patients as well as non-referred patients were analyzed and a questionnaire survey was conducted to the residents in the area of K-ku in order to evaluate the effects of the system. The distribution of sex, age and disease and the rate of admission were different between referred patients and non-referred patients. The matched-pair analysis of sex and age characteristics between referred patients and non-referred patients demonstrated that the system was effective in utilizing different functions of medical care services between hospitals and private clinics. Residents with a regular family physician showed a positive attitude towards the new system. Further consideration of the conditions of referral will be necessary to develop the system.