Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

Alcohol dependence syndrome and BDIM (before-discharge intervention method)--report 4, the family members' self-reports about BDIM]

One hundred fifty-three inpatients with alcohol dependence syndrome were treated with the structured BDIM (Before-Discharge Intervention Method). 82 patients of them have participated to self-help group meetings or kept having therapy as our outpatients or inpatients during the study period. We chose the families of the 82 patients as our study subject Out of the study subjects who took part in BDIM, 64 families (117 persons) answered our questionnaire. Among them 63 families (101 persons) gave their described answers of impressions and opinions about BDIM, which were summarized as follows. (1) Through BDIM the family members gained second thought on their alcoholic family member (IP: identified patient) and they could tell their new view to IP. BDIM enabled them to tell IP their sincere feeling and hope for recovery of IP. BDIM empowered both IP and IP's family members. (2) The family members became to know IP's orientation on his or her disease. They came to know IP's denial and understand him or her as he or she was. (3) The family members felt emotional ties among themselves and IP through BDIM. When the family members of a dysfunctional family took part together in BDIM, they could know the feelings, thoughts, experiences and hopes one another. The family members had a precious experience of mutual understanding among themselves and IP to hope for recovery together. (4) The family members appreciated BDIM as a effective therapy. In BDIM many of them regarded highly of giving their letters to IP as a useful method to convey their feeling and thoughts calmly to IP. (5) On the other hand some family members pointed out the difficulty for themselves to write on BDIM. For family members who are not good at writing a letter or tend only to blame IP through their letters, writing and giving letters to IP is not appropriate as a therapy. If family members feel strong anxiety or fear, it is safe not to practice BDIM.     

Abnormal fluorine-18-fluorodeoxyglucose uptake in benign esophageal leiomyoma

A benign esophageal leiomyoma with abnormally increased fluorine-18-fluorodeoxyglucose uptake on positron emission tomography (PET) was resected thoracoscopically. The tumor, of which the maximum standardized uptake value of the lesion was 4.7, was well defined and 38 mm in diameter. Neither mitotic activity nor degeneration was found histologically; and immunoreactivity for CD34, CD117, MIB-1, and glucose transporter-1 was negative immunohistochemically. A diagnosis of gastrointestinal stromal tumor was ruled out by an oncogenic kinase gene mutation study. This case cautions against PET-dependent evaluation for malignant potential of esophageal submucosal tumors.     

Late-onset type ornitine transcarbamirase deficiency (OTCD) with fulminant onset following a fatal prognosis]

A 16-year-old man was admitted to our hospital with nausea, general fatigue, and consciousness disturbance along with extreme hyperammoniemia eight days after the onset of symptoms. Familial history and the high concentration of orotic acid in urine lead us to a diagnosis of OTCD. We immediately initiated intensive treatment such as continuous hemodiafiltration and sodium benzoate administration; however, the patient died twelve days after admission. Since OTCD is not so rare and can be found in all ages, it should be considered fundamental for evaluation of hyperammoniemia. This case suggested that for a better prognosis of OTCD patients it is very important to prevent such an onset, and to make an as early as possible diagnosis and start to treatment.     

Health-related quality of life among persons living in Japan with a permanent colostomy.

OBJECTIVE: To compare the health-related quality of life (HRQOL) of persons with a permanent colostomy to that of the general Japanese population and explore the factors influencing HRQOL. DESIGN: A cross-sectional survey. SETTING AND SUBJECTS: A total of 255 persons with an ostomy who attended a meeting of the Japan Ostomy Association in the Kanto region of Japan. INSTRUMENTS: The HRQOL was assessed using Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Japanese version 1.2. Factors potentially influencing the HRQOL were age, sex, marital status, employment status, number of people in the household, time since colostomy, and diagnosis. METHODS: Questionnaires were distributed to the subjects and SF-36 scores were determined and compared with the corresponding national-norm data by Wilcoxon signed rank sum test. A logistic regression analysis was used to explore the influencing factors. RESULTS: The questionnaire response rate was 66.7%. Subjects with a urostomy or an ileostomy and those with missing data were excluded. Data from 102 subjects with a permanent colostomy were analyzed. The subjects' scores were significantly lower than the national-norm scores in the role-physical and social functioning scales. Being employed was associated with significantly lower scores or associated with a tendency toward lower scores. CONCLUSIONS: Scores in two scales in these subjects were lower than those of national-norm scores. Being employed had a negative impact on the HRQOL of subjects with a permanent colostomy. The results of this study provide reference data for future research and underscore the importance of support for persons with a colostomy.     

Morphologic demonstration of tubular obstruction in acute renal failure.

We used the qualitative Hanssen technique in albino rats to seek morphologic demonstration of tubular obstruction in two types of acute renal failure: one induced by folic acid and another by methemoglobin. Immediately after the intravenous injection of folic acid, 250 mg/kg body weight, the animals became almost anuric. Two to three hours after the injection, sodium ferrocyanide remained within the proximal convoluted tubules. After the intravenous injection of methemoglobin, 0.5 to 1.0 g/kg body weight, the animals became oliguric but not anuric. Sodium ferrocyanide injected with methemoglobin was seen mainly in distal tubules and collecting ducts 2 to 3 hours after the injection. The degree of tubular dilatation was more marked in the former model than in the latter, in agreement with the degree of oliguria. These morphologic findings were taken to indicate that the above two types of acute renal failure were caused by tubular obstruction rather than by intrarenal vasoconstriction and subsequent cessation of glomerular filtration. (Am J Pathol 87:323-330, 1977).     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin > imipramine > desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verified that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.     

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (² = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.     

Use of YAG laser combined with mucosal suturing for the treatment of polypoid vocal cord]

To improve low-pitched voices in cases with polypoid vocal cords, YAG laser irradiation combined with a mucosal suturing technique was attempted in 9 female cases with severe polypoid changes in their vocal cords. A YAG laser beam (5 to 10 W) was used to irradiate the upper surface of the polypoid vocal cord. The polypoid content of the cord was gradually coagulated, and the free edge of the cord appeared to slide up toward the burned area. The polypoid content was then removed and squeezed through an open wound made in the burned area using a conventional method. Bleeding was successfully controlled using the laser. After the excessive mucosal margin was trimmed and the contour of the vocal cord was adjusted, the wound was closed by 7-0 monofilament absorbable suture. Suturing was relatively easy because the mucosal edge was also coagulated. Postoperative evaluations of voice quality revealed an improvement in the GRBAS scale of voice quality as well as an elevation in voice pitch and an upwards shift in the voice range in all cases.