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.     

Is the Evaluation of the Global Quality of Life Determined by Emotional Status?

The present study investigated relationships between global QOL perceptions and well-being dimensions. Especially our goal was to evaluate the impact of generally recognised four broad dimensions of QOL (physical, functional, social and emotional well-being) on global QOL perceptions, additionally person's satisfaction with life achievements and economical situation were measured as well as social demographic variables. The subjects were a representative sample of Finns (n = 4613, from 25 to 65 years) of the FINRISK-97 study. Correlation coefficients and models of hierarchical regression indicated that physical, functional and social well-being as well as sociodemographic factors and satisfaction with life achievements are important factors of global QOL perceptions both among males and females. However percentages of variances explained with these measures were only moderately high, ranging from 1 to 10%. After measures of emotional well-being were entered into the models of hierarchical analyses of regression, variances explained grew dramatically over 20%. The results of the study indicated that global QOL judgements are likely to be based on current emotional state.     

Differences between urban and rural suicides

As part of a nation-wide psychological autopsy we examined the differences in DSM-III-R mental disorders, recent life events and other characteristics between urban (n=143) and rural (n=85) completed suicides in a random sample of 229 cases from the National Suicide Prevention Project in Finland for the period 1987-1988. Psychoactive substance use disorders (48% vs. 34%), cluster B personality disorders (24% vs. 9%) and psychiatric comorbidity (66% vs. 42%) were found more commonly among urban than rural suicides. Urban suicides were also more often reported to be preceded by a recent separation (25% vs. 8%), whereas rural suicide victims tended to have lacked a close companion of the opposite sex (36% vs. 18%) and to have had physical disorders (56% vs. 40%). Overall, urban and rural suicides may vary with regard to the prevalence of some mental disorders, their comorbidity, and physical disorders, as well as the preceding life situation. This variation may also imply the need for differences in strategies for suicide prevention in each setting.     

Adolescent suicides with adjustment disorders or no psychiatric diagnosis

Detailed characteristics of adolescent suicides (aged 13–19 years) with adjustment disorders (AD) (N=11) or no psychiatric diagnosis (N=3) in a nationwide adolescent suicide population (N=53) from Finland are presented. The data were collected in a psychological autopsy study of all suicides in Finland (N=1397) during a 12-month period in 1987–1988. Data collection included thorough interviews with the victims' family members and professionals, and information from official records. All the suicides with AD or no diagnosis were males. Most of these victims used highly lethal suicide methods. Previous psychiatric treatment and previous suicide attempts were rare. They were seldom under the influence of alcohol when committing suicide. The process leading to suicide seemed to be of relatively short duration. According to informant reports, withdrawn or narcissistic individual characteristics predominated in many cases. Psychosocial stressors preceding suicide often involved interpersonal losses or conflicts. Talking of suicidal intentions prior to the act was common, indicating the need to take seriously all adolescents' expressions of intended suicide, even in the absence of explicit psychopathology.

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Zusammenfassung Es werden detaiilierte Beschreibungen von Selbst-morden im Jugendalter, verbunden mit Anpassungsstörungen (N=11) oder keiner psychiatrischen Diagnose (N=3) vorgestellt. Diese stammten aus der Gesamtheit aller jugendlichen Selbstmörder (N=53) aus Finnland. Die Daten wurden in einer psychologischen Obduktionsstudie aller Selbstmörder Finnlands (N=1397) während eines einjährigen Zeitraumes zwischen 1987 und 1988 gesammelt. Die Datenerhebung umfaßte ausgiebige Interviews mit den Familienmitgliedern, beteiligten Fachkräften und Informationen von offizieller Seite. Die Selbstmörder mit Anpassungstörungen oder keiner Diagnose waren alle männlich. Die meisten dieser Opfer benützten sehr letale Suizidmethoden. Vorangegangene psychiatrische Behandlungen und Selbstmordversuche waren selten. Sie standen nur selten unter dem Enfluß von Alkohol, als der Selbstmord vollzogen wurde. Der Prozeß, der zu dem Suizid führte, schien von relativ kurzer Dauer zu sein. Entsprechend den Angaben der Informanden prädominierten in vielen Fällen zurückgezogene oder narzißtische Persönlichkeitsmerkmale. Psychosoziale Stressoren, die dem Suizid vorangingen, umfaßten interpersonelle Verluste oder Konflikte. Häufig wurde über die Suizidabsichten vor der Tat gesprochen. Dies verdeutlicht die Notwendigkeit, alle Suizidäußerungen von Jugendlichen ernstzunehmen, selbst dann, wenn eine explizite Psychopathologie fehlt.

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Résumé Les caractéristiques détaillées de suicides d'adolescents (âgés de 13 à 19 ans) avec troubles avec l'adaptation (AD) (N=11) ou l'absence de diagnostic psychiatrique (N=3) sur une population de suicides d'adolescents s'étendant sur l'ensemble du pays (N=53), la Finlande sont présentées. Les faits ont été collectés dans le cadre d'une étude d'autopsie psychologique de tous les suicides en Finlande (N=1397) pendant une période de 12 mois 1987–1988. Le recueil des faits incluait des interviews avec les membres de la famille des victimes et les professionels ainsi que les informations provenant de documents officiels. Tous les suicides avec un trouble de l'adaptation ou sans diagnostic étaient masculins. La plupart de ces victimes utilisait des méthodes hautement mortelles. Les traitements psychiatriques précédents et les tentatives précédentes de suicides étaient rares. Ils étaient rarement sous l'influence de l'alcool quand ils ont commis les suicides. Le processus conduisant au suicide semblait être de durée relativement brève. Selon les rapports d'information, une attitude de retrait ou des caractéristiques individuelles de retrait prédominaient dans la majorité des cas. Les facteurs de stress psycho-sociaux précédent le suicide impliquaient souvent des pertes inter-personnelles ou des conflits. Parler du désir du suicide devant le passage à l'acte était habituel indiquant la nécessité de prendre au sérieux tous les adolescents exprimant le désir de suicide, même en l'absence d'une psychopathologie explicite.

     

Factors influencing results of femoropopliteal bypass operations for lower limb ischemia

An ideal way to assess the effectiveness of femoropopliteal bypass procedures is to standardize patient- and surgeon-related variables by randomization. Through statistical analysis of multiple factors influencing patency, limb loss, death rate and hospital stay, the authors reviewed retrospectively 136 bypass procedures performed over 5 years. Variables that contributed significantly to the results were: preoperative symptoms (p = 0.037), graft material used (p = 0.016), age of the patient (p = 0.007), adequacy of runoff (p = 0.041) and smoking postoperatively (p = 0.013). Autogenous vein grafts were superior to prosthetic grafts, the cumulative patency at 5 years being 67.5% and 38.2% respectively. The authors emphasize that all patients needing vascular surgery should be advised to stop smoking, since in this study postoperative smoking increased the probability of limb loss and adversely affected the cumulative patency rate by interaction with other variables such as preoperative symptoms, graft material and age.     

Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.     

Biologic significance of surface microroughing in bone incorporation of porous bioactive glass implants

A novel chemical etching method was recently developed to create a controlled microrough surface on porous bioactive glass implants. Our earlier in vitro studies showed enhanced attachment of osteoblast-like MG63 cells on a microrough bioactive glass surface. The purpose of our current study was to confirm the in vivo significance of surface microroughening for bone bonding of bioactive glass. Porous bioactive glass cones made of sintered microspheres were surgically implanted in the anterior cortex of rabbit femurs. Peripheral quantitative computed tomography (pQCT), biomechanical push-out testing, histomorphometry, and electron microscopy (BEI-SEM) were used to analyze bone ingrowth and osseointegration at 7, 10, 14, 28, 56, and 84 days after implantation. The results showed that microroughening of the bioactive glass surface significantly enhanced the bone-bonding response of the biomaterial. The positive response was seen in one of the three bioactive glass compositions studied. The affinity index of new bone on the glass surface was significantly (p = 0.02) increased with a trend (p = 0.10) toward improved mechanical incorporation. New bone formation was dependent on the glass composition, and it was found to occur not only through the mechanism of bone ingrowth but also based on in situ osteogenesis within implant interstices. Based on these results, the procedure of microroughening could enhance the osteopromotive properties of certain bioactive glass compositions.     

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).