On the justification for civil commitment.

This paper explores some of the controversies in the debate regarding the justification of civil commitment. The sometimes conflicting values reflected in the mental health legislation, human rights principles, moral philosophy and psychiatric professional standards are discussed. In spite of the often substantial use of civil commitment in many countries, there are almost no scientifically sound studies addressing the outcome of coercive treatment. The paper establishes that the traditional arguments in favour of civil commitment, like lack of insight and competence as well as the effectiveness of civil commitment, are poorly founded. The paper concludes that there seems to be a general agreement that civil commitment of patients who are dangerous to themselves or others should be the responsibility of the mental health care system, while civil commitment for treatment purposes is more controversial and hard to justify.

Self-reported seasonal variation in depression at 78 degree north. The Svalbard Study.

STUDY OBJECTIVES: To explore and compare the one year prevalence of self-reported depression in two ethnically different populations. DESIGN: A cross-sectional study of each population (1988-89 and 1993). SETTING: Norwegians living in Longyearbyen, Svalbard, and Russians living in Barentsburg and Pyramiden, Svalbard, both representing the world's two northern most regularly inhabited settlements. PARTICIPANTS: 506 Norwegians (327 men and 179 women) and 446 Russians (314 men and 132 women), all 18 years or older, living on Svalbard. MAIN RESULTS: Among Russians, the one year prevalence of self-reported depression lasting for at least 2 weeks was 26.8% for men and 44.7% for women. Corresponding figures for the Norwegians were 10.7 and 15.6%. For the period with polar night the figures were 5.5 and 6.7% for Norwegians, and 21.7 and 37.1% for Russian men and women, respectively. Depression was most common in the youngest age-group among Russians and in the oldest age-group among the Norwegians. CONCLUSION: The one year prevalence of depression was 2-3 times higher among Russians compared to Norwegians living on Svalbard. For the period with polar night, the figures were 4-5 times higher for Russians. As both populations are exposed to the same amount of daylight, seasonal depression may therefor not solely be a matter of lack of daylight. Because the Russian population came from lower latitudes than the Norwegians, we hypothesize that insufficient acclimatization after migration to the north is essential for the understanding of seasonal variation in depression.

Sleeping problems at 78 degrees north: the Svalbard Study.

The aim of this study, was to compare the prevalence of sleeping problems in two ethnically different populations living under the same extreme arctic climate. A total of 453 Norwegians (319 males and 134 females) were compared with 450 Russians (317 males and 133 females), all aged 18 years or older, living on Svalbard, the northernmost regular settlement in the world. Among Russians, 81% of the male subjects and 77% of the female subjects reported sleeping problems lasting for at least 2 weeks. The corresponding figures for the Norwegians were 22% (for males) and 25% (for females). Among Russians, sleeping problems decreased with increasing age, but no such age trend was found in Norwegians. Whereas sleeping problems among Norwegians were approximately equally frequent throughout the year, the Russians reported more problems during the polar night. 'Problems falling asleep', 'not feeling rested in the morning' and 'walking up several times during the night' were the most frequent types of sleeping problems in both groups. Depression, shift work, loneliness, ability to concentrate, alcohol consumption and quality of life were associated with sleeping problems in Norwegian subjects, whereas depression, shift work, ability to concentrate, and worry were associated with sleeping problems in Russians. The prevalence of sleeping problems was nearly fourfold higher among Russian subjects than among Norwegians living on Svalbard. As the Russians were recruited from a lower latitude than the Norwegians, we postulate that their problems should be interpreted in terms of inadequate acclimatization after migration to the north.

Blood serum analyses in population studies: parallel analyses and degree of agreement in a Norwegian-Russian co-project. The Svalbard Study.

In a survey of more than 300 russian coal workers living on Svalbard, parallel laboratory analyses of gamma-glutamyltransferase, serum total cholesterol, high density lipoprotein, and triglycerides were performed in Tromsö, Norway and in Archangelsk, Russia. Mean values for gamma-glutamyltransferase and serum total cholesterol were significantly higher in Tromsö than in Archangelsk while mean values of triglycerides and high density lipoproteins were significantly lower in Tromsö than in Archangelsk. Linear regression plots revealed both systematical and arbitrary differences between the two laboratories. Because no "true" standards were available, we were unable to assess the accuracy of laboratory results. We conclude that laboratory measurements from Norway and Russia are not directly comparable. Future research programs between the two laboratories should attempt to include calibrated standards of test serum from which to identify sources of variation. Alternatively, the serum tests should always only be analyzed at one site.

The General Health Questionnaire: how many items are really necessary in population surveys?

This paper seeks to investigate whether only a few questions selected from the General Health Questionnaire (GHQ) may be used to measure the degree of mental distress in population surveys. Data from 2112 men and women, 18 to 70 years old from two cross-sectional studies conducted in northern Norway and the island Spitzbergen in the Arctic, were used. Correlation analysis of Likert scores from a 20-item version of GHQ (GHQ-20) with Likert scores based on four and six items selected by multiple regression analysis or by competent physicians was performed. The correlation coefficients between the scores from the subsets of four items and the full GHQ-20 questionnaire were high (greater than 0.80) in all examined subgroups of the populations. Increasing the number of questions from four to six only marginally increased the correlation coefficients. Thus, a simple linear sum of Likert scores based on a few GHQ items can be used to measure the degree of mental distress in populations surveys.

Selective stability-indicating high-performance liquid chromatographic assay for recombinant human regular insulin.

This report presents a selective HPLC assay capable of separating recombinant human regular insulin from insulin decomposition and transformation products. The assay utilizes an isocratic delivery of mobile phase, a C18 peptide column, UV detection and is performed at ambient temperature. The standard curve ranges from 0.2 to 2.5 U/ml. The inter-day and intra-day variabilities are less than 7 and 5%, respectively, at the concentrations studied. The accuracy and precision are within 5% over the range of the standard curve.

The Svalbard study 1988-89: a unique setting for validation of self-reported alcohol consumption.

The Norwegian island of Spitzbergen, Svalbard offers a unique setting for validation studies on self-reported alcohol consumption. No counterfeit production or illegal import exists, thus making complete registration of all sources of alcohol possible. In this study we recorded sales from all agencies selling alcohol on Svalbard over a 2-month period in 1988. During the same period all adults living permanently on Svalbard were invited to take part in a health screening. As part of the screening a self-administered questionnaire on alcohol consumption was introduced to the participants. We found that the self-reported volume accounted for approximately 40 percent of the sales volume. Because of the unique situation applying to Svalbard, the estimate made in this study is believed to be more reliable compared to other studies using sales volume to validate self-reports.

Rational design of hirulog-type inhibitors of thrombin.

The two crystal structures of thrombin complexed with its most potent natural inhibitor hirudin and with the active-site inhibitor D-Phe-Pro-Arg-CH2Cl [Rydel, T.J. et al., J. Mol. Biol., 221 (1991) 583; Bode, W. et al., EMBO J., 8 (1989) 3467] were used as a basis to design a new inhibitor, combining the high specificity of the polypeptide hirudin with the simpler chemistry of an organic compound. In the new inhibitor, the C-terminal amino acid residues 53-65 of hirudin are linked by a spacer peptide of four glycines to the active-site inhibitor NAPAP (N alpha-(2-naphthyl-sulfonyl-glycyl)-DL-p-amidinophenylalanyl-piperi dine). Energy minimization techniques served as a tool to determine the preferred configuration at the amidinophenylalanine and the modified piperidine moiety of the inhibitor. The predictions are supported by the interaction energies determined for D- and L-NAPAP in complex with thrombin, which are in good agreement with experimentally determined dissociation constants. The conformational flexibility of the linker peptide in the new inhibitors was investigated with molecular dynamics techniques. A correlation between the Pl' position and the interactions of the linker peptide with the protein is suggested. Modifications of the linker peptide are proposed based on the distribution of its main-chain torsion angles in order to enhance its binding to thrombin.

Metabolism of the steroidal aromatase inhibitor atamestane in rats, cynomolgus monkeys and humans. Isolation and identification of the major metabolites.

The metabolism of the steroidal aromatase inhibitor atamestane was studied in the rat, the cynomolgus monkey and in the human. Metabolite patterns were recorded in plasma, urine and bile (rat only) before and after enzymatic cleavage of sulfate and glucuronide conjugates. Atamestane was rapidly and extensively metabolized by all three species. Major metabolites which were observed in the human, could be isolated from urine pools of treated monkeys by preparative high performance liquid chromatography and were identified by GC/MS and 1H-NMR analysis. The metabolite patterns observed in the animals and in the human were similar, although some species- and sex-related differences were observed. There seem to be two principal routes by which atamestane is metabolized: one route is characterized by the attack of 17 beta-hydroxysteroid dehydrogenase, the other route includes hydroxylation of the 1-methyl group with subsequent attack by 5 beta-reductase, followed by a hydroxylation at position C-6. Some of the metabolites which were identified still had some pharmacological activity, although less marked than the parent compound.

[Changes in the use of compulsory measures in Norwegian psychiatric institutions]. / Utviklingen av tvangsmiddelbruk i norske psykiatriske institusjoner.

This paper presents the second screening concerning the use of coercive measures in Norwegian mental health institutions. The use of mechanical restraint, seclusion and forced medication was recorded during the first six months of 1989 and of 1990. We found no change in the use of coercive measures from 1989 to 1990, nor did we find any differences when the results of this screening was compared with those of the first screening carried out in 1986-88. Mechanical restraint was the most commonly used coercive measure, and a total of 9402 hours of such constraint was recorded the first six months of 1990. In many cases, a substantial part of the total amount of mechanical restraint in the different institutions at different times referred to a single patient, which created large variations in the use of coercion. No correlation was found between the use of coercion on one hand and size of ward and staff ratio on the other; factors that otherwise are believed to be of importance for use of coercion.

Biotransformation of the antidepressant DL-rolipram. I. Isolation and identification of metabolites from rat, monkey, and human urine.

The metabolic pathway of DL-rolipram was studied in two animal species and in man. Metabolites were isolated from rat, rhesus monkey, and from human urine by preparative HPLC and identified by MS and NMR analysis. In total, the structures of 7 degradation products could be elucidated. Rolipram was metabolized by ether cleavage at the methoxy and cyclopentyloxy groups and by hydroxylation in positions 2 or 3 of the cyclopentyloxy ring followed by sulphation. Additionally, but exclusively in man, the 5-position of the pyrrolidone ring was hydroxylated.

Biotransformation of proterguride in the perfused rat liver.

The metabolic pathway of the dopaminagonistic ergoline derivative, proterguride, was studied in vitro in a rat liver perfusion experiment. Metabolites were isolated by preparative HPLC and identified by MS and NMR analyses. In total, seven compounds could be identified. The metabolic steps involved in the biodegradation of proterguride are N-deethylation, N-oxidation, hydroxylation, and/or dehydrogenation and oxidative cleavage of the indole ring.

Suicide among women related to number of children in marriage.

The hypothesis of a negative association between rates of suicide and number of children in marriage was investigated in a prospective study of 989,949 women followed up for 15 years (1970 through 1985) with 1190 deaths from suicide. Women who had never married exhibited higher relative risks for suicide than married parous and married nonparous women for all age groups younger than 65 years at the start of follow-up. Among the married, the parous women had lower relative risks than nonparous women for all ages. For both premenopausal and postmenopausal women, a strong linear decrease in relative risk for suicide with increasing number of children in marriage was found. The effect of number of children was independent of social class measured as years of completed schooling. The findings provide the first empirical support for theories of parenthood and suicide advanced by Durkheim almost 100 years ago.

Metabolism of dexamethasone: sites and activity in mammalian tissues.

We have used in vitro techniques to study the metabolism of dexamethasone. Tissue slices, homogenates and microsomal fractions of various mammalian organs from rats and humans have been used. We focused particularly on the question of whether or not dexamethasone (Dexa) is oxidized at the C11-OH group by 11 beta-hydroxysteroid-dehydrogenase. High activities of this enzyme system for Dexa were localized in renal cortex and rectum. Material from both human and murine liver was ineffective. The main metabolite formed from Dexa in renal and intestinal systems was identified by different mass-spectrometric techniques including on line HPLC mass spectrometry as 11-dehydro-dexamethasone. This finding was corroborated by the observation that both corticosterone and glycyrrhetinic acid block the metabolic transformation of Dexa.

The binding of triazine herbicides to the photosynthetic reaction center of Rhodopseudomonas viridis. Energy minimization studies.

The binding of six herbicides of the triazine family to the photosynthetic reaction center of Rhodopseudomonas viridis was investigated with energy-minimization techniques, in order to correlate experimental with calculated data. The inhibitors were modeled in the active site according to the X-ray structure analysis of the complex formed between the triazine terbutryn (2-ethylamino-4-t-butylamino-6-methylthio-s-triazine) and the reaction center of R. viridis [Michel, H., Epp. O. & Deisenhofer, J. (1986) EMBO J. 5, 2445-2451]. 40 different energy minimizations were carried out with varying cutoff radii, partial charges on inhibitor atoms and dielectric constants, i.e. 10 different combinations of these were tested. The impact of these parameters on the calculated binding and interaction energy was either examined for all protein/triazine complexes or, in the case of the dielectric constant, a smaller sample was used. The calculated energies are dominated by van der Waals interactions, which change by up to 20% when extending the cutoff radius from 0.8 nm to 1.5 nm. The use of uniform or distance-dependent dielectric constant or partial charges on the inhibitor atoms does not severely influence the resulting structures, but shows a great impact on the calculated energies. In the two groups of triazines, each containing three inhibitors with methoxy or methylthio substituents, correlations of biological and calculated data were found quite often, but only once with all six triazines. The energy-minimized structures were compared and analysed. A third hydrogen bond, not seen in the X-ray analysis of the reaction center/tertubryn complex, was found between the t-butylamino moiety of terbutryn (and equivalent moieties in the other triazines) and the carbonyl oxygen of TyrL222.

New alcohol markers--how useful are they in population studies: the Svalbard Study 1988-89.

Regular high consumption of alcohol in selected populations have, with high precision, been identified by two new alcohol markers; carbohydrate-deficient transferrin and mitochondrial aspartate aminotransferase. To test these markers in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST) were measured in the Norwegian population, 310 males and 171 females, aged 18 to 60 years, living at Svalbard. Using self-reported alcohol intake as gold standard, sensitivity, specificity, positive predictive value, and likelihood-ratio were estimated according to different cutoff-points for alcohol intake and for the tests. In contrast to earlier studies, the sensitivity was in general low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for any of the tests. Whereas CDT showed its best discriminatory power at lower intake of alcohol, GGT discriminated best at higher levels. Parallel and serial analysis of CDT and GGT indicated a conditional independence between the tests, as well as at higher and at lower levels of alcohol consumption. mAST was judged as not suitable in population studies.