A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

Correlates of suicide in building industry workers.

Suicide within the construction industry in Queensland, Australia was reportedly high in a recent Royal Commission report. The current study examined the incidence and causes of suicide in this industry using psychological autopsy and focus group investigations. A total of 64 male suicides occurred over the seven-year period, representing a crude suicide rate of 40.3 per 100,000, significantly greater than the working age Australian male rate. Young employees were at excessive risk with separation/divorce, relationship problems, and untreated psychiatric conditions the major contributors. Focus groups emphasized the importance of work/home interface factors and industry-specific factors preceding suicide.     

The reversal of cisplatin-protein interactions by the modulating agent WR2721 and its metabolites WR1065 and WR33278

Summary The reversibility of cisplatin-protein interactions by the modulating agent WR2721, its active thiol-metabolite WR1065, and the symmetrical disulfide WR33278 was studied using the model compounds (Pt(diethylenetriammine) monofunctionally bound to the sulfur in glutathione (Pt(dien)SG) and Pt(diethylenetriammine) monofunctionally bound to the sulfur in S-methylglutathione (Pt(dien)SMeG). Both model compounds could be quantified by high-performance liquid chromatography (HPLC) with UV detection. The Pt-cysteine-like bond in Pt(dien)SG could not be reversed by any of the WR compounds or by the strong nucleophiles thiosulfate (TS) and diethyldithiocarbamate (DDTC). However, the Ptmethionine-like bond in Pt(dien)SMeG could be reversed by WR1065, although the reversal was slow (k₂=0.142m ^–1 s^–1) as compared with that obtained using the modulating agents TS (k₂=10.1m ^–1 s^–1) and DDTC (k₂=3.66m ^–1 s^–1). WR2721 was hardly able to reverse the Pt-S bond in Pt(dien)SMeG (k₂=0.00529m ^–1 s^–1), and WR33278 showed no capacity to do so. The activity ofcis-diamminedichloroplatinum(II) (CDDP)-inactivated fumarase was not appreciably restored by any of the WR compounds (16%, 7.7%, and 0 for 20mm WR1065, WR2721, and WR33278, respectively) in contrast to the strong nucleophile DDTC (61% for 2mm DDTC). These in vitro studies provide information at the molecular level that may explain why WR2721, in contrast to DDTC, does not provide protection against cisplatin-induced nephrotoxicity when it is given after platinum-containing chemotherapy. The results support the present clinical use of WR2721 prior to the administration of platinum compounds.This study was financially supported by the Netherlands Cancer Fund (grant IKA 87-12) and by US Bioscience     

The HK/MBD Questionnaire: Replication and Validation of Distinct Factors in a Nonclinical Sample

Although Tarter et al.'s (1977) HK/MBD questionnaire has been found useful in subtyping populations of clinical alcoholics, its potential utility in nonclinical populations has yet to be determined. The current study examined the family history, personality, and substance use/abuse correlates of Tarter et al.'s HK/MBD questionnaire and factor analytically derived subscales (Alterman and McLellan, 1986) in a nonclinical sample of 580 young, adult males. In addition, a factor analysis of the HK/MBD questionnaire was undertaken to assess the extent to which the factor structure determined on a clinical alcoholic sample replicates in a nonclinical sample. Results indicated that each of the HK/MBD subscales showed relatively unique patterns of correlations with the various personality measures employed suggesting that they are measuring separate constructs. Perhaps of greatest importance, the HK/MBD items that appear to be of greatest relevance for understanding substance use/abuse are those related to antisocial behavior. Finally, the factor structure of the HK/MBD questionnaire in the nonclinical sample was found to be quite similar to the structure obtained in a clinical sample. These results demonstrate the multidimensional structure of the HK/MBD questionnaire and the utility of using the more homogeneous subscales in research with both clinical and nonclinical samples.     

Dual Exposure to Sevoflurane Improves Anesthetic Preconditioning in Intact Hearts

Background: Anesthetic preconditioning (APC) with sevoflurane reduces myocardial ischemia-reperfusion injury. The authors tested whether two brief exposures to sevoflurane would lead to a better preconditioning state than would a single longer exposure and whether dual exposure to a lower (L) concentration of sevoflurane would achieve an outcome similar to that associated with a single exposure to a higher (H) concentration.

Methods: Langendorff-prepared guinea pig hearts were exposed to 0.4 mm sevoflurane once for 15 min (H1-15; n = 8) or 0.4 mm (H2-5; n = 8) or 0.2 mm sevoflurane (L2-5; n = 8) twice for 5 min, with a 5-min washout period interspersed. Sevoflurane was then washed out for 20 min before 30 min of global no-flow ischemia and 120 min of reperfusion. Control hearts (n = 8) were not subjected to APC. Left ventricular pressure was measured isovolumetrically. Ventricular infarct size was determined by tetrazolium staining and cumulative planimetry. Values are expressed as mean +/- SD.

Results: The authors found a better functional return and a lesser percentage of infarction on reperfusion in H2-5 (28 +/- 9%) than in H1-15 (36 +/- 8%; P < 0.05), L2-5 (43 +/- 6%; P < 0.05), or control hearts (52 +/- 7%; P < 0.05).     

Clinical predictors of suicidal acts after major depression in bipolar disorder: a prospective study

Objective:  This study determined the clinical predictors of suicidal behavior during a 2-year follow-up of patients with bipolar disorder presenting with a major depressive episode (MDE).
Method:  Sixty four patients with DSM-III-R bipolar disorder were assessed at presentation for treatment of an MDE. Correlates of past suicidal behavior were determined by comparing patients with and without a history of suicide attempts using a t -test, Wilcoxon test or chi-squared test of independence on individual explanatory variables. Putative predictors of attempts during the follow-up period were tested separately using Cox proportional hazards regression analysis.
Results:  Twelve of 64 patients had at least one suicide attempt in the follow-up period, five of them attempted in the first 2 months and seven around or shortly after the 1-year follow-up visit. All attempters had a history of past suicide attempts. Most predictors of future suicidal behavior were correlates of past suicidal behavior. Family history of suicide acts and comorbid borderline personality disorder predicted early attempts, while younger age, high hostility scores, number of past attempts, subjective pessimism as reflected in depression and suicidal ideation, and few reported reasons for living predicted suicidal acts during the whole period.
Conclusion:  In this data set of bipolar patients we noted an intriguing picture of two clusters of suicide attempts. Hostility was the strongest risk factor. These findings may have implications in both the identification of at-risk patients and the timing of clinical interventions including aggressive pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive symptomatology.     

Aggression and substance abuse in bipolar disorder

Objectives:  The goal of this retrospective study was to examine factors differentiating persons with bipolar disorder who did or did not have comorbid lifetime substance use disorders (SUD) at an index assessment. We also explored the chronology of onset of mood and SUD.
Methods:  We studied 146 subjects with DSM-defined bipolar disorder. Subgroups with and without lifetime SUD were compared on demographic and clinical measures.
Results:  Substance abuse disorders in this bipolar sample were associated with male sex, impulsive-aggressive traits, comorbid conduct and Cluster B personality disorders, number of suicide attempts and earlier age at onset of a first mood episode. In a multivariable logistic regression analysis, male sex and aggression and possibly earlier age at mood disorder onset were associated with SUD. In those with or without SUD, the first mood episode tended to be depressive and to precede the onset of SUD.
Conclusions:  In persons with bipolar disorder, an earlier age of onset and aggressive traits appear to be factors associated with later development of comorbid SUD.     

Minimal displacement of novel self-anchoring catheters suitable for temporary prostate implants.

Catheters were developed that can be fixed in the prostate gland by self-expanding parts for use in PDR brachytherapy. Daily CT-scans were made to investigate the magnitude of catheter displacement. The mean absolute displacement during the 3 day treatment was 1.2 mm. The resulting minor alterations in dose-volume parameters were of no clinical importance.     

Diagnose akuter Transfusionsreaktionen

The erroneous transfusion of AB0-incompatible red cells may result in hemolysis and complement-mediated shock (acute hemolytic transfusion reaction, AHTR), leading to death in less than 10%. The mistake will be detected by re-checking the patient’s and the blood product’s identity. Evidence of the incompatible transfusion is supplied by serology and, in cases of a fatal outcome, by immunohistochemistry. Differential diagnoses to be distinguished from AHTR are other immunologically mediated events like the most important transfusion-related acute lung injury (TRALI), febrile non-hemolytic transfusion reaction (FNHTR), allergic transfusion reactions, along with a variety of nonimmunologic incidents like transfusion-transmitted bacterial infections, hypervolemia, and other rare events such as citrate reaction, air embolism, and foreign body embolism. If the outcome is lethal, the question of causality has to be answered by a comprehensive evaluation including the clinical data as well as serological, microbiological, autoptic, and histological findings.