Cardiological risk factors for depressive symptoms after a first myocardial infarction.

OBJECTIVE: To detect possible cardiological risk factors in the acute phase of MI for developing depressive symptoms after first MI. DESIGN: Retrospective analysis of cardiac and psychiatric data of 111 consecutive patients admitted with a first MI. METHODS: During one year, all consecutive patients with a first MI, less than 12 hours chest pain and a maximal aspartate aminotransferase (ASAT) value of at least 80 U/l, admitted to the University Hospital of Maastricht, were screened for the presence of depressive symptoms using the 90-item 'Symptom checklist' (SCL-90) questionnaire at one month post-MI. Inclusion criteria were fulfilled by 111 patients; 28 patients refused to participate in the study. RESULTS: No correlation was found between LVEF, peak ASAT, peak CK value and characteristics, location or mode of treatment of the MI and depressive symptoms post-MI. A statistically significant negative correlation was found between SCL-90 depression score and cardiac tissue loss as defined by cumulative ASAT release at 24, 48 and 72 hours after the acute event (p values 0.029, 0.028 and <0.009, respectively) at the one month post-MI screening. CONCLUSIONS: No cardiological parameters were correlated to depressive symptoms post-MI. If there was a connection at all, this appeared to be a negative correlation between infarct size as measured by ASAT release and the occurrence of depressive symptoms at one month post-MI.

Sensitivity and specificity of observer and self-report questionnaires in major and minor depression following myocardial infarction.

This study evaluated screening abilities of self-report questionnaires for depression in first myocardial infarction (MI) patients. One month post-MI, 206 patients with first MI were screened for major and minor depression using the 90-item Symptom Check List (SCL-90), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the 17-item Hamilton Depression Rating Scale (Ham-D). The Structured Clinical Interview for DSM-IV criteria was used as the gold standard. Sensitivity and specificity for different cutoff points, using relative operating characteristics curves, were assessed. The internal consistency for all scales was good. When screening for major and minor depression, the optimal cutoff scores are lower than those for screening major depression only. The SCL-90, BDI, HADS, and Ham-D proved to have acceptable abilities for screening post-MI major and minor depression.

Depression and myocardial infarction: relationship between heart and mind.

There is a relationship between depression and Myocardial Infarction (MI) as higher levels of depression and severe depression (major vs minor) are associated with higher morbidity and mortality due to cardiac events, which are mainly caused by arrhythmia. Second, severity of MI is not or even inversely related to development of depression. Depression post-MI goes often unrecognized as only 10% of depressed MI patients are diagnosed as such. This underestimation of depression is attributed to its atypical profile, tendency of physicians to interpret depressive symptoms as a transient and 'natural' reaction to a life-threatening event, and the scarce knowledge of risk factors associated with development of post-MI depression. During the first 18 months following MI major depression occurs in 15-30% of patients. Depression should be assessed in an early stage as depression has the highest prevalence in hospital and in the first 6 months post-MI. Risk factors for developing post-MI depression include complications during hospitalization, prescription of benzodiazepines during hospitalisation, previous history of depression, and not being able to stop smoking. Selective Serotonin Reuptake Inhibitors (SSRIs) appear to be first choice treatment in post-MI depression. As yet there is no information on the efficacy and safety of Serotonin and Noradrenalin Reuptake Inhibitors (SNRIs).

Clinical correlates of depression following myocardial infarction.

OBJECTIVE: Post-MI depression increases mortality, especially in the first 18 months after MI. Identifying patients at risk for post-MI depression is therefore important. In the present study we investigated possible correlates for post-MI depression on an a priori basis. METHOD: Based on the literature, four clinically easily attainable variables were selected as possible correlates for post-MI depression. These were prescription of benzodiazepines during acute hospitalization, cardiac complications during acute hospitalization, history of depression, and not being able to stop smoking within six months after MI. A consecutive cohort of 173 first-MI patients was screened with the SCL-90 depression scale and DSM-III-R criteria for major depression. Of this cohort 35 depressed patients were compared with 35 non-depressed post-MI patients, matched for gender, age, and severity of MI. RESULTS: In univariate analyses, complications during hospitalisation (OR = 2.14; CI = 0.89-5.14), prescription of benzodiazepines (OR = 3.67; CI = 1.11-12.1), history of depression (OR = 3.0; CI = 0.87-10.4), and not being able to stop smoking (OR = 4.5; CI = 1.11-18.2) were clinical correlates for post-MI depression. Multivariate analyses showed that none of these variables were independent of the others in predicting depression. CONCLUSIONS: A number of easily measurable patient characteristics identify those MI-patients at risk of post-MI depression. Further investigations should focus on the predictive value of these factors in relation to post-MI depression.

The relationship between depressive and vital exhaustion symptomatology post-myocardial infarction.

OBJECTIVE: Many peri-myocardial infarction patients experience decreased wellbeing, which is either conceptualized as depression or as vital exhaustion. The objective of the present study is to investigate whether or not depression and vital exhaustion are separate entities. It was hypothesized that, if depression and vital exhaustion are separate phenomena, the correlation between two depression questionnaires would be higher than those between either of the two depression questionnaires and a vital exhaustion questionnaire. METHOD: Subjects were 143 patients who had recently experienced a first acute myocardial infarction (MI). At 1, 3, 6 and 12 months post-MI, patients completed two self-report depression questionnaires (the Zung-SDS and the Depression scale of the SCL-90), and a vital exhaustion questionnaire (the Maastricht Questionnaire). Correlation coefficients were calculated for the two depression questionnaires and the vital exhaustion questionnaire. Furthermore, an exploratory principal component analysis was performed on the combined items of the three questionnaires. RESULTS: Strong and virtually identical correlations were found between the three measures at all four time-points. A one-factor model was the best fit in the exploratory principal component analysis. CONCLUSION: The present results do not support the hypothesized separate conceptual identity of depression and vital exhaustion.

Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial.

OBJECTIVE: Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI. METHODS: Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography. RESULTS: The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. CONCLUSIONS: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event.

Cardiac side-effects of two selective serotonin reuptake inhibitors in middle-aged and elderly depressed patients.

Selective serotonin reuptake inhibitors (SSRIs) are the 'new' drugs of first choice for the treatment of depression in the older patient. Systematic studies on the effects of SSRIs on cardiac function are scarce, despite the high prevalence of cardiac disorders in the older depressed patient. This is a study which systematically assessed cardiac function by echocardiography in middle-aged and elderly depressed patients treated with SSRI. In a double-blind randomized trial, 20 patients were assigned to receive fluvoxamine 100 mg/day [DOSAGE ERROR CORRECTED] or fluoxetine 20 mg/day [DOSAGE ERROR CORRECTED] for 6 weeks. Cardiac function was assessed by left ventricle ejection fraction, aortic flow integral and early or passive/late or active mitral inflow, and electrocardiography. Neither SSRI significantly affected cardiac function. Compared with patients without a history of myocardial infarction and/or hypertension, patients with such a history showed a significant improvement in left ventricular ejection fraction. Despite our small study sample, these data indicate that both fluoxetine and fluvoxamine do not affect cardiac function adversely.

Local reactions of the saponin Quil A and a Quil A containing iscom measles vaccine after intramuscular injection of rats: a comparison with the effect of DPT-polio vaccine.

A short-term toxicity study was performed to investigate local reactions and hematological changes after im injection of Quillaia A (Quil A; 50 or 600 micrograms/ml) an essential component of an immunostimulating complex (iscom), a novel form of a subunit vaccine, and of iscom measles vaccine containing 360 micrograms Quil A/ml. The effects were compared with those caused by a sterile phosphate-buffered saline solution and by diphtheria-pertussis-tetanus-polio (DPT-polio) vaccine. Groups of six male rats were injected im with 0.25 ml of the test solution: on Day 0 in the left and on Day 7 in the right musculus gastrocnemius. On Day 14 the animals were killed, and the left and right inguinal lymph nodes were weighed. These organs and the left and right musculus gastrocnemius were investigated microscopically. The only hematological changes observed occurred in the group injected with DPT-polio vaccine: a decrease in the Hb value and in the number of erythrocytes and an increase in mean corpuscular hemoglobin content and in the number of leucocytes. The weights of the left and right inguinal lymph nodes were significantly increased in rats injected with DPT-polio vaccine, iscom measles vaccine, and the high dose of Quil A. The most intense granulomatous inflammatory reaction, mainly consisting of activated macrophages, was observed at the injection sites of all animals of the DPT-polio group. Only one animal injected with the iscom measles vaccine showed a moderate inflammatory reaction of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicology of gallates: a review and evaluation.

The propyl, octyl and dodecyl esters of gallic acid have been studied extensively in a large number of animal experiments involving oral dosing. Experimental data on general toxicity and studies on reproduction, teratogenicity and mutagenicity are also available. Most of the key toxicity studies, however, date back to the 1950s, do not meet current standards of toxicity testing and do not provide evidence for carcinogenic or mutagenic action of the gallates. Mutagenicity studies with octyl gallate and dodecyl gallate are lacking. The biokinetics of propyl gallate apparently differ from those of octyl and dodecyl gallate, the octyl and dodecyl esters being absorbed and hydrolysed to a lesser degree than the propyl ester. In toxicity studies with propyl gallate, growth retardation, anaemia, kidney and liver changes and hyperplasia of the forestomach were the most prominent effects at dose levels above 10,000 mg/kg feed. At 5000 mg/kg feed, liver enzyme induction was seen. In the available studies with octyl gallate or dodecyl gallate as the test compound, effects were found at 3000 mg/kg feed or higher levels. In studies performed with the various gallates, no effects were observed at a dose level of 1000 mg/kg feed, a level that was adopted as the no-effect level by the FAO/WHO Joint Expert Committee on Food Additives (JECFA) in 1976. This committee established an acceptable daily intake (ADI) for man of 0.2 mg/kg body weight (as a sum of propyl, octyl and dodecyl gallates). A re-evaluation of the toxicity of gallates indicates that a 'classic' long-term toxicity study of propyl gallate meeting current standards is required. As yet, the available toxicological evidence indicates that gallates may be used safely as antioxidants.

[Toxicologic studies on irradiated feed in pigs]. / Toxicologisch onderzoek van bestraald dieet bij varkens.

Toxicological investigations in experimental animals given irradiated feed and studies on the possible transfer of toxic factors from this feed to the animal are reviewed. Irradiated feed did not affect reproduction of rats and pigs. Extensive toxicity studies in pigs continued over a sixteen-week period and rats (2 1/2 years) did not reveal any changes which were attributable to irradiation to the feed.

Environmental toxicology, its history and future with special attention to the situation in the Netherlands.

Large scale pollution of the environment by pesticides and other chemicals only started in the fifties and early sixties. Chlorinated hydrocarbon pesticides and methyl mercury compounds appeared to have a marked impact on the populations of many animal species, especially birds. It is recognized that prof. dr. H. van Genderen, who retired this month, made a most valuable contribution to the timely detection of these problems in the Netherlands. Environmental toxicologists engaged in studies to predict environmental hazards by chemicals require toxicological skill as well as insight into the structure and functioning of ecosystems.

Biotransformation and porphyringogenic action of hexachlorobenzene and its metabolites in a primary liver cell culture.

Hexachlorobenzene (HCB) is metabolized in a primary culture of chick embryo liver cells and causes porphyrin accumulation within 24 h after administration. The HCB-metabolites, pentachlorothiophenol (PCThP), pentachlorobenzene (PeCB) and pentachlorophenol (PCP) identified in liver cell culture are already known from long-term experiments with rats. The pattern of accumulated porphyrins is comparable with the pathological porphyrin pattern observed in oral feeding studies with warm blooded laboratory animals. Protein bound radioactivity was found in cell cultures treated with [14C] HCB. Addition of the monooxygenase-inhibitor piperonyl butoxide or ascorbic acid decreased the irreversible binding of 14C-metabolites. The results show that biotransformation of HCB fulfils an essential role in the onset of porphyria. Since none of the main HCB-metabolites could induce a pathological porphyrin pattern, a reactive intermediate capable of reacting with glutathione or thiol-groups of uroporphyrinogen decarboxylase (UROG-D) is believed to be responsible for the inhibition of UROG-D. The chick embryo liver cell system may be considered as a useful and sensitive system for studying the metabolism of xenobiotics in relation to their toxicity.

Biological activity of technical Aroclor 1254 compared to Aroclor 1254 residues: swine fat residues fed to broiler cockerels.

Fat from Aroclor 1254-treated swine was rendered and incorporated into the diets of broiler chicks for 3-4 weeks. The technical Aroclor 1254 which was fed to the swine was also mixed into control lard for comparison at dietary concentrations of 0.07-9.0 mg/kg. The swine-residue PCB seemed to have a higher proportion of strong microsomal inducers, but the technical PCB was slightly more effective in inducing ethoxy resorufin and p-nitro-anisole (pNA) O-dealkylases than the swine-residue PCB. No overt signs of toxicosis were apparent and none of the diets resulted in changes in growth, relative organ weights, microsomal protein or high affinity pNA O-dealkylase. Increases in cytochrome(s) P-450 were significant only at the higher dietary concentrations (approx. 9 mg/kg) while ethoxyresorufin O-dealkylase was induced at dietary concentrations below 1 mg/kg.