The influence of successful prophylactic drug treatment on cognitive dysfunction in bipolar disorders

Background:  Cognitive variables such as negative self-evaluations have been discussed as vulnerability factors for depressive syndromes. In the context of bipolar disorders dysfunctional cognitive structures have received little interest as these patients seem to be less disturbed during the euthymic interval than patients with major depression.
Methods:  In the present study, the self-esteem of remitted patients with DSM-III-R diagnosis of major depression (n=20), bipolar disorder (n=20) and healthy controls (n=20) was measured with the Frankfurt Self-concept Scale (FSKN).
Results:  1) Statistical analysis by analysis of variance (ANOVA) showed no significant differences as to age, sex, etc. between the psychiatric groups. The clinical groups showed lower self-esteem ratings in comparison to healthy controls. 2) Four groups (T1–T4) of remitted patients with bipolar disorders (20 in each group) were successfully maintained on mood stabilizers (lithium or carbamazepine) and classified by the duration of their episode-free period. T1 included those who were episode-free for only the week before discharge from hospital. T2 were symptom-free for <30 months. T3 were episode-free for >30 months and <60 months. T4 were episode-free for >60 months. The comparison of their FSKN self-esteem ratings by ANOVA suggests that self-esteem improves during successful prophylactic treatment. A posteriori contrasts indicate a normalized self-esteem after a bipolar episode-free period of at least 47 months.
Conclusions:  Dysfunctional cognitions can be demonstrated in unipolar as well as in bipolar patients. Successful episode-preventive medication with mood stabilizers seems to counteract lowered self-esteem. Adjunctive cognitive therapy might help to optimize the long-term course of bipolar disorder.     

Relationships between fibrinolytic and inflammatory parameters in human adipose tissue: strong contribution of TNFalpha receptors to PAI-1 levels

Plasminogen activator inhibitor type 1 (PAI-1), a risk marker of atherosclerosis, is highly expressed in adipose tissue from obese subjects. PAI-1 is also considered as an acute phase protein. Recently, adipose tissue has been described as a source of inflammatory cytokines. Therefore, our aim was to study the relationships between PAI-1, and IL-6, TNF, TNF receptors (TNFRSF1s) and TGFbeta1, in plasma and adipose tissue from obese (n = 60) and lean (n = 28) subjects. Study has been extended to plasminogen activators (t-PA and u-PA). Compared to lean subjects, obese subjects exhibited higher plasma levels of all the studied parameters (except for TGFbeta1) whereas in adipose tissue only PAI-1, t-PA and TGFbeta antigen levels differed. In the obese population, plasma PAI-1 levels were weakly associated with circulating TNF, and this relationship disappeared after adjustment for plasma t-PA. Adipose tissue PAI-1 levels were positively associated with TNFRSF1s and TGFbeta, the strongest relationship being observed with TNFRSF1A, which explained 82% of PAI-1 variability. TNF and IL-6 were the main contributors to t-PA variability in plasma and in adipose tissue, respectively. Our results argue on the relevance of TNFRSF1s in the regulation of PAI-1 expression by adipose tissue. Association between t-PA, which is mainly produced by endothelial cells, and IL-6 or TNF suggest that inflammation might be involved in angiogenesis in adipose tissue.     

Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants

BACKGROUND: Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications. OBJECTIVE: To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins. Design: Population-based cohort study in a sample of the Rotterdam Study. SUBJECTS: All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available. METHODS: Patients were followed until an INR >/= 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR >/= 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure. RESULTS: Of the 1,124 patients in the cohort, 351 developed an INR >/= 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs. CONCLUSION: In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.     

High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients

The prevention of venous thromboembolism in medical patients remains questioned. All consecutive outpatients admitted in our medical unit were considered for inclusion in this study which aimed to estimate the prevalence of asymptomatic venous thrombosis on admission and the incidence during hospital stay. Exclusion criteria were: age <18 years, suspicion of venous thromboembolism, stay <4 days, ongoing anticoagulant therapy. Venous compression ultrasonography of the lower limbs was performed within 48 h. 234 patients were included. The prevalence of asymptomatic deep vein thrombosis on admission and the incidence during hospital follow-up were respectively 5.5% (95% confidence interval, 3.1 to 9.5%) and 2.6 per 1,000 person-days (95% confidence interval, 0.0 to 5.2). The prevalence and the incidence reached respectively 17.8% (95% confidence interval, 8.5 to 32.6%) and 6.0 per 1,000 person-days (95% confidence interval, 0.0 to 12.7) among patients over 80 years. A high prevalence of asymptomatic deep vein thrombosis on admission was suggested particularly among elderly medical patients.     

A novel mutation in the SURF1 gene in a child with Leigh disease,peripheral neuropathy,and cytochrome-c oxidase deficiency

We report a 16-month-old boy with psychomotor regression, muscle hypotonia, peripheral neuropathy, and lactic acidosis. Brain magnetic resonance imaging showed a bilateral abnormal signal in the substantia nigra and in the subthalamic nucleus, suggestive of Leigh disease. Histochemical analysis of skeletal muscle showed decreased cytochrome-c oxidase activity. Biochemical analysis of respiratory chain enzymes in muscle homogenate and in cultured fibroblasts showed isolated cytochrome-c oxidase deficiency. Western blot analysis in fibroblasts showed the absence of Surf1 protein. Genetic analysis of the SURF1 gene revealed that the patient was compound heterozygous for a previously reported mutation at the splice-junction site of intron 3 (240 + 1G > T), and for a novel 4-bp deletion in exon 6 (531_534delAAAT). Our data further enlarge the spectrum of mutations in SURF1 gene in patients with Leigh disease and cytochrome-c oxidase deficiency, contributing to better characterization of the clinical and neuroradiologic features of this group of patients for genotype-phenotype correlations.     

The dimensional symptom structure of schizophrenia and its association with temperament and character

Recent studies suggest that personality may influence symptom expression and social functioning in schizophrenia. This study investigated the relationships between personality and symptom dimensions in schizophrenia patients. Fifty-two schizophrenia patients and 25 five healthy subjects were assessed using the Temperament and Character Inventory (TCI). The patients were also assessed for positive and negative symptoms using SAPS and SANS and scored according to Andreasen's (1995: Andreasen, N.C., Arndt, S., Alliger, R., Miller, D., Flaum, M. 1995. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch. Gen. Psychiatry, 52, 341-351) classical three dimensional model and by the five dimensional model of Toomey et al. (1997: Toomey, R., Kremen, W.S., Simpson J.C., Samson, J.A., Seidman, L.J., Lyons, M.J., Faraone, S.V., Tsuang, M.T. 1997. Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients. Am. J. Psychiatry, 154, 371-377). Comparisons between patients and controls revealed significant differences on various TCI scores consistent with a global disorganization of personality in schizophrenia involving both basic neurophysiological and potentially genetically determined traits (i.e. temperament) and developmental aspects of personality (i.e. character). Correlation analysis showed distinct associations between symptoms and personality dimensions. The results suggest that the negative and disorganized dimensions of schizophrenia are related temperamental factors, whereas the psychotic symptoms are more related to characterological abnormalities. The observed patterns of associations also underline the heterogeneity of the classical negative and positive dimensions of schizophrenia.     

Hippocampal expression of the calcium sensor protein visinin-like protein-1 in schizophrenia

Hippocampal cytoarchitectural abnormalities may be part of the cerebral substrate of schizophrenia. Amongst the chemical components being abnormal in brains of schizophrenics are altered calcium concentrations and reduced expression of the neurotrophin receptor, trkB. We studied by immunohistochemical methods the distribution of visinin-like protein-1 (VILIP-1), which is a calcium sensor protein and at the same time a trkB mRNA binding protein, in hippocampi of nine schizophrenic patients and nine matched control subjects. In normal hippocampi VILIP-1 immunoreactivity was found in multiple pyramidal cells and interneurons. A portion of VILIP-1 immunoreactive interneurons co-express calretinin (60%) and parvalbumin (<10%). In schizophrenics fewer pyramidal cells but more interneurons were immunostained. Our data point to an involvement of the protein in the altered hippocampal circuitry in schizophrenia.     

Quality-of-life assessment in patients who had been surgically treated for cerebellar pilocytic astrocytoma in childhood

OBJECT: After radical surgery for childhood cerebellar astrocytomas, patients are considered to be cured. Long-term follow up demonstrates that these patients survive, with most of them leading a normal life. The study reported here was aimed at assessing the quality of life (QOL) of these adults, which is defined as a person's sense of well-being, as derived from his or her current experience of life as a whole. METHODS: Twenty patients who had undergone surgery between 1970 and 1985 were enrolled in the study. In four patients ventriculoperitoneal shunts were in place; two of these patients had required more than six shunt revisions. At present, all patients have clear neuroimaging studies and their Karnofsky Performance Scale (KPS) scores are as follows: 70 in three, 80 in seven, 90 in six, and 100 in four. A QOL questionnaire was administered to the patients and to a control group consisting of 20 healthy volunteers of matching age and sex. The chi-square test was applied to compare patients and controls. Traditional questions on the level of education, work, whether the patients have their own families, and whether they possessed a driver's license were asked at the end of the questionnaire. In all the dimensions assessed except one (sex life), the difference between patients and control volunteers was significant, socializing and adolescence being the most striking ones. This was also true when the three patients with the lowest KPS scores and the worst QOL results were excluded. CONCLUSIONS: By traditional standards, these patients appear to fare quite well. Nevertheless, their self-reported life experience is unsatisfying when compared with the control group. The authors conclude that psychosocial factors are critical to complete recovery and the QOL of children who undergo successful operations for benign cerebellar astrocytoma.