The influence of 4–week treatment with sertraline on the combined T3/TRH test in depressed patients

In the present study, the influence of a 4–week treatment with sertraline on the regulation of hypothalamic–pituitary–thyroid (HPT) axis activity in depression was investigated, in particular the impact of sertraline on the thyroid receptor (TR)–mediated negative feedback control as measured by the combined T3/TRH test. In 20 drug–free patients (8 men,12 women) suffering from a major depressive episode according to DSM-IV criteria the single TRH–stimulation test (administration of 200 μg TRH at 09:00h) was carried out followed by a combined T3/TRH test (pre–treatment with 40 μg 3,5,3’–triiodothyronine [T3] the night before; administration of 200 μg TRH at 09:00h the next day). After 4 weeks of treatment with sertraline at a standard dosage of 50 mg/day, both the single TRH test and the combined T3/TRH test were repeated in the depressed patients. Using repeated–measures ANOVA for statistical analysis, antidepressant therapy with sertraline did not have any significant impact on the TRH–induced TSH and prolactin stimulation (ΔTSH, ΔPRL) during the single TRH test nor during the combined T3/TRH test, neither in responders (n = 10) nor in non–responders (n = 10). Moreover, the percentage suppression of TRH–induced TSH stimulation (ΔTSH) after pre–treatment with 40 μg T3 was comparable before (–61.07 %) and after the 4–week treatment with sertraline (–58.92 %). Apparently, the therapeutic efficacy of antidepressants such as sertraline is not related to the regulation of HPT axis activity in depressed patients.     

Glutathione peroxidase-1 and homocysteine for cardiovascular risk prediction: results from the AtheroGene study

OBJECTIVES: This prospective study was designed to evaluate the effect of joint determination of two important contrary biomarkers--homocysteine and glutathione peroxidase (GPx)-1--on cardiovascular risk stratification. BACKGROUND: Homocysteine plasma levels have been associated with cardiovascular risk. Experimental data suggest that antioxidative GPx-1 activity modulates cardiovascular risk associated with homocysteine. METHODS: In 643 patients with coronary artery disease, we performed a prospective study to assess the risk of homocysteine plasma levels and GPx-1 activity on long-term cardiovascular risk with a median follow-up of 7.1 years. RESULTS: Both homocysteine and GPx-1 were among the strongest univariate predictors of future cardiovascular risk, even after adjustment for cardiovascular confounders. Homocysteine levels were significantly elevated in individuals with future cardiovascular events (15.4 vs. 13.4 micromol/l; p < 0.0001); GPx-1 activity was lower (45.3 +/- 13.1 vs. 50.2 +/- 11.0 U/g hemoglobin; p < 0.0001). In patients with GPx-1 activity below the median value, homocysteine plasma levels above the median were associated with a 3.2-fold (95% confidence interval 1.8 to 5.6; p < 0.0001) increase in cardiovascular risk, whereas it lost its independent risk prediction in individuals with increased antioxidative capacity, as reflected by high GPx-1 activity. In contrast to single determination, combined assessment revealed a significant increase in the area under the curve of cardiovascular risk predictive models from 0.72, including traditional risk factors to 0.75 and also including homocysteine levels and GPx-1 activity. CONCLUSIONS: Plasma homocysteine levels and GPx-1 activity are complementary in identifying individuals at high cardiovascular risk. Joint determination of both biomarkers provides substantial information on top of classic risk factors in cardiovascular risk assessment.     

Nipah virus encephalitis reemergence, Bangladesh

We retrospectively investigated two outbreaks of encephalitis in Meherpur and Naogaon, Bangladesh, which occurred in 2001 and 2003. We collected serum samples from persons who were ill, their household contacts, randomly selected residents, hospital workers, and various animals. Cases were classified as laboratory confirmed or probable. We identified 13 cases (4 confirmed, 9 probable) in Meherpur; 7 were in persons in two households. Patients were more likely than nonpatients to have close contact with other patients or have contact with a sick cow. In Naogaon, we identified 12 cases (4 confirmed, 8 probable); 7 were in persons clustered in 2 households. Two Pteropus bats had antibodies for Nipah virus. Samples from hospital workers were negative for Nipah virus antibodies. These outbreaks, the first since 1999, suggest that transmission may occur through close contact with other patients or from exposure to a common source. Surveillance and enhancement of diagnostic capacity to detect Nipah virus infection are recommended.     

CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels

Monocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-alpha, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-alpha, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16+ monocytes than controls (13.6% versus 11.4%; p<0.001). Logistic regression analysis including quartiles of CD14+CD16+ monocytes showed that CD14+CD16+ monocytes were associated with prevalence of CAD (OR 4.9, 95% CI 2.5-19.1, for subjects in the fourth quartile in comparison to subjects in the first quartile). The association between CD14+CD16+ monocytes and CAD remained independently significant after adjustment for most potential confounders (OR 5.0, 95% CI 1.2-20.0). Serum concentrations of TNF-alpha were elevated in subjects within the highest quartiles of CD14+CD16+ monocytes (p=0.018). Our study showed that increased numbers of CD14+CD16+ monocytes are associated with coronary atherosclerosis and TNF-alpha. In accordance, recent animal studies suggest a possibly important role of these monocytes in the development of atherosclerosis.     

Management of atherothrombosis with clopidogrel in high-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH): study design and baseline data

BACKGROUND: The CAPRIE study showed the superiority of clopidogrel over acetylsalicylic acid (ASA) for reducing the combined risk of major atherothrombotic events in patients with recent myocardial infarction (MI), recent ischaemic stroke (IS) or established peripheral arterial disease. The benefit of clopidogrel over ASA is amplified in high-risk patients. Proof of concept for the benefit of clopidogrel in addition to ASA in patients with coronary manifestations of atherothrombosis was provided by the CURE trial. METHODS: MATCH is a randomized, double-blind, placebo-controlled trial that compares clopidogrel and ASA versus clopidogrel alone in high-risk patients with recently symptomatic cerebrovascular disease. Eligible patients have experienced a transient ischaemic attack (TIA) or IS within the last 3 months and have evidence of at least 1 additional risk factor within the last 3 years (prior IS, MI, stable or unstable angina pectoris, diabetes or symptomatic peripheral arterial disease). Patients were randomized to receive ASA 75 mg once daily or placebo, with both groups receiving clopidogrel 75 mg once daily as part of standard therapy. The primary end point is the composite of IS, MI, vascular death and rehospitalization for an acute ischaemic event. The duration of treatment and follow-up is 18 months for each patient. RESULTS: Enrollment was completed in April 2002, with 7,599 patients randomized to receive the study medication. The mean age at randomization was 66 years, and the qualifying event was IS in 78.9% of patients and TIA in 21.1%. The baseline features of the study cohort indicate a population that is at a high risk for atherothrombotic recurrence. CONCLUSION: MATCH is a major ongoing trial that will provide important data on the benefit of clopidogrel and ASA compared with clopidogrel alone for reduction of vascular ischaemic events in patients with recent TIA or IS who are at high risk of atherothrombotic event recurrence.     

Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression

BACKGROUND: Substantial evidence supports a role for dysfunction of the serotonin transporter in the pathogenesis of major depression. Several studies have found reciprocal interactions between the serotonergic system and both brain-derived neurotrophic factor and glutamate, which are known to modulate or affect hippocampal morphologic characteristics. OBJECTIVE: To examine the influence of a polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene on hippocampal volumes in patients with major depression and healthy controls. DESIGN: Baseline investigation of a prospective magnetic resonance imaging study with a 4-year follow-up period. PATIENTS: We examined 40 inpatients with major depression as well as 40 healthy controls matched for age, sex, and handedness. MAIN OUTCOME MEASURES: Subjects underwent high-resolution magnetic resonance imaging. Furthermore, genotyping for the 5-HTTLPR biallelic polymorphism was performed, which consists of a 44-base pair insertion (L allele) or deletion (S allele). RESULTS: Patients with the L/L homozygous genotype had significantly smaller hippocampal gray matter (left hemisphere: P=.003; right hemisphere: P=.01) and white matter volumes (left hemisphere: P=.001; right hemisphere: P=.002) than controls with this genotype. No significant differences were found between patients and controls with the L/S or S/S genotype. Moreover, patients with the L/L genotype had significantly smaller hippocampal white matter volumes than those with the L/S or S/S genotype (P=.03). CONCLUSIONS: These findings suggest that homozygosity for the L allele is associated with decreased hippocampal volumes in patients with major depression but not in healthy controls. A possible explanation is that the interaction between the serotonergic system and neurotrophic factors as well as excitatory amino acid neurotransmission may affect hippocampal morphologic characteristics.     

Zur Problematik der Kombination von Clozapin mit Benzodiazepinen

Serious adverse events and even sudden death have been reported during administration of the combination of clozapine and benzodiazepines. However, this combination does not necessarily result in increased frequency of serious adverse events. Thus it is not regarded as an absolute contraindication and might be useful in distinct clinical situations, e.g., during the occurrence of a malignant neuroleptic syndrome, "catatonic dilemma," or severe agitation during clozapine treatment. In the following report, certain suggestions on how to deal with this combination therapy are provided which may provide a basis for discussion that ultimately may lead to the formulation of guidelines for this combination therapy. Such guidelines may help psychiatrists in dealing with this combination in clinical situations. Moreover, the formulation of such guidelines would help with forensic issues in case of serious adverse events occurring during this combination therapy.     

Klinisches Bild, Diagnostik und Therapie granulomatöser Entzündungen ohne Erregernachweis bei 6 Patienten mit septischer Granulomatose (CGD)

Background. Patients with Chronic Granulomatous Disease,CGD, do not only suffer from often life- threatening infections, but also from inflammatory granulomatous complications. These granulomas may be caused by persisting pathogens although a mainly non-infectious pathogenesis is very likely. Such granuloma formation may also lead to life- threatening complications. Methods and patients. In six CGD patients granulomas in inflamed organs were diagnosed by ultrasound and x-ray and in four cases confirmed by histology.After most careful exclusion of an infectious cause five patients were treated with steroids (lung (3), stomach (1),colon (1)) and one with mesalazine (stomach).We describe the follow up of these patients in a period from 1 to 5 years. Results. In all six patients inflammatory lesions resolved or did not progress.This was in some cases followed by crucial improvement in originally severly impaired organ function. No infections were observed. Conclusion. After most careful exclusion of an infectious origin and under sufficient antibacterial and fungostatic prophylaxis granulomas in patients with CGD should be treated with immunosuppressive drugs. If the clinical course of such an inflammation is severe steroids are mandatory.