Extreme eutrophication and salinisation in the Coorong estuarine-lagoon ecosystem of Australia's largest river basin (Murray-Darling).

Estuaries in rainfall poor regions are highly susceptible to climatic and hydrological changes. The Coorong, a Ramsar-listed estuarine-coastal lagoon at the end of the Murray-Darling Basin (Australia), has experienced declining ecological health over recent decades. Twenty years of environmental data were analysed to assess patterns and drivers of water quality changes. Large areas of the Coorong are now persistently hyper-saline (salinity >80 psu) and hypereutrophic (total nitrogen, TN > 4 mg L-1, total phosphorus, TP > 0.2 mg L-1, chlorophyll a > 50 µg L-1) which coincided with reduced flushing due to diminished freshwater inflows and increasing evapo-concentration. Sediment quality also was related to flushing, with higher concentrations of organic carbon, TN, TP and sulfides as salinity increased. While total nutrient levels are very high, dissolved inorganic nutrients are generally low. Increased lagoonal flushing would be beneficial to reduce the hypersalinisation and hypereutrophication and improve ecosystem health.

Sudden unexpected cardiac death and postmortem identification of a novel RYR2 gene mutation.

A 13-year-old female was found lifeless at home. The autopsy and consecutive histological and toxicological examinations showed blood-rich and edematous lungs and foamy bloody content in the airways. No morphologic pathological findings were seen, especially no bleeding sources. Toxicological findings were unremarkable. The specific cause of death remained unclear. Due to reported losses of consciousness, a moleculargenetic postmortem testing was performed. A so far undescribed mutation in the cardiac ryanodine receptor gene RyR2 was detected. This mutation is suitable to explain the case history as well as the morphological findings. The cardiac ryanodine receptor gene RyR2 encodes the ryanodine receptor type 2, an ion channel in the cardiomyocytes. The ion channel regulates the influx of calcium ions and thus influences myocardial activity. Mutations in this channel may result in the catecholaminergic polymorphic ventricular tachycardia (CPVT), a cardiac arrhythmia that can lead to syncope and sudden cardiac death. This case demonstrates the usefulness and need of molecular autopsy, in particular to identify and treat possibly affected family members.

[Genetic testing to prevent sudden cardiac death]. / Genetische Diagnostik zur Vermeidung des plötzlichen Herztods.

Successfully incorporating genetic testing into clinical practice to prevent sudden cardiac death (SCD) requires (1) appropriate recognition of an inherited cardiovascular condition, (2) identification of appropriate family members at risk and for genetic testing, (3) selection of the appropriate genetic test and information about the expected diagnostic yield, (4) understanding the complexity of result interpretation and distinct handling of incidental findings and (5) providing effective communication and medical advice regarding the genetic and medical results and implications to the patient and his family. Molecular autopsy in SCD victims will be of future importance to determine the cause of death. Interdisciplinary patient care should be provided in specialized centers with a high level of cardiogenetic expertise and is recommended to provide precise and individualized patient management.

Molecular genetic diagnostics for ventricular arrhythmias and sudden cardiac death syndromes.

Inherited forms of ventricular arrhythmias are rare diseases, but a major cause for severe cardiac events, sudden unexplained death syndromes, and death in young adults, infants, and children. Each disorder is genetically heterogeneous (5-20 genes per disease) and molecular testing may include both core genes and less common disease genes as well. Owing to the rapid development and feasibility of sequencing technologies enabling a parallel analysis of several hundred genes up to a whole exome, disease mutations can be identified very efficiently, but have to be seen in the complexity and natural variance of the human genome. Precise phenotypic knowledge and advanced gene variant interpretation are important to ensure adequate patient diagnostics and management. This article focuses on the genetic causes of inherited arrhythmia forms predisposing patients to sudden cardiac death and discusses practical issues and skills for molecular testing.

[The challenge of treating bipolar outpatients]. / Herausforderungen der ambulanten Behandlung von Patienten mit bipolar-affektiven Störungen.

The course of bipolar illness comprises a wide range, which may vary between one single episode once every five years and a severe ultra rapid cycling course with mood changes within days. Even with optimal pharmacological treatment the functional outcome in bipolar patients is still poor. Underlying pathomechanisms are not fully understood yet. This article addresses three possible illness specific-aspects: cognitive defects, high relapse frequency and poor adherence. Causes as well as therapeutic interventions for these therapeutic pitfalls are summarised.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

OBJECTIVE: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. METHOD: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. RESULTS: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. CONCLUSION: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

[Bipolar depression. Spectrum of clinical pictures and differentiation from unipolar depression]. / Bipolare Depression. Spektrum klinischer Erscheinungsbilder und Abgrenzbarkeit von der unipolaren Depression.

Patients with bipolar disorder often present initially with a major depressive episode. The correct diagnosis at the first presentation could help to find an effective medication regimen, to prevent antidepressant-induced rapid cycling and to reduce antidepressant-induced manic episodes, e.g. though combination therapy with a mood stabilizer. Consistent predictors for an underlying bipolar illness are an early age of onset, a highly recurrent illness course with more than five episodes, the presentation of atypical features, psychotic symptoms, the presence of psychiatric comorbidities like anxiety disorders, history of suicide attempts (especially at an early age), positive family anamnesis for bipolar disorder, and a rapid evolvement of the depressive episode. So far there are no pathognomonic markers for bipolar disorder. Therefore we propose to assess the risk of each patient for having bipolar disorder individually. Patients who are at a high risk should at least be informed and should be closely monitored for the development of manic episodes.

Preliminary results of a fine-grain analysis of mood swings and treatment modalities of bipolar I and II patients using the daily prospective life-chart-methodology.

OBJECTIVE: The study aimed to increase the knowledge about the detailed course differences between different forms of bipolar disorder. METHOD: Using the prospective life-chart-clinician version, we compared the fine-grain analysis of mood swings and treatment modalities of 18 bipolar II with 31 bipolar I patients. RESULTS: During an observational period of a mean of 26 months we observed an increase of euthymic days, and a decrease of (sub)depressive and (hypo)manic days. Days in a (sub)depressed state were more frequent than days of (hypo)mania as well as days of subdepression or hypomania in comparison to days of full-blown depression or mania. Bipolar II patients showed an increase in hypomanic days receiving more frequently antidepressants. Bipolar I patients, with a decrease of manic days, were significantly taking more often mood stabilizers. CONCLUSION: Treatment in a specialized bipolar clinic improves the overall outcome, but bipolar II disorder seems to be still treated sub-optimally with a possible iatrogenic increase of hypomanic days.

Lamotrigine in bipolar disorder: results of a mirror-image evaluation using the NIMH Lifechart-Methodology.

BACKGROUND: Lamotrigine (LTG) is characterized by prophylactic efficacy against bipolar depression (BPD). We evaluated retro- and prospectively the naturalistic treatment outcome with LTG analysing lifecharts of patients from the bipolar outpatient clinic. METHODS: Lifechart-data of 20 patients routinely treated with LTG for the first time were evaluated, comparing number and duration of manic, depressive and mixed episodes prior to LTG and after initiation of treatment (mirror-image evaluation). The mean prospective evaluation period based on the lifechart was 18.1 months. Also we compared the number and severity of "switches" from depression in mania. Additionally, CGI-BP, YMRS, IDS-C and GAF scores at the monthly visits were compared for time after LTG initiation. RESULTS: We found no significant differences in the absolute number of manic, depressive and mixed episodes, respectively, before and after initiation of LTG. The number of "switches" did not differ significantly. A significant difference in duration of time patients suffered from a depressive state before and after initiation of LTG was observed in favour of LTG treatment (p=.006). A similar finding was observed for the time spent in mixed episodes (p<.001). No significant difference was observed for scores of mood scales at the monthly visits (CGI-BP, YMRS, IDS-C, GAF). LIMITATIONS: Generalizability of these results is limited due to the uncontrolled design and the issues in comparing prospective and retrospective data. CONCLUSION: These data underline not only the antidepressant profile of LTG, but also the usefulness of the Lifechart-Methodology (LCM) in the evaluation of treatment outcome under routine conditions.

Association of cognitive deficits with elevated homocysteine levels in euthymic bipolar patients and its impact on psychosocial functioning: preliminary results.

OBJECTIVES: Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients. METHODS: A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3(rd) edition (WAIS-III) subtest Letter-Number Sequencing Test (LNST) and the HAWIE-R (German version of the WAIS-R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at -80 degrees C. Total Hcy concentration was measured using high-performance liquid chromatography. RESULTS: In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE-R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 +/- 3.2 microm/L in the patient group and 7.8 +/- 2.1 microm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels. CONCLUSIONS: Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.

[Physician's information requirements before providing vaccines]. / Zur Aufklärungspflicht des Arztes vor Impfungen.

Vaccination is one of the most successful and cost-effective tools for disease prevention. However, the success makes vaccination its own worst enemy: adverse vaccine events, i. e., those caused by the vaccine or those associated with immunization by co-incidence or only suspected, become more visible than the consequences of the natural disease itself. Not surprisingly, discussions regarding the benefit and risk of immunization have become increasingly prominent in many industrially developed countries such as Germany. In addition to balanced health information provided to the public and the medical community, increased attention should be paid to the physician's duty of disclosure before providing vaccines. Annually, the German Advisory Committee on Immunization (STIKO) publishes updated recommendations on immunization policies including recommendations for information requirements. Information should be provided on the disease, the nature and benefit of the vaccine, the duration of immunity and the need for boosters, possible side effects and complications, and other important is-sues. Considering a case of a complication following immunization, the German Federal Court of Justice decided recently on the duty of disclosure regarding the risk of vaccines. The decision has been taken into consideration by the STIKO. Special attention should be paid to information requirements when providing licensed but not yet officially recommended vaccines.

[Meningococcal disease]. / Meningokokken-Erkrankungen. Viele schwere und tödliche Verläufe sind vermeidbar.

Due to a high complication and case fatality rate, meningococcal diseases are important health problems both in tropical countries experiencing severe epidemics as well as in countries of moderate climate zones. Worldwide N. meningitidis of sero-groups A, B, and C are predominant and to a lesser extent serogroups W (135) and Y play a role, whereas in Europe more than 90 % of meningococcal diseases are caused by serogroups B and C of N. meningitidis. In Germany and other developed countries the majority of cases occur in very young children and adolescents. Since many years, meningococcal polysaccharide vaccines against diseases due to N.meningitidis serogroup A, C, Y and W (135) are commercially available. Unfortunately, a vaccine against diseases caused by N. meningitidis serogroup B is still under development. The recently developed and licensed conjugated meningococcal vaccines against N. meningitidis serogroup C are also protective against disease in very young children. Eight countries in Western Europe as well as Australia have already established country-wide immunization programs for children and adolescents. Within only 2 to 3 years, well managed programs have achieved far-reaching control of meningococcal C disease in UK and the Netherlands. In Germany, the Advisory Committee on Immunization (STIKO recommends immunization for selected risk groups. The current increase of the percentage of meningococcal C diseases to 28 - 30 % gives reason for further discussion regarding immunization strategies. How-ever, the STIKO expressively declares, that in addition to the recommendation for risk groups, the physician can use all vaccines licensed in Germany without any restriction. It is his/her responsibility to advice the patients regarding immunization possibilities against the life-threatening meningococcal disease, particularly if cases are occurring.

[Treatment of acute bipolar disorder. Intriguing balancing act between mania and depression]. / Therapie der akuten bipolaren Erkrankung. Kniffliger Balanceakt zwischen Manie und Depression.

The term bipolar disorder is no longer limited to the classical manic-depressive condition, but now subsumes a wide spectrum of illnesses. As a consequence of this expansion of the classification systems, the therapeutic utility of lithium and other mood stabilizing agents has to be defined anew. The majority treatment recommendations differentiate, symptom-related, between euphoric mania, mixed conditions, mania with psychotic symptoms and rapid cycling manic episodes. Current acute treatment includes, in addition to lithium, in particular carbamazepine and valproate, but also newer antiepileptic drugs such as lamotrigine or atypical neuroleptic agents such as olanzapine and risperidone. Due to the high suicidal risk, patients with bipolar depression often need to be given an antidepressant as well. It must, however, be remembered that in patients with rapid cycling, antidepressants may re-trigger mania.

[Psychopharmacotherapy of bipolar affective diseases]. / Psychopharmakotherapie bipolarer affektiver Erkrankungen.

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Clinical relevance and treatment possibilities of bipolar rapid cycling.

Bipolar rapid cycling (RC) is defined as 4 or more affective episodes within 1 year. It has been postulated that RC is related to a poor response to lithium, to the same extent as mixed episodes or other atypical symptoms of the illness. This article reviews the current status of alternative pharmacological or otherwise supportive therapies of RC. Biological parameters and characteristics of the illness associated with RC like gender prevalence in women, hyperthyroidism, catecholamine-O-methyltransferase allele, the influence of sleep, different subtypes of bipolar disorder and the risk of antidepressant-induced cycling will be discussed in detail.

Clozapine as add-on medication in the maintenance treatment of bipolar and schizoaffective disorders. A case series.

Atypical neuroleptics are increasingly used in the treatment of bipolar and schizoaffective disorders. Currently, numerous controlled short-term studies are available for clozapine, olanzapine, risperidone or quetiapine, but long-term data are still missing. Three patients (2 with bipolar disorder, 1 with schizoaffective disorder) are described who showed a marked reduction of affective symptomatology after clozapine had been added to mood stabilizer pretreatment. The patients were seen once a month before and after the introduction of clozapine for at least 6 months. Treatment response was evaluated using different rating scales (IDS, YMRS; GAF; CGI-BP) and the NIMH Life Chart Methodology. All patients showed a marked improvement after the add-on treatment with clozapine had been initiated. Clozapine was tolerated well with only transient and moderate weight gain and fatigue as only side effects. This case series underlines the safety and efficacy of clozapine as add-on medication in the treatment of bipolar and schizoaffective disorders.