Coexistence of antithrombin deficiency and suspected inferior vena cava atresia in an adolescent and his mother - case report and clinical implications.

BACKGROUND: Antithrombin deficiency (ATD) is an autosomal dominant thrombophilia presenting with varying phenotypes. In pediatric patients with ATD, thrombosis typically develops during the neonatal period or adolescence. However, to date there are no consistent recommendations on the therapeutic management of children with ATD. Inferior vena cava atresia (IVCA) belongs to a range of congenital or acquired vena cava malformations and is described as an independent risk factor for thrombosis. The present case report explores two cases of combined ATD and IVCA in an adolescent and his mother. CASE PRESENTATION: A 14-year-old male presented with extensive deep venous thromboses (DVTs) of both lower extremities as well as an IVCA. The patient had previously been diagnosed with an asymptomatic ATD without therapeutic consequences at that time. His mother was suffering from an ATD and had herself just been diagnosed with IVCA, too. The DVTs in the adolescent were treated by systemic anticoagulation and catheter-directed local thrombolysis causing favourable results. Yet, despite adequate oral anticoagulation the DVTs in both lower extremities reoccurred within 1 week after the patient was discharged from hospital. This time, thrombolysis could not be fully achieved. Surprisingly, probing and stenting of the IVCA was achieved, indicating an acquired IVCA which could have occurred after undetected thrombosis in early childhood. Genetic analyses showed the same mutation causing ATD in both son and mother: heterozygote missense mutation c.248 T > C, p.(Leu83Pro), within the heparin binding domain of antithrombin. This mutation was never reported in mutation databases before. CONCLUSIONS: To our knowledge this is the first case report discussing combined ATD and IVCA in two family members. Since ATDs present with clinical heterogeneity, taking a thorough family history is crucial for the anticipation of possible complications in affected children and decisions on targeted diagnostics and therapeutic interventions. Affected families must be educated on risk factors and clinical signs of thrombosis and need an immediate diagnostic workup in case of clinical symptoms. IVCA in patients with ATD could occur due to thrombotic occlusion at a very early age. Therefore, in case of family members with IVCA and ATD ultrasound screening in newborns should be considered.

[Sepsis-associated encephalopathy : A nationwide survey on diagnostic procedures and neuromonitoring in German intensive care units]. / Sepsis-assoziierte Enzephalopathie : Eine bundesweite Umfrage zu Verfahren der Diagnostik und des Neuromonitorings auf deutschen Intensivstationen.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is one of the most frequent causes of neurocognitive impairment in intensive care patients. It is associated with increased hospital mortality and poor long-term neurocognitive outcome. To date there are no evidence-based recommendations for the diagnostics and neuromonitoring of SAE. OBJECTIVE: The aim of the study was to evaluate the current clinical practice of diagnostics and neuromonitoring of SAE on intensive care units (ICU) in Germany. MATERIAL AND METHODS: Based on available literature focusing on SAE, a questionnaire consisting of 26 items was designed and forwarded to 438 members of the Scientific Working Group for Intensive Care Medicine (WAKI) and the Scientific Working Group for Neuroanesthesia (WAKNA) as an online survey. RESULTS: The total participation rate in the survey was 12.6% (55/438). A standardized diagnostic procedure of SAE was reported by 21.8% (12/55) of the participants. The majority of participants preferred delirium screening tools (50/55; 90.9%) and the clinical examination (49/55; 89.1%) to detect SAE. Brain imaging (26/55; 47.3%), laboratory/biomarker determination (15/55; 27.3%), electrophysiological techniques (14/55; 25.5%) and cerebrospinal fluid examination (12/55; 21.8%) are less frequently performed. The follow-up examination of SAE is most frequently performed by a clinical examination (45/55; 81.8%). Neuromonitoring techniques, such as continuous electroencephalography (31/55; 56.4%), transcranial doppler sonography (31/55; 56.4%) and near-infrared spectroscopy (18/55, 32.7%) are not frequently used. We observed statistically significant differences between the theoretically attributed importance and clinical practice. The great majority of respondents (48/55; 87.3%) endorse the development of guidelines containing recommendations for diagnostics and neuromonitoring in SAE. DISCUSSION: This explorative survey demonstrated a great heterogeneity in diagnostics and neuromonitoring of SAE in German ICUs. Uniform concepts have not yet been established but are desired by the majority of study participants. Innovative biomarkers of neuroaxonal injury in blood and cerebrospinal fluid as well as electrophysiological and brain imaging techniques could provide valuable prognostic information on the neurocognitive outcome of patients and would thus be a useful addition to the clinical assessment of ICU patients with SAE.

[Diagnostic Workup and Treatment of Antibody-Related Encephalomyelitis]. / Diagnostik und Therapie von autoantikörpervermittelten Enzephalomyelitiden.

The results of laboratory tests for antineuronal antibodies in immune-mediated encephalitis nowadays are not only relevant for diagnostic purposes but are instead closely connected to outcome measures and treatment response. Besides the mere detection of antibodies, investigating the cerebrospinal fluid is indispensible to rule out an infectious etiology of encephalitis prior to the initiation of immunosuppressive treatment, whereas imaging studies are relevant to gain information on the temporal course of disease and for ruling out other etiologies, e. g. hippocampal gliomas. This work gives an overview on the clinical course and findings of laboratory, electroencephalography (EEG) and imaging studies in relevant types of autoimmune mediated encephalitis. Furthermore, it gives a synopsis on contemporary treatment strategies.

Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial.

BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated efficacy in the treatment of major depression and has suggested efficacy in the treatment of alcoholism. However, no completed trials with any selective serotonergic medication have been reported in patients who display both major depression and alcoholism, despite previous observations that both depression and alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one patients diagnosed as having comorbid major depressive disorder and alcohol dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and alcohol consumption were obtained throughout the 12-week course of the study. RESULTS: The improvement in depressive symptoms during the medication trial was significantly greater in the fluoxetine group than in the placebo group. Total alcohol consumption during the trial was significantly lower in the fluoxetine group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing the depressive symptoms and the alcohol consumption of patients with comorbid major depressive disorder and alcohol dependence. It is unknown whether these results generalize to the treatment of less depressed and less suicidal alcoholics.

Pharmacokinetics of tranylcypromine in patients who are depressed: relationship to cardiovascular effects.

We investigated the pharmacokinetics of tranylcypromine, as well as the relationship between plasma levels of this agent and its effects on blood pressure and pulse rate. Tranylcypromine was absorbed rapidly after oral dosing, with the peak level being attained within 0.67 to 3.50 hours. Absorption was biphasic in seven of nine subjects. Elimination of tranylcypromine also was rapid, with a t 1/2 between 1.54 and 3.15 hours. From 2 to 7 hours after dosing, standing systolic and diastolic blood pressures were lowered and standing pulse was raised, compared with baseline. Onset of the effect on standing systolic blood pressure was correlated with the time of peak plasma tranylcypromine concentration. Maximum orthostatic drop of blood pressure and rise of pulse rate occurred 2 hours after dosing. Mean plasma tranylcypromine concentrations were correlated with mean orthostatic drop of systolic blood pressure and rise of pulse rate. Patients who have clinically significant hypotensive reactions to this agent may benefit from changes in their dose regimen aimed at minimizing peak tranylcypromine levels.

Disproportionate suicidality in patients with comorbid major depression and alcoholism.

OBJECTIVE: The two purposes of this study were to provide a comprehensive description of the clinical features of patients who presented to an intake psychiatric setting with major depression and alcohol dependence and to determine which clinical features distinguished this dual-diagnosis group from patients with the two relevant single diagnoses. METHOD: During a recent 5-year period, a total of 107 patients who came to a psychiatric facility for initial evaluation were diagnosed as having both major depression and alcohol dependence. The clinical profile of this dual-diagnosis group was compared to that of nondepressed alcoholics (N = 497) and nonalcoholic patients with major depression (N = 5,625), assessed at the same facility, on the basis of information from the Initial Evaluation Form, a semistructured instrument containing a standardized symptom inventory that includes ratings of severity. RESULTS: The psychiatric symptom that most strongly distinguished the depressed alcoholics from the two comparison groups was the level of suicidality. The depressed alcoholics differed significantly from the nonalcoholic depressed patients on only two depressive symptoms, suicidality (59% higher) and low self-esteem (22% higher); they were also significantly distinguished from the nonalcoholic depressed patients by factors such as greater impulsivity, functional impairment, and abnormal personal and social history markers. CONCLUSIONS: Suicidality was disproportionately greater than other psychiatric symptoms in the depressed alcoholics. The clinical profile of depressed alcoholics suggests that they suffer an additive or synergistic effect of two separate disorders, resulting in a disproportionately high level of acute suicidality upon initial psychiatric evaluation.

Fluoxetine versus placebo for the marijuana use of depressed alcoholics.

The aim of this analysis was to evaluate the efficacy of the SSRI antidepressant fluoxetine versus placebo for the marijuana use of depressed alcoholics. There are no previous reports involving and SSRI antidepressant for marijuana abuse. This analysis involved a subsample of 22 depressed alcoholic marijuana users out of a total of 51 depressed alcoholics. The entire sample was involved in a 12-week double-blind, placebo-controlled study evaluating the efficacy of fluoxetine versus placebo in depressed alcoholics. During the course of the trial, the cumulative number of marijuana cigarettes used was almost 20 times as high in the placebo group as in the fluoxetine group. Also, the number of days of marijuana use during the study was five times higher in the placebo group than in the fluoxetine group. These data suggest efficacy for fluoxetine in decreasing marijuana use of depressed alcoholics.

Fluoxetine trial in suicidal depressed alcoholics.

The selective serotonergic agonist fluoxetine has demonstrated efficacy in the treatment of depression and has suggested efficacy in the treatment of alcoholism. However, no trials with any selective serotonin agonist have been reported in patients who display both major depression and alcoholism. In this study, 12 patients with DSM-III-R diagnoses of major depressive disorder and alcohol dependence were treated openly with fluoxetine for 8 weeks, with doses ranging from 20 mg to 40 mg p.o. qAM. All 12 patients reported prominent suicidal ideation upon admission to our hospital; 6 had made serious suicide attempts shortly before admission. Statistically significant improvements were noted on measures of depression and postdischarge alcohol consumption. No paradoxical increases in suicidality were noted. These findings suggest that fluoxetine has potential for treating the depressive symptoms and the excessive alcohol intake of depressed alcoholics.

Double-blind fluoxetine in depressed alcoholic smokers.

Treatment trials involving smoking in alcoholics with major depression are scarce, despite the common co-occurrence of these disorders. In this study, 25 smokers with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were randomized to fluoxetine or placebo in a 12-week, double-blind, parallel group trial. Almost half (48%) of the patients had made a suicide attempt in the week before hospitalization (where recruitment was performed), and 84 percent reported suicidal ideations during that week. Those in the fluoxetine group demonstrated a significant within-group decrease in smoking during the course of the study, whereas those in the placebo group did not. Those in the fluoxetine group smoked 27 percent fewer cigarettes than those in the placebo group, although this difference was not statistically significant. Cumulative alcohol consumption during the 12 weeks of the pharmacotherapy trial was four times as high in the placebo group as in the fluoxetine group, though this difference was not statistically significant in this limited-sized sample. The change in smoking was significantly associated with a change in drinking. These preliminary findings suggest that fluoxetine has the potential for treating the smoking and drinking behaviors of depressed alcoholic smokers.

Preliminary report: double-blind, placebo-controlled study of fluoxetine in depressed alcoholics.

The selective serotonergic agonist fluoxetine has demonstrated efficacy in the treatment of depression and has possible efficacy in the treatment of nondepressed and depressed alcoholics. However, no double-blind, placebo-controlled trials with any selective serotonergic medication have been reported in patients who have both major depression and alcoholism. In this study, 21 patients with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were randomized to fluoxetine or placebo in a 12-week, double-blind, parallel group trial. The patients reported a high level of current episode (52.4%), prior episode (61.9%), and lifetime (76.2%) suicidal behavior. Total alcohol consumption during the 12-week treatment course was significantly lower in the fluoxetine group than the placebo group, after controlling for baseline differences in consumption. The fluoxetine group demonstrated a four-fold greater improvement in depressive symptoms, but this difference did not reach statistical significance in this small sample. These preliminary findings suggest that fluoxetine has potential for treating the excessive alcohol ingestion of depressed alcoholics and may have potential for treating the depressive symptoms of these patients as well.