Endovascular thrombectomy provides durable, symptomatic relief in iliocaval tumor thrombosis.

AIMS: Iliocaval venous tumor thrombus is a morbid condition associated with chronic venous stasis, lower extremity edema/pain, extensive thrombus burden and high mortality secondary to critical flow obstruction, intracardiac thrombus extension and tumor embolization. Typically resistant to medical therapy, management is primarily surgical, presenting challenges for medically complex patients with widespread or end-stage disease. Mechanical or aspiration thrombectomy represents an appealing treatment strategy but data are lacking. MATERIALS AND METHODS: We performed a single-center, 10-year, retrospective review of patients with pathology-confirmed, iliocaval tumor thrombus who underwent thrombectomy. 14 patients met inclusion criteria and were managed by 18 procedures over this period. RESULTS: The most common malignancy was renal-cell carcinoma (n=7; 50%); other types included germ cell (n=2; 14%), other genitourinary (n=2; 14%), neuroendocrine (n=1; 7%), soft tissue (n=1; 7%), and skin cell malignancies (n=1; 7%). All patients had thrombus involving the distal inferior venous cava (IVC), 50% had bilateral iliac involvement and 29% atrial involvement. Common indications were venous obstruction symptoms (n=11; 65%) and evidence of embolism (n=6; 35%). All patients tolerated the procedures without acute complication. The technical success rate was 94%, with marked improvement of flow and reduction in thrombus burden, and 79% had subjective symptomatic improvement. All patients survived for >2 weeks and 50% had long-term survival of >1 year, with 86% of these patients having renal-cell carcinoma (RCC). Three patients underwent multiple thrombectomies within days to weeks, with ultimate symptomatic improvement. CONCLUSIONS: Overall, our study results suggest mechanical or aspiration thrombectomy as a safe and efficacious treatment for patients with iliocaval tumor thrombus.

Enkephalin knockout male mice are resistant to chronic mild stress.

Enhanced stress reactivity or sensitivity to chronic stress increases the susceptibility to mood pathologies such as major depression. The opioid peptide enkephalin is an important modulator of the stress response. Previous studies using preproenkephalin knockout (PENK KO) mice showed that these animals exhibit abnormal stress reactivity and show increased anxiety behavior in acute stress situations. However, the consequence of enkephalin deficiency in the reactivity to chronic stress conditions is not known. In this study, we therefore submitted wild-type (WT) and PENK KO male mice to chronic stress conditions, using the chronic mild stress (CMS) protocol. Subsequently, we studied the CMS effects on the behavioral and hormonal level and also performed gene expression analyses. In WT animals, CMS increased the expression of the enkephalin gene in the paraventricular nucleus (PVN) of the hypothalamus and elevated the corticosterone levels. In addition, WT mice exhibited enhanced anxiety in the zero-maze test and depression-related behaviors in the sucrose preference and forced swim tests. Surprisingly, in PENK KO mice, we did not detect anxiety and depression-related behavioral changes after the CMS procedure, and even measured a decreased hormonal stress response. These results indicate that PENK KO mice are resistant to the CMS effects, suggesting that enkephalin enhances the reactivity to chronic stress.

Behavioral effects in adult rats of chronic prepubertal treatment with the cannabinoid receptor agonist WIN 55,212-2.

Human and animal studies provide evidence for vulnerable periods of brain development for deleterious effects of cannabinoids. We have recently shown that pubertal chronic cannabinoid treatment leads to long-lasting behavioral deficits, whereas a comparable treatment in adult rats did not affect the animals' behavior. In the present study we examined the effects of an identical chronic cannabinoid treatment in juvenile rats, just before the onset of puberty. Treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN) (1.2 mg/kg) or vehicle was extended over 25 days throughout the prepubertal period (postnatal days 15-40) in juvenile rats. The rats received a total of 20 injections intraperitoneally. Adult rats were tested for object recognition memory, performance in a progressive ratio (PR) operant behavior task, locomotor activity and prepulse inhibition (PPI) of the acoustic startle response. Juvenile chronic WIN administration had no effect on object recognition memory, PR performance and locomotor activity in adulthood. However, a PPI deficit was observed in WIN-treated rats when tested as adults that could be reversed by the acute administration of the dopamine receptor antagonist haloperidol (0.1 mg/kg). Additionally, juvenile cannabinoid treatment reduced the number of rearings, as well as the time spent in the center of the open field in adult rats, suggesting increased anxiety. Juvenile chronic cannabinoid treatment induced behavioral disturbances in adult rats that are less severe than those observed after pubertal cannabinoid administration. However, based on the observations of sensorimotor gating deficits and increased anxiety, we conclude that the prepubertal developmental phase, in addition to puberty, also represents a vulnerable time period for persistent adverse effects of cannabinoids.

Hemispheric lateralization at different levels of human auditory word processing: a functional magnetic resonance imaging study.

We used functional magnetic resonance imaging to disentangle the functional anatomy of brain systems involved in the processing of auditory word form and meaning. Three monitoring tasks on auditory stimuli, aimed at phonetic, lexical and semantic processing, were used. We found no lateralization of temporal lobe activations, when word processing was contrasted versus the complex phonetic task. Bilateral middle temporal activations (Brodmann Area [BA] 21) were attributed to processing of word-form. Areas specific to semantic processing were restricted to the left hemisphere: the posterior middle frontal (BA 9) and posterior parietal (BA 7/40) cortex, as well as an inferior temporal area (BA 20/21). Our data suggest, that left hemispheric dominance for auditory word comprehension occurred at the level of semantic processing.

Morphological and orthographic similarity in visual word recognition.

The differential impact of orthographic and morphological relatedness on visual word recognition was investigated in a series of priming experiments in Dutch and German. With lexical decision and naming tasks, repetition priming and contiguous priming procedures, and masked and unmasked prime presentation, a pattern of results emerged with qualitative differences between the effects of morphological and form relatedness. With lexical decision, mere orthographic similarity between primes and targets (e.g., keller-KELLER, cellar-ladle) produced negative effects, whereas morphological relatedness (e.g., kellen-KELLE, ladles-ladle) consistently resulted in facilitation. With the naming task, positive priming effects were found for morphological as well as for mere form similarity. On the basis of these results, a model of the lexicon is proposed in which information about word form is represented separately from morphological structure and in which processing at the form level is characterized in terms of activation of, and competition between, form-related entries.

Effects of valproate and E-2-en-valproate on functional and morphological parameters of rat liver. III. Influence of fasting.

Valproate (VPA) therapy has been associated with a rare but fatal hepatotoxicity. Several possible biochemical mechanisms responsible for the hepatotoxicity have been proposed, but the matter has not been decided. There is some evidence that VPA-associated hepatotoxicity may represent the consequences of a VPA overload on a limited mitochondrial beta-oxidation capacity, causing abnormalities in metabolic pathways. If this assumption is true, fasting-induced increase of endogenous fatty acids, which compete with VPA for beta-oxidation, should enhance the hepatotoxic potential of VPA. Indeed, involuntary fasting because of anorexia, e.g., in children with febrile infections, has been discussed as one clinical risk pattern preceding VPA-associated hepatic fatalities. In the present experiments, the effects of fasting on functional and morphological parameters of the liver were studied in young male rats chronically treated with VPA. E-2-en-VPA (trans-2-en-VPA), a major active metabolite of the beta-oxidation pathway of VPA, was used for comparison. Both drugs were administered at doses of 250 mg/kg i.p. 3 times daily for 1 week. In control rats, a 40-h fasting period resulted in marked mobilization of liver lipid and glycogen stores, alterations in liver enzyme activities, and hyperammonemia. In rats treated with VPA, fasting reduced beta-oxidation of the drug, but seemed not to increase its hepatotoxic potential. Compared to experiments without fasting, alterations in liver enzymes and ammonia levels induced by VPA were less marked or absent in fasted rats, and histopathological examination of liver sections did not indicate degenerative liver lesions in response to drug treatment. Thus, compared to previous rat studies on VPA without fasting, fasting appeared to attenuate VPA's hepatotoxic potency, possibly as a result of fasting-induced increases in carnitine levels. In rats treated with E-2-en-VPA, no indication of hepatotoxicity was evident, and alterations in functional hepatic parameters were less pronounced than with VPA. The data do not indicate that fasting or poor nutrition are risk factors for VPA-associated hepatic injury.

Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity.

Of a cohort of 470 epileptic patients in whom valproate (VPA) serum metabolites had been measured, 170 subjects without symptoms or signs of hepatic side effects were chosen as a reference group to establish the usual metabolic pattern. A wide interindividual variation of VPA metabolite concentrations was noted. Infants receiving VPA monotherapy and comedication with other antiepileptic drugs (AEDs) showed lower concentrations of the potential hepatotoxin 4-ene-VPA than did older children. In 11 patients with early symptoms and signs of possible fatal VPA-associated hepatotoxicity, the following spectrum of benign clinical conditions was observed: unusually severe side effect during initiation of VPA therapy (1 patient), high VPA dosage (2 patients), reversible impairment of coagulation with bleeding manifestations in association with a slight increase in transaminase levels (1 child), and reversible liver dysfunction associated with febrile illness (7 patients). Reversible or irreversible fulminant liver failure had occurred in 5 children. Three of the 4 children with a fatal outcome had massive lactic acidosis. In all patients with probable VPA-associated hepatotoxicity, some aspects of VPA metabolism differed distinctly from that of the reference group, but the inter-individual profile of metabolites varied considerably, even in the subgroup of 4 children who died. Impairment of VPA beta-oxidation and increase of metabolites of alternative metabolic pathways (omega- and omega 1-hydroxylation, dehydrogenation reactions) were the most frequent findings. Increased values of 2-n-propyl-4-pentenoic acid metabolite of VPA (4-ene-VPA), could be detected only in 1 of the 5 patients with fulminant liver failure and in one other child with a slight hepatic dysfunction, indicating that this VPA metabolite is not the decisive hepatotoxin or indicator of hepatotoxicity. Because we cannot distinguish between benign and life-threatening hepatic adverse reactions on the basis of VPA metabolites, all identified changes are considered secondary to an as-yet-unknown primary metabolic event. The most toxic compound could be VPA itself, which may unmask an inborn or an acquired metabolic defect in the processing of fatty acids.

Zinc concentrations in mouse embryo and maternal plasma. Effect of valproic acid and nonteratogenic metabolite.

The effect of a single teratogenic dose of the antiepileptic drug valproic acid and its nonteratogenic metabolite, 2-en-valproic acid, on zinc concentrations in mouse plasma, embryo, and decidua on d 9 of gestation was investigated. The substances were injected subcutaneously (sc) as their sodium salts. In this mouse model, valproic acid induced between 20% (400 mg/kg dose) and 60% (600 mg/kg dose) incidence of exencephaly in living fetuses; 2-en-valproic acid was not teratogenic at these dose levels. The zinc concentrations in plasma were significantly increased 1 and 2 h after administration of both substances. The embryonic zinc concentrations were increased 2 and 4 h after application of both substances. The concentrations of zinc in the decidua were not affected. The similarity of effects of valproic acid and its nonteratogenic analog on zinc concentrations in maternal plasma and embryo suggests that the teratogenicity of a single administration of valproic acid in the mouse is not owing to interference with the zinc metabolism in this species.

Qualitatively different organizational structures of lexical knowledge in the left and right hemisphere.

The present study investigates and discusses the organization of lexical knowledge in the intact left and right hemisphere within the framework of hemisphere-specific cognitive modes of processing. Using a divided visual field technique, word pairs of concrete nouns had to be judged. Semantic relation was either intraconceptual (coordinates) or interconceptual (locative). The results suggest that the left hemisphere, lexical structures are predominantly based on intraconceptual relationships corresponding to its analytic sequential processing mechanism, whereas in the right hemisphere, lexical entries are exclusively associated by means of interconceptual relationships in accordance with its "gestalthaft" holistic processor.

[The bronchusplasty with lung-resections -- a conservative method of operation in tumor surgery (author's transl)]. / Die Bronchusplastik bei Lungenresektionen -- eine organerhaltende Operationsmethode in der Tumorchirurgie

Report regarding 32 patients with bronchusplasty in lung resections on account of semimalignant and malignant tumors. Operative indications, -technique, postoperative complications and results up to now are discussed.