When should clinicians search for GLUT1 deficiency syndrome in childhood generalized epilepsies?

UNLABELLED: GLUT1 deficiency (GLUT1D) has recently been identified as an important cause of generalized epilepsies in childhood. As it is a treatable condition, it is crucial to determine which patients should be investigated. METHODS: We analyzed SLC2A1 for mutations in a group of 93 unrelated children with generalized epilepsies. Fasting lumbar puncture was performed following the identification of a mutation. We compared our results with a systematic review of 7 publications of series of patients with generalized epilepsies screened for SLC2A1 mutations. RESULTS: We found 2/93 (2.1%) patients with a SLC2A1 mutation. One, carrying a novel de novo deletion had epilepsy with myoclonic-atonic seizures (MAE), mild slowing of head growth, choreiform movements and developmental delay. The other, with a paternally inherited missense mutation, had childhood absence epilepsy with atypical EEG features and paroxysmal exercise-induced dyskinesia (PED) initially misdiagnosed as myoclonic seizures. Out of a total of 1110 screened patients with generalized epilepsies from 7 studies, 2.4% (29/1110) had GLUT1D. This rate was higher (5.6%) among 303 patients with early onset absence epilepsy (EOAE) from 4 studies. About 50% of GLUT1D patients had abnormal movements and 41% a family history of seizures, abnormal movements or both. CONCLUSION: GLUT1D is most likely to be found in MAE and in EOAE. The probability of finding GLUT1D in the classical idiopathic generalized epilepsies is very low. Pointers to GLUT1D include an increase in seizures before meals, cognitive impairment, or PED which can easily be overlooked.

Experience and intermediate-term results using the Contegra heterograft for right ventricular outflow reconstruction in adults.

OBJECTIVES: The Contegra bioprosthesis (valved heterologous bovine jugular vein) is used for reconstruction of the right ventricular outflow tract (RVOT) in congenital heart malformations and pulmonary valve replacement in different settings. Compared to pulmonary homografts, the Contegra conduit is readily available 'on the shelf'. So far, its use was mainly described in children. The aim of this study is to evaluate the feasibility and the outcome of Contegra graft implantation in the adult. METHODS: Between November 1999 and December 2007, a total of 32 Contegra grafts were implanted in 31 patients (24 men and 7 women), with a mean age of 35.7+/-10.5 years (range 18-54 years). All operations have been completed through median sternotomy with cardiopulmonary bypass. Indications included: Ross procedure for aortic valve disease (n=22); re-operation of corrected Fallot-tetralogy (n=5); isolated pulmonary valve disease (n=2); re-operation of double outlet right ventricle (DORV) (n=1); pulmonary stenosis in congenital dilated cardiomyopathy (DCM) (n=1). Conduit sizes included 22 mm (n=31), 20 mm (n=1). RESULTS: There was no hospital mortality and no valved conduit related early morbidity. In the median follow-up of 38 months (range 1-99 months) of 28 patients there was one late death, not conduit related (total mortality 3.6%). Re-operation for symptomatic graft stenosis was realised in two patients, 7 and 16 months after primo-implantation, corresponding to graft related late morbidity of 7.1%. CONCLUSIONS: In this small review of 32 operations using the Contegra graft for RVOT reconstruction in adult cardiac surgery for different indications, we observed good postoperative mid-term results concerning conduit function. Mean transpulmonary pressure gradients remain low (13.3+/-6.6 mmHg postoperative, 14.5+/-7.9 mmHg at follow-up). The use of the Contegra graft seems to be a good alternative to the homograft with low operative mortality and morbidity. Long-term outcome data are not available and further investigations must be performed to evaluate results.

Phytobezoar by aloe vera as long term complication after oesophagectomy resolved using cellulase.

Bezoars are uncommon diseases caused by the presence of indigestible mass of strange material in the gastrointestinal tract. Gold-standard treatment remains unclear and there are not clinical guidelines to follow. We present a very rare case of 53-year-old man suffering phytobezoar in a gastroplasty after oesophagectomy due to aloe vera ingestion as natural medicine. Finally it was solved with cellulase. Therefore, this is a scarcely complication after esophagectomy. Cellulase is a very good option to treat phytobezoar avoiding reintervention in this kind of patient.

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.

Phytobezoar by aloe vera as long term complication after oesophagectomy resolved using cellulase.

Bezoars are uncommon diseases caused by the presence of indigestible mass of strange material in the gastrointestinal tract. Gold-standard treatment remains unclear and there are not clinical guidelines to follow. We present a very rare case of 53-year-old man suffering phytobezoar in a gastroplasty after oesophagectomy due to aloe vera ingestion as natural medicine. Finally it was solved with cellulase. Therefore, this is a scarcely complication after esophagectomy. Cellulase is a very good option to treat phytobezoar avoiding reintervention in this kind of patient.

A search for the origin of cadmium in the soil of the Swiss Jura

The top soil of a 14.5 km(2) region at la Chaux-de-Fonds in the Swiss Jura is exceptionally rich in cadmium. It contains an average of 1.3 mg per kg of soil. The spatial distribution of the metal has no simple pattern that could be explained by atmospheric deposition or agricultural practices. Thin soil contained most of its Cd at the surface; in thicker soil Cd is mainly concentrated between 60 and 80 cm depth. No specific minerals or soil fractions could account for these accumulation, and the vertical distribution of Cd is best explained by leaching from the topsoil and further adsorption within layers of nearly neutral pH. The local Jurassic sedimentary rocks contained too little Cd to account for the Cd concentrations in the soil. Alpine gravels from glacial till were too sparse in soils to explain such a spreading of Cd. Moreover this origin is contradictory with the fact that Cd is concentrated in the sand fraction of soils. The respective distributions of Fe and Cd in soils, and soil fractions, suggested that the spreading of iron nodules accumulated during the siderolithic period (Eocene) was not the main source of Cd. Atmospheric deposition, and spreading of fertiliser or waste from septic tanks seem the only plausible explanation for the Cd concentrations, but at present few factors allow us to differentiate between them.

Impact of Balanced or Unbalanced Karyotype At Diagnosis On Prognosis of CML: Long-Term Observation From 1346 Patients of the Randomized CML Study IV

Introduction: Acquired genetic instability in chronic myeloid leukemia (CML) as a consequence of the translocation t(9;22)(q34;q11) and the resulting BCR-ABL fusion causes the continuous acquisition of additional chromosomal aberrations and mutations and thereby progression to accelerated phase (AP) and blast crisis (BC). At least 10% of patients in chronic phase (CP) CML show additional alterations at diagnosis. This proportion rises during the course of the disease up to 80% in BC. Acquisition of chromosomal changes during treatment is considered as a poor prognostic indicator, whereas the impact of chromosomal aberrations at diagnosis depends on their type. Patients with major route additional chromosomal alterations (major ACA: +8, i(17)(q10), +19, +der(22)t(9;22)(q34;q11) have a worse outcome whereas patients with minor route ACA show no difference in overall survival (OS) and progression-free survival (PFS) compared to patients with the standard translocation, a variant translocation or the loss of the Y chromosome (Fabarius et al., Blood 2011). However, the impact of balanced vs. unbalanced (gains or losses of chromosomes or chromosomal material) karyotypes at diagnosis on prognosis of CML is not clear yet. Patients and methods: Clinical and cytogenetic data of 1346 evaluable out of 1544 patients with Philadelphia and BCR-ABL positive CP CML randomized until December 2011 to the German CML-Study IV, a randomized 5-arm trial to optimize imatinib therapy by combination, or dose escalation and stem cell transplantation were investigated. There were 540 females (40%) and 806 males (60%). Median age was 53 years (range, 16-88). The impact of additional cytogenetic aberrations in combination with an unbalanced or balanced karyotype at diagnosis on time to complete cytogenetic and major molecular remission (CCR, MMR), PFS and OS was investigated. Results: At diagnosis 1174/1346 patients (87%) had the standard t(9;22)(q34;q11) only and 75 patients (6%) had a variant t(v;22). In 64 of 75 patients with t(v;22), only one further chromosome was involved in the translocation; In 8 patients two, in 2 patients three, and in one patient four further chromosomes were involved. Ninety seven patients (7%) had additional cytogenetic aberrations. Of these, 44 patients (3%) lacked the Y chromosome (-Y) and 53 patients (4%) had major or minor ACA. Thirty six of the 53 patients (2.7%) had an unbalanced karyotype (including all patients with major route ACA and patients with other unbalanced alterations like -X, del(1)(q21), del(5)(q11q14), +10, t(15;17)(p10;p10), -21), and 17 (1.3%) a balanced karyotype with reciprocal translocations [e.g. t(1;21); t(2;16); t(3;12); t(4;6); t(5;8); t(15;20)]. After a median observation time of 5.6 years for patients with t(9;22), t(v;22), -Y, balanced and unbalanced karyotype with ACA median times to CCR were 1.05, 1.05, 1.03, 2.58 and 1.51 years, to MMR 1.31, 1.51, 1.65, 2.97 and 2.07 years. Time to CCR and MMR was longer in patients with balanced karyotypes (data statistically not significant). 5-year PFS was 89%, 78%, 87%, 94% and 69% and 5-year OS 91%, 87%, 89%, 100% and 73%, respectively. In CML patients with unbalanced karyotype PFS (p<0.001) and OS (p<0.001) were shorter than in patients with standard translocation (or balanced karyotype; p<0.04 and p<0.07, respectively). Conclusion: We conclude that the prognostic impact of additional cytogenetic alterations at diagnosis of CML is heterogeneous and consideration of their types may be important. Not only patients with major route ACA at diagnosis of CML but also patients with unbalanced karyotypes identify a group of patients with shorter PFS and OS as compared to all other patients. Therefore, different therapeutic options such as intensive therapy with the most potent tyrosine kinase inhibitors or stem cell transplantation are required.

Modelling short-term ultraviolet exposure as an alternative to individual dosimetry

Background: Excessive exposure to solar Ultra-Violet (UV) light is the main cause of most skin cancers in humans. Factors such as the increase of solar irradiation at ground level (anthropic pollution), the rise in standard of living (vacation in sunny areas), and (mostly) the development of outdoor activities have contributed to increase exposure. Thus, unsurprisingly, incidence of skin cancers has increased over the last decades more than that of any other cancer. Melanoma is the most lethal cutaneous cancer, while cutaneous carcinomas are the most common cancer type worldwide. UV exposure depends on environmental as well as individual factors related to activity. The influence of individual factors on exposure among building workers was investigated in a previous study. Posture and orientation were found to account for at least 38% of the total variance of relative individual exposure. A high variance of short-term exposure was observed between different body locations, indicating the occurrence of intense, subacute exposures. It was also found that effective short-term exposure ranged between 0 and 200% of ambient irradiation, suggesting that ambient irradiation is a poor predictor of effective exposure. Various dosimetric techniques enable to assess individual effective exposure, but dosimetric measurements remain tedious and tend to be situation-specific. As a matter of facts, individual factors (exposure time, body posture and orientation in the sun) often limit the extrapolation of exposure results to similar activities conducted in other conditions. Objective: The research presented in this paper aims at developing and validating a predictive tool of effective individual exposure to solar UV. Methods: Existing computer graphic techniques (3D rendering) were adapted to reflect solar exposure conditions and calculate short-term anatomical doses. A numerical model, represented as a 3D triangular mesh, is used to represent the exposed body. The amount of solar energy received by each "triangle is calculated, taking into account irradiation intensity, incidence angle and possible shadowing from other body parts. The model take into account the three components of the solar irradiation (direct, diffuse and albedo) as well as the orientation and posture of the body. Field measurements were carried out using a forensic mannequin at the Payerne MeteoSwiss station. Short-term dosimetric measurements were performed in 7 anatomical locations for 5 body postures. Field results were compared to the model prediction obtained from the numerical model. Results: The best match between prediction and measurements was obtained for upper body parts such as shoulders (Ratio Modelled/Measured; Mean = 1.21, SD = 0.34) and neck (Mean = 0.81, SD = 0.32). Small curved body parts such as forehead (Mean = 6.48, SD = 9.61) exhibited a lower matching. The prediction is less accurate for complex postures such as kneeling (Mean = 4.13, SD = 8.38) compared to standing up (Mean = 0.85, SD = 0.48). The values obtained from the dosimeters and the ones computed from the model are globally consistent. Conclusion: Although further development and validation are required, these results suggest that effective exposure could be predicted for a given activity (work or leisure) in various ambient irradiation conditions. Using a generic modelling approach is of high interest in terms of implementation costs as well as predictive and retrospective capabilities.

Comparison of early cortical networks in efficient and inefficient visual search: an event-related potential study.

Functional magnetic resonance imaging studies have indicated that efficient feature search (FS) and inefficient conjunction search (CS) activate partially distinct frontoparietal cortical networks. However, it remains a matter of debate whether the differences in these networks reflect differences in the early processing during FS and CS. In addition, the relationship between the differences in the networks and spatial shifts of attention also remains unknown. We examined these issues by applying a spatio-temporal analysis method to high-resolution visual event-related potentials (ERPs) and investigated how spatio-temporal activation patterns differ for FS and CS tasks. Within the first 450 msec after stimulus onset, scalp potential distributions (ERP maps) revealed 7 different electric field configurations for each search task. Configuration changes occurred simultaneously in the two tasks, suggesting that contributing processes were not significantly delayed in one task compared to the other. Despite this high spatial and temporal correlation, two ERP maps (120-190 and 250-300 msec) differed between the FS and CS. Lateralized distributions were observed only in the ERP map at 250-300 msec for the FS. This distribution corresponds to that previously described as the N2pc component (a negativity in the time range of the N2 complex over posterior electrodes of the hemisphere contralateral to the target hemifield), which has been associated with the focusing of attention onto potential target items in the search display. Thus, our results indicate that the cortical networks involved in feature and conjunction searching partially differ as early as 120 msec after stimulus onset and that the differences between the networks employed during the early stages of FS and CS are not necessarily caused by spatial attention shifts.

Effects of short-term high-fructose diets in humans: modulation by environmental factors

It is currently suspected that sugar overconsumption, and more specifically fructose, may promote the development of obesity and of several cardio-metabolic disorders. However, environmental factors, such as fish oil and dietary proteins, may prevent some deleterious effects of fructose. The aim of this thesis was to identify potential environmental factors that may modulate the metabolic effects of fructose. The first study was designed to evaluate the impact of endurance exercise in healthy young men fed a high-fructose, isocaloric diet. Fructose-induced effects on lipid profile were totally prevented by endurance exercise and may be explained by an enhanced clearance of TRL-TG and the inhibition of de novo lipogenesis. As energy intake was adjusted to energy requirement, we can conclude that exercise acts on fructose metabolism independently of energy imbalance. The second study aimed at determining whether coffee and more specifically chlorogenic acid consumption may prevent fructose-induced intrahepatic lipids accumulation, hypertriglyceridemia and hepatic insulin resistance, through a stimulation of lipid oxidation. Coffee did not prevent the fructose-induced increase in IHCL or plasma TG. Interestingly, the three coffees tested prevented the decrease in hepatic insulin sensitivity, independently of their content in caffeine or chlorogenic acid. Finally, in the third study, we evaluated the effect of essential amino acid supplementation on the increase of hepatic lipids induced by a high-fructose diet. This intervention slightly decreased IHCL concentration. The exact mechanisms remain unidentified but may involve an increased secretion of VLDL-TG. In conclusion, the environmental factors evaluated allow to prevent some of the deleterious effects of fructose and suggest that recommendations on fructose consumption should also take into account environmental factors.

Assessment of liver tumor response by high-field (3T) MRI after radiofrequency ablation: Short- and mid-term evolution of diffusion parameters within the ablation zone.

PURPOSE: To compare the apparent diffusion coefficient (ADC) values of malignant liver lesions on diffusion-weighted MRI (DWI) before and after successful radiofrequency ablation (RF ablation). MATERIALS AND METHODS: Thirty-two patients with 43 malignant liver lesions (23/20: metastases/hepatocellular carcinomas (HCC)) underwent liver MRI (3.0T) before (<1month) and after RF ablation (at 1, 3 and 6months) using T2-, gadolinium-enhanced T1- and DWI-weighted MR sequences. Jointly, two radiologists prospectively measured ADCs for each lesion by means of two different regions of interest (ROIs), first including the whole lesion and secondly the area with the visibly most restricted diffusion (MRDA) on ADC map. Changes of ADCs were evaluated with ANOVA and Dunnett tests. RESULTS: Thirty-one patients were successfully treated, while one patient was excluded due to focal recurrence. In metastases (n=22), the ADC in the whole lesion and in MRDA showed an up-and-down evolution. In HCC (n=20), the evolution of ADC was more complex, but with significantly higher values (p=0.013) at 1 and 6months after RF ablation. CONCLUSION: The ADC values of malignant liver lesions successfully treated by RF ablation show a predictable evolution and may help radiologists to monitor tumor response after treatment.

Adaptive search and information updating in sequential mate choice

Classical treatments of problems of sequential mate choice assume that the distribution of the quality of potential mates is known a priori. This assumption, made for analytical purposes, may seem unrealistic, opposing empirical data as well as evolutionary arguments. Using stochastic dynamic programming, we develop a model that includes the possibility for searching individuals to learn about the distribution and in particular to update mean and variance during the search. In a constant environment, a priori knowledge of the parameter values brings strong benefits in both time needed to make a decision and average value of mate obtained. Knowing the variance yields more benefits than knowing the mean, and benefits increase with variance. However, the costs of learning become progressively lower as more time is available for choice. When parameter values differ between demes and/or searching periods, a strategy relying on fixed a priori information might lead to erroneous decisions, which confers advantages on the learning strategy. However, time for choice plays an important role as well: if a decision must be made rapidly, a fixed strategy may do better even when the fixed image does not coincide with the local parameter values. These results help in delineating the ecological-behavior context in which learning strategies may spread.

Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.

PURPOSE: To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. METHODS: Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy. RESULTS: Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a- and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer. CONCLUSIONS: HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD.