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Purpose BluePrint (BP) is an 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes. In most cases, breast tumors have one dominant subtype, representative of a single activated pathway. However, some tumors show a statistically equal representation of more than one subtype, referred to as dual subtype. This study aims to identify and examine dual subtype tumors by BP to understand their biology and possible implications for treatment guidance. Methods The BP scores of over 15,000 tumor samples from EBC patients were analyzed, and the differences between the highest and the lowest scoring subtypes were calculated. Based upon the distribution of the differences between BP scores, a threshold was determined for each subtype to identify dual versus single subtypes. Results Approximately 97% of samples had one single activated BluePrint molecular subtype, whereas ~ 3% of samples were classified as BP dual subtype. The most frequently occurring dual subtypes were the Luminal-Basal-type and Luminal-HER2-type. Luminal-Basal-type displays a distinct biology from the Luminal single type and Basal single type. Burstein’s classification of the single and dual Basal samples showed that the Luminal-Basal-type is mostly classified as ‘luminal androgen receptor’ and ‘mesenchymal’ subtypes, supporting molecular evidence of AR activation in the Luminal-Basal-type tumors. Tumors classified as Luminal-HER2-type resemble features of both Luminal-single-type and HER2-single-type. However, patients with dual Luminal-HER2-type have a lower pathological complete response after receiving HER2-targeted therapies in addition to chemotherapy in comparison with patients with a HER2-single-type. Conclusion This study demonstrates that BP identifies tumors with two active functional pathways (dual subtype) with specific transcriptional characteristics and highlights the added value of distinguishing BP dual from single subtypes as evidenced by distinct treatment response rates.

Background: The addition of pertuzumab to neoadjuvant trastuzumab-containing chemotherapy significantly improves pathological complete response (pCR) rates in patients with HER2-positive breast cancer. However, effects on long-term survival outcomes have been modest. While prior studies suggest that only a subset of patients benefits most from the addition of pertuzumab, a reliable biomarker for response prediction has not been established. BluePrint is an 80-gene molecular subtyping test that classifies breast tumors as Basal-, Luminal- or HER2-subtype. Recent data shows that some tumors have more than one activated pathway and can be classified as dual subtype. Secondary analyses from the Aphinity trial (NCT01358877) suggest that pertuzumab benefit is largely restricted to patients with single-activated HER2-type tumors and less pronounced in patients with other single- or dual-activated subtypes. In this study, we evaluated BluePrint subtype as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab in a large nationwide cohort of patients. Methods: We collected data of all patients with stage II-III HER2-positive breast cancer who received neoadjuvant chemotherapy and trastuzumab between January 2013 and January 2016 from the Netherlands Cancer Registry. Pertuzumab was not reimbursed in the Netherlands during this period but was available to patients participating in the TRAIN2 clinical trial (NCT01996267). Pre-treatment biopsies were collected and tumor cell percentage was adequate in 404 patients who received pertuzumab and in 432 matched control patients who did not receive pertuzumab. Matching factors included treatment with anthracyclines (yes vs. no), age and hormone receptor status. BluePrint molecular subtypes were determined sucessfully through microarray in 680 patients. Pathological complete response (pCR) and overall survival (OS) were analyzed by treatment arm and BluePrint subtypes, using logistic and Cox regression analyses. Results: Microarray data was available for 334 patients who received pertuzumab and 346 patients who did not. Tumors were classified as single HER2 (77.6%), Luminal-HER2 (11.3%), single Luminal (8.4%), or other (2.6%). Overall, pCR rate was 65.0% in patients who received pertuzumab and 38.9% in patients who did not. In patients with single HER2-type tumors, pCR rate was significantly higher with pertuzumab (77.0% vs. 46.0%, multivariate adjusted odds ratio [aOR] 3.92, 95% confidence interval [CI] 2.60 - 5.98). In patients with other subtypes, pCR rate was lower overall and not significantly different with or without pertuzumab (23.5% vs. 13.5%, aOR 2.50, 95% CI 0.98 - 6.89). In addition, multivariate Cox regression analyses showed a significant OS benefit with pertuzumab in patients with single HER2-type tumors (adjusted hazard ratio [aHR] 0.33, 95% CI 0.16 - 0.67), but not in other subtypes (aHR 0.94, 95% CI 0.31 - 2.83). However, tests for interactions between pertuzumab and BluePrint subtypes were not significant. Conclusion: We confirmed the results of a prior secondary analysis of the Aphinity trial that the benefit of adding pertuzumab to (neo)adjuvant trastuzumab-based chemotherapy seems most pronounced in patients with a molecularly defined single-activated HER2-subtype. In other subtypes, pathological complete response rates and long-term outcomes are worse overall and no clear benefit of pertuzumab was seen, although tests for interaction between pertuzumab treatment and BluePrint subtype were not significant. Citation Format: Marte C Liefaard, Anna van der Voort, Joyce Sanders, Shiva Vonk, Hugo M Horlings, Sabine Siesling, Linda de Munck, Elise van Leeuwen-Stok, Miranda Kleijn, Lorenza Mittempergher, Midas M Kuilman, Esther H Lips, Gabe S Sonke. Effect of pertuzumab plus neoadjuvant trastuzumab-based chemotherapy in early-stage HER2-positive breast cancer according to BluePrint molecularly defined breast cancer subtypes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD15-07.

Physics letters / B 763, 16 - 19 (2016). doi:10.1016/j.physletb.2016.10.015, Published by North-Holland Publ., Amsterdam

A novel method for measuring nuclear reactions in inverse kinematics with stored ion beams was successfully used to extract the nuclear-matter radius of $^{58}\mathrm{Ni}$. The experiment was performed at the experimental heavy-ion storage ring at the GSI facility using a stored $^{58}\mathrm{Ni}$ beam at energies of 100 and 150 MeV/u and an internal helium gas-jet target. Elastically scattered $\ensuremath{\alpha}$-recoils at low momentum transfers were measured with an in-ring detector system compatible with ultrahigh vacuum. Experimental angular distributions were fitted using density-dependent optical model potentials within the eikonal approximation. This permitted the extraction of the point-matter root-mean-square radius of $^{58}\mathrm{Ni}$ with an average value of 3.70(7) fm. Results from this work are in good agreement with several experiments performed in the past in normal kinematics. This pioneering experiment demonstrates a major breakthrough towards future investigations with far-from-stability stored beams using the present technique.

We have measured the nuclear-matter distribution of the doubly-magic N = Z nucleus Ni-56 by investigating elastic proton scattering in inverse kinematics. The radioactive beam of Ni-56 was injected and stored in the experimental storage ring (ESR, GSI) and interacted with an internal hydrogen gas-jet target. The high revolution frequency of the ions in the ring enabled a high luminosity, despite the low density of the target being used. This way, measurements at very low momentum transfers became possible. By measuring the energy and the scattering angle of the recoiling protons, we were able to separate the elastic reaction channel from inelastic scattering to the first excited 2(+) state of Ni-56 and deduced the differential cross section of Ni-56 (p, p)(56) Ni. The data were analyzed within the framework of the Glauber multiple-scattering theory in order to extract the nuclear-matter radius and radial matter distribution of Ni-56. Parameterizing the matter distribution with the phenomenological Symmetrized Fermi distribution, a preliminary value of 3.5 fm for the rms matter radius was deduced. This experiment was part of an EXL (EXotic nuclei studied in Light-ion induced reactions at storage rings) campaign at GSI in 2012 and was the first successful investigation of nuclear reactions with a stored radioactive beam ever.

In the first campaign of the exotic nuclei studied with light-ion induced reaction in storage rings (EXL) collaboration at the existing storage ring experimental heavy-ion storage ring (ESR) at Helmholtz Center for Heavy Ion Research (GSI), we performed the first experiments using a stored beam of 58Ni and an internal helium gas-jet target aiming for the investigation of isoscalar giant resonances in inverse kinematics. In this experiment, inelastically scattered recoil particles (at very forward angles, °) were detected with a dedicated setup, including ultra-high vacuum (UHV)-compatible double-sided silicon strip detector (DSSDs). Preliminary results show evidence for the excitation of the isoscalar giant monopole resonance (ISGMR) in the 58Ni nucleus. This opens the opportunity to study in the near future giant resonances also with stored radioactive beams, like 56Ni, and extract important information about the nuclear matter incompressibility. In the present work the current status of the data analysis and results are shown and discussed.

The investigation of light-ion induced direct reactions using stored and cooled radioactive beams, interacting with internal targets of storage rings, can lead to substantial advantages over external target experiments, in particular for direct reaction experiments in inverse kinematics at very low momentum transfer, q. This new and challenging experimental technique enables high-resolution measurements down to very low q and provides a gain in luminosity from accumulation and recirculation of the stored beams. For performing first experiments of this kind a dedicated experimental setup housing several DSSD (Double-sided Silicon Strip Detector) and Si(Li) detectors for recoil particles, well suited for meeting the demanding UHV (Ultra High Vacuum) conditions of a storage ring, was recently designed, constructed and installed at the internal target of the ESR storage ring at GSI. From the interaction of a stored 56Ni beam with an internal H2 target, good quality differential cross section data for elastic proton scattering, measured with the aim to determine the radial shape of the nuclear matter distribution of 56Ni, were obtained. Preliminary results are presented. Being the first reaction experiment ever performed with a stored radioactive beam on a world-wide scale, this experiment can be considered as a breakthrough for nuclear structure and astrophysics studies, and, in addition, as a successful proof-of-principle of the new experimental concept. In addition, preliminary results from a feasibility study on inelastic α-scattering from 58Ni in inverse kinematics, where it was demonstrated that the Isoscalar Giant Monopole Resonance in 58Ni can be investigated by the present technique down to CM angles below 1 degree, are discussed. Such an experiment, performed in the future with the doubly magic 56Ni, would provide important information on the EOS of nuclear matter.

The European physical journal / Web of Conferences 66, 03093 (2014). doi:10.1051/epjconf/20146603093, Published by EDP Sciences, Les Ulis

Evidence is increasing that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis, a neurodegenerative disease characterized by selective motoneuron death. To study the role of mitochondrial dysfunction in the pathways leading to motoneuron death, we developed an in vitro model of chronic motoneuron toxicity, based on malonate-induced inhibition of complex II in the mitochondrial electron transport chain. Treatment with malonate resulted in a dose-dependent decrease in cellular ATP levels. We observed that motoneurons were significantly more vulnerable to mitochondrial inhibition than control neurons in the dorsal horn. We could reproduce this dose-dependent phenomenon with the complex IV inhibitor sodium azide. The free radical scavenger alpha-phenyl-N-tert-butylnitrone, the AMPA/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione, and riluzole, a drug that is currently used for the treatment of amyotrophic lateral sclerosis, were protective against malonate-induced motoneuron death. Furthermore, the caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and z-Asp-Glu-Val-Asp-fluoromethyl ketone were both protective against malonate toxicity. Our model shows that chronic mitochondrial inhibition leads to selective motoneuron death, which is most likely apoptotic.

Differences in the expression and catalytic activity of hepatic biotransformation enzymes account for species differences in xenobiotic metabolism, including that of aflatoxin B1 (AFB1). The main objectives of this study were (1) to define the procedure for isolation and culture of bovine hepatocytes, (2) to characterize the biotransformation capacity of bovine hepatocytes for AFB1, and (3) to develop an HPLC method for the simultaneous analysis of AFB1 and its metabolites. Bovine hepatocytes were isolated and cultured in monolayers. Metabolic function of these hepatocytes was assessed by measuring total cytochrome P450 (CYP450) content, glutathione S-transferase (GST) activity, ethoxyresorufin O-deethylation (EROD), testosterone hydroxylation, and α-naphthol glucuronidation. When using these cultures to study the biotransformation of AFB1, the principal metabolites of AFB1 were AFM1 and AFB1-dihydrodiol (AFB1-dhd). Minor amounts of AFB1−glutathione conjugate (AFB1−GSH) and a polar metabolite were also de...

21st International School on Nuclear Physics and Applications & the International Symposium on Exotic Nuclei, Varna, Bulgaria, 7 Sep 2015 - 12 Sep 2015; Journal of physics / Conference Series Conference Series 724(1), 012026 - (2016). doi:10.1088/1742-6596/724/1/012026, The EXL project aims to study nuclear structure by direct reactions in inverse kinematics at the storage rings of the future FAIR facility. In this contribution, we present the status of the project: the technical implementation at the ESR at GSI and preliminary results of the EXL campaign in 2012, the first using also a radioactive beam., Published by IOP Publ., Bristol

As a first step of the EXL project scheduled for the New Experimental Storage Ring at FAIR a precursor experiment (E105) was performed at the ESR at GSI. For this experiment, an innovative differential pumping concept, originally proposed for the EXL recoil detector ESPA, was successfully applied. The implementation and essential features of this novel technical concept will be discussed, as well as details on the detectors and the infrastructure around the internal gas-jet target. With Ni-56(p, p)Ni-56 elastic scattering at 400 MeV u(-1), a nuclear reaction experiment with stored radioactive beams was realized for the first time. Finally, perspectives for a next-generation EXL-type setup are briefly discussed.

Aflatoxin B(1) (AFB(1)) biotransformation comprises cytochrome P450-mediated reactions resulting in hydroxylated and demethylated metabolites as well as AFB(1) epoxides. As the latter are highly nucleophilic, the species-specific rate of epoxidation and the ability for rapid conjugation to glutathione by glutathione S-transferase determines the individual susceptibility to AFB(1). Here we show the time- and dose-dependent rate of AFB(1)-metabolism in bovine hepatocytes. Aflatoxin M(1) (AFM(1)) is the most prominent metabolite formed within the first 2-8 hr of incubation, whereas AFB(1)-dhd is detectable in medium mainly after a prolonged incubation period. The delayed formation of AFB(1)-dhd corresponds to the cytotoxicity demonstrated by the MTT assay. alpha-Naphthoflavone and ketoconazole, inhibitors of CYP1A and CYP3A, respectively in humans, were used to evaluate the contribution of specific P450 isoenzymes in bovine biotransformation of AFB(1). Initial experiments confirmed that alpha-naphthoflavone and ketoconazole inhibited ethoxyresorufin O-deethylation and testosterone 6beta-hydroxylation also in bovine hepatocytes. Both inhibitors reduced AFM(1) and AFB(1)-dhd formation concentration dependently, suggesting that both enzyme groups contribute to the formation of these metabolites. However, the formation of AFM(1) was less inhibited by both compounds than the formation of AFB(1)-dhd.

It is well known that cattle ingesting aflatoxin B1 contaminated feed commodities excrete aflatoxin M1 into their milk. As aflatoxin M1 originates from hepatic metabolism, measures to prevent aflatoxin M1 formation need to be directed to either the immobilization of aflatoxin B1 in the gastrointestinal tract or the modification of hepatic metabolism of aflatoxin B1. Here we studied the influence of oltipraz and a second dithiolthione, (1,2) dithiolo (4,3-c)-1,2-dithiole-3,6 dithione (DDD) on bovine hepatic aflatoxin B1 biotransformation. Oltipraz inhibited aflatoxin B1 metabolism as no aflatoxin M1 and no aflatoxin B1-dihydrodiol, the second metabolite found in bovine hepatocytes, was formed. DDD did not significantly inhibit aflatoxin B1 metabolism. It could be demonstrated that the inhibition of aflatoxin B1 metabolism was due to the inhibition of several cytochrome P450 enzyme activities by oltipraz. In contrast, DDD inhibited only ethoxyresorufin O-deethylation activity. These findings suggest a high efficacy of oltipraz in inhibiting aflatoxin M1 contamination of milk from dairy cows exposed to aflatoxin B1 contaminated feeds.

17 alpha-Boldenone (17 alpha-BOL) and/or 17 beta-boldenone (17 beta-BOL) appear occasionally in fecal matter of cattle. In addition to 17 alpha-BOL, a whole array of boldenone related substances can be found in the same samples. In vitro experiments with microsomal liver preparations and isolated hepatocytes combined with the excretion profiles found in urine and feces samples of in vivo experiments made it possible to identify several metabolites of 17 beta-BOL in 17 beta-BOL positive feces samples. In one animal treated with 17 beta-BOL, no 17 beta-BOL or its metabolites were present before treatment and most of these compounds disappeared gradually in time after the treatment was stopped. It is not clear what the origin is of 17 alpha-BOL and boldenone metabolites in samples screened routinely for the abuse of anabolic steroids and considered to be 'negative' because of the absence of 17 beta-BOL since other workers showed some evidence that 17 alpha-BOL can be of endogenous origin. However, in our hands, most of these 17 alpha-BOL positive samples, obtained during routinely performed screenings of cattle, contained large amounts of delta 4-androstene-3,17-dione (AED), which normally is absent from routinely screened negative samples. Furthermore, AED was absent in all samples obtained from the animals treated with 17 beta-BOL. We have no direct evidence that 17 alpha-BOL or 17 beta-BOL is of endogenous origin.

Current veterinary residue analysis mainly focuses on the monitoring of residues of the administered parent compound. However, it is possible that larger amounts of metabolites are excreted and that they can have a prolonged excretion period. In order to unravel specific metabolic steps and to identify possible biological markers, two in vitro liver models were used, i.e. monolayer cultures of isolated hepatocytes and liver microsomes, both prepared from liver tissue of cattle. Chostebol, boldenone, norethandrolone (NE) and ethylestrenol (EES) were used as model substrates. Results show that the metabolic profiles derived from in vitro experiments are predictive for the in vivo metabolic pathways of the steroids evaluated in this study. By means of this strategy, it is possible to identify 17 alpha-ethyl-5 beta-estrane-3 alpha,17 beta-diol (EED) as a common biological marker for NE and EES. By in vivo experiments it was shown that EED is particularly important for the detection of the abuse of NE or EES because of its high excretion levels and its prolonged presence as compared with the parent compounds or any other metabolite.

Between 1988 and 1994, 441 patients were successfully resuscitated outside hospital in the city of Rotterdam, of whom 276 (63%) were discharged from hospital alive. Long-term survival was studied amongst those who were discharged alive. The duration of follow-up averaged 6.71 years. A survival rate of 88% after 1 year, 81% after 3 years, 77% after 5 years and 73% after 7 years was found. After multivariate analysis, age, diagnosis and gender were found to be independent and significant predictors of survival. No significant difference in survival was found in patients who had been resuscitated by emergency personnel, physicians and bystanders. Patients who were still alive were sent a EuroQol-questionnaire. No differences in outcomes between the four groups were found. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, learning programmes for resuscitation should be continued.

Institutionalized patients with Down syndrome (n = 307) were monitored for 5 to 10 years prospectively to determine prevalence of Alzheimer-type dementia. Clinical signs, cognitive functioning, and EEGs were assessed. When possible, postmortem neuropathological examinations were conducted. Progressive mental and physical deterioration was found for 56 of the residents. Mean age at onset of dementia was 56 years. Prevalence increased from 11% between ages 40 and 49 to 77% between 60 and 69. All patients 70 and over had dementia. Neuropathological findings were consistent with clinical diagnosis. Use of a dementia checklist, cognitive skills inventory, and EEG reliably detected Alzheimer-type dementia at an early stage.

We studied the role of electroencephalography (EEG) in the diagnosis of Alzheimer-type dementia in patients with Down's syndrome. 197 patients with Down's syndrome were monitored for 5 to 8 years. Aspects of cognitive functioning were assessed twice yearly. EEGs were scored in a blind fashion, and changes in the EEG were compared to changes in cognitive functioning. When possible, a neuropathological post-mortem examination was performed. Cognitive functioning was drastically reduced in 29 patients. The dominant occipital rhythm became slower at the onset of the cognitive deterioration, and eventually disappeared. In 11 of these patients neuropathological examination showed a severe form of Alzheimer's disease. Changes in the frequency of the dominant occipital rhythm could distinguish between Alzheimer's disease or other causes as underlying the cognitive decline. Slowing of the dominant occipital rhythm seems to be related to Alzheimer's disease in patients with Down's syndrome, and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration. The EEG is thus an important tool in the clinical diagnosis of Alzheimer-type dementia in patients with Down's syndrome.

In a controlled retrospective study of 27 Down patients the occurrence of the neuropathological signs of Alzheimer's disease was investigated. The patients were divided into two groups: group I with neuropathologically proven Alzheimer and group II without Alzheimer's disease. All patients of group I had been older than 54 years at death, while all patients of group II were younger. All patients of group I suffered from severe dementia, none of group II did. The early clinical symptoms, changes in social competence and EEG alterations were combined in a dementia detection method suitable for mentally deficient patients.

SUMMARY AND CONCLUSIONS 1 In an aselective group of 107 patients who clinically showed absences (petit mal), grand mal, or a combination of petit mal and grand mal, with EEG paroxysms of bilaterally synchronous spike-wave complexes in all cases, and who were all given Ethosuximide, the influence of this drug on the grand mal seizures was studied.The anti-epileptic medication of none of these patients was exclusively Ethosuximide. 2 In the 32 patients with a history of absences only, no instance of grand mal provocation was seen. 3 Among the 14 patients with grand mal only, there were only four in whom the effect of Ethosuximide on the grand mal could be evaluated with some degree of certainty. The result was unmistakably favourable in one case; in three cases there was no effect. 4 The patient who showed improvement, however, did not become free of attacks. Even before institution of Ethosuximide therapy, his EEG had shown a temporal focus in addition to paroxysms of slow bilaterally synchronous spike-wave complexes. 5 Only in 22 of the 61 cases of combined petit mal and grand mal did it seem possible to evaluate the effect of Ethosuximide. The results were: pronounced improvement in 5, no result in 10, and aggravation in 7 cases. 6 Among the 7 patients showing exacerbation there was one who, prior to Ethosuximide medication, showed a temporal focus in addition to centrencephalic epileptic activity; in another patient, a temporal focus not previously seen, occurred during Ethosuximide medication. This last observation corresponds with the experience of other investigators (1, 3). 7 The two patients with spike-wave variants in the EEG and clinical evidence of grand mal, absences and akinetic seizures in one case, and grand mal and partial akinetic seizures in the other, belonged to the group showing an unfavourable response of grand mal to Ethosuximide. 8 Although the material was too small to interpret results as anything but mere indications, it must be observed that we found nothing to indicate with certainty that some EEG features seen before Ethosuximide medication warrant a prediction of the subsequent effect of the drug on grand mal seizures. With regard to the other data which were compared, there is an indication that the presence of akinetic attacks may herald a possible exacerbation of grand mal seizures upon Ethosuximide medication. 9 We believe we are well-advised in taking into account the possibility of exacerbation of grand mal seizures in all mixed forms of petit mal and grand mal treated with Ethosuximide. On the other hand there is the chance of a favourable effect of Ethosuximide on the grand mal, which entails a risk of increased grand mal seizures upon reduction of the Ethosuximide dosage (7, and personal observation). RESUME ET CONCLUSIONS 1 Nous avons etudie l'influence de 1'Ethosuximide sur les crises de grand mal d'un groupe non selectionne de 107 patients souffrant d'une epilepsie exprimee sur 1'E.E.G. par des paroxysmes bilateraux et synchrones de pointe-ondes et caracterisee par des crises petit mal ou des crises grand mal ou les deux a la fois. La medication anti-epileptique d'aucun de ces patients n'etait pas exclusivement l'Ethosuximide. 2 Des 32 sujets qui ne presentaient que des absences petit mal, aucun ne fit de crise de grand mal pendant le traitement. 3 armi les 14 sujets qui ne presentaient que des crises de grand mal, l'effet de la therapeutique ne put etre quantifie de facon satisfaisante que chez 4 d'entre eux. Une seule fois il fut favorable, dans les 3 autres cas le nombre des crises ne fut pas modifie. 4 Les crises du patient qui s'est ameliore n'ont pas disparu completement. Ce malade montrait, avant l'institution du traitement par l'Ethosuximide, un foyer E.E.G. temporal en plus de decharges bilaterales et synchrones de pointe-ondes lents. 5 Des 61 cas de petit mal melees a du grand mal, 22 seulement permirent une quantification satisfaisante des resultats. Chez ces 22 sujets le nombre des crises de grand mal diminua 5 fois, augmenta 7 fois et demeura inchange 10 fois. 6 Parmi les 7 patients aggraves, il y avait un qui montrait, outre des decharges centrencephaliques, un foyer temporal pre-existant au traitement, tandis qu'un autre malade montra un foyer temporal seulement au cours de la therapeutique. Ce dernier correspond a des faits deja mentionnes par d'autres investigateurs (1, 3). 7 Les 2 malades ayant sur l'E.E.G. des paroxysmes bilateraux et synchrones de pointe-ondes lents et presentant cliniquement des crises de grand mal, des absences et des crises akinetiques, respectivement des crises de grand mal et des crises akinetiques partielles, font partie du groupe dont les crises de grand mal se sont aggravees au cours du traitement par l'Ethosuximide. 8 Bien que notre materiel soit trop reduit pour permettre autre chose que de prudentes remarques, nous croyons devoir signaler que nous n'avons pas observe de signes E.E.G. permettant de predire, avant l'institution du traitement, les effets de l'Ethosuximide sur les crises de grand mal et que l'existence de crises akinetiques peut faire redouter une exacerbation eventuelle des crises de grand mal sous l'effet de ce traitement. 9 Nos resultats confirment d'une part l'eventualite bien connue d'une exacerbation des crises de grand mal sous l'effet de l'Ethosuximide chez les sujets souffrant des crises generalisees mixtes de type grand mal et petit mal. D'autre part ils demontrent que ce meme produit peut avoir un effet favorable sur le grand mal chez d'autres sujets qui risquent alors une aggravation sous l'effet d'un sevrage brutal du produit (7, et experience personnelle).

Since the serum potassium level is under beta 2-adrenergic influence, we studied serum potassium values on admission in psychiatric patients. Data are reported on 683 patients from nine major diagnostic groups. Among these nine groups significant differences were found concerning the mean serum potassium level and incidence of hypokalemia. Significant differences existed between the alcohol withdrawal and attempted suicide groups compared to the dysthymic, bipolar manic, schizophrenic and nonschizophrenic psychosis groups. Like alcohol withdrawal, attempted suicide is assumed to be a hyper-adrenergic state. Although the relative contribution of factors like nutritional state, aldosterone, insulin, and beta 2-receptor density or sensitivity is unclear, the catecholamine-potassium relationship deserves further study.