Pre-and post-surgical non-functional pituitary adenomas and their relationship with high levels of serum glucose.

OBJECTIVES: This clinical, analytical, retro-prospective, auto-controlled, not randomized, and not blinded study, aimed to investigate the association of changes in the serum glucose levels with the pre-and-post changes in the size tumor in mm3 in the Non-Functional pituitary adenomas. METHODS: Pre-and post-surgical MRI, as well as the measurements in the serum glucose levels and immunohistochemical techniques were performed in all the patients in the study, with a mean followed-up until 208.57 days. A comparison was made between the reductions in tumor size of hormonally active pituitary adenomas (HSPAs) vs NFPAs. RESULTS: Seventy-four patients were included in this study, of whom, 46 were NFPAs. The decrease in the NFPAs tumor size after surgery was statistically significant (P ≤ 0.0001). The Mean of the differences of both type of tumors in mm3 were -9552 ± 10287. Pre-surgery, the mean of the HSPAs were 8.923 ± 2.078; and the NFPAs were 14.161 ± 1.912. The differences in the tumor size were statistically significant (p = 0.039). Post-surgical, the mean of the HSPAs were 2.079 ± 971, with a (p = 0.14): and the NFPAs were 4.609 ± 1.205. After surgery of the NFPAs, most of the patients-maintained serum levels ≤ 100 mg/dL, with a statistical significance (P ≤ 0.0003). CONCLUSION: This study demonstrates for the first time the correlation between the presence of pre-and post- surgical changes in the NFPAs, with modifications in the levels of serum glucose, and the comparison, pre- and post-surgical between the tumor size of HSPAs and NFPAs.

Pre- and post-clinical-radiological and surgical evaluation of patients with pituitary adenoma and metabolic syndrome.

BACKGROUND: Pituitary adenomas are benign tumors located in the anterior hypophysis. Its appearance is associated with the development of parameters related to metabolic syndrome; therefore, surgical treatment could reduce associated morbimortality. METHODS: Pre- and post-surgical MRI, using the Hardy-Wilson and Knosp classification, and clinical data according to the American Association of Clinical Endocrinology (AACE) criteria for metabolic syndrome: all the patients were followed-up until 208.57 days were reviewed on 217 consecutive patients with pituitary surgery. RESULTS: Seventy-four patients were included in this study. There was a significant reduction in tumor size in mm3 [average pre- and post-surgery respectively: 12,362 mm3 (±12,397); 3,910 mm3 (±7,160)], (p < 0.0001). This was confirmed by the Hardy-Wilson and Knosp classification, where most patients went from grade IV C (33.7%) to grade 0 (12.1%), IA (20.2%), IIB (21.36%), and IIC (16.2%); as well as from grade 4 (24.3%) to grade 0 (45.9%), respectively. After surgery, there were statistically significant reductions in total serum levels of glucose [average pre- and post-surgery, respectively: 116 mg/dL (±26.9); 90 mg/dL (±10.2)], (p < 0.001), triglycerides [average pre- and post-surgery, 240 mg/dL (±102); 171 mg/dL (±60.5)], (p = 0.001); and HDL-c [average pre- and post-surgery, respectively: 39 mg/dL (±11.8); 44.6 mg/dL (±8.4)], (p = 0.029). The other parameters remained unchanged. CONCLUSION: This is the first study to demonstrate the relationship between the presence of pituitary adenoma and significative changes in serum glucose, triglycerides and c-HDL related to metabolic syndrome.

Multi-element contamination in soils from major mining areas in Northeastern of Brazil.

Mining has become one of the main factors in the global biogeochemical cycle of potentially toxic elements. Therefore, it is considered one of the anthropogenic activities with the greatest negative impact on the environment. These impacts are maximized in semiarid regions, where mining activities can lead to soil degradation and decrease in land productivity. This study aimed to assess the level of contamination in natural, urban, and agricultural soils of three important mining areas, where approximately 80,000 people live, and pollution levels have never been determined before. For this purpose, soil samples were collected around iron, uranium, and vanadium mines, as well as in the main human settlements of the region. The concentrations of 34 elements were determined by instrumental neutron analysis activation (INAA) and inductively coupled plasma optical emission spectrometry (ICP OES) techniques. Pollution indices (CF, EF, mCd, PLI, and REEP) revealed that there is a moderate to heavy level of pollution for 89% of the analyzed elements. Additionally, an extreme contamination level was observed in 78% of the samples, for at least one element. Statistical analyses were performed to identify patterns in the distribution and common sources of pollution. The results suggest that the concentrations for Al, Ba, Hf, Na, Pb, Rb, REE, Ta, Th, U, Zn, and Zr are associated with geogenic causes. However, the influence of anthropogenic sources such as agriculture and mining on the accumulation of these elements in soils should not be disregarded. In contrast, the contents of As, Br, Cd, Co, Cr, Cs, Cu, Fe, K, Mn, Ni, Sc, Ti, and V reflect the direct impact of anthropogenic sources.

HHRISK: A code for assessment of human health risk due to environmental chemical pollution.

Chemical environmental pollution is currently one of the most concerning environmental problem on a global scale, due to the high risks posed to ecological systems and human health. Risk assessment methodologies are valuable tools for preventive management and the mitigation of human health risks. However, the application of these methodological tools involves several steps and the knowledge of many variables, which can hinder its correct implementation. The main objective of this work was the development of the computational code for human health risk assessment: HHRISK (Human Health Risk). This code allows for an agile and accurate risk assessment based on the methodology established by the U.S. Environmental Protection Agency (U.S. EPA). Different from other published methods, the HHRISK code includes a new spatiotemporal matrix for the analysis of the aggregated risk (for multiple exposure pathways) and the cumulative (for exposure to multiple chemicals). HHRISK was applied to two case studies published dealing with the assessment of risk to human health through exposure to toxic metals, obtaining satisfactory results. The concordance between the average results obtained with the HHRISK and those reported by the authors confirm the validity of the implemented model. The inclusion of a greater spatiotemporal detail of the risks allowed to carry out a more accurate analysis and to propose new subsidies for a more efficient risk mitigation management by affected place and period of time.

Bioaccumulation of nickel in tomato plants: risks to human health and agro-environmental impacts.

Anthropogenic activities such as agriculture, industry, and mining have contributed significantly to the accumulation of heavy metals in the soil, which in turn cause problems to human health and to the environment. The present work aims to study the effects of nickel (Ni) on the development of tomato plants, the risks to human health associated to the consumption of contaminated tomatoes, and the consequences to the environment. The experiment was carried out in greenhouse environment for a period of 120 days, and the plants were cultivated in soils with four different concentrations of Ni: 0, 35, 70, and 105 mg kg-1. The concentration of nickel in each part (root, stem, leaf, and fruit) of the tomato plant was measured at four different stages of the cycle: 30, 60, 90, and 120 days, by inductively coupled plasma optical emission spectrometer (ICP-OES). At the end of the cycle, the concentration of certain macro- and micronutrients was also determined and related to the corresponding Ni concentration in the soil. The distribution of Ni in the parts of the plant was analyzed from the bioaccumulation factor temporal behavior. Nickel concentrations found in the fruit were too low to pose a risk to human health. As a result of this research, it was verified that soils with nickel concentrations close to 70 mg kg-1, which is the limit established by the CONAMA resolution (420/2009), may actually represent an optimum concentration value for the development of tomato plants. It also increases productivity per plant and reduces the use of resources such as water and agricultural inputs.

Occupational respiratory allergy in peach crop workers.

BACKGROUND: Occupational respiratory diseases in workers of peach tree crops have been reported punctually and have been associated with sensitization to proteins present in both pollen and leaf tree. We report the study of 37 workers with respiratory symptoms related to occupational exposure to peach trees. METHODS: Prick tests and specific IgE determinations were performed with extracts from leaves and branches of peach tree. Immunodetection in leaf extract was realized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis SDS-PAGE-immunoblotting with patient sera and rabbit serum anti-Pru p 3. Immunodetection inhibition was performed with rPru p 3 and pollen profilins. The clinical relevance of sensitization was demonstrated by specific bronchial challenge test (SBCT) with peach leaf extract. RESULTS: Most patients suffered symptoms when peach trees had leaves, specifically during thinning and harvesting fruit (rhinoconjunctivitis: 100% and asthma: 67.5%). Sensitization to leaf extract was demonstrated in 86% of patients. IgE-immunoblotting with peach leaf extract revealed in six patient sera a pair of bands of 10 and 16 kDa, and in nine a 16-kDa band. Those bands could be two isoforms of peach leaf lipid transfer proteins( LTP), so the recognition frequency of some LTP isoform by our patient sera was 42%. 33% of the sera recognized a doubled band of about 14.5 kDa and this recognition was inhibited by nPho d 2. The SBCT with peach leaf extract was positive in the asthmatic sensitized patients tested. CONCLUSIONS: Sensitization to peach leaves was the cause of occupational respiratory symptoms in our patients. Some patient sera revealed IgE-binding proteins matching LTP and/or profilin.

First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

INTRODUCTION/BACKGROUND: Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. AIM: The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. PATIENTS/METHODS: Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (<5 BU) received 50-100 IU FVIII kg(-1) daily, or every other day; 'high responders' (≥5 BU) received 100 IU FVIII kg(-1) every 12 h. RESULTS: Forty of 48 patients (83.3%), had at least one risk factor for poor ITI-prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. CONCLUSION: Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success.

Public resource usage in health systems: a data envelopment analysis of the efficiency of health systems of autonomous communities in Spain.

OBJECTIVES: The efficiency in the management of public resources is one of the main pillars of the welfare state. The objective of this work is to analyze the efficiency of the public resources that regional governments in Spain (Autonomous Communities (AC)) invest in health systems (HS). STUDY DESIGN: A dataset from of the Ministry of Health, Social Services and Equality of Spain has been used, which contains the most important indicators from the National HS. The following variables have been chosen in this study: the health care expenses per resident, the percentage of this investment that is forwarded to labour expenses, frequency of hospital care services, frequency of specialized external health care services and, primary health care services in medicine and nursing per resident. METHODS: To this end, Data Envelopment Analysis (DEA) is applied, which enables researchers and managers to obtain measurements of efficiency of the analyzed regions, and to propose corrective steps to achieve efficiency for inefficient HS. Moreover, the super-efficiency measurement is shown for a constant and a variable scale. RESULTS: The results show that there are three groups of AC, first a group composed by six HS that are globally efficient, a second group composed by eight HS that are globally inefficient, and a third group composed by three HS that are efficient in some terms and their efficiency can be improved. CONCLUSIONS: It is concluded that DEA is an appropriate method for evaluating efficiencies of health systems and giving the adjustments for the application of economic, social and organizational policies to improve their efficiencies.

Spatio-temporal variability in the cannibalistic behaviour of European hake Merluccius merluccius: the influence of recruit abundance and prey availability.

Cannibalistic behaviour of European hake Merluccius merluccius was studied through the analysis of 49 836 gut contents belonging to individuals from 6 to 82 cm in total length (L(T)). Samples were collected every autumn between 1993 and 2009. The results showed that the consumption of conspecific individuals was consistent over space and time. The abundance, spatial distribution patterns and L(T) structure of M. merluccius recruits were the main variables involved in M. merluccius cannibalism. A geographical pattern was found since increasing cannibalism was observed in areas of recruit aggregations. The L(T) spectrum of recruits in autumn was also a key factor and dependent on the spawning period. When adults spawned from late spring to summer, an increasing cannibalism trend was found in autumn, due to the ideal size structure of the prey (M. merluccius recruits) for predators. Depth was also a significant variable, and a cannibal peak was detected at depths ranging between 50 and 200 m, coinciding with a spatial overlap of predator (pre-adults) and prey (recruits). The cannibalistic behaviour of M. merluccius began at c. 12 cm, although 75% were mid-sized individuals between 16 and 30 cm. Additionally, 90% of prey-hake were recruits <18·5 cm. Some biological and ecological aspects such as growth rate, spawning period, predation and competition interactions and the effect of some oceanographic events on M. merluccius cannibalism are also discussed.

Production, Nutritional Quality and In vitro Methane Production from Andropogon gayanus Grass Harvested at Different Maturities and Preserved as Hay or Silage.

Andropogon gayanus is an important grass due to its high biomass production, drought tolerance and favorable growth on low fertility acidic soils. Currently, there is little research on the impact of growth stage on the nutritional quality or the degree of CH4 production that may arise from this forage during ruminal fermentation. The objectives of this study were to determine the effects of regrowth stage of A. gayanus on its chemical composition, in vitro production of gas and CH4, as well as in vitro dry matter (DM) digestibility when grown under tropical Brazilian conditions and conserved as hay or as silage. The nutritional value of A. gayanus grass declined with increasing maturity; however digestible DM yield linearly increased. After 112 d of regrowth, A. gayanus produced higher quality silage (higher lactate and lower pH and butyrate content) and higher DM yield. However, the low levels of crude protein at this time would make protein supplementation a necessity for proper rumen fermentation. No differences in CH4 kinetic parameters were found with advancing maturity or preservation method (hay or silage).

F8 gene dosage defects in atypical patients with severe haemophilia A.

We performed molecular analysis of the factor 8 gene (F8) in 272 unrelated Spanish patients with haemophilia A (HA) and detected a mutation by routine analysis in 267 of them (98.1%). No mutation was detected in the remaining five patients despite clinical and laboratory confirmation of HA. The aim is to describe the molecular alterations in F8 discovered by gene dosage methodologies in three of these patients. For methodology, F8 sequencing, intragenic marker analysis, multiplex ligation-dependent probe amplification and quantitative real time-PCR were followed. One patient had Klinefelter syndrome (47,XXY) and a large deletion spanning exons 1-12 masked by the other F8 allele; the second patient showed a large duplication spanning exons 2-10 and the third patient revealed a non-contiguous double duplication of exons 14 and 23-25. The remaining two patients had mild HA and dosage results were normal. The application of gene dosage methods is useful to define haemophilic patients in whom mutations are not detected using other routine methods. Nevertheless, in a small percentage of patients (<1%), no molecular pathology can be identified after testing several genetic methodologies.

Expression of progranulin (Acrogranin/PCDGF/Granulin-Epithelin Precursor) in benign and malignant ovarian tumors and activation of MAPK signaling in ovarian cancer cell line.

It has been recently demonstrated that progranulin is overexpressed in ovarian cancer and that this protein is involved in the stimulation of cell proliferation, malignancy, and chemoresistance in ovarian cancer. The goal of the present study was to establish the differences in progranulin expression among normal, benign, and malignant ovarian tissues and to identify the signal transduction pathways activated by progranulin in an ovarian cancer cell line. Compared with benign tumors and normal ovarian tissue, progranulin mRNA and protein were overexpressed in malignant tumors. Survival analysis by the Kaplan-Meier method showed a correlation between high mRNA expression levels with poor survival outcome. Progranulin activated the MAPK-signaling pathway in NIH-OVCAR-3 cells. Progranulin expression may be potentially involved in the pathogenesis and malignant progression of ovarian cancer, and thus may represent a therapeutic target for this particular malignancy.

International league of associations for rheumatology recommendations for the management of psoriatic arthritis in resource-poor settings.

BACKGROUND: Psoriatic arthritis (PsA) is a challenging heterogeneous disease. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) last published their respective recommendations for the management of PsA in 2015. However, these guidelines are primarily based on studies conducted in resource replete countries and may not be applicable in countries in the Americas (except Canada and USA) and Africa. We sought to adapt the existing recommendations for these regions under the auspices of the International League of Associations for Rheumatology (ILAR). PROCESS: The ADAPTE Collaboration (2009) process for guideline adaptation was followed to adapt the EULAR and GRAPPA PsA treatment recommendations for the Americas and Africa. The process was conducted in three recommended phases: set-up phase; adaptation phase (defining health questions, assessing source recommendations, drafting report), and finalization phase (external review, aftercare planning, and final production). RESULT: ILAR recommendations have been derived principally by adapting the GRAPPA recommendations, additionally, EULAR recommendations where appropriate and supplemented by expert opinion and literature from these regions. A paucity of data relevant to resource-poor settings was found in PsA management literature. CONCLUSION: The ILAR Treatment Recommendations for PsA intends to serve as reference for the management of PsA in the Americas and Africa. This paper illustrates the experience of an international working group in adapting existing recommendations to a resource-poor setting. It highlights the need to conduct research on the management of PsA in these regions as data are currently lacking.Key Points• The paper presents adapted recommendations for the management of psoriatic arthritis in resource-poor settings.• The ADAPTE process was used to adapt existing GRAPPA and EULAR recommendations by collaboration with practicing clinicians from the Americas and Africa.• The evidence from resource-poor settings to answer clinically relevant questions was scant or non-existent; hence, a research agenda is proposed.

Prophylaxis in 10 patients with severe haemophilia A and inhibitor: different approaches for different clinical situations.

The effect of bypassing agents is not as predictable as replacement therapy with the deficient factor in inhibitor patients. Consequently, these patients have more levels of arthropathy than patients without inhibitors. Prophylaxis for inhibitor patients has gained attention over the last decade and some papers have reported that bypassing agents could work in the prevention of arthropathy. However, there is a lack data to support any specific agent or regimen or even to recommend their use in different clinical conditions. We report ten patients with haemophilia A and inhibitors treated prophylacticaly with bypassing agents (5 with FEIBA and 5 with NovoSeven). The variable conditioning the choice of one agent or the other was the intention to initiate of immune tolerance induction therapy (ITI) in the future. In 8/10 patients (4 in FEIBA group and 4 in rFVIIa group) there was a decrease of bleeding episodes while 9/10 maintained or increased their joint range of motion (ROM). In the rFVIIa prophylaxis group, prophylaxis can be considered primary since all of them had had less than one joint bleed before prophylaxis. Economic analysis showed that prophylaxis is an expensive treatment. In our experience both agents seem to be safe and effective in reducing the number of bleeds in patients with inhibitors. The anamnestic response provoked by FEIBA could be an issue while awaiting a decline in titres before ITI can be initiated and so rFVIIa may be the best option for prophylaxis in patients with inhibitors who have not yet begun ITI.

Resource utilization by deep-sea sharks at the Le Danois Bank, Cantabrian Sea, north-east Atlantic Ocean.

The feeding habits of birdbeak dogfish Deania calcea, velvet belly lantern shark Etmopterus spinax and blackmouth catshark Galeus melastomus at Le Danois Bank, Cantabrian Sea, south Bay of Biscay were studied in relation to their bathymetric distribution. Deep-sea sharks were collected during two multidisciplinary surveys carried out in October 2003 and April 2004 at the Le Danois Bank. Two different habitats were defined: (1) the top of the bank, ranging from 454 to 642 m depth and covered by fine-sand sediments with a low percentage of organic matter, and (2) the inner basin located between the bank and the Cantabrian Sea's continental shelf, at depths of 810-1048 m, which was characterized by a high proportion of silt and organic matter. Deania calcea was not present at the top of the bank but was abundant below 642 m, while E. spinax was abundant in the shallower top of the bank but was not found in the deeper inner basin. There was almost no bathymetric overlap between these two deep-sea shark species. Galeus melastomus was found over the whole depth range. There seemed to be an ontogenetic segregation with depth for this species, however, since 80% of the specimens collected at the top of the bank were < 600 mm total length (L(T)) (mean 510 mm L(T)), whereas larger individuals (mean 620 mm L(T)) inhabited deeper zones. Galeus melastomus exhibited a significantly higher feeding intensity than both E. spinax at the top of the bank and D. calcea in the inner basin. Little dietary overlap between D. calcea and G. melastomus in the inner basin was found, with D. calcea being an ichthyophagous predator while the diet of G. melastomus at these depths was composed of a variety of meso-bathypelagic shrimps (e.g. Acantephyra pelagica, Pasiphaea spp. and Sergia robusta), cephalopods and fishes. The diets of E. spinax and G. melastomus at the top of the bank showed a high dietary overlap of euphausiids, which represented the main prey taxa for both species. Euphausiids declined in abundance with depth which was reflected in the diet of G. melastomus. The cluster analysis of prey affinities among hauls depicted two major groups, corresponding to the two different habitats (top of the bank and inner basin). Redundancy analysis also indicated top-basin segregation, with euphausiids representing the main prey taxa at the top of the bank and bathypelagic shrimps in the inner basin. Euphausiids and Micromesistius poutassou were key prey within the Le Danois Bank ecosystem since they were positively selected by the three deep-sea shark species. These results show that the feeding ecology of these predators in Le Danois Bank ecosystem is highly influenced by depth-related variables, as a result of changes in prey availability. Overall results were analysed in relation to the deep-sea Le Danois ecosystem structure and functioning.

Adverse reproductive outcomes in urban women with adeno-associated virus-2 infections in early pregnancy.

BACKGROUND: We demonstrated recently that adeno-associated virus-2 (AAV-2) DNA was detected significantly more frequently in placental trophoblast cells from cases of severe pre-eclampsia than from normal term deliveries. Here, we sought to determine if maternal AAV-2 infection early in pregnancy preceded adverse outcomes resulting from placental dysfunction. METHODS: We collected first trimester maternal serum samples and compared anti-AAV-2 IgM antibody levels (indicating primary infection or reactivation of latent AAV-2) between controls delivered at term (n = 106) and three groups of cases: spontaneous abortions (n = 34), spontaneous preterm deliveries (n = 24) and women with at least one outcome usually attributed to placental dysfunction, including pre-eclampsia, intrauterine growth restriction (IUGR) or stillbirth (n = 20). The seroprevalence of immunoglobulin G (IgG) antibodies against AAV-2 and IgM antibodies against viruses that promote AAV-2 replication [adenovirus and cytomegalovirus (CMV)] were also determined. RESULTS: First trimester maternal IgM seropositivity was 5.6 times more prevalent among pre-eclampsia/IUGR/stillbirth cases (P = 0.0004) and 7.6 times more prevalent among preterm deliveries (P < 0.0001) than among controls. CMV and adenovirus IgM antibodies and chronic AAV-2 infections (IgG seropositivity) were not associated with adverse pregnancy outcomes. CONCLUSIONS: Primary or reactivated AAV-2 infection (maternal IgM seropositivity) early in pregnancy was associated with adverse reproductive outcomes associated with placental dysfunction, including pre-eclampsia, stillbirth and spontaneous preterm delivery.

A Note on the bias in SVMs for multiclassification.

During the usual SVM biclassification learning process, the bias is chosen a posteriori as the value halfway between separating hyperplanes. A note on different approaches on the calculation of the bias when SVM is used for multiclassification is provided and empirical experimentation is carried out which shows that the accuracy rate can be improved by using bias formulations, although no single formulation stands out as providing better performance.

[Central nervous system neuromodulation for the treatment of epilepsy. II. Mechanisms of action and perspectives]. / Neuromodulation du système nerveux central dans le traitement des épilepsies. II . Mécanismes d'action et perspectives.

OBJECTIVES: Review of available evidence of the mechanisms of action underlying the anticonvulsant effect of current applied to various CNS structures. MATERIAL AND METHODS: Studies were conducted from observations of patients with drug-resistant seizures and treated with neuromodulation. Seizures originated from various cortical areas with secondary generalization or were initially generalized without a focal origin, either clinically or on EEG or SEEG. Intracranial recordings and SEEG were performed using subdural grids or depth electrodes implanted either for recordings or therapeutic deep brain stimulation (DBS). In a group of mesial temporal lobe epilepsy patients investigated with subdural or SEEG electrodes, the epileptogenic focus area was stimulated for 15 days before anterior temporal lobectomy. The surgical specimen was examined using standard and electronic microscopy and autoradiography in order to identify several neurotransmitter receptors. They also were compared to other surgical specimens from epileptic patients who had intracerebral recordings but without stimulation (epileptic controls) and to autopsy specimens from subjects with no history of epilepsy (nonepileptic controls). RESULTS: High-frequency (HF) stimulation increases the after-discharge threshold of the stimulated site and alters the cycles of potentials evoked by a test stimulation using a paradigm of coupled stimulations. HF stimulation also decreases local cerebral blood flow in the stimulated area as demonstrated on SPECT. Parahippocampal cortex HF stimulation significantly increases the GABAergic benzodiazepine receptor density in the stimulated area. In addition, centromedianum (CM) thalamic nucleus HF stimulation suppresses thalamic and cortical spike-waves, as well as secondary synchronous discharges visible on EEG. Conversely, low-frequency (3-Hz) bilateral CM stimulation induces a typical absence clinically and on EEG. CONCLUSION: High-frequency stimulation is responsible for an inhibition of local and propagated epileptogenesis. Low-frequency stimulation may trigger or enhance epileptogenesis when applied on epileptogenic regions.