[Inherited bleeding disorders in adolescents with excessive menstrual bleeding. Should we evaluate the fibrinolytic pathway?] / Trastornos hereditarios de la coagulación en adolescentes con sangrado menstrual excesivo, ¿debemos evaluar la vía fibrinolítica?

INTRODUCTION: Heavy Menstrual Bleeding (EMB) is a frequent problem in adolescence. The prevalence of inherited bleeding disorders (IBD) as a cause of EMB is not well established and the involvement of fibri nolytic pathway defects has been poorly explored. OBJECTIVE: To determine the prevalence of IBD and fibrinolysis defects in adolescents with EMBs. PATIENTS AND METHOD: 93 adolescents (11 to 18 years old) were included. Personal and family history of bleeding were obtained through a standard ized questionnaire. The following lab tests were performed: prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor quantification, and platelet count and function. Those patients who were not diagnosed with IBD were further evaluated with clot lysis time assay. RESULTS: 41 patients (44%) were diagnosed as IBD (Von Willebrand disease n = 28, platelet func tion defects n=8, mild hemophilia n = 5. Decreased clot lysis time was found in 31 patients. 54% of patients diagnosed with IBD had EMB as the first hemorrhagic manifestation. CONCLUSION: These results support the need to evaluate the coagulation process, including the fibrinolytic pathway in the study of adolescents with EMB.

Trastornos hereditarios de la coagulación en adolescentes con sangrado menstrual excesivo, ¿debemos evaluar la vía fibrinolítica? / Inherited bleeding disorders in adolescents with excessive menstrual bleeding: should we evaluate the fibrinolytic pathway?

Resumen: Introducción: El Sangrado Menstrual Excesivo (SME) es un problema frecuente en la adolescencia. La prevalencia de trastornos hereditarios de la coagulación (THC) como causa del SME no está bien establecida y la participación de defectos de la vía fibrinolítica ha sido poco explorada. Objetivo: Determinar la prevalencia de THC y defectos de la fibrinólisis en adolescentes con SME. Pacientes y Método: Se incluyeron 93 adolescentes, edad 11 a 18 años. Los antecedentes personales y familiares de sangra do se obtuvieron con un cuestionario estandarizado. Se controló exámenes: tiempo de protrom- bina (TP), tiempo de tromboplastina parcial activada (TTPa), estudio del factor Von Willebrand, recuento y función plaquetaria. Los pacientes que no fueron diagnosticados como THC, se evaluaron adicionalmente con el tiempo de lisis del coágulo. Resultados: 41 pacientes (44%) fueron diagnos ticados como THC: Enfermedad de Von Willebrand n = 28, defectos de la función plaquetaria n = 8, hemofilia leve n = 5. Se confirmó disminución del tiempo de lisis del coágulo en 31 pacientes. El 54% de pacientes diagnosticado como THC, tuvo SME como la primera manifestación hemorrágica. Conclusión: Estos resultados apoyan la necesidad de evaluación de la coagulación, incluyendo la vía fibrinolítica, en el estudio de adolescentes con SME.

Abstract: Introduction: Heavy Menstrual Bleeding (EMB) is a frequent problem in adolescence. The prevalence of inherited bleeding disorders (IBD) as a cause of EMB is not well established and the involvement of fibri nolytic pathway defects has been poorly explored. Objective: To determine the prevalence of IBD and fibrinolysis defects in adolescents with EMBs. Patients and Method: 93 adolescents (11 to 18 years old) were included. Personal and family history of bleeding were obtained through a standard ized questionnaire. The following lab tests were performed: prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor quantification, and platelet count and function. Those patients who were not diagnosed with IBD were further evaluated with clot lysis time assay. Results: 41 patients (44%) were diagnosed as IBD (Von Willebrand disease n = 28, platelet func tion defects n=8, mild hemophilia n = 5. Decreased clot lysis time was found in 31 patients. 54% of patients diagnosed with IBD had EMB as the first hemorrhagic manifestation. Conclusion: These results support the need to evaluate the coagulation process, including the fibrinolytic pathway in the study of adolescents with EMB.

[Clinical and pathophysiological description of nummular headaches: a case series]. / Descripción clínica y fisiopatológica de la cefalea numular: serie de casos.

INTRODUCTION: Nummular headache was initially described as an infrequent primary headache characterised by chronic circumscribed mild-to-moderate pain in a small area of the head that may present with exacerbations. Since its initial description, dozens of cases of nummular headache have been reported which broaden the clinical and pathophysiological spectrum. AIMS: To review and establish the clinical characteristics of nummular headache, to analyse the epidemiology in our setting and to clarify some unanswered pathophysiological issues. PATIENTS AND METHODS: The study involved 83 cases (42 women and 41 men) who were diagnosed with nummular headache from July 2008 and followed up until 2018 at the Fundacion Alcorcon Hospital. The mean age of onset was 46 years. The time to diagnosis was seven months. RESULTS: The pain was moderate-intense and oppressive, with exacerbations in 62.5% of cases. The average size of the symptomatic area was 2.4 ± 0.7 cm, with a parietal (47%), temporal (24%), frontal (12%) or occipital (6%) location. It presented a chronic (82%) or episodic (18%) pattern. Symptoms of local sensory dysfunction were observed in 25 patients and three others showed skin alterations. Spontaneous remission was observed in 36% of cases, and the most commonly used drugs were non-steroidal anti-inflammatory drugs, paracetamol and gabapentin. Botulinum toxin was effective. CONCLUSIONS: Nummular headache is a disorder with well-defined characteristics and is considered an entity in its own right. Our data indicate that its origin lies in the epicranial structures. The conjunction of pain, sensory dysfunction and trophic disorders suggests a local form of a complex regional syndrome.

TITLE: Descripción clínica y fisiopatológica de la cefalea numular: serie de casos.Introducción. La cefalea numular se describió inicialmente como una cefalea primaria infrecuente caracterizada por dolor circunscrito crónico en una pequeña área craneal, de intensidad leve-moderada y que puede presentar exacerbaciones. Desde su descripción inicial se han publicado decenas de casos de cefalea numular que amplían el espectro clínico y fisiopatológico. Objetivos. Revisar y establecer las características clínicas de la cefalea numular, analizar la epidemiología en nuestro medio y aclarar incógnitas fisiopatológicas. Pacientes y métodos. Se estudiaron 83 casos (42 mujeres y 41 varones), que fueron diagnosticados de cefalea numular desde julio de 2003 a julio de 2008, y seguidos hasta 2018 en el Hospital Universitario Fundación Alcorcón. La edad media de inicio fue de 46 años. El tiempo de evolución hasta el diagnóstico fue de siete meses. Resultados. El dolor fue moderado-intenso y opresivo, con exacerbaciones en el 62,5% de los casos. El tamaño medio del área sintomática fue de 2,4 ± 0,7 cm, con una localización parietal (47%), temporal (24%), frontal (12%) u occipital (6%). Presentó un patrón crónico (82%) o episódico (18%). Mostraron síntomas de disfunción sensitiva local 25 pacientes, y otros tres, cambios en la piel. La remisión espontánea se observó en el 36% de los casos, y los fármacos más utilizados fueron los antiinflamatorios no esteroideos, el paracetamol y la gabapentina. La toxina botulínica fue eficaz. Conclusiones. La cefalea numular es un trastorno con características bien definidas y con entidad propia. Nuestros datos indican que su origen está en las estructuras epicraneales. La conjunción de dolor, disfunción sensitiva y alteraciones tróficas indica una forma local de síndrome regional complejo.

Synthesis and Evaluation of a Molecularly Imprinted Polymer for the Determination of Metronidazole in Water Samples.

A molecularly imprinted polymer was developed and evaluated for selective determination of metronidazole (MNZ) in wastewater. This was achieved by using sodium methacrylate as monomer, toluene as porogen, ethylene glycol dimethacrylate as crosslinker, azobisisobutyronitrile as initiator and metronidazole as template molecule to generate the selectivity of the polymer for the compound, as well as non-imprinted polymers were synthesized. Two different polymerization approaches were used, bulk and emulsion and the polymers obtained by emulsion presented higher retention percentages the MIP 2-M presented the higher retention (83%). The performed method, was validated in fortified water, showing linearity from 10 up to 1000 ng/mL; limit of detection and quantification for compound were between 3 and 10 ng/mL, respectively. Finally, the method was applied in samples of a wastewater treatment plant in the city of San Luis Potosí, México, and the concentrations of MNZ in these samples were 84.1-114 ng/mL.

Application of Focused Ultrasound-Assisted Extraction for the Quantification of Persistent Organic Pollutions in Liver Tissue of Giant Toad (Rhinella marina).

A simple and rapid focused ultrasound extraction method was developed for the determination of Persistent Organic Pollutants (POPs) in liver tissue obtained of giant toad (Rhinella marina) using a gas chromatography coupled to a mass detector with electron impact ionization. The performed method for POPs, was validated in fortified matrix, showing linearity from the LOQ up to 100 ng/mL; LODs and LOQs for each compound were between 1.7 and 4.8 and 3.5-7.5 ng/mL, respectively. Recovery rates were among 79%-116% for POPs determined. Finally, the method was applied in liver samples of giant toads found in a malarial area in Mexico. The sensitivity of the proposed method was good enough to ensure reliable determination of target analytes at concentration levels commonly found in this kind of samples.

The Direct Referral to Endovascular Center criteria: a proposal for pre-hospital evaluation of acute stroke in the Madrid Stroke Network.

BACKGROUND AND PURPOSE: For patients with acute ischaemic stroke due to large-vessel occlusion, it has recently been shown that mechanical thrombectomy (MT) with stent retrievers is better than medical treatment alone. However, few hospitals can provide MT 24 h/day 365 days/year, and it remains unclear whether selected patients with acute stroke should be directly transferred to the nearest MT-providing hospital to prevent treatment delays. Clinical scales such as Rapid Arterial Occlusion Evaluation (RACE) have been developed to predict large-vessel occlusion at a pre-hospital level, but their predictive value for MT is low. We propose new criteria to identify patients eligible for MT, with higher accuracy. METHODS: The Direct Referral to Endovascular Center criteria were defined based on a retrospective cohort of 317 patients admitted to a stroke center. The association of age, sex, RACE scale score and blood pressure with the likelihood of receiving MT were analyzed. Cut-off points with the highest association were thereafter evaluated in a prospective cohort of 153 patients from nine stroke units comprising the Madrid Stroke Network. RESULTS: Patients with a RACE scale score ≥ 5, systolic blood pressure <190 mmHg and age <81 years showed a significantly higher probability of undergoing MT (odds ratio, 33.38; 95% confidence interval, 12-92.9). This outcome was confirmed in the prospective cohort, with 68% sensitivity, 84% specificity, 42% positive and 94% negative predictive values for MT, ruling out 83% of hemorrhagic strokes. CONCLUSIONS: The Direct Referral to Endovascular Center criteria could be useful for identifying patients suitable for MT.

Biomonitoring of persistent organic pollutants (POPs) in child populations living near contaminated sites in Mexico.

The aim of this study was to conduct a POP biomonitoring programme for children in high-risk areas. We evaluated 247 serum samples from children between the ages of 6 and 12years old from two zones in Mexico: (1) indigenous zones, which included Cuatlamayan (CUA), Tocoy (TOC), and Santa Maria Picula (SAM); and (2) industrial zones, which included Tercera Chica (TC), Industrial San Luis (IND) and Rincon de San Jose (SJR); Mundo Nuevo (MN); and Alpuyeca (ALP). Our results showed that α-endosulfan was similar to CUA, TOC, SAM, TC and MN (178.6-306.9ng/g lipid). ß-Endosulfan levels were higher in ALP (901.5ng/g lipid), followed by CUA (139.9ng/g lipid) and TOC, SAM, TC and MN, which had similar levels (55.4-64.5ng/g lipid). For endosulfan sulfate, the ALP community had the highest concentration levels (1096.4ng/g lipid), whereas CUA and TOC (212.3 and 289ng/g lipid, respectively) had concentrations similar to those found in SAM and TC (99.5 and 119.1ng/g lipid, respectively). DDE levels were found in malaria-endemic areas of SAM, CUA and TOC (1782.2, 1358.3 and 57.0ng/g lipid), followed by MN (35.1ng/g lipid). HCB concentration levels were found to be higher in MN and SJR (691.8 and 575.4ng/g lipid, respectively), followed by CUA and TC (363.9 and 269.1ng/g lipid, respectively), with levels similar to those found in TOC and SAM (191.8 and 181.9ng/g lipid, respectively). Finally, PCB 101 concentration levels were found to be the highest in ALP (1032.7ng/g lipid), followed by similar levels of SJR and IND (567.5 and 327.3ng/g lipid, respectively) and TC and MN, with 109.1 and 144.5ng/g lipid, respectively. The evidence provided by this exploratory study indicates that the evaluation of the health risks posed to children living in contaminated areas is a high priority health issue.

Assessment of exposure to mixture pollutants in Mexican indigenous children.

The aim of the present work was to complete an exposure assessment in three Mexican indigenous communities using the community-based health risk assessment, which is the first step in the CHILD framework. We used 1-hydroxypyrene (1-OHP) as an exposure biomarker to polycyclic aromatic hydrocarbons (PAHs) and trans, trans-muconic acid (t,t-MA) as an exposure biomarker to benzene, persistent organic pollutants (POPs), lead, manganese, arsenic, and fluoride. Anthropometric measurements were also taken. In these communities, high percentages of children with chronic malnutrition were found (28 to 49 %) based on their weight and age. All communities showed a high percentage of children with detectable levels of four or more compounds (70 to 82 %). Additionally, our results showed that in indigenous communities, children are exposed to elevated levels of certain environmental pollutants, including manganese with 17.6, 16.8, and 7.3 µg/L from SMP, TOC, and CUA, respectively. Lead and HCB levels were similar in the indigenous communities (2.5, 3.1, and 4.2 µg/dL and 2.5, 3.1, and 3.7 ng/mL, respectively). 1-OHP and t,t-MA levels were higher in TOC (0.8 µmol/mol of creatinine, 476 µg/g of creatinine, respectively) when compared with SMP (0.1 µmol/mol of creatinine, 215.5 µg/g of creatinine, respectively) and CUA (0.1 µmol/mol of creatinine, 185.2 µg/g of creatinine, respectively). DDE levels were 30.7, 26.9, and 9.6 ng/mL in CUA, SMP, and TOC, respectively. The strength of this study is that it assesses exposure to pollutants with indications for the resultant risk before an intervention is made by the CHILD program to manage this risk in the indigenous communities. Considering the large number of people, especially children, exposed to multiple pollutants, it is important to design effective intervention programs that reduce exposure and the resultant risk in the numerous indigenous communities in Mexico.

Stability, nutrient availability and hydrophobicity of biochars derived from manure, crop residues, and municipal solid waste for their use as soil amendments.

We aimed to study the influence of feedstock properties, pyrolysis temperature and holding time on stability, nutrient contents and hydrophobicity of biochars derived from pig manure, crop residues and municipal solid waste. Biochars were prepared at 300 °C, 400 °C, 500 °C and 700 °C for 1 h, 2 h, 4 h and 5 h. All properties were influenced by feedstock except for pH and hydrophobicity. Temperature influenced all properties, whereas no effect of holding time was observed except for hydrophobicity and thermal stability. Increasing temperature increased aromatization and stability. Low temperatures provided higher cation exchange capacity and available nutrients, and lower salinity and alkalinity. Precipitation of phosphates and carbonates occurred with charring, explaining the decrease of available nutrients. Biochars produced at 300 °C showed high hydrophobity, which disappeared over 500 °C owing to the loss of labile aliphatic compounds. The high pH and carbonates contents at >500 °C resulted in suitable biochars for soil liming and decreasing soil metals availability.

Application of Focused Ultrasound-Assisted Extraction to the Determination of Persistent Organic Pollutants (POPs) in Soil Samples.

A simple and rapid focused ultrasound extraction (FU) based method is presented for the determination of persistent organic pollutants (POPs) in soil using a gas chromatography coupled to a mass detector with electron impact ionization. The main experimental parameters affecting the FU step have been optimized by applying a PERMANOVA and PCO analysis allowing us to obtain a maximum amount of information with a minimum number of assays. The limits of detection for POPs fell within the 0.9-6.8 ng/g d.w. interval; a linear method was used with correlation coefficients (r) higher than 0.99. Recovery percentages at low concentrations (25 ng/g d.w.) were 75.8%-110%, and at high concentrations (75 ng/g d.w.) 82.3%-109%; the evaluated precision as RSD% of repeatability and reproducibility were within a range of 0.5%-11% and 0.3%-18%, respectively.

Rapid analysis of persistent organic pollutants by solid phase microextraction in serum samples.

A simple and rapid headspace solid-phase microextraction (HS SPME) based method is presented for the determination of Persistent Organic Pollutants (POPs) in human serum by gas chromatography (GC) coupled to mass detector (MS) with electron impact ionization (EI). As an outcome of the assessment of several polymer phases; the one with the best result was the PDMS fiber (100 µm). A multivariate analysis of variance by permutations (PERMANOVA) was performed to establish the optimal extraction conditions as a function of temperature and time variables. The results were 1 mL serum+200 µL H2SO4 9M+1 mL of deionized water at 600 rpm with a temperature of 80°C for 50 min to expose the fiber. The limits of detection (LOD) for POPs pesticides fell within the 0.22-5.41 ng/mL interval, and within 0.07-1.79 ng/mL for PCBs; a linear method was used with correlation coefficients (r) higher than 0.99. Recovery percentages at low concentrations (15 ng/mL) were 67.8-120.2%, and at high concentrations (75 ng/mL) 80.2-119.2%. Evaluated precision as percentage Relative Standard Deviation (RSD%) of repeatability and reproducibility was within a range of 0.5-9% and 0.3-21%, respectively. This analytical method prevents some of the main problems for quantifying POPs in human serum, such as the elimination of the solvents, sample handling, integration of extraction steps, pre-concentration and introduction of samples; consequently, the time and cost of analyzing the sample can be significantly reduced. The method developed was applied to determine exposure to POPs in samples of children living in different polluted sites in Mexico. In children living in indigenous communities results show exposure to DDE (median 29.2 ng/mL range 17.4-52.2 ng/mL) and HCB (median 2.53 ng/mL range 2.50-2.64 ng/mL); whereas in the industrial scenario, exposure to HCB (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (median Σ-PCBs 22.2 ng/ml range 8.2-74.6 ng/mL) and finally in petrochemical scenario was demonstrated exposure to HCB (median 2.81 ng/mL range 2.61-3.4 ng/mL) and PCBs (Σ-PCBs median 7.9 ng/mL range 5.4-114.5 ng/mL).

Umbilical cord blood transplantation in hematologic diseases in patients over 15 years old: long-term experience at the Pontificia Universidad Católica de Chile.

Most patients who require a sibling stem cell transplantation do not have a matched donor. In our experience, only 1/3 patients have a matched unrelated donor (MUD); therefore, the majority of the patients will require umbilical cord blood (UCB). Patients treated for hematologic diseases with UCB transplants were included. UCB selection and conditioning regimens were performed according to the Minnesota group. Graft-versus-host disease (GVHD) prophylaxis, infection prevention, and patient care were performed according to institutional guidelines. We analyzed patients and graft demography, neutrophil and platelet recovery, chimerism kinetics, GVHD incidence, overall (OS), progression-free survival (PFS) and transplant-related mortality (TRM). We included 29 patients with a median age of 34.8 years (range 15-55). Eighteen were male and the median weight was 72.6 kg (range 54-100). Nineteen patients had acute leukemia. Myeloablative (MA) conditioning was used in 27 patients. Seventeen received double UCB (DUCB) grafts. Median total nucleated cell (10(7)/kg) was 4.2 (range 3.9-4.9) and 4.4 (range 2.8-6.3) for single UCB (SUCB) and DUCB transplants, respectively. Median time for neutrophil engraftment was 24.7 (range 14-43) and 25.8 days (range 14-52) after SUCB and DUCB transplants, respectively. Median time for platelet engraftment was 147 (range 30-516) and 81 days (range 37-200) after SUCB and DUCB transplants, respectively. All the patients receiving MA conditioning had >95% chimerism shortly after transplant. Cumulative incidence of grades II-IV and III-IV acute GVHD was 41% and 20%, respectively. Localized chronic GVHD was seen in 14% of the patients. Median follow-up was 16.7 months (range 1-63). Five-year OS and PFS were 38% and 39%, respectively. One-year TRM was 42%. UCB transplantation is associated with potential cure of hematologic malignancies and our results are similar to other series. Studies are needed to decrease mortality and improve immune reconstitution.

Ciliary ganglioplegic migraine: migraine-related prolonged mydriasis.

BACKGROUND: Transient, unilateral mydriasis has been reported in migraine patients, and this has been regarded as a possible co-morbidity between migraine and Adie's tonic pupil. Mydriasis that outlasts the duration of migraine attacks is rare. METHODS: Through an eight-year period we have studied all patients referred to our neurological clinic because of migraine attack with mydriasis. All the patients underwent thorough neurologic and ophthalmologic examinations including MRI of the brain and testing of the pupil response to ocular instillation of dilute pilocarpine (0.125%). RESULTS: Seven women and two men, with a mean age of 33.8 ± 12.3 years (range: 19-52) were included. The patients presented during one hemicranial migraine attack with an ipsilateral mydriasis that persisted for a mean of three months, while migraine headaches remained with their typical episodic course. In all the patients a cholinergic supersensitivity in the symptomatic pupil was demonstrated, thus pointing to a dysfunction of the ipsilateral ganglionic parasympathetic fibers. CONCLUSIONS: Synchronous co-localization of the features suggests a pathogenic link between the pupil dysfunction and migraine, rather than a simultaneous coexistence of two independent disorders. Likely explanations include a latent Adie's pupil that could have been triggered during a particular migraine attack; a ciliar ganglionic lesion/dysfunction produced by the migrainous process; an ophthalmoplegic migraine with selective parasympathycoparesis; or an episodic ciliar ganglionitis with migrainous features. Ciliary ganglioplegic migraine is proposed as a nominal term pointing to the possible anatomic source of the migrainous-related pupil dysfunction; the pathogenesis remains unknown.

Assessment of dioxin-like soil contamination in Mexico by enzyme-linked immunosorbent assay.

In this work, we describe the results of a preliminary soil assessment program for the detection of dioxins at different sites in Mexico performed by immunoassay. We studied five different sectors considered relevant sources of dioxins: Anaversa and Tekchem industrial areas where organochlorine pesticides were manufactured and released by accidental explosions, secondary smelters, brick kilns, and rural dwellings. In the context of the Agency for Toxic Substances and Disease Registry (ATSDR) guidelines, only the brick kilns sites can be considered as low-risk areas. The dioxin concentrations detected in the vicinity of the Anaversa and Tekchem chemical plants and secondary smelters exceed the screening level of 0.05 ppb set by the ATSDR, and therefore further site-specific studies are needed. The dioxin levels found in all soot samples from indigenous dwellings where wood is used for indoor cooking were above the evaluation level. Considering that the studied areas are representative examples of dioxin sources in less developed countries, our work demonstrates the useful application of dioxin immunoassays as a tool for dioxin screening for environmental assessment programs in developing countries.

Pressure pain sensitivity of the scalp in patients with nummular headache: a cartographic study.

Nummular headache (NH) is characterized by focal pain fixed within a small round or elliptical area of the head surface. Sensory dysfunction is apparently restricted to the symptomatic area, but a thorough analysis of cranial pain sensitivity has not been performed. Pressure pain sensitivity maps were constructed for 21 patients with NH and 21 matched healthy controls. In each subject pressure pain thresholds (PPT) were measured on 21 points distributed over the scalp. In each patient PPT were also measured in the symptomatic area and at a non-symptomatic symmetrical point. In both groups an anterior to posterior gradient was found on each side, with no significant differences of PPT measurements between sides or groups. In patients with NH, only the symptomatic area showed a local decrease of PPT (significant in comparison with the non-symptomatic symmetrical point, P < 0.001). These findings further support that NH is a non-generalized disorder with a peripheral source.

Ophthalmoplegic migraine. Two patients with an absolute response to indomethacin.

Two patients suffering from ophthalmoplegic migraine had a strictly unilateral headache absolutely responsive to indomethacin, but not to other non-steroidal anti-inflammatory drugs, analgesics or corticosteroids. Such observations raise a therapeutic alternative and suggest that ophthalmoplegic migraine may present with different headache phenotypes.

Use of the Rey-Osterrieth Complex Figure Test for neurotoxicity evaluation of mixtures in children.

The aim of this study was to assess the value of the children's version of the Rey-Osterrieth Complex Figure Test as a screening test in a population exposed to different mixtures of neurotoxicants. Copy and Immediate Recall scores were evaluated through the test. Children were recruited from three sites; an area with natural contamination by fluoride and arsenic (F-As), a mining-metallurgical area with lead and arsenic contamination (Pb-As) and a malaria zone with the evidence of fish contaminated with dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). Children aged 6-11 years old, living in one of the three polluted sites since birth were recruited (n=166). The exposure was evaluated as follows: fluoride and arsenic in urine, lead in blood and DDT, dichlorodiphenyldichloroethylene (DDE) and PCBs in serum. To evaluate the test performance, z-scores for Copy and Immediate Recall were calculated. The proportion of children by residence area with performance lower than expected by age (below -1 SD) for Copy and Immediate Recall was in the F-As area (88.7% and 59%) and in the DDT-PCBs area (73% and 43.8%), respectively. In the Pb-As area, the proportion was 62% for both tests. After adjustment, Copy correlated inversely with fluoride in urine (r=-0.29; p<0.001) and Immediate Recall correlated inversely with fluoride in urine (r=-0.27; p<0.05), lead in blood (r=-0.72; p<0.01), arsenic in urine (r=-0.63; p<0.05) and DDE (r=-0.25; p<0.05). This study provided evidence that children included in this research are living in high risk areas and were exposed to neurotoxicants. Poor performance in the test could be explained in some way by F, Pb, As or DDE exposure, however social factors or the low quality of school education prevalent in the areas could be playing an important role.

Bifocal nummular headache: the first three cases.

Nummular headache (NH) has been defined as a focal head pain that is exclusively felt in a small area of the head surface. Here we describe three patients who presented with focal head pain in two separate areas. This finding seems to be consistent with bifocal NH and further enlarges the clinical diversity of this headache disorder. The pathogenic mechanisms of NH may be active in multiple cranial areas in some particular patients.

Nummular headache secondary to an intracranial mass lesion.

Nummular headache is a coin-shaped, chronic cephalalgia usually considered to stem from epicranial tissues. We describe a patient complaining of circumscribed pain in the head as the only symptom of a subtentorial meningioma. This observation underlines the need to revise the concept of circumscribed, referred pains in the head arising from pain-sensitive intracranial structures.