Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.

Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Indoor radon exposure and excess of lung cancer mortality: the case of Mexico-an ecological study.

Radon is a radioactive gas that can migrate from soils and rocks and accumulate in indoor areas such as dwellings and buildings. Many studies have shown a strong association between the exposure to radon, and its decay products, and lung cancer (LC), particularly in miners. In Mexico, according to published surveys, there is evidence of radon exposure in large groups of the population, nevertheless, only few attention has been paid to its association as a risk factor for LC. The aim of this ecological study is to evaluate the excess risk of lung cancer mortality in Mexico due to indoor radon exposure. Mean radon levels per state of the Country were obtained from different publications and lung cancer mortality was obtained from the National Institute of Statistics, Geography and Informatics for the period 2001-2013. A model proposed by the International Commission on Radiological Protection to estimate the annual excess risk of LC mortality (per 105 inhabitants) per dose unit of radon was used. The average indoor radon concentrations found rank from 51 to 1863 Bq m-3, the higher average dose exposure found was 3.13 mSv year-1 in the north of the country (Chihuahua) and the mortality excess of LC cases found in the country was 10 ± 1.5 (range 1-235 deaths) per 105 inhabitants. The highest values were found mainly in the Northern part of the country, where numerous uranium deposits are found, followed by Mexico City, the most crowded and most air polluted area in the country. A positive correlation (r = 0.98 p < 0.0001) was found between the excess of LC cases and the dose of radon exposure. Although the excess risk of LC mortality associated with indoor radon found in this study was relatively low, further studies are needed in order to accurately establish its magnitude in the country.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.

Early appearance of functional plasma cells (CD138+CD98+) in non-immunized neonate mice.

Plasma cells (PCs) are terminally differentiated antibody-secreting cells, derived from activated B-lymphocytes in response to either T-independent or T-dependent antigens. The plasma cell population is scarce in circulation in non-immunized individuals. It is established that neonates are incapable of mounting an efficient immune response due to the immaturity of the immune system. However, this disadvantage is well overcome through the antibodies neonates receive from breastmilk. This implies that neonates will be only protected against antigens the mother had previously encountered. Thus, the child might be potentially susceptible to new antigens. This issue prompted us to seek for the presence of PCs in non-immunized neonate mice. We found a PC population identified as CD138+/CD98+ cells since day one after birth. These PCs were positive for Ki67 and expressed Blimp-1, B220, and CD19, which suggests the populations are plasmablasts and PCs with heterogeneous phenotype. These PCs were also determined to secrete antibodies, although mainly isotype IgM. Altogether, the results indicated that neonate PCs can produce antibodies against antigens they encounter in the first weeks of life, most likely coming from food, colonizing microbiota, or the environment.

Adequacy and prognostic impact of treatment for severe exacerbation of chronic obstructive pulmonary disease. / Adecuación e impacto pronóstico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease (COPD) exacerbation, to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients' prognosis. METHODOLOGY: We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital. We collected demographic and clinical variables (degree of dyspnoea and obstruction, previous exacerbations, comorbidities), readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the Spanish COPD guidelines (GesEPOC). We performed a univariate, multivariate and survival analysis. RESULTS: The study included 108 patients, and the mean age was 71.48±11.65 years. The readmission rate was 26.4% at 3 months and 43.4% at 1 year. The hospital mortality rate was 3.9%, the mortality rate at 3 months was 21.9%, and the mortality rate at 1 year was 27.4%. The patients hospitalised in the internal medicine department had higher mortality during hospitalisation (p=.043), at 3 months (p=.028) and at 1 year (p=.007) compared with the rates for the pneumology department. Overall compliance with the clinical guidelines was 63% for the clinical evaluation (less for the patients in internal medicine: 56.1% vs. 73.8%, p=.063). For the treatment, the compliance was 26.9% for GOLD and 28.7% for GesEPOC. Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions (p=.041) and hospital mortality (p=.007) and 3-month mortality (p=.05). CONCLUSIONS: The clinical profile of the patients is currently similar to that previously reported, but their clinical progression was poorer. Overall compliance with the clinical guidelines for drug treatment was low, and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions.

[Childhood spinal tumours]. / Tumores espinales infantiles

We report a large series of 48 childhood spine tumors diagnosed and treated at our Hospital between 1986 and 2006. Spinal tumors in children are a rare and heterogeneous condition that frequently are diagnosed late because of their uncharacteristic clinical picture. Symptoms are usually limited to diffuse back pain or spinal deformities, prior to leg paresis or sphincter dysfunction. Diagnosis is usually made with MRI or CT. Treatment is surgical in most cases. The prognosis is variable due to the diverse histological findings and it may require the use of complementary treatments as chemotherapy or radiation.

Pharmacokinetics of low and maintenance dose valganciclovir in kidney transplant recipients.

Valganciclovir is commonly used for cytomegalovirus (CMV) prophylaxis in renal transplant patients. A fixed dose of 900 mg daily is typically recommended, however, there has never been a formal pharmacokinetic study comparing various doses in renal transplant patients. We therefore compared the pharmacokinetic characteristics of intravenous ganciclovir (IV GCV) and oral ganciclovir (GCV) with two different doses of valganciclovir (VGCV) in an open-label crossover study. Ten adult kidney recipients participated in a four-phase crossover treatment schedule of IV GCV (2.5 mg/kg every 12 h), VGCV (900 mg daily), VGCV (450 mg daily) and oral GCV (1000 mg Q8 H). IV GCV and oral VGCV 900 mg daily achieved similar values for AUC(0-24) (median 60.63 vs. 62.86 microg/h/mL). Oral VGCV 450 mg achieved comparable AUC(0-24) values as oral GCV 1000 mg Q8 H (median AUC(0-24) 35.9 vs. 29.04 microg/h/mL). Oral VGCV 900 mg daily provided systemic GCV exposure similar to IV GCV and confirms PV 16 000 study results. Further, VGCV 450 mg daily provided comparable systemic exposure versus oral GCV. Due to its favorable pharmacokinetic profile, data herein suggest that VGCV can be used in the early post-kidney transplant period, and that 450 mg daily provides ample drug exposure for effective CMV prophylaxis in kidney transplant patients.

[Spinal cord compression due to a epidural lipoma]. / Compresión medular por lipoma epidural dorsal.

INTRODUCTION: The spinal extradural space is normally occupied by adipose tissue and a venous plexus, so it should be not surprising that lipomas arise and reach sufficient size to compress symptomatically the spinal cord. Nevertheless, the spinal epidural lipomas are rare and benign tumours may present as a progressive spinal cord compression syndrome. Magnetic resonance imaging is useful in demonstrating the full extent and characteristics of these lesions, the severity of cord compression and the location in the canal. Usually, the lesion is amenable to total surgical extirpation and the functional prognosis is good. Histopathologically the tumour consists of a mature adipose cells matrix intermixed with vascular endothelial channels, that is the reason why it is also named angiolipomas. CASE REPORT: A 47 year-old woman complained of dorsal and bilateral submamarian pain lasting two years and progressive loss of sensibility and weakness in her legs. Following magnetic resonance studies a posterior spinal cord compression by an extradural tumour at T3-T7 levels was observed. She was operated on and we found an extradural yellow tumour easily to dissect and it was completely removed. One year later she is asymptomatic. CONCLUSIONS: Spinal epidural lipoma is a benign tumour which initially presents itself with local or radicular pain accompanied by progressive spinal cord compression syndrome. The choice treatment is laminectomy and total excision. Probably, this is one of the easiest tumours to remove of the spinal canal and a source of satisfaction because a complete recovery can usually be achieved.

Molecular epidemiology of Shiga toxin-producing O113:H21 isolates from cattle and meat.

The serotype O113:H21 is considered one of the relevant non-O157 STEC serotypes associated with severe human infections. Due to the increased detection of O113 strains and their relationship with clinical cases, which emphasizes the importance of this serogroup as an emerging pathogen, our aim was to determine the characteristics of STEC O113:H21 strains circulating in bovine cattle and retail meat from Argentina. For this purpose, we determined the presence and combinations of various virulence genes (and their variants) related to adhesion and toxicity in a collection of 34 isolates. Their genetic relatedness using multiple-locus variable-number tandem repeat analysis (MLVA) was also studied. Subtyping of stx genes indicated that O113:H21 strains circulating in Argentina mainly present stx2a alone or together with stx2c or, less frequent, with stx2d , all of which are subtypes associated with human disease. We found plasmid markers, such as saa, ehxA and subA, in a higher proportion than previous studies, and five variants of saa, two of which were novel ones. In relation to MLVA subtyping, we detected a limited diversity among the isolates considering that several loci were not discriminative and, that in some farms, the same clone seemed to remain circulating throughout the year. The O113:H21 strains studied harbour several toxin and adhesion genes (saa, espP, fimCD, ehaA, iha, hcpA, elfA, lpfO113, ecpA, subA, cdt-V) and Stx subtypes associated with human disease. Results also highlighted that subtyping of stx and saa is useful to discriminate O113:H21 strains that share virulence genes. In conclusion, this study shows that a number of O113:H21 strains that occur in foods and bovines could be pathogenic for humans. This situation calls for further attention in the prevention and control of foodborne disease caused by these strains.

Paraneoplastic pemphigus associated with Castleman's disease: usefulness of the laboratory of autoimmunity in the diagnosis of this disease.

We report on a case of paraneoplastic pemphigus associated with Castleman's disease. Clinical pathologic features were not conclusive. Diagnosis was established thanks to the detection of seric autoantibodies directed against intercellular substance by indirect immunofluorescence on monkey esophagus. The positive result of this test prompted us to reevaluate the patient and to detect the occult neoplasia. The demonstration of autoantibodies against plakins is the key marker of this disease but depends on tests that may not be readily available in many places like immunoprecipitation, immunoblotting, or indirect immunofluorescence over rat bladder. In this setting, tests like indirect immunofluorescence over monkey esophagus, although unspecific, may aid in reaching the appropriate diagnosis. This case illustrates the importance of the laboratory of autoimmunity in the diagnosis of this type of pemphigus.

Delayed intracerebral hemorrhage after ventriculoperitoneal shunt insertion. Case report and literature review.

We present another case of delayed intracerebral hemorrhage after a ventriculoperitoneal (VP) shunting procedure. In this case, a right occipital intraparenchymal hematoma and associated intraventricular hemorrhage occurred six days after the operation for hydrocephalus secondary to subarachnoid hemorrhage in a 64 year old woman. It is a rare complication of VP shunting, with few cases reported previously in the literature. The presumed mechanism is the erosion of a cerebral blood vessel secondary to a close contact with the ventricular catheter; bleeding disorder, vascular malformation, head trauma or brain tumor were excluded in this patient.

[Painful ophthalmoplegia (pseudotumor of the orbit and Tolosa-Hunt syndrome)]. / Oftalmoplejía dolorosa (pseudotumor y síndrome de Tolosa-Hunt).

INTRODUCTION: The Tolosa-Hunt Syndrome (THS) and the Pseudotumor of the Orbit (PTO) each have three common clinical hallmarks: unilateral periorbital pain, cranial nerve palsies and a fast response to corticosteroid therapy. CASE REPORT: 48-year-old female with a right VI nerve paralysis, later develops a right III nerve paralysis. It is important to be able to differentiate between THS and PTO, and this is done on the basis of the complementary tests. DISCUSSION: Apart from neuroradiologic findings, the clinical presentation and histopathology of these two conditions are very similar, making it difficult to distinguish between them. Aspects common to both pathological processes are discussed.

Conocimiento de los costarricenses sobre parasitosis en la población infantil / Knowledge of Costa Ricans about parasitosis in children population / Conhecimento dos costarriquenhos sobre parasitoses na população infantil

Objetivo: los parásitos son organismos que viven en el interior o sobre otra especie para su propio beneficio. Logran afectar plantas, animales y humanos. Los niños son más vulnerables a infectarse, pero la incidencia ha disminuido en Costa Rica gracias a la mejora en salubridad. El objetivo de este estudio fue evaluar el conocimiento general que tiene la población costarricense con respecto a las parasitosis infantiles. Metodología: se realizó un estudio observacional, descriptivo de tipo transversal, a una muestra de 196 sujetos. Se presentó encuesta a costarricenses mayores de 18 años que tuvieran un dispositivo con acceso a internet. Se consultó sobre el conocimiento del cuadro clínico de las parasitosis infantiles en Costa Rica. Resultados: la mayoría de los participantes eran universitarios (68.3%). El 89.9% cree que los parásitos de las mascotas pueden infectar a los humanos. Los parásitos más conocidos fueron los piojos 173 (88.3%). La parte del cuerpo que se considera más afectada por los parásitos es el estómago (75.5%). La principal medida preventiva contra las parasitosis más conocidas es lavarse las manos (67.9%). Conclusión: muchos participantes creen que los humanos se pueden infectar por los mismos parásitos de los animales. Los piojos fueron los parásitos más conocidos y las garrapatas las menos conocidas. La mayoría considera el vómito o la diarrea como los síntomas principales de las parasitosis y creen que el estómago es el más afectado en una infección. Además, señalan que la principal medida preventiva para evitar el contagio es el lavado de manos.

Objective: parasites are organisms that live inside or on another species for their own benefit, managing to affect plants, animals, and humans. Children are more vulnerable to infection, but the incidence has decreased thanks to the improvement in Costa Rican sanitation. The aim was to evaluate the general knowledge that the Costa Rican population has regarding childhood parasitosis. Methodology: an observational, descriptive, cross-sectional study was carried out on a sample of 196 subjects. A survey was conducted among Costa Ricans over 18 years of age who had a device with internet access. The participants were asked about their knowledge on the clinical picture of childhood parasitosis in Costa Rica. Results: most of the participants were college students (68.3%). 89.9% of them believe that pet parasites can infect humans. The best-known parasites were lice, marked by 173 (88.3%) people. The stomach is the part of the body considered most affected, with 148 (75.5%) responses. The main known preventive measure is washing hands with soap and water, answered by 133 participants (67.9%). Conclusion: Many participants believe that humans can be infected by the same parasites as animals. Lice were the best known and ticks the least. Most of the people consider vomiting and/or diarrhea as one of the main symptoms and believe that the stomach is the most affected part during the infection. In addition, they consider that the main preventive measure to avoid contagion is hand washing.

Objetivo: Parasitas são organismos que vivem em ou sobre outra espécie para seu próprio benefício. Eles conseguem afetar plantas, animais e humanos. As crianças são mais vulneráveis à infecção, mas a incidência diminuiu na Costa Rica graças a melhorias no saneamento. O objetivo deste estudo foi avaliar o conhecimento geral que a população costarriquenha tem sobre parasitas infantis.Metodologia: estudo observacional, descritivo, transversal, com amostra de 196 sujeitos.Uma pesquisa foi apresentada a costarriquenhos maiores de 18 anos que possuíam um dispositivo com acesso à internet. O conhecimento do quadro clínico de parasitas infantis na Costa Rica foi consultado.Resultados:a maioria dos participantes era universitária (68.3%). 89.9% acreditam que parasitas de animais de estimação podem infectar humanos. Os parasitas mais conhecidos foram os piolhos 173 (88.3%). A parte do corpo considerada mais afetada pelos parasitas é o estômago (75.5%). A principal medida preventiva contra os parasitas mais conhecidos é a lavagem das mãos (67.9%).Conclusão: muitos participantes acreditam que humanos podem ser infectados pelos mesmos parasitas de animais. Os piolhos foram os parasitas mais conhecidos e os carrapatos os menos conhecidos. A maioria considera vômito ou diarreia como os principais sintomas dos parasitas e acredita que o estômago é o mais afetado em uma infecção. Além disso, apontam que a principal medida preventiva para evitar o contágio é a lavagem das mãos.

Extended gamma-ray sources around pulsars constrain the origin of the positron flux at Earth.

The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera-electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed. We demonstrate that the leptons emitted by these objects are therefore unlikely to be the origin of the excess positrons, which may have a more exotic origin.

[Descriptors of breathlessness in Mexican Spanish]. / El lenguaje de la disnea. Una visión desde el español de México.

OBJECTIVE: Breathlessness is the most common symptom of cardiovascular or pulmonary disease. The term encompasses a wide range of descriptors used by patients, however. Identifying those descriptors can be useful for analyzing symptoms and understanding how they arise. The aim of this study was to characterize the descriptors of breathlessness used in Mexican Spanish and to consider their association with various states of respiratory distress and cardiovascular or pulmonary disease. MATERIAL AND METHODS: A questionnaire was based on 21 descriptors of breathlessness, some of which had no equivalents in English. The subjects included 15 healthy individuals during a cardiopulmonary stress test, 13 healthy subjects after a carbon dioxide rebreathing procedure, and 10 healthy women during pregnancy. We also included 16 patients with confirmed heart disease in stable condition, 15 patients during exacerbation of asthma, 20 with stable chronic obstructive pulmonary disease, and 15 with diffuse interstitial lung disease also in stable condition. Descriptors of breathlessness were then grouped based on the results of cluster analysis. RESULTS: Seven clusters of phrasal descriptors were identified as possibly representative of types of dyspnea. These clusters of descriptors were categorized as follows: agitation, suffocation, smothering, inhalation, exhalation, panting, and rapidity. Associations between types of dyspnea and the groups of participants were identified based on how frequently they used the terms. CONCLUSIONS: At least 7 clusters or groups of descriptors of breathlessness were identified as equivalent to 7 types of dyspnea; some items have no equivalent in English. Healthy subjects with respiratory distress or certain groups of patients with cardiovascular or pulmonary disease are associated with certain types of dyspnea.

Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers.

BACKGROUND: St John's Wort is a popular herbal product used by approximately 7% of patients with epilepsy. Previous reports have described reductions in concentrations of CYP3A4 substrates indinavir and cyclosporine (INN, ciclosporin) associated with St John's Wort. OBJECTIVE: Our objective was to determine the effect of St John's Wort on steady state carbamazepine and carbamazepine-10,11-epoxide pharmacokinetics. METHODS AND SUBJECTS: Eight healthy volunteers (5 men; age range, 24-43 years) participated in this unblinded study. Subjects received 100 mg of carbamazepine twice daily for 3 days, 200 mg twice daily for 3 days, and then 400 mg once daily for 14 days. Blood samples were collected before and 1, 2, 4, 6, 8, 10, 12, and 24 hours after the dose on day 21. The subjects then took 300 mg of St John's Wort (0.3% hypericin standardized tablet) 3 times daily with meals and with carbamazepine for 14 days. On day 35, blood sampling was repeated. Plasma samples were analyzed for carbamazepine and carbamazepine-10,11-epoxide with HPLC. We compared carbamazepine and carbamazepine-10,11-epoxide noncompartmental pharmacokinetic parameter values before and after St John's Wort with a paired Student t test. RESULTS: We found no significant differences before or after the administration of St John's Wort in carbamazepine peak concentration (7.2 +/- 1 mg/L before versus 7.6 +/- 1.3 mg/L after), trough concentration (4.8 +/- 0.5 mg/L before versus 4.3 +/- 0.8 mg/L after), area under the plasma concentration-time curve (142.4 +/- 12.9 mg x h/L before versus 143.8 +/- 27.2 mg x h/L after), or oral clearance (2.8 +/- 0.3 L/h before versus 2.9 +/- 0.6 L/h after). Similarly, no differences were found in peak concentration (2 +/- 0.5 mg/L before versus 2.1 +/- 0.4 mg/L after), trough concentration (1.3 +/- 0.3 mg/L before versus 1.4 +/- 0.3 mg/L after), and area under the plasma concentration-time curve (37.5 +/- 7.4 mg x h/L before versus 41.9 +/- 10.3 mg x h/L after) of carbamazepine-10,11-epoxide. CONCLUSIONS: The results suggest that treatment with St John's Wort for 14 days did not further induce the clearance of carbamazepine.