Osteomielitis crónica multifocal recurrente en pediatría: un reto diagnóstico / Chronic recurrent multifocal osteomyelitis in pediatrics: a diagnostic challenge

La osteomielitis crónica multifocal recurrente (OMCR) es una enfermedad autoinflamatoria que cursa con inflamación ósea aséptica y puede acompañarse de clínica multisistémica. Presentamos el caso de un varón de 14 años con dolor a nivel de la metáfisis tibial de 2 semanas de evolución y fiebre. En la radiografía se objetivó lesión lítica en metáfisis tibial. Se realizó RM que mostró lesión ósea intramedular con edema óseo perilesional. Se realizó biopsia guiada por TAC descartando malignidad y siendo los cultivos microbiológicos negativos. Posterior a la punción presentó empeoramiento clínico y fiebre por lo que iniciaron antibioterapia ante sospecha de sobreinfección. Ante la persistencia de fiebre se realizó RM-body que halló segunda lesión activa a nivel vertebral, diagnosticándose de OMCR y evolucionando bien con antinflamatorios. La OMCR es una entidad de difícil diagnóstico. El diagnóstico diferencial es extenso con enfermedades infecciosas, tumores y otras enfermedades autoinflamatorias. Es crucial su diagnóstico precoz y tratamiento adecuado para prevenir sus secuelas derivadas

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease that presents with aseptic bone inflammation and can be accompanied by multisystemic symptoms. We present the case of a 14-year-old male with a 2-week history of pain located at the tibial metaphysis and fever. X-ray revealed a lytic lesion in the tibial metaphysis. MRI revealed an intramedullary bone lesion with perilesional bone oedema. CT-guided biopsy discounted malignancy and microbiological cultures were negative. The patient's symptoms and fever worsened after the biopsy; therefore antibiotherapy was commenced for a suspected superinfection. A body MRI was performed given the persistence of the fever, which found a second active lesion in the spine that was diagnosed as CRMO and progressed well with anti-inflammatories. CRMO is an entity that is difficult to diagnose. Differential diagnosis is extensive with infectious diseases, tumours and other autoinflammatory diseases. Prompt diagnosis and appropriate treatment are crucial to prevent sequelae

Chronic recurrent multifocal osteomyelitis in pediatrics: A diagnostic challenge. / Osteomielitis crónica multifocal recurrente en pediatría: un reto diagnóstico.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease that presents with aseptic bone inflammation and can be accompanied by multisystemic symptoms. We present the case of a 14-year-old male with a 2-week history of pain located at the tibial metaphysis and fever. X-ray revealed a lytic lesion in the tibial metaphysis. MRI revealed an intramedullary bone lesion with perilesional bone oedema. CT-guided biopsy discounted malignancy and microbiological cultures were negative. The patient's symptoms and fever worsened after the biopsy; therefore antibiotherapy was commenced for a suspected superinfection. A body MRI was performed given the persistence of the fever, which found a second active lesion in the spine that was diagnosed as CRMO and progressed well with anti-inflammatories. CRMO is an entity that is difficult to diagnose. Differential diagnosis is extensive with infectious diseases, tumours and other autoinflammatory diseases. Prompt diagnosis and appropriate treatment are crucial to prevent sequelae.

No evidence of cellular alterations by MilliTesla-level static and 50 Hz magnetic fields on S. cerevisiae.

In an attempt to determine whether magnetic field (MF) exposures might induce cellular alterations, S. cerevisiae yeast cells were exposed to static or sinusoidal 50 Hz homogeneous MF (0.35 mT, 1.4 mT, and 2.45 mT) for 1 h and 72 h. Unsynchronized cells grown exponentially while exposed to MF, containing cells in all stages of the mitotic cell cycle. MF was generated by a pair of Helmholtz coils (40 cm in diameter, coaxial, separated by 20 cm). Survival, cell cycle distribution, colony forming ability, and mutation frequency were assayed. No differences in the above-mentioned parameters were observed in MF exposed samples in relation to unexposed controls, suggesting that homogeneous MF at these intensities do not produce appreciable cellular alterations in this organism under typical in vitro growth conditions.

No effect of 50 Hz 2.45 mT magnetic field on the potency of cisplatin, mitomycin C, and methotrexate in S. cerevisiae.

Drug resistance is an obstacle for chemotherapy success. Because of this, this work aims to improve the cell killing effect of antineoplastic drugs by magnetic field (MF) co-exposure. S. cerevisiae cells were exposed to 2.45 mT, sinusoidal 50 Hz MF, during 48 h, and the drugs cisplatin (cisPt), mitomycin C (MMC), or methotrexate (MTX); 100 and 1,000 microg/ml. Survival was assayed by the drop test. The results showed that MF exposures do not induce alterations in the potency of cisPt, MMC, and MTX on these cells in relation to untreated controls. In addition, a strong correlation between temperature and potency of cisPt was found, which contribute to the establishment of the importance of an exhaustive control of temperature in experiments carried out with temperature sensitive antineoplastic agents in co-exposure with MF; avoiding differences between MF-exposed samples and unexposed controls and contributing to the performance of experiments under well-defined and controlled conditions.

Iron(III) chloride hexahydrate does not enhance methotrexate cytotoxicity on Saccharomyces cerevisiae.

Methotrexate is a potent inhibitor of dihydropholate reductase that has been used as effective antineoplastic treatment due to its capacity to inhibit cell growth. In a previous work published in Bioelectrochemistry 2003;60:81-86, we reported a statistically significant increment of 40.1 and 29.4% in methotrexate potency when MCF-7 breast cancer cells were exposed simultaneously to iron(III) chloride hexahydrate (FeCl(3).6H(2)O) and methotrexate. The aim of this study was to investigate whether iron(III) could produce, on a Saccharomyces cerevisiae wild-type strain, alterations on methotrexate potency by the drop test survival assay and proliferation studies measured after 24 and 96 h of exposure. The data presented in the current report indicate that FeCl(3).6H(2)O (1, 10, 100 and 500 microg/ml) does not induce modulation of the action of methotrexate (10, 100 and 500 microg/ml) in S. cerevisiae yeast cells when they are exposed simultaneously for 24 and 96 h.

Static and 50 Hz magnetic fields of 0.35 and 2.45 mT have no effect on the growth of Saccharomyces cerevisiae.

The present work reports the growth effects induced by static and sinusoidal 50 Hz magnetic fields (MF) on the haploid yeast strain Saccharomyces cerevisiae WS8105-1C. Magnetic fields were generated by a pair of Helmholtz coils (40 cm in diameter) with 154 turns of copper wire in each and separated 20 cm. The experiments were performed at 0.35 and 2.45 mT, and yeasts were exposed to MF during 24 and 72 h in the homogeneous field area. Growth was monitored by measuring the optical density at 600 nm. The data presented in the current report indicate that static and sinusoidal 50 Hz MF (0.35 and 2.45 mT) do not induce alterations in the growth of S. cerevisiae.

Methotrexate cytotoxicity on MCF-7 breast cancer cells is not altered by exposure to 25 Hz, 1.5 mT magnetic field and iron (III) chloride hexahydrate.

The action of electromagnetic fields (EMF) on different pathways related to cell physiology, proliferation, toxicity of chemicals, gene expression, etc., are currently being investigated although the results are still not conclusive and even conflicting. In laboratory and animal studies, EMF has been found to produce a great variety of effects such as: increase in ornithine decarboxylase activity in breast, increase in beta-galactosidase gene expression and oncogene transcription after exposure to 50/60 Hz. Animal studies have shown that the use of EMF can enhance drug delivery across biological barriers (rat abdominal skin), using benzoic acid as the drug candidate. It has been reported by different authors that pulsed EMF (PEMF) can produce alterations in antineoplastic drugs potency. In the present study, we investigated the effects of PEMF on methotrexate cytotoxicity in MCF-7 breast cancer cells and the effects with simultaneous exposure to FeCl3. The data presented in the current report indicate that PEMF (25 Hz, 1.5 mT) do not induce modulation of the action of methotrexate (with and without iron-III) in MCF-7 cells when they are exposed to PEMF for 2 h/day during 3 days.

[P-glycoprotein, a membrane pump that represents a barrier to chemotherapy in cancer patients]. / La glicoproteína-P una bomba de membrana que representa una barrera a la quimioterapia de los pacientes con cáncer.

Multidrug resistance (MDR) in oncology is considered to be the main cause of chemotherapy failure in the treatment of patients with cancer. The resistance mechanism consists in decrease intracellular drug accumulation by P-glycoprotein (Gp-P) overexpression. This protein acts as a drug-extracting pump that needs energy in the process. The efflux takes place by mean of a pore in the cell membrane that consist in twelve segments. The activity of this pump is regulated by protein kinase C and shows homology with other transport systems. The analysis of the presence of Gp-P and the characterization of MDR phenotype in biopsy material could be important in the overcome of the resistance to cancer chemotherapy.

Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line.

The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1(cch). The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P < 0.01), exhibiting 6.1% of survival at 47.5 microg/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 microg/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P < 0.001). Cisplatin showed a significant reduction in the % of survival (44.2-39.1%, P < 0.05) at 25 Hz and 47.5 microg/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1(cch), with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation.

La glicoproteína-P una bomba de membrana que representa una barrera a la quimioterapia de los pacientes con cáncer / P-glycoprotein, a membrane pump that represents a barrier to chemotherapy in cancer patients

La resistencia oncológica a múltiples agentes antineoplásicos o MDR se considera una de las mayores causas de fallo clínico en el tratamiento quimioterápico de pacientes con cáncer. El mecanismo de resistencia consiste en una disminución en la acumulación intracelular de droga por sobreexpresión de la glicoproteína-P (Gp-P). Esta proteína actúa como una bomba extrusora de drogas, dependiente de energía. El eflujo se realiza a través de un canal que forma en la membrana plasmática, constituido por doce segmentos transmembranales. La actividad de esta bomba extrusora esta regulada por la proteína quinasa C y presenta homología con otros sistemas de transporte. El análisis de la presencia de Gp-P y la caracterización del fenotipo MDR en biopsias tumorales podría tener gran importancia en el abordamiento del problema clínico que representa la resistencia tumoral a la quimioterapia (AU)

Multidrug resistance (MDR) in oncology is considered to be the main cause of chemotherapy failure in the treatment of patients with cancer. The resistance mechanism consists in decrease intracellular drug accumulation by P-glycoprotein (Gp-P) overexpression. This protein acts as a drug-extracting pump that needs energy in the process. The efflux takes place by mean of a pore in the cell membrane that consist in twelve segments. The activity of this pump is regulated by protein kinase C and shows homology with other transport systems. The analysis of the presence of Gp-P and the characterization of MDR phenotype in biopsy material could be important in the overcome of the resistance to cancer chemotherapy (AU)

Riesgo laboral y residencial por exposición a campos electromagnéticos / Labour and residential risk due to electromagnetic fields exposition

En los últimos años hemos asistido a un incremento, por su número y diversidad, de las fuentes de campos eléctricos y magnéticos (CEM) utilizadas con fines individuales, industriales y comerciales. Al mismo tiempo, diversos estudios científicos han sugerido que la exposición a CEM emitidos por esos aparatos podría tener efectos perjudiciales para la salud. El presente trabajo realiza una revisión acerca de la relación o influencia de los CEM (centrándonos en los campos de frecuencia industrial) sobre el sistema reproductor, alteraciones psicológicas y desarrollo de cáncer. Hasta la actualidad, la comunidad científica no ha establecido una relación causal entre exposición residencial y laboral a campos de frecuencia industrial y riesgo para la salud humana (AU)

25 Hz electromagnetic field exposure has no effect on cell cycle distribution and apoptosis in U-937 and HCA-2/1cch cells.

It is reported that exposure to 50 Hz extremely low-frequency electromagnetic field (ELF-EMF) can produce apoptosis and small variations in cell cycle distribution on different cell lines. In order to study the effect of ELF-EMF on tumoral cells in vitro, two cell lines (U-937, from a histiocytic lymphoma, and HCA-2/1cch, from a human colon adenocarcinoma) were exposed to 25 Hz, 1.5 mT, for 2 h and 45 min. Cell cycle distribution, apoptosis (spontaneous and dexamethasone-induced) and cell growth were evaluated. Neither significant alteration in cell cycle phases nor induction of apoptosis was observed. Nevertheless, the relative cell number was found to decrease to 55.84+/-7.35% (p <0.05, Student's t-test) for HCA-2/1cch cells after exposure to EMF in the presence of dexamethasone. The presence of dexamethasone during the EMF exposure could probably produce a decrease in the cell growth of this cell line.

Multidrug resistance increment in a human colon carcinoma cell line by colchicine.

The most important mechanism in drug resistance is the multidrug resistance (MDR) phenomenon. It is possible to select MDR cells by in vitro exposure to cytotoxic agents. The resistance is due to the hyperexpression of the P-glycoprotein (P-Gp) that take drugs out from the cells. In this study, a colchicine resistant subline (HCA-2/1cch) was selected from a human colon adenocarcinoma after a short period of drug exposure, as an in vitro model of drug resistance selection. These cells showed cross-resistance to other drugs, which were not present in the medium during selection. The relative resistance was 3.32 for colchicine, 3.15 for vinblastine, 2.62 for vincristine and 5.22 for mitomycin C. P-glycoprotein levels were assayed by flow cytometry. It was found that a significant increase of 2.35 and 1.59 had occurred in the peak and mean channel of fluorescence, respectively, indicating an increment of P-glycoprotein expression in relation to the parental line. Moreover, verapamil (10 microg/ml) produced a partial reversion of multidrug resistance. The sensitisation rates were 7.41 for colchicine, 1.25 for vinblastine, 2.36 for vincristine and 1.17 for mitomycin C. The data obtained suggest that colchicine exposure period (10 weeks) and dose (0.5 microg/ml) assayed were sufficient to produce an increment in multidrug resistance. This resistance could be due to higher level of P-Gp expression.

Detection of microcalcifications by means of multiscale methods and statistical techniques.

The detection of clustered microcalcifications can help the radiologist to detect early breast cancer. Microcalcifications exhibit some important characteristics, such as small size and high luminosity. Use of a computer-aided diagnosis (CAD) method can prevent them being overlooked. In this report, a multiresolution analysis is performed based on a multilevel wavelet transformation. Decomposition produces sub-band images which become visible only as details of the different scales. Thereafter, all the images will be combined in a final image, in order to obtain an image that contains all the interest details at the scale where microcalcifications tend to appear. Once the image, called detail image, is obtained, it is necessary to determine which details correspond with microcalcifications. Statistical analysis of the histogram permits classification of the zones likely to contain microcalcifications. Applying this statistical techniques over the whole image and representing the results in a two-dimensional map, clustered microcalcification regions are clearly distinguishable.

Organ doses, detriment and genetic risk from interventional vascular procedures in Málaga (Spain).

Nowadays, the radiological risk from simple X-ray procedures is well known. The purpose of this work has been to estimate the population risk from digital angiographic and interventional procedures and to compare it with the one from simple procedures in the same population. The population risk has been estimated according to the following quantities: genetically significant dose, somatic significant dose, collective effective dose, annual per caput effective dose and detriment. These have been estimated from dose area product and organ dose. Organ dose values were estimated with the Eff-Dose software. A population of 605410 people were included in the study. In 1996, 1312 patients were to digital interventional vascular procedures in Malaga, and 159 of them were selected in this research project to obtain the dose area product and organ dose. The results obtained for the quantities evaluated are: genetically significant dose, 4.1 microGy; somatic significant dose, 0.9 mSv; collective effective dose, 11.65 person-Sv: annual per caput effective dose, 0.02 mSv and detriment, 0.65 radiogenic cancers per year. These procedures supply a high radiation dose, so they should have a greater contribution to population dose and risk than simple examinations. However, our results indicate just the opposite.

P-glycoprotein, glutathione and glutathione S-transferase increase in a colon carcinoma cell line by colchicine.

The acquisition of resistance to anticancer agents used in chemotherapy is the main cause of treatment failure in malignant disorders, provoking tumours to become resistant during treatment, although they initially respond to it. The main multidrug resistance (MDR) mechanism in tumour cells is the expression of P-gly-coprotein (P-gly), that acts as an ATP-dependent active efflux pump of chemotherapeutic agents. Furthermore, an increased detoxification of compounds mediated by high levels of glutathione (GSH) and glutathione S-transferase (GST), has been found in resistant cells. We developed a study aiming to evaluate the evolution of the main drug resistance markers in tumour cells: P-gly, GSH and GST, during the acquisition of resistance to colchicine, for the purpose of studying the adaptation process and its contribution to the MDR phenomenon. A human colon adenocarcinoma cell line was exposed to colchicine during 82 days, being P-gly, GSH levels and GST activity evaluated by flow cytometry, spectrofluorimetry and spectrophotometry, during exposure time. P-gly and GSH levels increased gradually during the exposure to colchicine, reaching 2.35 and 3.21 fold each. On day 82, GST activity increased 1.84 fold at the end of the exposure period. Moreover, an increment in drug cross-resistance was obtained that ranges from 2.62 to 5.22 fold for colchicine, vinblastine, vincristine and mitomycin C. The increments obtained in P-gly, GSH and GST could probably contribute to the MDR phenomenon in this human colon adenocarcinoma cell line.

Growth modification of human colon adenocarcinoma cells exposed to a low-frequency electromagnetic field.

The influence of variable low-intensity, low-frequency electromagnetic fields on culture cells is investigated. Human colon adenocarcinoma cells were exposed to a rectangular and variable magnetic field (1 and 25 Hz; 1.5 mT peak). Cultures were exposed to a dose for 15 and 360 minutes, and after 24 hours incubation, cell viability was measured with neutral red stain. The group treated for 15 minutes showed a statistically significant increase in cell growth with 1 Hz (p < 0.002) and 25 Hz (p < 0.003). In contrast, a significant decrease in cell growth was found in those cultures treated with 1 Hz for 360 minutes (p < 0.02). The effects reported could be influenced by the magnetic field frequency and the exposure time.

Patient dose in radiologically guided interventional vascular procedures: conventional versus digital systems.

PURPOSE: To calculate the difference in the patient radiation dose in radiologically guided interventional vascular procedures between conventional and digital systems and to estimate the effective dose and the energy imparted with the digital system. MATERIALS AND METHODS: A total of 318 procedures (in 318 patients) in 15 different examination groups were analyzed. The dose-area product was determined by using a transmission chamber fitted to an x-ray-tube light-beam diaphragm; the effective dose was determined by using software. RESULTS: Urinary and biliary tract procedures showed small differences in the average dose-area product between conventional and digital systems. The dose-area products in the vascular procedures were higher with the digital than with the conventional system. The average effective dose and energy imparted were 0.88 mSv and 129 mJ, respectively, in the subcutaneous placement of a reservoir for analgesic administration and as much as 25.7 mSv and 829 mJ, respectively, in spermatic vein embolization. CONCLUSION: The dose-area product was higher with the digital system than with the conventional system in 13 of the 15 groups. To reduce the patient dose in vascular interventional radiology procedures, the training of personnel and the frequent use of conventional fluoroscopy and low-dose imaging are required.