Versatile theranostics agents designed by coating ferrite nanoparticles with biocompatible polymers.

Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 ± 5 nm in diameter) and to vary the aggregation state in order to study their effect on relaxometric and heating properties. Two different coating strategies have been deeply developed; one based on the formation of an amide bond between citric acid coated nanoparticles (NPs) and amine groups present on the polymer surface and the other based on the NP encapsulation. Relaxometric properties revealed that proton relaxation rates strongly depend on the coating layer hydrophilicity and the aggregation state of the particles due to the presence of magnetic interactions. Thus, while PEG coating reduces particle aggregation by increasing inter-particle spacing leading to reduction of both T1 and T2 relaxation, dextran and chitosan lead to an increase mainly in T2 values due to the aggregation of particles in bigger clusters where they are in close contact. Dextran and chitosan coated NPs have also shown a remarkable heating effect during the application of an alternating magnetic field. They have proved to be potential candidates as theranostic agents for cancer diagnosis and treatment. Finally, cytotoxicity of PEG conjugated NPs, which seem to be ideal for intravenous administration because of their small hydrodynamic size, was investigated resulting in high cell viability even at 0.2 mg Fe ml(-1) after 24 h of incubation. This suspension can be used as drug/biomolecule carrier for in vivo applications.

Short-chain PEG molecules strongly bound to magnetic nanoparticle for MRI long circulating agents.

This study developed an approach for the synthesis of magnetic nanoparticles coated with three different polyethylene glycol (PEG)-derived molecules. The influence of the coating on different properties of the nanoparticles was studied. Magnetite nanoparticles (7 and 12 nm in diameter) were obtained via thermal decomposition of a coordination complex as an iron precursor to ensure nanoparticle homogeneity in size and shape. Particles were first coated with meso-2,3-dimercaptosuccinic acid by a ligand exchange process to remove oleic acid, followed by modification with three distinct short-chain PEG polymers, which were covalently bound to the nanoparticle surface via 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride activation of the carboxylic acids. In all cases, colloidal suspensions had hydrodynamic sizes <100 nm and low surface charge, demonstrating the effect of PEG coating on the aggregation properties and steric stabilization of the magnetic nanoparticles. The internalization and biocompatibility of these materials in the HeLa human cervical carcinoma cell line were tested. Cells preincubated with PEG-coated iron nanoparticles were visualized outside the cells, and their biocompatibility at high Fe concentrations was demonstrated using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Finally, relaxivity parameters (r1 and r2) were used to evaluate the efficiency of suspensions as magnetic resonance imaging contrast agents; the r2 value was similar to that for Resovist and up to four times higher than that for Sinerem, probably due to the larger nanoparticle size. The time of residence in blood of the nanoparticles measured from the relaxivity values, and the Fe content in blood was doubled for rats and rabbits due to the PEG on the nanoparticle surface. The results suggest that this PEGylation strategy for large magnetic nanoparticles (>10nm) holds promise for biomedical applications.

Magnetic resonance methods and applications in pharmaceutical research.

This review presents an overview of some recent magnetic resonance (MR) techniques for pharmaceutical research. MR is noninvasive, and does not expose subjects to ionizing radiation. Some methods that have been used in pharmaceutical research MR include magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) methods, among them, diffusion-weighted MRI, perfusion-weighted MRI, functional MRI, molecular imaging and contrast-enhance MRI. Some applications of MR in pharmaceutical research include MR in metabonomics, in vivo MRS, studies in cerebral ischemia and infarction, degenerative joint diseases, oncology, cardiovascular disorders, respiratory diseases and skin diseases. Some of these techniques, such as cardiac and joint imaging, or brain fMRI are standard, and are providing relevant data routinely. Skin MR and hyperpolarized gas lung MRI are still experimental. In conclusion, considering the importance of finding and characterizing biomarkers for improved drug evaluation, it can be expected that the use of MR techniques in pharmaceutical research is going to increase in the near future.

[Bone scintigraphy findings in patients with recently diagnosed adenocarcinoma of the prostate: relationship with prostate specific antigen levels]. / Hallazgos de la gammagrafía ósea en pacientes con adenocarcinoma de próstata recién diagnosticado: relación con los niveles de antígeno específico prostático.

BACKGROUND AND OBJECTIVES: Although it has been suggested that bone scintigraphy (BS) may not be necessary in patients with prostate adenocarcinoma (PA) and normal prostate specific antigen (PSA) plasma levels, controversy still remains. The objective of the study was to evaluate the existing relationship between PSA plasma levels and BS findings in patients with a recently diagnosed PA in order to assess whether BS may be omitted on the basis of the PSA levels in these patients. METHODS: The 475 patients (70+/-7 years old) consecutively diagnosed of PA between 1994 and 1998 in our institution made up the study population. PSA plasmatic levels were determined and BS was performed (body planar study after 99mTc-methyl diphosphonate 900 MBq administration) in all the patients. RESULTS: In 362 patients (76.2%), BS was negative, in 108 (22.7%) positive and undetermined in the remaining 5 patients (1.1%). The mean PSA level in the whole study population was 74+/-267 ng/ml (range 0.4-4.200) and was higher in patients with positive GO (218+/-512 vs 31+/-89, p<0,0001). As PSA increased, the rate of patients with positive BS was significantly higher, this being 0%, 16.4%, 9.7%, 14.0%, 31.0% and 48.3% in patients with PSA 4, 4.1-10; 10.1-20; 20.1-30; 30.1-40, and >40 ng/ml, respectively (p<0.0001). In patients with positive BS, the PSA levels were 20 and 10 ng/ml in 30.6% and 18.6% of the patients, respectively. CONCLUSION: According to our experience, there is a significant association between PSA plasma levels and the BS results in patients with recently diagnosed PA. However, a significant proportion of patients with bone metastasis have normal PSA levels, and therefore BS should be performed in all patients with recently diagnosed PA regardless of the PSA levels.

Hallazgos de la gammagrafía ósea en pacientes con adenocarcinoma de próstata recién diagnosticado: relación con los niveles de antígeno específico prostático / Bone scintigraphy findings in patients with recently diagnosed prostate adenocarcinoma: relationship with the prostate specific antigen levels

Introducción y objetivos: Aunque se ha sugerido que en los pacientes con adenocarcinoma de próstata (AP) la existencia de unos niveles plasmáticos no elevados de antígeno específico prostático (PSA) podría hacer innecesaria la realización de gammagrafía ósea (GO), aún existen controversias al respecto. El objetivo del estudio fue analizar la relación existente entre los niveles de PSA y los hallazgos de la GO en pacientes con diagnóstico de AP, con objeto de evaluar si en nuestra experiencia la indicación de la GO puede ser omitida en función de los niveles de PSA en estos pacientes. Métodos: La población de estudio está compuesta por los 475 pacientes (70ñ7 años de edad) diagnosticados de AP entre 1994 y 1998. A todos los pacientes se les realizó GO (estudio planar de cuerpo completo tras la administración de 900 MBq de 99mTC-metil difosfonatos) y determinación de los niveles plasmáticos de PSA. Resultados: En 362 pacientes la GO fue negativa (76,2 por ciento) en 108 (22,7 por ciento) positiva y dudosa en los restantes cinco pacientes (1,1 por ciento). El nivel de PSA en el total de la población de estudio fue 74ñ267 ng/ml (rango 0,4-4.200). Los pacientes con metástasis óseas tenían unos niveles de PSA más elevados (218ñ512 vs 31ñ89, p40 ng/ml, respectivamente (p<0,0001). El 30,6 por ciento de los pacientes con metástasis tenían unos niveles de PSA 20 ng/ml, y el 18,6 por ciento 10 ng/ml. Conclusión: Según nuestra experiencia, en los pacientes con AP existe una relación entre los niveles plasmáticos de PSA y la probabilidad de presentar metástasis en la GO. Sin embargo, una proporción importante de pacientes con metástasis tienen unos niveles no elevados de PSA, por lo que la GO debería ser realizada con todo paciente con AP, independientemente de los niveles basales de PSA (AU)

Utilidad de los exámenes hematológicos preoperatorios de rutina en cirugía pediátrica / Usefulness of routine pre-operative hematologic analysis in pediatric surgery

El concepto de examen de rutina preoperatorio ha sido cuestionado en los últimos años,tanto a nivel de publicaciones científicas,como en la práctica clínica cotidiana.En el presente estudio retrospectivo se evalúa la utilidad de los siguientes exámenes hematológicos preoperatorios:tiempo parcial de tromboplastina(KPTT)tiempo de protombina y hematocrito,analizándose los parámetros de alteración.Se estudió la ecolución clínica de los pacientes con laboratorio anormal.El bajo porcentale de pacientes con pruebas alteradas y la prácticamente ausencia de complicaciones en este grupo,apoyan hipótesis de dar mayor importancia a la historia clínica y al examen físico para orientar evolución y/o factibilidad de la cirugía

Utilidad de los exámenes hematológicos preoperatorios de rutina en cirugía pediátrica / Usefulness of routine pre-operative hematologic analysis in pediatric surgery

El concepto de examen de rutina preoperatorio ha sido cuestionado en los últimos años,tanto a nivel de publicaciones científicas,como en la práctica clínica cotidiana.En el presente estudio retrospectivo se evalúa la utilidad de los siguientes exámenes hematológicos preoperatorios:tiempo parcial de tromboplastina(KPTT)tiempo de protombina y hematocrito,analizándose los parámetros de alteración.Se estudió la ecolución clínica de los pacientes con laboratorio anormal.El bajo porcentale de pacientes con pruebas alteradas y la prácticamente ausencia de complicaciones en este grupo,apoyan hipótesis de dar mayor importancia a la historia clínica y al examen físico para orientar evolución y/o factibilidad de la cirugía

[Chronic prostatitis: diagnostic and therapeutic considerations]. / Prostatitis crónica: consideraciones diagnósticas y terapéuticas.

Chronic prostatitis, whether of bacterial or non-bacterial origin, is a pathological entity commonly considered difficult to diagnose and to manage. In an attempt to provide a better understanding of the usefulness of Stamey-Meares fractional culture as a diagnostic test, the findings obtained with this technique in 34 patients, 5 with bacterial chronic prostatitis (BCP) and 29 with non-bacterial chronic prostatitis (NBCP) were analyzed. The multiresistance found in the antibiogram in 3 cases and the lack of correlation between these findings and the seminoculture, demonstrate that this technique should continue to be considered indispensable. Also, the value that should be appointed to the existence of organisms with non-proven pathogenicity is discussed. Some bases for a rational management are proposed and the various treatment alternatives, including the use of myorelaxants which in this series allowed to achieve resolution of the symptomatology in 59% cases are analyzed.

[Renal abscess in patients diagnosed with AIDS and disseminated tuberculosis]. / Abscesos renales en pacientes diagnosticados de SIDA con tuberculosis diseminada.

Presentation of two cases of renal abscess formation in patients with stage IV C-1 AIDS and active associated tuberculosis. The microorganism isolated in the first case was S. aureus. Culture of the second cases was artefacted since antibiotic administration had already been started. Also, both patients showed abdominal abscesses, at spleen and liver level in the first case, and prostatic level in the second case, both compatible with Mycobacterium tuberculosis dissemination. Both cases showed a lethal evolution. The role played by the immunodeficiency as a precipitating agent in the extrapulmonary tuberculosis and in the formation of renal abscesses is analyzed.

Aberrant left pulmonary artery with tracheal stenosis without vascular sling.

We report a case of abnormal origin of the left pulmonary artery from the right pulmonary artery, associated with tracheal stenosis but with no vascular sling. This is the first such case, to our knowledge, without vascular sling.

[Ureteral triplicity: trifid ureter with ipsilateral ureterocele and renal dysplasia in an adult with testicular seminoma]. / Triplicidad ureteral: uréter trífido con ureterocele ipsilateral y displasia renal en adulto con seminoma testicular.

Ureteral triplicity is a rare abnormality of which there are less than a hundred cases reported up to date. The possible absence of clinical signs can explain why this malformation passes unnoticed specially when there are blind branches and dysplastic renal segments. The paper presents the case of a 43 year-old male, attending the clinic on a testicle tumour consultation, in which in spite of the previously mentioned circumstances a preoperative diagnosis of trifid ureter with ipsilateral ureterocele and renal dysplasia was reached owing to the use of C.A.T.

Percutaneous nephrostomy in pyonephrosis.

A series of 76 pyonephrotic kidneys in 73 patients were drained by percutaneous nephrostomy (PN) tube and examined to evaluate the contribution of this technique to the treatment of pyonephrosis. In 71 patients, clinical symptoms disappeared 24-48 h after the procedure. Two patients died from sepsis subsequent to anuria and underlying malignancy. Once the acute phase had remitted, interventional procedures were carried out in 39 cases, and constituted the definitive therapy in 36. In 32 cases, elective surgery was the definitive therapy, including the 3 cases not resolved after interventional procedures. Three patients in whom the obstruction cleared spontaneously following PN needed no additional treatment. Major complications included 6 cases of sepsis, all of which resolved satisfactorily with proper medical therapy.

Startle epilepsy: a clinical study.

Twelve patients with perinatal anoxic encephalopathy, 1 with encephalitis, and 1 with Down's syndrome had startle epilepsy. Hemiparesis, startle-induced seizures involving the hemiparetic side, focal electroencephalographic abnormalities, and unilateral lesions evident on computed tomographic scan were found in 6 patients, all of whom responded favorably to carbamazepine. The remaining 8 patients had severe intellectual impairment, bilateral motor deficits, generalized startle-induced seizures, diffuse and lasting electroencephalographic abnormalities, and widespread cerebral lesions evident on computed tomographic scan. Of these, 2 patients with Lennox-Gastaut syndrome responded to clonazepam, 4 others responded to valproic acid, and 2 others, with predominantly focal hemispheric lesions, improved on a regimen of carbamazepine.