Pilot scale validation campaign of gel dosimetry for pre-treatment quality assurance in stereotactic radiotherapy.

PURPOSE: Complex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes. MATERIALS AND METHODS: A modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other. RESULTS: A quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in timeframes of ≈ 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively. CONCLUSIONS: Gel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients.

Acute toxicity and bioaccumulation of tributyltin in tissues of Urolophus jamaicensis (yellow stingray).

Tributyltin oxide (TBTO) is the main constituent of tin-based antifouling marine paint used on the hulls of ships to prevent the growth of fouling organisms. TBTO was shown to be hazardous to nontarget organisms. The stingray, Urolophus jamaicensis, may represent the ideal study organism for the adverse effects of TBTO to elasmobranches. This study investigated the toxicity and accumulation of tin in the gill tissue of the stingray U. jamaicensis after acute exposure to TBTO. This work demonstrates the alterations in the morphological architecture of the gill using electron and light microscopy, the induction of stress proteins, and peroxidative damage in response to tributyltin (TBT) exposure. A captured population of U. jamaicencis was housed in isolated, static tank systems. After a minimum 30-d acclimation period, the animals were exposed to one of 5 experimental doses of TBTO (4 microg/L, 2 microg/L, 1 microg/L, 0.5 microg/L, or 0.05 microg/L). A sixth group served as a control population. At 3h following treatment, animals were sacrificed and gill tissue was extracted, processed, and stored for analysis. Results indicate that U. jamaicensis is hypersensitive to TBT exposure. The elasmobranch gill showed a distorted, swollen epithelium with exfoliation following acute exposure to as little as 0.05 microg/L TBTO for 3 h. Graphite furnace atomic absorption spectroscopy (GFAAS) results indicate that tissues of treated animals contained a significantly increased tin concentration as compared to controls. Western blot analysis demonstrated the induction of the stress proteins Hsp 70 and HO1. 4-Hydroxynonenol (4HNE) adduct formation determined by Western blot analysis provides further evidence that observed membrane degradation is a result of lipid peroxidation.

Age-dependent changes in myocardial ultrastructure during anoxia.

We have examined left ventricular function and structure of male C57BL/6J mice at 3 and 24 months of age prior to, during and 5 min following a 3-min exposure to anoxia. During anoxia young hearts were characterized structurally by the presence of clear, abnormal non-membrane bound lipid-like vacuoles closely associated to mitochondria. Myelin figures were also present, and mitochondrial ATPase was considerably reduced. By the end of the 3-min period of anoxia hearts in young mice had irreversibly failed, and upon reoxygenation mitochondria underwent further degradation, including loss of internal structure. While continuing to function throughout anoxia, hearts of old mice had normal appearing myofibrillar, mitochondrial and sarcoplasmic structures. During reoxygenation occasional myelin figures were seen in senescent myocardium, although mitochondrial ATPase was not affected. At all times of anoxia and recovery pathological changes were more extensive in young mice than in their aged counterparts.

Normal and altered cytoarchitecture of the inner ear.

Scanning electron microscope gave new insights into real morphology of the inner ear and has enhanced basic research. In fact, during the last twenty years, the cellular system that composes the organ of Corti and the vestibular apparatus has been clearly described by many authors. We now have a better understanding of each cell type and that they have a physiological functioning as ear and vestibular system. In addition, new insights into the damage caused by many drugs, such as aminoglucosides, can be investigated by studying the morphological changes and the reparative process following the injury. Animals such as guinea pigs can be used as ideal models to investigate the alterations in the sensory epithelium of the cochlear and vestibular receptors following ototoxic poisoning.

Influence of age, gender, height and education on vibration sense. A study by tuning fork in 192 normal subjects.

We measured perception time of the vibratory stimulus from a 128 cps tuning fork in 96 male and 96 female normal subjects equally subdivided into 8 age decades. The following sites were examined: clavicula, olecranon, styloid apophysis of ulna and radius, anterosuperior spina of ilium, rotula (patella), internal and external malleolus. Reproducibility between different examiners and between tests by the same examiner on different days was good. There was a marked regional variation with longer perception times at the distal regions of upper limbs. A non linear age-related decrease in vibration sense was found in all regions. Males had longer perception times at clavicula, females at distal limbs; the latter finding might be explained by shorter stature in females. Perception times at distal limbs were longer in subjects with higher education levels. The study provides normative data for vibration sense in different regions and defines the effects on it of age, gender, height and education.

Cocarcinogenic and tumor-promoting capabilities of anthralin.

Numerous chemicals to which humans are exposed either therapeutically or as a result of living in an industrial environment constitute a potential threat as carcinogens, mutagens, and/or tumor promoters and cocarcinogens. Anthralin, and antipsoriatic agent, acts as a tumor promoter for Balb/c-3T3 mouse embryo cell cultures that were previously exposed to a low dose of either benzo-a-pyrene (BaP), an indirect-acting carcinogen needing metabolic conversion for its carcinogenic action, or beta-propiolactone (BPL), a direct-acting carcinogen which needs no metabolic conversion. As a cocarcinogen, i.e., when exposure of cells to anthralin was simultaneous with exposure to the carcinogen, anthralin enhanced neoplastic transformation only when the carcinogen was BaP. Several explanations are explored. The possibility that cocarcinogens and tumor promotion occur by separate mechanisms is suggested.

The relationship between stress protein induction and the oxidative defense system in the rat hippocampus following kainic acid administration.

The time and dose-dependent effects of kainic acid (KA) induced excitotoxicity on the oxidative defense system and the relationship to the induction of stress proteins were investigated in the rat hippocampus. Male Long-Evans rats were injected subcutaneously with 5.0, 7.5, or 10 mg KA/kg. Rats were sacrificed and the hippocampus removed and processed for biochemical and electrophoretic analysis. The activity of glutathione peroxidase (GPx) increased significantly at the 5 mg KA/kg dose, while malondialdehyde (MDA) levels significantly increased at 7.5 mg KA/kg when measured at 24 h. A dose of 10 mg KA/kg depleted significantly hippocampal glutathione (GSH) levels at 8, 16 and 24 h post-treatment while GPx activity was increased significantly at 2, 4, 8 and 16 hr post-treatment. The 10 mg KA/kg increased significantly hippocampal MDA levels at 2 h post-treatment and decreased significantly thereafter. The induction of stress proteins increased in a dose and time dependent manner. The expression of Hp72 and Hsp32 increased significantly at 16 h with a maximum induction observed at 24 h post-treatment. The data suggests that KA toxicity is mediated through the formation of reactive oxygen species resulting in alterations in the oxidative defense system. The expression of stress proteins following KA administration may reflect a concomitant but alternate response to excitotoxic events.

The effects of disulfiram on the hippocampus and cerebellum of the rat brain: a study on oxidative stress.

The purpose of this investigation was to study the relationship between disulfiram (DS) toxicity, lipid peroxidation, and copper in order to further elucidate the mechanisms of DS toxicity. Male Sprague-Dawley rats were dosed with either 375, 750 or 1500 mg/kg disulfiram via oral intubation for 1, 3 and 6 weeks. In the hippocampus and cerebellum, the increased accumulation of copper, increased production of malondialdehyde (MDA), increased activity of glutathione peroxidase along with alterations in glutathione and glutathione disulfide concentrations was indicative of oxidative stress. The production of MDA was directly related to the level of copper in both areas of the brain indicating that excess copper may be the primary cause of DS neurotoxicity.

The effects of ebselen on cisplatin and diethyldithiocarbamate (DDC) cytotoxicity in rat hippocampal astrocytes.

Ebselen is a seleno-organic compound with documented cytoprotective properties. Little work has been done, however, demonstrating ebselen's cytoprotective properties in neural cell lines. In order to examine the effects of this compound and its mechanism of action, astrocytes were exposed to two known neurotoxicants, cisplatin and diethyldithiocarbamate (DDC). Cells were pretreated with 30 microM ebselen and subsequently treated with either 150 microM DDC for 1 h or 250 and 500 microM cisplatin for 24 h. Results indicate significant increases in viability in cells pretreated with ebselen and exposed to cisplatin. Ebselen pretreatment did not significantly increase viability in cells exposed to DDC. Light and scanning electron microscopy studies confirm the viability studies. Gross morphological damage was seen in cells treated with cisplatin, however, cells pretreated with ebselen and then exposed to cisplatin, appeared similar to controls. No differences were noted in cells pretreated with ebselen and then exposed to DDC or cells treated with DDC alone. In order to examine the mechanism of protection of this compound, glutathione status was examined. Results show that ebselen does not significantly increase reduced or oxidized glutathione (GSH, GSSG). All cell groups treated with cisplatin showed an increase in GSH levels. Ebselen showed protection in glutathione depleted cells at the 250 microM cisplatin dose. DDC treatment showed no significant increase in either reduced or oxidized glutathione. We conclude that ebselen significantly protects against cisplatin, but not DDC toxicity. We further conclude that this protection is not related to changes in glutathione status in the rat hippocampal cell line as has been reported in other cell types.

A scanning electron-microscopic study of the effects of methylmercury on the neuronal cytoskeleton.

Cultured mouse neuroblastoma cells, Neuro-2a (c1300), were exposed to 2.5 and 5.0 microM methylmercury (MeHg) with or without the concomitant administration of 10 mM glutathione for 24 h. Treated cells viewed by scanning electron microscopy (SEM) appeared sponge-like and were surrounded by fragments of cytoplasmic processes. SEM cytoskeletal preparations of treated cells showed a collapsed matrix containing globular bodies. Microtubules were not seen in treated cells, but intermediate and microfilaments were observed. SDS-PAGE analysis of cytoskeletal extracts revealed bands ranging in size from 90 to 27 kDa in all treatment groups except in the 5.0 microM-MeHg-treated group. This group showed a single band co-migrating with actin. Cells exposed to glutathione alone or concomitantly with MeHg appeared similar to control cells under all experimental conditions. These observations suggest that MeHg may predominantly affect microtubules to form a condensation product.

The induction of amyloid precursor protein and alpha-synuclein in rat hippocampal astrocytes by diethyldithiocarbamate and copper with or without glutathione.

alpha-Synuclein is the major component of Lewy bodies. Its aggregation can be accelerated by copper, iron, or beta-amyloid (Abeta) and has been thought to provide a nucleation center during the formation of amyloid plaques. The main structural component of amyloid plaque is Abeta, which is derived from a larger protein, amyloid precursor protein (APP). Xenobiotics have been implicated in the etiology of the neurodegenerative disease. Mechanisms of diethyldithiocarbamate (DDC) neurotoxicity involve copper chelation and interactions with SH groups resulting in oxidative stress. In this study, rat hippocampal astrocytes were treated with DDC (75 microM), CuCl(2) (0.2 microM), or DDC (75 microM) plus CuCl(2) (0.2 microM) for 1h. Cells were allowed to recover with or without 10 mM GSH. Results showed an increase of APP and alpha-synuclein production occurring in a time-dependent manner. At 4 h post-treatment, cells contained small positively stained material deposited throughout the cytosol for APP and by 8 h post-treatment increases were seen in both APP and alpha-synuclein. Immunoblots supported immunocytochemical results. Glutathione (GSH) decreased the accumulation of these proteins at 8 h post-treatment.

The protective effects of zinc on diethyldithiocarbamate cytotoxicity on rat astrocytes in vitro.

The neurotoxicity of diethyldithiocarbamate (DDC) has been documented for decades. In particular, cytotoxic effects against rat astrocytes have been noted by a decrease in cell viability and numerous ultrastructural defects. This study indicates an in vitro protective effect by zinc administration prior to DDC insult. Cell groups pre-treated with 50 microM ZnCl2 prior to the addition of 35 microg/ml DDC showed significant protection when compared with cells treated with DDC alone. Zinc reduced the DDC-mediated toxicity to astrocytes as indicated by an increase in cell adherence and viability. Morphological evaluation indicated a significant decrease in ultrastructural alterations. Metallothionein (MT), a metal regulatory protein known to be induced by zinc was studied to determine its role in this mechanism of protection. Immunocytochemistry and immunoblots showed increased presence of MT in all zinc treated groups. This suggests a protective effect against DDC cytotoxicity on rat astrocytes in vitro may be associated with an increase in MT concentration.

The protective effects of glutathione against methylmercury cytotoxicity.

Mouse neuroblastoma cells exposed to 2.5 and 5.0 microM methylmercury for 24 h appeared rounded with the loss of processes. Immunohistochemical staining directed against beta-tubulin revealed severe alterations in microtubular architecture. Non-membrane-bound condensation product was visualized ultrastructurally in the treated cells and appeared similar to what was seen histochemically. Reduced and oxidized glutathione levels suggest that methylmercury may manifest its deleterious effects via oxidation of tubulin sulfhydryls, and by alterations due to peroxidative injury. Cells exposed to methylmercury showed a decrease in glutathione peroxidase activity. Simultaneous administration of 10 mM glutathione with 2.5 and 5.0 microM methylmercury dramatically prevented cell injury.

A double-blind cross-over trial of amantadine hydrochloride in Friedreich's ataxia.

We performed a double-blind cross-over study with amantadine hydrochloride in 12 patients with Friedreich's disease and 2 with autosomal dominant cerebellar ataxia. Patients were randomly assigned to a placebo-amantadine or amantadine-placebo sequence. The interval between the treatments was two weeks. Patients were graded according to a functional ataxia scoring scale and videotaped in basal conditions and 90 min after a single oral dose of 100 mg amantadine or placebo. Three evaluators independently scored the videotapes. Statistical analysis showed no significant effect of amantadine in Friedreich's disease.

Cytotoxic changes induced in rat-liver cells by short-term exposure to acetylethyltetramethyltetralin.

The livers of Sprague-Dawley female rats examined by electron microscopy after oral administration of one, two or three doses of acetylethyltetramethyltetralin (AETT) demonstrated that this compound is a hepatotoxin which induces classic degenerative changes as well as effects on the nucleolus. This suggests that AETT not only affects cytoplasmic homeostasis but may also have an effect upon protein synthesis.

An investigation of the toxic effects of combustion products--analysis of smoke components.

A comprehensive experimental design was developed to study the effects of thermal degradation products formed by the combustion of building materials on the behavior of rats. Three materials were studied. They were Douglas fir, wool, and polyvinyl chloride. Each material was tested under both flaming and nonflaming modes of combustion. The smoke and gases produced by each material were analyzed by specific gas detector tubes, gas chromatography/mass spectrometry, and infrared spectroscopy. Products measured during combustion included oxygen, carbon monoxide, carbon dioxide, hydrogen cyanide, and hydrocarbons. Part of a much larger study, this paper will deal with the analytical aspects of the experimental design.

[Erosive gastritis associated with cryptosporidium in 2 patients with AIDS]. / Gastritis erosiva asociada a criptosporidium en dos pacientes con SIDA.

Occurrence of vomiting and diarrhea in patients with acquired immunodeficiency syndrome was most frequently attributed to enteropathogens organism that invade the gastrointestinal tract because of the immunologic unbalance of the host... Among several causes the cryptosporidium has been detected quite often and its predominant localization was the gastrointestinal tract, although other extraintestinal sites has also been reported. In both cases, erosive congestive gastritis was found, while histological examination showed cryptosporidium in gastric biopsy specimens.

[Sialolithiasis of the submandibular gland: therapeutic options and technical notes]. / Scialolitiasi della sottomandibolare: opzioni terapeutiche e note di tecnica.

The Authors report their experience in the surgical treatment of submandibular sialolithiasis, particularly as far as simple sialolithotomy of Wharton's duct and submandibular gland resection are concerned. Care must be taken to minimize the risk of nerve damage (marginal mandibular branch of the facial nerve; lingual nerve; hypoglossal nerve).

El ateneo como estrategia de educación médica continua. Del mito griego al hospital de hoy. / Athenaeum as a strategy of continuous medical education. From the greek myth to the hospital today

La educación médica continua se define como el conjunto de acciones y recursos dirigidos a cambiar las conductas de los profesionales para mejorar los resultados de su actividad asistencial diaria frente a los pacientes. O bien, toda acción que realiza un médico para seguir aprendiendo y permanecer actualizado, una vez finalizada su formación universitaria. Las estrategias para conseguir tal fin, son la realización de cursos, la ra congresos y/o jornadas, las actividades hospitalarias (recorridas de sala, supervisión y ateneos), la lectura y discusión de artículos biomédicos en internet o en publicaciones en papel en el denominado ateneo bibliográfico, el intercambio con colegas, la consulta con otros profesionales y los cursos a distancia. En el presente artículo, se plantea el ejercicio del ateneo como una de las principales fuentes de aprendizaje al proponer una verdadera reflexión sobre la práctica profesional (AU)

Continuing medical education is defined as the set of actions and resources aimed at changing the behavior of professionals to improve the results of their daily care activity in front of patients. Or, any action that a doctor performs to continue learning and remain updated, once his university education is completed. The strategies to achieve this goal are the completion of courses, the attendance at conferences and/or conferences, hospital activities (visits to the ward, supervision and athenaeums), the reading and disicussion of biomedical articles on the internet or in publications on paper. The so-called bibliographic athenacum, the exchange with colleagues, the consultations with other professionals and the distance courses. In the present article, the exercise of the athenaemum is considered as one of the main sources of learning by proposing a true reflection on professional practice (AU)

Trombosis biauricular masiva fatal en un paciente con sida y criptococosis meníngea / FATAL MASSIVE ATRIAL THROMBOSIS IN A PATIENT WITH AIDS AND MENINGEAL CRYTOCOCCOSIS

La trombosis auricular masiva impide el pasaje de la sangre a través del orificio mitral Un paciente de 39 años de edad, HIV positivo, con diagnóstico previo de criptococosis meníngea cumplía tratamiento antifúngico con fluconazol por vía oral, consulta por mialgias y dolor cervical. Fallece repentinamente 24 horas después de su internación. La necropsia determinó la presencia de una trombosis biauricular masiva. La criptococosis meníngea es una infección oportunista que se presenta en pacientes HIV positivos con inmunodeficiencia avanzada. Clínicamente se manifiesta por un síndrome meníngeo, por lo general incompleto, o sólo con persistencia de fiebre y cefalea, sin signos meníngeos. La letalidad de la criptococosis meníngea es elevada. La causa del fallecimiento obedece a una enfermedad no relacionada con el sida

Massive atrial thrombosis prevents passage of blood through the mitral orifice. A 39-year-old HIV-positive patient with previous diagnosis of meningeal cryptococcosis and receiving antifungal treatment with oral fluconazole, consults for myalgias and neck pain and dies suddenly 24 hours after admission. Necropsy determined the presence of massive biauricular thrombosis. Meningeal cryptococcosis is an opportunistic infection that occurs in HIV-positive patients with severe immunodeficiency. Clinically it is manifested by an incomplete meningeal syndrome, or only with persistence of fever and headache, without meningeal signs. The lethality of meningeal cryptococcosis is high. The cause of the death is due to a disease not related to AIDS