Glass-coated ferromagnetic microwire-induced magnetic hyperthermia for in vitro cancer cell treatment.

Limitations in effectiveness and the invasive nature of current cancer treatment options emphasize the need for further clinical advancements. Among other approaches, targeted hyperthermia is as a new strategy aimed at targeting cancerous cells to improve the efficacy of radiotherapy or cytotoxic drugs. However, the testing of magnetic vehicles has mainly focused on the use of nanoparticles. In this work, Fe77B10Si10C3 glass-coated amorphous magnetic microwires were assessed for the first time as magnetic vehicles with high potential for the localized heating of osteosarcoma cells by means of an AC magnetic field. The results from the in vitro assays performed inside a microfluidic device demonstrated the ability of these magnetic microwires to induce malignant cell death. Exposing the system to different magnetic fields for less than 1 h provoked a reduction up to 89% of the osteosarcoma cell population, whereas healthy myoblastoma cells remained nearly unaffected. The proposed technology demonstrates in vitro the effectiveness of these microwires as vehicles for targeted magnetic hyperthermia.

Effectiveness of nanoencapsulated methotrexate against osteosarcoma cells: in vitro cytotoxicity under dynamic conditions.

Cancer is a leading cause of mortality in the world, with osteosarcoma being one of the most common types among children between 1 and 14 years old. Current treatments including preoperative chemotherapy, surgery and postoperative chemotherapy produce several side effects with limited effectiveness. The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment. However, in vitro validation of these vehicles is limited due to fluid stagnation in current techniques, in which nanoparticles sediment onto the bottom of the wells killing the cells by asphyxiation. In the current series of experiments, results obtained with methotrexate-lipid nanoparticles under dynamic assay conditions are presented as a promising alternative to current free drug based therapies. Effects on the viability of the U-2 OS osteosarcoma cell line of recirculation of cell media, free methotrexate and blank and methotrexate containing lipid nanoparticles in a 11 µM concentration were successfully assessed. In addition, several designs for the microfluidic platform used were simulated using COMSOL-Multiphysics, optimized devices were fabricated using soft-lithography and simulated parameters were experimentally validated. Nanoparticles did not sediment to the bottom of the platform, demonstrating the effectiveness of the proposed system. Moreover, encapsulated methotrexate was the most effective treatment, as after 72 h the cell population was reduced nearly 40% while under free methotrexate circulation the cell population doubled. Overall, these results indicate that methotrexate-lipid nanoparticles are a promising targeted therapy for osteosarcoma treatment.

Description of endoscopic ventricular anatomy in myelomeningocele.

OBJECTIVE: The purpose of this work is to present our endoscopic neuroanatomical findings of a series of myelomeningocele and hydrocephalus patients, treated with endoscopic third ventricular cisternostomy (ETVC), in order to describe ventricular configuration abnormalities in this group of patients, in which this neurosurgical procedure has limited performance. METHOD: We checked the videos of 10 endoscopic third ventricular cisternostomies of myelomeningocele patients taken during 24 months as from December 1998. A previous guideline is designed to record anatomic variables in the lateral ventricles, IIIrd ventricle, and basal cisterns. The topic is analyzed in view of the necropsy and imaging background data. RESULTS: The ETVC of lateral ventricles showed: absence of septum (9/10); absence of anteroseptal vein (8/10); absence of choroid plexus and thalamostriate vein (0/10); absence of fornix (1/10): small foramen of Monro (4/10). The ETVC of the IIIrd ventricle showed: impossibility of recognizing any mammillary bodies (4/10); presence of septations (5/10); presence of atypical veins in the floor (6/10); translucent floor (5/10); floor umbilications (5/10); absence of infundibulum (4/10); arachnoid adherences (7/10); and visual contact of basilar artery (4/10). CONCLUSION: There are categorical structural alterations in the ventricular system of myelomeningocele patients that are well correlated with previous necropsy and imaging reports. The ventricular system of dysraphic children presents severe anatomic alterations, which alter the reference points of the classical endoscopic third ventricular cisternostomy.

¿Las construcciones y obras civiles aumentan el riesgo de infección de herida operatoria? / The constructions and building site increase the risk of surgical wound infection?

Objetivo: El propósito de este trabajo es informar sobre los efectos de los trabajos de construcción en las tasas de infección de herida en hernioplastia y artroplastia de cadera, la evolución de las tasas y las medidas de intervención para prevenir la ocurrencia de brotes de infección de herida operatoria, durante las obras en el Hopital de Coquimbo durante los años 2001-2002. Finalmente, se proponen recomendaciones sobre medidas de protección para pacientes en riesgo de infecciones cuando se realizan obras dentro de un hospital. Método: Estudio prospectivo, longitudinal, descriptivo y analítico, desarrollado entre enero de 2001 y marzo de 2003. Se midió el material particulado en suspensión dentro de los pabellones quirúrgicos, antes y durante los trabajos de remodelación. El indicador de resultado fue la tasa de infección trimestral de herida operatoria de hernia inguinal con malla y artroplastia de cadera con implante de prótesis. La medida de efecto se midió mediante riesgo relativo (RR). Resultados: La norma sobre el valor máximo de polvo para el funcionamiento de los pabellones es 180 mcg/m³ aire. Antes de los trabajos el valor fue de 60 mcg/m³. Durante los trabajos los valores subieron hasta 1.000 mcg/m³. Luego de instalar filtros HEPA el material particulado disminuyó bajo 100 mcg/m³. Hernioplastia: La tasa de infección antes de los trabajos fue 0,7 y 2,2 durante las obras (p= 0,22); el RR asociado a las obras fue de 3,1. La tasa de infección antes de aire ultra filtrado fue 1,5 y con el uso de aire filtrado en pabellones quirúrgicos fue de 1,8 (p= 0,56). El RR asociado a usar aire filtrado fue de 1,2. Artroplastia de cadera: La tasa de infección antes de los trabajos fue 0,7 y 2,7 durante las obras (p= 0,18), con RR asociado a las obras de 3,8. La tasa de infección antes de aire ultra filtrado fue 2,1 y con el uso de aire filtrado en pabellones quirúrgicos fue de 2,4 (p= 0,61). El RR asociado a usar aire filtrado fue de 1,1. La ausencia de diferencia estadística de los resultados se puede atribuir a tamaño de muestra. Conclusiones: El aumento del material particulado en suspensión y sedimentable se asocian a un aumento de la morbilidad infecciosa de la herida operatoria de hernioplastia inguinal y de artroplastia de cadera. El uso de aire filtrado redujo la polución de material particulado, sin embargo no resultó suficiente para reducir las tasas de infección.

Process performance models in the optimization of multiproduct protein production plants.

In this work we propose a model that simultaneously optimizes the process variables and the structure of a multiproduct batch plant for the production of recombinant proteins. The complete model includes process performance models for the unit stages and a posynomial representation for the multiproduct batch plant. Although the constant time and size factor models are the most commonly used to model multiproduct batch processes, process performance models describe these time and size factors as functions of the process variables selected for optimization. These process performance models are expressed as algebraic equations obtained from the analytical integration of simplified mass balances and kinetic expressions that describe each unit operation. They are kept as simple as possible while retaining the influence of the process variables selected to optimize the plant. The resulting mixed-integer nonlinear program simultaneously calculates the plant structure (parallel units in or out of phase, and allocation of intermediate storage tanks), the batch plant decision variables (equipment sizes, batch sizes, and operating times of semicontinuous items), and the process decision variables (e.g., final concentration at selected stages, volumetric ratio of phases in the liquid-liquid extraction). A noteworthy feature of the proposed approach is that the mathematical model for the plant is the same as that used in the constant factor model. The process performance models are handled as extra constraints. A plant consisting of eight stages operating in the single product campaign mode (one fermentation, two microfiltrations, two ultrafiltrations, one homogenization, one liquid-liquid extraction, and one chromatography) for producing four different recombinant proteins by the genetically engineered yeast Saccharomyces cerevisiae was modeled and optimized. Using this example, it is shown that the presence of additional degrees of freedom introduced by the process performance models, with respect to a fixed size and time factor model, represents an important development in improving plant design.

Optimal design of protein production plants with time and size factor process models.

In this work we propose an optimization model for the design of a biotechnological multiproduct batch plant. A first level of detail posynomial model is constructed for each unit, as well as decisions regarding the structural optimization of the plant. A particular feature of this model is that it contains composite units in which semicontinuous items operate on the material contained by batch items. This occurs in the purification steps, in particular with the microfilters operating between retentate and permeate vessels, and with the homogenizer and ultrafilters operating on the material contained in a batch holding vessel. Also, the unit models rely on batch operating time expressions that depend on both the batch size and the size of semicontinuous items. The model takes into account all of the available options to increase the efficiency of the batch plant design: unit duplication in-phase and out-of-phase and intermediate storage tanks. The resulting mathematical model for the minimization of the plant capital cost is a mixed integer non-linear program (MINLP), which is solved to global optimality with an implementation of the outer approximation/ equality relaxation/ augmented penalty (OA/ER/AP) method. A plant that produces four recombinant proteins in eight processing stages is used to illustrate the proposed approach. An interesting feature of this example is that it represents an attempt to standardize a plant for the production of both therapeutic and nontherapeutic proteins; the model applied is generic and can thus be applied to any such modular plant. Results indicate that the best solution in terms of minimal capital cost contains no units in parallel and with intermediate storage tank allocation.

[Necrotizing fasciitis]. / Fascitis necrotizante.

Necrotizing soft tissue infection or necrotizing fasciitis is a rapidly progressive inflammation that leads to necrosis of subcutaneous tissues and fascia with secondary necrosis of skin. It is usually attributed to group AB hemolytic streptococci but may be caused by anaerobic bacteria. It occurs with higher frequency in elders, diabetics, alcoholics and patients with impaired immunity. Report mortality rates range from 14 to 80%. An early and timely surgical debridement with remotion of all necrotic tissue is mandatory. Wounds must be closed with splint skin grafts as soon as the local viability of tissues has been assured and the general conditions of the patients allow the procedure. Antibiotics nutritional and hemodynamic support are also necessary.

[Shortened preoperative preparation in diffuse hyperthyroid goiter: experience in 34 patients]. / Preparación preoperatoria abreviada en los bocios difusos hipertiroídeos. Experiencia en 34 pacientes.

Conventional preparation of goitrous hyperthyroid patients using lugol and propranolol may take 2 weeks. This period may be shortened using sodium iopodate and dexamethasone. We used 500 mg of sodium iopodate and 1 mg dexamethasone for 4 days in 34 hyperthyroid patients. Surgical indication derived from failure to medical treatment (68%), large goiter (27%) or adverse reaction to PTU (6%). Clinical euthyroidism was achieved after 4 days in all patients. T3 levels decreased from 482 +/- 26.2 to 137.6 +/- 3.7 ng/dl and T4 from 20.6 +/- 1.04 to 15.2 +/- 0.5 micrograms/dl (p < 0.005). Surgery was uneventful in 33 patients, one subject developed supraventricular tachycardia responsive to verapamil. Electron microscopy of the removed thyroid tissue revealed marked decrease of superficial villi and large phagosomes. Thus, sodium iopodate and dexamethasone are effective and safe for preoperative preparation of hyperthyroid patients.

[Lymphomas of the parotid region]. / Linfomas de la región parotídea.

Parotid gland lymphomas are very uncommon. Two patients with this condition were treated in the last decade. Surgery should be used only for diagnosis and becomes unnecessary when adenopathy is present, since a lymph node biopsy will establish the diagnosis.

Clinical evaluation of flap viability with a dermal surface fluorometer.

A dermal surface fluorometer was used to monitor vascular perfusion in 22 patients who underwent reconstructive surgical procedures with a variety of flaps (e.g., skin flaps, musculocutaneous flaps, fasciocutaneous flaps, and Z-plasties). Sodium fluorescein (1.5 mg per kilogram of body weight) was administered intravenously at the completion of the operative procedure. Quantitative fluorescence readings were obtained at different points in each flap by means of the surface fluorometer (Fluoroscan). The readings were taken at several time intervals and compared with those of normal skin (control). A perfusion ratio was determined in each case according to the following formula: flap reading/(normal skin control reading X 100). Partial necrosis occurred in 4 patients, correlating with low fluorescein perfusion measurements. From our findings, it appears that a perfusion ratio of 15% or greater 10 minutes following injection will accurately predict tissue viability. No systemic reactions were observed in these patients. We believe that this minimally invasive technique should be of considerable assistance in the postoperative evaluation of flap viability.