Frecuencia de hígado graso no alcohólico diagnosticado por ecografía abdominal en pacientes obesos / Frequency of fatty liver nonalcoholic diagnosed by abdominal ultrasound in patients obese

El hígado graso no alcohólico (HGNA) es una complicación asociada a la obesidad, debido a la acumulación excesiva de grasa en el hígado. Con el objetivo de determinar la frecuencia de hígado graso no alcohólico diagnosticado por ecografía abdominal en pacientes que asisten a la Unidad del Manejo Integral del Paciente Obeso del Hospital de Clínicas, FCM ­ UNA, se realizó un estudio observacional descriptivo retrospectivo que incluyó a 188 pacientes, de los cuales 146 fueron mujeres y 42 hombres, la edad media en los pacientes con diagnóstico de HGNA fue de 41,3±11,4 años con un rango de edad de 20 a 65 años. Los resultados señalan la frecuencia de HGNA con el 56,9% (n=107) por ecografía abdominal, siendo 39,9% (n=75) mujeres y 17% (n=32) hombres, mientras que 43,1% (n=81) presentó hígado de aspecto normal. El 43,9% (n=47) de los pacientes con HGNA exhibió obesidad grado III. Al comparar la circunferencia abdominal en los 107 pacientes con HGNA se obtuvo una media de 139,1±97,8 cm. Con respecto al grado de esteatosis el 43,1% (n=81) mostró grado 0, 31,9% (n=60) grado 1, 20,7% (n=39) grado 2 y 4,3% (n=8) grado 3. Se observaron en los datos de laboratorio elevación de las transaminasas GPT 35,5% (n=38), 25,2% (n=27) en la GOT y 24,3% (n=26) FA, se notó aumento en los valores de las bilirrubinas directa e indirecta, 65,4% (n=70) BD y 69,2% (n=74) BI, por otra parte el 47,7% (n=51) enseñó CT elevado, 49% (n=45,7) HDL disminuido, 36,4% (n=39) LDL elevado y 29% (n=31) con triglicéridos elevados. Se halló que el 69,1% (n=74) de los pacientes con HGNA tienen HTA. Al realizar la comparación de las variables mencionadas entre los pacientes con y sin HGNA, arrojó que las transaminasas GPT, GOT y triglicéridos estuvieron en niveles más altos en los pacientes con HGNA. Se evidenció que la obesidad es un factor determinante para el desarrollo de HGNA, la caracterización del perfil hepático y lipídico, asimismo la presión arterial constituyen puntos fundamentales para asociar el aumento de estos con la presencia de HGNA.

Nonalcoholic fatty liver disease (NAFLD) is a complication associated with obesity, due to excessive accumulation of fat in the liver. In order to determine the frequency of NAFLD diagnosed by abdominal ultrasound in patients attending the unit Comprehensive Patient Management Obese the Hospital of Clinics, FCM - UNA, a retrospective observational study involving performed in 188 patients, of which 146 were women and 42 men, average age in patients with NAFLD diagnosis was 41,3±11,4 years with an age range of 20 - 65 years. The results indicate the frequency of NAFLD with 56,9% (n=107) for abdominal ultrasound, being 39,9% (n=75) women and 17% (n=32) were men, while 43,1% (n=81) presented liver normal. 43.9% (n=47) of patients with NAFLD showed grade III obesity. By comparing the abdominal circumference in 107 patients with NAFLD an average of 139,1±97,8 cm was obtained. With respect to the degree of steatosis 43,1% (n=81) showed grade 0, 31,9% (n=60) grade 1, 20,7% (n=39) grade 2 and 4,3% (n=8) grade 3 were observed in laboratory data GPT transaminases elevation of 35,5% (n=38), 25.2% (n=27) in the GOT and 24,3% (n=26) FA, increased values of direct and indirect bilirubin, 65,4% (n = 70) BD and 69.2% (n=74) BI was noted, moreover 47,7% (n=51) CT taught high, 49% (n=45,7) decreased HDL, 36,4% (n=39) high LDL and 29% (n=31) with elevated triglycerides. It was found that 69,1% (n=74) of patients with NAFLD have hypertension. When comparing the variables mentioned among patients with and without NAFLD, he threw the GPT, GOT transaminases and triglycerides were at higher levels in patients with NAFLD. It was evident that obesity is a determining factor NAFLD development, characterization of liver and lipid profile, blood pressure also are key points to associate these increased with the presence of NAFLD.

Caracterización morfológica del músculo bíceps femoral del perro / Morphological characterization of biceps femoris muscle in the dog

A partir de estudios previos realizados sobre la anatomía del musculo bíceps femoral en el perro y con el objetivo de avanzar en la caracterización inmunohistoquímica y nerviosa de este musculo, estudiamos la existencia de subvolúmenes musculares. Utilizamos la disección roma en piezas musculares aisladas fijadas y tratadas con ácido nítrico al 25%. Las divisiones de las ramas del nervio isquiático involucradas fueron utilizadas como guía en la disección. Se determinaron tres subvolúmenes, uno involucrando a la cabeza caudal y dos en el vientre correspondiente a la cabeza craneal que fueron denominados caudal, proximal y distal respectivamente. Realizamos mediciones del largo de las fibras musculares, dirección, dirección y densidad macroscópica de las mismas para caracterizar los compartimientos. Estos subvolúmenes deberán tenerse en cuanta al realizar estudios electromiográficos del musculo bíceps femoral y al evaluar las alteraciones en la locomoción producto de las alteraciones nerviosas y musculares en el nervio pelviano del canino.

From previous studies on the anatomy of the femoral biceps muscle in the dog and with the aim of advancing in immunohistochemical and nervous characterization of this muscle, we studied the existence of subvolumes in muscle structure. We used blunt dissection in isolated muscle pieces fixed and treated with 25% nitric acid. The divisions of the sciatic nerve branches involved were used to guide the dissection. Three subvolumes were identified; one, involving the caudal head, and two in the cranial head belly; they were called caudal, proximal and distal respectively. We measured muscle fiber length, orientation, and macroscopic density to characterize these compartments. These subvolumes must be considered when muscle electromyography research is carried out, and for locomotion changes evaluation due to lesions in nerve and muscle structure of the canine pelvic limb.

Conocimientos, actitudes y prácticas del personal de enfermería sobre medidas de prevención de neumonías asociadas a la ventilación mecánica en la unidad de cuidados intensivos de adultos del Instituto de Previsión Social / Knowledge, attitudes and practices of nursing staff about preventive measures for pneumonias associated with mechanical ventilation in the adult intensive care unit of the Social Security Institute

El equipo de enfermería tiene un papel fundamental en la prevención y control de las infecciones intrahospitalarias. El objetivo del estudio fue determinar el grado de conocimiento, actitudes y prácticas en relación a las medidas de prevención de neumonías asociada a la ventilación mecánica (NAV) en profesionales de enfermería de la Unidad de Cuidados Intensivos de Adultos del Instituto de Previsión Social en el año 2009. El estudio es observacional descriptivo de corte transversal, la recolección de datos se realizó mediante una encuesta de 10 preguntas de selección múltiple y el muestreo fue por conveniencia de los profesionales de enfermería que aceptaron participar del estudio. Las variables analizadas fueron nivel de conocimientos sobre el manejo de la vía aérea artificial, métodos de desinfección de dispositivos de intubación, posición del paciente; los aspectos actitudinales analizados fueron tanto la importancia del cumplimiento así como la ejecución de los protocolos. Participaron del estudio 36 de 70 profesionales de enfermería de la unidad, 41,7% demostró conocimiento adecuado sobre las medidas de prevención, respondiendo correctamente 5 o 6 preguntas de las 10 planteadas; 19,4% respondió correctamente entre 7 a 9 preguntas, ni un solo encuestado demostró tener conocimiento absoluto sobre las medidas de prevención de las NAV. A pesar de que los resultados reflejaron déficit en el grado de conocimiento, la actitud fue positiva. Los indicadores relacionados a la práctica mostraron necesidad de mejorar el nivel de conocimiento sobre medidas preventivas implementando una estrategia de educación continua para estos profesionales.

The Effects of N-acetylcysteine on ifosfamide efficacy in a mouse xenograft model.

BACKGROUND/AIM: Nephrotoxicity is observed in 30% of children treated with ifosfamide. We have shown that n-acetylcysteine (NAC) successfully mitigates nephrotoxicity of ifosfamide in cell and rodent models. However, before this treatment is evaluated clinically, it must be established that NAC does not interfere with the efficacy of ifosfamide. MATERIALS AND METHODS: Mice implanted with Ewing's sarcoma tumours received the following treatments: saline, ifosfamide, ifosfamide + NAC concurrently, pre-treatment with NAC + ifosfamide, or NAC alone. RESULTS: Median volumes of EW-7 tumour xenografts in mice treated with ifosfamide (n=8), ifosfamide with concurrent NAC therapy (n=7), and NAC pre-treatment (n=6) (p<0.05) were significantly reduced compared to median tumour volumes of control mice (n=6). None of the NAC treatments affected ifosfamide-mediated reduction in tumour volumes. CONCLUSION: NAC does not interfere with the efficacy of ifosfamide in a EW-7 xenograft model. These results support the clinical evaluation of NAC as a strategy against ifosfamide-induced nephrotoxicity in children.

Combining small interfering RNAs targeting thymidylate synthase and thymidine kinase 1 or 2 sensitizes human tumor cells to 5-fluorodeoxyuridine and pemetrexed.

Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment, but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumor milieu, and may modulate resistance to TS-targeting drugs. Combined down-regulation of these enzymes is an attractive strategy to enhance cancer therapy. We have shown previously that antisense-targeting TS enhanced tumor cell sensitivity to TS-targeting drugs in vitro and in vivo. Because both TS and TKs contribute to increased cellular dTMP, we hypothesized that TKs mediate resistance to the capacity of TS small interfering RNA (siRNA) to sensitize tumor cells to TS-targeting anticancer drugs. We assessed the effects of targeting TK1 or TK2 with siRNA alone and in combination with siRNA targeting TS and/or TS-protein targeting drugs on tumor cell proliferation. Down-regulation of TK with siRNA enhanced the capacity of TS siRNA to sensitize tumor cells to traditional TS protein-targeting drugs [5-fluorodeoxyuridine (5FUdR) and pemetrexed]. The sensitization was greater than that observed in response to any siRNA used alone and was specific to drugs targeting TS. Up-regulation of TK1 in response to combined 5FUdR and TS siRNA suggests that TK knockdown may be therapeutically useful in combination with these agents. TKs may be useful targets for cancer therapy when combined with molecules targeting TS mRNA and TS protein.

Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement Structural and functional characterization of a vaccine candidate

The Schistosoma mansoni fatty acid binding protein (FABP), Sm14, is a vaccine candidate against, S. mansoni and F. hepatica. Previously, we demonstrated the importance of a correct fold to achieve protection in immunized animals after cercariae challenge [[10]. C.R.R. Ramos, R.C.R. Figueredo, T.A. Pertinhez, M.M. Vilar, A.L.T.O. Nascimento, M. Tendler, I. Raw, A. Spisni, P.L. Ho, Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein: structural, functional and immunoprotection analysis. J. Biol. Chem. 278 (2003) 12745-12751.]. Here we show that the reduction of vaccine efficacy over time is due to protein dimerization and subsequent aggregation. We produced the mutants Sm14-M20(C62S) and Sm14-M20(C62V) that, as expected, did not dimerize in SDS-PAGE. Molecular dynamics calculations and unfolding experiments highlighted a higher structural stability of these mutants with respect to the wild-type. In addition, we found that the mutated proteins, after thermal denaturation, refolded to their active native molecular architecture as proved by the recovery of the fatty acid binding ability. Sm14-M20(C62V) turned out to be the more stable form over time, providing the basis to determine the first 3D solution structure of a Sm14 protein in its apo-form. Overall, Sm14-M20(C62V) possesses an improved structural stability over time, an essential feature to preserve its immunization capability and, in experimentally immunized animals, it exhibits a protection effect against S. mansoni cercariae infections comparable to the one obtained with the wild-type protein. These facts indicate this protein as a good lead molecule for large-scale production and for developing an effective Sm14 based anti-helminthes vaccine.

Suplementación parenteral de cobre en vacas gestantes: efecto sobre postparto y terneros / Parenteral supplementation of copper in gestation cows: effect on postpartum and calves

Objetivo. Evaluar el efecto del cobre en vacas gestantes sobre el comportamiento reproductivo posparto y la salud del ternero. Materiales y métodos. Se estudiaron 80 vacas divididas en dos grupos de 40 animales cada uno. El grupo A fue tratado con 2 ml de CuSO4 (2.5%) subcutáneamente. El tratamiento se inició a los 8 meses de gestación, y se repitió a los 30 y 90 días post parto. El grupo B, se uso como control. A las vacas se les analizó el perfil hematoquímico, intervalo parto primer servicio (IPPS), intervalo parto concepción (IPC), intervalo parto-parto (IPP), índice de natalidad (IN), índice de inseminación (II) y la eficiencia en la detección de la hembra en estro (EDHE) y a los terneros los parámetros hematoquímicos. Los datos se procesaron mediante Statgraphics Plus 5.0, para las diferencias entre medias de los datos hemoquímicos y reproductivos se aplicó (ANOVA) y comparaciones de proporciones IN y EDHE. Se empleó la correlación y regresión simple para demostrar la relación del cobre con las demás parámetros estudiados. Resultados. La administración subcutánea de cobre incrementó los niveles de dicho elemento en sangre, hierro y hemoglobina (p< 0.001); así como la disminución del IPPS, IPC, IPP, IN, EDHE, e II (p< 0.05). En los terneros se aumentó la cupremia (p< 0.001), la hemoglobina (p< 0.01) y las proteínas totales (p< 0.05). Conclusiones. El tratamiento aplicado incrementó los indicadores hematoquímicos y reproductivos en los animales tratados.

Subcutaneous adipose tissue cytokine production is not responsible for the restoration of systemic inflammation markers during weight loss.

CONTEXT: It has been suggested that weight loss can improve systemic inflammation associated with obesity by decreasing the adipose production of pro-inflammatory cytokines. This suggestion, however, remains controversial. OBJECTIVE: To analyse the effect of weight loss on peripheral inflammatory markers and subcutaneous adipocytokine production. DESIGN: Patients were studied at baseline, at the end of the weight loss period, and after 2 weeks of weight stabilisation. SUBJECTS: Nineteen morbid obese non-diabetic patients and 20 lean control subjects. INTERVENTION: During the weight loss period patients followed a 6-week low-calorie diet. MEASUREMENTS: Plasma levels of inflammatory markers, maximal in vitro whole-blood cytokine production, subcutaneous adipose tissue expression and content of several cytokines. RESULTS: Obese subjects had higher circulating levels of C reactive protein (CRP), serum amyloid A (SAA), interleukin IL-6, IL-1 and soluble tumor necrosis factor receptors (sTNFR). Weight loss was associated with a significant decrease in CRP, SAA, leucocytes and plasma IL-6. Maximal in vitro cytokine production of IL-1 and sTNFR1 increased during this period. Weight loss did not induce significant changes in the adipose concentrations of IL-6, IL-1 or sTNF-receptors. However, adipose expression of IL-6, IL-1, TNFalpha, membrane cofactor protein-1 and adiponectin increased at the end of the weight loss period. During weight maintenance, circulating inflammatory parameters increased and in some cases returned to baseline. CONCLUSIONS: A low-calorie diet is associated with an improvement in the systemic inflammatory status. This seems to be due to energy restriction rather than to adipose mass loss, since inflammatory levels return to baseline soon after weight stabilisation. Furthermore, a negative energy balance and fat mobilisation are associated with increased subcutaneous cytokine adipose expression.

Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin.

Treatment of advanced stages of prostate carcinoma with histone-deacetylase inhibitors entails expression of human procarboxypeptidase-A4 (hPCPA4). The three-dimensional structure of hPCPA4 has been solved and shows the features of related metallocarboxypeptidase zymogens, with a preformed alpha/beta/-hydrolase active-enzyme moiety (hCPA4) and an inhibiting pro-domain (PD). The protease moiety recalls a sphere, out of which a spherical cone has been cut. This results in a funnel-like structure, at the bottom of which the active-site cleft resides. The border of this funnel is shaped by loops, which are responsible for the interaction with the PD, characterised by a large interface area and relatively few contacts. Such an inhibitory mode is evocative of the recently reported structure of the human inhibitor latexin in its complex with hCPA4. The main contacting structure of latexin is similar to the one employed for PD inhibition. In both cases, active-site blocking relies mainly on a loop provided by the central part of a beta sheet.

Construction of an immunotoxin with the pore forming protein StI and ior C5, a monoclonal antibody against a colon cancer cell line.

Sticholysin I (StI), a potent cytolysin isolated from the sea anemone Stichodactyla helianthus, was linked to the monoclonal antibody (mAb) ior C5. StI acts by forming hydrophilic pores in the membrane of the attacked cells leading to osmotic lysis. ior C5 is a murine IgG1, which recognizes the tumor associated antigen (TAA) ior C2. The cytolysin and the mAb were coupled by using the heterobifunctional cross-linking reagent sulfosuccinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (SMCC). Two hybrid molecules composed by one ior C5 and one or two StI molecules were obtained (named conjugated I and II, respectively). The purified conjugates were evaluated by a binding affinity assay against an ior C2-positive colon cancer cell line (SW948). Both molecules were able to recognize the antigen (Ag) in the same way that unconjugated ior C5 does. The activity of both conjugates against human erythrocytes and SW948 cells was assessed. They lost most of their hemolytic activity but their residual activity was very similar. Nevertheless, when their cytotoxicity was studied on the SW948 cell line, only conjugate II killed efficiently the cells, indicating a specific mAb-Ag interaction. In this chimeric molecule the ratio between the cytotoxic and the hemolytic activity was larger than that of the free cytolysin. This fact indicates an increase of the specificity of the toxic effect toward the SW948 cell line and consequently an increase of the difference between its hemolytic and cytotoxic doses. The results herein support the feasibility of directing StI to the surface of cancer cells expressing ior C2 Ag via the mAb ior C5.

Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein Molecular, functional, and immunoprotection analysis

The Schistosoma mansoni Sm14 antigen belongs to the fatty acid-binding protein family and is considered a vaccine candidate against at least two parasite worms, Fasciola hepatica and S. mansoni. Here the genomic sequence and the polymorphism of Sm14 have been characterized for the first time. We found that the conserved methionine at position 20 is polymorphic, being exchangeable with threonine (M20T). To evaluate the function of the amino acid residue at this position, we have also constructed the mutant Sm14-A20 besides the two native isoforms (Sm14-M20 and Sm14-T20). The three purified recombinant His6-tagged Sm14 proteins (rSm14-M20, rSm14-T20, and rSm14-A20) present a predominant â-barrel structure as shown by CD spectroscopy. Thermal and urea unfolding studies evidenced a higher structural stability of rSm14-M20 over the other forms (rSm14M20>rSm14-T20>rSm14-A20). All of the Sm14 proteins were able to bind 11-(dansylamino)undecanoic acid (DAUDA) without substantial difference in the binding affinity. However, rSm14-M20 exhibited a higher affinity for natural fatty acids than the rSm14-T20 and rSm14-A20 proteins as judged by competitive experiments against DAUDA (rSm14-M20>rSm14-T20> rSm14-A20). The rSm14-M20 or rSm14-T20 isoforms but not the rSm14-A20 mutant was able to induce significant protection against S. mansoni cercariae challenge in immunized mice. The level of protection efficacy correlates with the extent of structure stability of the recombinant Sm14 isoforms and mutant.

Cambios seculares de las medidas antropométricas en la población paraguaya en nacidos durante el periodo de 1960 a 1984 / Secular trends of the anthropometric measurements of the paraguayan population born between 1960 to 1984

Objetivo: Evaluar las variaciones de peso, talla e índice de masa corporal. Se compararon estos parámetros en una muestra de 1940 varones jóvenes (18+-0,8 años) paraguayos nacidos en un periodo de 15 años entre 1960 a 1984 al ingreso al servicio militar. Los sujetos fueron seleccionados por muestreo aleatorio estratificando por año de nacimiento en cantidad suficiente para detectar un coeficiente de regresión mínimo de 0,20. Se observó un sostenido aumento, altamente significativo, con coeficiente de regresión de 0,36, 0,24 y 0,27 para el peso, la talla y el índice de masa corporal, respectivamente, en el periodo de estudio. Estos incrementos también se evidenciaron mediante el análisis estratificado por quin quenios, resultando más importantes en los periodos 1975-1979 y 1980-1984. Adicionalmente, se observó que los menores valores de los parámetros estudiados se observan en los sujetos de menor nivel educativo y provenientes del entorno rural. Esta primera comprobación de las variaciones antropométricas seculares de la población joven de Paraguay debe seguirse por un cuidadoso estudio de sus probables causas y de sus potenciales consecuencias para la salud.

Algunos factores de riesgo de la desnutrición proteicoenergética / Some risk factors of protein-energy malnutrition

Con el objetivo de analizar la influencia de algunos factores de riesgo sobre la desnutrición proteicoenergética se llevó a cabo un estudio de casos y controles en la policlínica 'Luis Enrique de la Paz' de Yara, Cuba, durante el año 2001. Los casos se constituyeron por 34 niños menores de 15 años, para los que se seleccionaron 68 controles; los datos se organizaron en tablas de contingencias y se realizaron cálculos estadísticos a través del 2 y el OR, con sus intervalos de confianza, además del coeficiente de correlación . Los resultados ubicaron a la estrechez económica de vida en el primer lugar (OR= 9,50).Mejorando esta condición se reduciría la desnutrición proteicoenergética en un 89 por ciento; le siguió en orden de importancia el parasitismo intestinal (OR= 7,27), identificado también como factor de riesgo, al igual que las infecciones respiratorias repetidamente y el bajo nivel de instrucción de los padres. Se correlacionó moderadamente la estrechez económica de vida con el parasitismo y el nivel de instrucción. Una vez identificado el riesgo será posible establecer pautas preventivas para disminuir la incidencia de este morboso proceso (AU)

Preparation and comparative evaluation of 99mTc-labeled 2-iminothiolane modified antibodies and CITC-DTPA immunoconjugates of anti-EGF-receptor antibodies.

The use of antibodies as targeting agents for the delivery of radioisotopes to tumors is a promising concept that has received widespread attention since the advent of monoclonal antibody (mAb) technology. The following studies are described in this article: the 99mTc-randiolabeling of 2-iminothiolane (2-IT) modified antibodies and 6-p-isothiocyanatobenzyl- diethylene-triamine penta-acetic acid (CITC-DTPA) immunoconjugates of anti-EGF-receptor antibodies murine ior egf/r3 and humanized h-R3; the analytical methods for quality control of the radiopharmaceutical such as instant thin layer chromatography-silica gel (ITLC-SG); the biological assessment of the radiolabeled molecule using flow cytometry analysis; in vitro stability studies with cysteine and DTPA challenge and the biodistribution studies in 4NMRI xenografted nude mice with U-87 human glioblastoma multiforme and MDA-MB-468 breast cancer cell lines. Labeling efficency of (96.48 +/- 0.70%) (98.42 +/- 0.38%), (94.8 +/- 1.25%) and (96.41 +/- 0.89%) was achieved for 99mTC-2-IT ior efg/r3, 99mTc-CITC-DTPA- ior egf/r3, 99mTc-CITC-DTPA- h-R3 and 99mTc-DIACIM h-R3, respectively. Radiocolloids were less than 2.0% in all cases. The biological activity measured by flow cytometry analysis using the MDA-MB-468 breast cancer cell line showed an immunoreactivity fraction greater than 85% in all concentrations of each immunoconjugate. Challenge studies demonstrated no evidence of transcomplexation of 99mTc to 1.0 mM DTPA for 2-IT modified antibody ior egf/r3 and CITC-DTPA immunoconjugates and only 8.7%, 4.9% and 5.0% of the 99mTc-radiolabeled was transcomplexed to 1.0 mM cysteine after 1 h incubation at 37 degrees C for 2-IT modified antibody ior egf/r3, CITC-DTPA ior egf/r3 and CITC-DTPA h-R3, respectively. Biodistribution studies with 2-IT modified antibodies and CITC-DTPA immunoconjugates indicated high tumor uptake in both cell lines with both immunoconjugates and no accumulation of the radiolabeled antibodies in normal organs.

Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study.

High levels of growth factors and their receptors have been demonstrated in human tumors. Gliomas and meningiomas are characterized by overexpression of epidermal growth factor receptor (EGF-R). Ior egf/r3, is a neutralizing murine monoclonal antibody (MAb) against EGF-R, and was generated at the Cuban Institute of Oncology. The antibody recognizes EGF-R with high affinity, inhibiting tyrosine kinase activation. A clinical trial was conducted in brain tumor patients to evaluate toxicity, immunogenicity, and clinical benefit of escalating doses of the antibody. Nine patients with histologically confirmed gliomas or meningiomas, who had active or recurrent disease after receiving conventional treatment, received four intravenous doses of ior egf/r3. Total dosages ranged from 160 to 480 mg. As inclusion criteria, radioimmunoscintigraphy with the same MAb labeled with 99mTechnetium (99mTc) was performed. Immune response against the murine antibody was also evaluated. After four doses of ior egf/r3 MAb, no significant toxicity was found, except in one patient who developed a grade 4 allergic adverse event. This reaction was probably related with previous sensitization to the same MAb and the development of human anti-mouse antibodies (HAMA) response. Despite no major objective antitumor responses, eight patients had stable disease on the 6-month evaluation, and two patients remain alive after four years of MAb therapy.

Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats.

Brain tumors are often incurable despite current aggressive treatment modalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h-R3 is a humanized antiepidermal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re-h-R3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5 -microl dose (2.5 microl into the left and 2.5 microl into the right lateral ventricles) of neutral solution containing 50 microg of h- R3 labeled with 49.5 +/- 1.7,284 +/- 13.7 or 579 +/- 23.7 muCi of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Body weights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of 188Re-h-R3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevertheless, further studies are necessary to discard learning and behavioral problems.

Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats

Brain tumors are often incurable despite current aggressive treatment modalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h-R3 is a humanized antiepidermal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re-h-R3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5- µl into the right lateral ventricles) of neutral solution containing 50 µg of h-R3 labeled with 49.5ñ1.7, 284ñ13.7 ir 579ñ23.7 µCi of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Body weights were recorded on days 0,7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of 188Re-h-R3 is tolerable and causes minimal local and systemic toxicity effects in rats. Never-theless, further studies are necessary to discard learning and behavioral problems(AU)

[Clinical-epidemiological study of patients with juvenile myoclonic epilepsy in Santa Catarina State, Brazil]. / Estudo clínico-epidemiológico de pacientes com epilepsia mioclônica juvenil em Santa Catarina.

We aimed to characterize the clinical profile and to establish the prevalence of juvenile myoclonic epilepsy (JME) among 939 consecutive patients referred to our epilepsy clinic. Inclusion criteria in the study were: a) myoclonic jerks, preferably on awakening; b) beginning of the symptoms between 8 and 26 year-of-age; c) typical pattern of electroencephalographic discharges; and d) good response to sodium valproate (VPA). In a retrospective design, 26 cases of JME were identified (prevalence 2.8%). Most of these patients were female (73.1%). Mean age at onset of symptoms was 13 (range 7-18). Tonic-clonic seizures were reported in 92.3% and absence seizures in 19.2%. Besides, 92.3% of the patients had typical EEG epileptiform activity and 76.9% had good response to VPA with daily dose ranging from 500 mg to 1500 mg.

[Prevalence of neurocysticercosis among epileptic in-patients in the west of Santa Catarina--southern Brazil]. / Neurocisticercose em pacientes internados por epilepsia no hospital regional de Chapecó região oeste do estado de Santa Catarina.

Neurocysticercosis (NC) is an endemic condition in several areas of Brazil. It is most likely the major responsible for the high prevalence of epilepsy in our country, estimated in 1-2% of general population. We performed a study to evaluate NC as aetiology of epilepsy in the west of Santa Catarina. This state belong to southern Brazil and it has a very developed economy. However, due the widespread swine farming in the west district, many of them without any sanitary control, the national health authorities have considered all this area at risk to NC. The study was carried out in Chapecó, the main town in that region, where CT Scan service was started in 1995. All patients put on hospital care due epileptic seizures in 1995-96 were considered. Febrile convulsions were excluded of the sample. We found a very expressive prevalence rate of NC among patients suffering from epilepsy. Roughly 24% of these patients, showed unequivocal tomography evidences for the diagnosis of NC. Our data suggest cysticercosis as a real endemic trouble in the area and, overdosis of information in proper language, diffuse to the whole population, seems to be the only remedy to fight against it. Moreover, we should pay special attention to everyone related to swine farming, does not matter how this activity has been classified.

Prevalence of diabetes mellitus and associated cardiovascular risk factors in an adult urban population in Paraguay.

A cross-sectional study was conducted on a 20-74-year-old population in an urban white-Hispanic population in Paraguay to determine the prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT), and associated cardiovascular disease (CVD) risk factors. In total 1606 subjects completed the study (response rate 80.3%; 1094 women, 512 men). The overall prevalences were: DM 6.5%, IGT 11.3%, hypertension 17.1%, and obesity 31.6% with more obesity in women (35.7% vs 22.8%, p < 0.05). Age-standardized prevalences were: DM 6.5%, IGT 13.5% in females and DM 5.5%, IGT 7.2% in males. DM and IGT subjects had two or more CV risk factors significantly more often than the normal population. In conclusion, DM, IGT, hypertension, and obesity are common in this South American Hispanic urban population, particularly in women. Public health measures, such as lifestyle education, are required to decrease these noncommunicable diseases.