[Psychometric properties of a quality of life questionnaire specific to liver transplant]. / Propiedades psicométricas de un cuestionario específico de calidad de vida en trasplante hepático.

OBJECTIVE: To translate and evaluate the psychometric properties of a quality of life questionnaire specific to liver transplant patients. MATERIAL AND METHODS: The questionnaire was administered to 60 patients on the waiting list for liver transplant in the Cruces Hospital Transplant Unit, and again at 6 months after the transplant. The reliability, validity, sensitivity to change, and minimum detectable change (MDC) were studied. Two questionnaires, the SF-36 (Health Survey Short Form 36) and HADS (Hospital Anxiety and Depression Scale), were used to evaluate the convergent validity. RESULTS: The specific questionnaire presented a Cronbach s alpha coefficient of over 0.7. The factor analysis demonstrates a single dimension. Correlations with the areas of SF-36 varied between -0.34 and -0.71 in the preoperative phase, and between -0.21 and -0.67 at 6 months. With respect to the HAD-anxiety scale, the coefficients were 0.44 in the preoperative phase and 0.51 at 6 months, and for the HAD-depression scale these were 0.64 and 0.39, respectively. Discriminant validation studies confirm that the questionnaire shows differences between patients with cirrhosis of various etiologies and severities. In the study of sensitivity to change, values were obtained for the SES (standardised effect size) and SRM (standardised response mean) indices of 0.92 and 0.99, respectively. Furthermore, 58.33% of patients had scores higher than MDC. CONCLUSIONS: The specific questionnaire has adequate psychometric properties. Its use in these patients may therefore be recommended as another scale for evaluating the results of this intervention.

Propiedades psicométricas de un cuestionario específico de calidad de vida en trasplante hepático / Psychometric properties of a quality of life questionnaire specific to liver transplant

Objetivo: traducir y evaluar las propiedades psicométricas de un cuestionario de calidad de vida específico para pacientes sometidos a trasplante hepático. Material y métodos: el cuestionario fue administrado a 60 pacientes en lista de espera de trasplante hepático de la Unidad de Trasplante del Hospital de Cruces, y a los 6 meses tras la intervención. Se estudió la fiabilidad, la validez, la sensibilidad al cambio y el mínimo cambio detectable (MCD). Para evaluar la validez convergente se utilizaron dos cuestionarios, SF-36 (Health Survey Short Form 36) y el HAD (Hospital Anxiety and Depression Scale). Resultados: el cuestionario específico presenta un coeficiente alfa de Cronbach superior a 0,7. El análisis factorial demuestra una única dimensión. Las correlaciones con las áreas del SF-36 oscilaron entre -0,34 y -0,71 en el preoperatorio, y entre -0,21 y -0,67 a los 6 meses. Respecto al HAD-ansiedad, los coeficientes eran 0,44 en el preoperatorio y 0,51 a los 6 meses, y para HADdepresión de 0,64 y 0,39 respectivamente. Los estudios de validez discriminante confirman que el cuestionario muestra diferencias entre pacientes con cirrosis de diversas etiologías o gravedad. En el estudio de la sensibilidad al cambio se obtuvieron unos valores para los índices TEE (tamaño del efecto estandarizado) y MRE (media de respuesta estandarizada) de 0,92 y 0,99 respectivamente. Además, un 58,33% de los pacientes superaba el MCD. Conclusiones: el cuestionario específico posee adecuadas propiedades psicométricas, lo cual puede aconsejar su utilización en estos pacientes, como otra medida más para evaluar los resultados de esta intervención

Objective: to translate and evaluate the psychometric properties of a quality of life questionnaire specific to liver transplant patients. Material and methods: the questionnaire was administered to 60 patients on the waiting list for liver transplant in the Cruces Hospital Transplant Unit, and again at 6 months after the transplant. The reliability, validity, sensitivity to change, and minimum detectable change (MDC) were studied. Two questionnaires, the SF-36 (Health Survey Short Form 36) and HADS (Hospital Anxiety and Depression Scale), were used to evaluate the convergent validity. Results: the specific questionnaire presented a Cronbach's alpha coefficient of over 0.7. The factor analysis demonstrates a single dimension. Correlations with the areas of SF-36 varied between -0.34 and -0.71 in the preoperative phase, and between -0.21 and -0.67 at 6 months. With respect to the HAD-anxiety scale, the coefficients were 0.44 in the preoperative phase and 0.51 at 6 months, and for the HAD-depression scale these were 0.64 and 0.39, respectively. Discriminant validation studies confirm that the questionnaire shows differences between patients with cirrhosis of various etiologies and severities. In the study of sensitivity to change, values were obtained for the SES (standardised effect size) and SRM (standardised response mean) indices of 0.92 and 0.99, respectively. Furthermore, 58.33% of patients had scores higher than MDC. Conclusions: the specific questionnaire has adequate psychometric properties. Its use in these patients may therefore be recommended as another scale for evaluating the results of this intervention

Retina: degeneración macular relacionada con la edad: conceptos actuales / Retina: age related macular degeneration: actualization concepts

La mácula está encargada de la visión fina y detallada; de la visión central. La misma es visible a través de la oftalmoscopía directa. Desafortunadamente, esta sujeta a acciones deletéreas por el organismo, producto del proceso de envejecimiento de los seres humanos; entre estas tenemos a la Degeneración Macular Relacionada con la Edad; trastorno degenerativo que se caracteriza clínicamente por la presencia de Drusens y alteraciones pigmentarias del EPR en sus etapas tempranas y por Atrofia Geográfica, Neovascularización Coroidea, Desprendimiento del EPR y Cicatrización Fibrosa en sus etapas tardías y que conduce a una importante disminución de la agudeza visual y ceguera. Tan importante que representa la primera causa de ceguera legal en la población mayor de 65 años. Por consiguiente, en el presente trabajo se hace una revisión de esta patología que afecta a la mácula

Síndrome de McKittrick-Wheelock. A propósito de 2 casos / McKittrick-Wheelock syndrome. Report of two cases

Los adenomas vellosos colorrectales son tumores frecuentes que normalmente provocan una escasa sintomatología. Presentamos por su rareza 2 casos clínicos, en los cuales debido al gran tamaño tumoral se produjeron graves alteraciones hidroelectrolíticas, originando el denominado síndrome de McKittrick-Wheelock. Se revisan someramente los posibles mecanismos etiopatogénicos. Asimismo, se hace hincapié en el tratamiento con indometacina como paso previo a la intervención quirúrgica (AU)

A new enzyme-linked immunosorbant assay for the measurement of human vitamin D receptor.

The hormonal actions of 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are mediated by its cognate receptor protein, the vitamin D receptor (VDR). Despite the growing importance of the VDR system as a modulator of cell growth and differentiation, convenient assays for quantitative measurement of VDR are not readily available, and [(3)H]1,25(OH)(2)D(3) ligand binding assays remain the standard method. In this paper, we present data to validate and characterize the usefulness of a new VDR enzyme-linked immunosorbant assay (ELISA) kit developed for the measurement of VDR in biological samples. In this assay, samples are added to microtitration wells coated with anti-VDR antibody and incubated with a second anti-VDR antibody that is biotinylated. The antibody receptor complex is then detected with streptavidin-labeled horseradish peroxidase followed by incubation with a chromogenic substrate, tetramethylbenzidine. The assay was found to be sensitive and accurate for measurements of VDR and compared favorably with the conventional radioligand binding assay (RBA). The interassay variation ranged from 5% to 25% and the intraassay variation was less than 5%. The ELISA presents several advantages over existing methodology, including the use of nonradioactive detection systems, lower protein and sample volume requirements, as well as convenience and speed. The assay can be completed in as short a time as 3 h, avoiding overnight incubations. Data are also presented to demonstrate the ability of the ELISA to detect both occupied and unoccupied VDR, making it a valuable research tool in settings where 1,25(OH)(2)D(3) is present. However, the ELISA, as currently formulated, is only useful for the detection of human VDR.

Conceptually new 20-epi-22-oxa sulfone analogues of the hormone 1alpha,25-dihydroxyvitamin D(3): synthesis and biological evaluation.

New C,D-ring side-chain-modified sulfone 4a, with natural 1alpha, 3beta-hydroxyl groups but lacking the 25-hydroxyl group characteristic of the natural hormone 1alpha,25-dihydroxyvitamin D(3) (1), has been prepared and characterized. Novel synthetic features include: (1) chemoselective oxidation of only a primary silyl ether in a primary-secondary bis-silyl ether intermediate and (2) smooth reductive etherification without interference by a neighboring sulfonyl group. Sulfone 4a, but not its 1beta, 3alpha-diastereomer 4b, is powerfully antiproliferative and transcriptionally active in vitro but desirably noncalcemic in vivo. Although sulfone 4a, designed to resemble Leo Pharmaceutical Co.'s KH-1060 (3), is recognized by catabolic enzymes, the selective biological profile of sulfone 4a is likely not due to its metabolites that are formed in only minor amounts.

PPARgamma agonists enhance human vascular endothelial adhesiveness by increasing ICAM-1 expression.

Early atherosclerotic lesions are characterized by increased monocyte adhesion to the overlying endothelium. Oxidized LDL (oxLDL) stimulates the adhesion of human monocytes to endothelial cells, in part, by increasing expression of ICAM-1. However, the cellular role of oxLDL in endothelial adhesiveness is not well understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is expressed in vascular endothelial cells. Whether it can be activated by a synthetic ligand, troglitazone, as well as by natural ligands, oxLDL and its lipid components (i.e., 9- and 13-HODE), has not yet been explored. This study was undertaken to determine whether PPARgamma is expressed in ECV304 human vascular endothelial cells and if so to define the biological effects of its activation by these agonists. Our results demonstrate that PPARgamma mRNA is expressed in ECV304 cells, and transfected cells with a PPARE luciferase construct respond to these agonists. In addition, ligand-dependent PPARgamma activation increased ICAM-1 protein expression and enhanced adherence of monocytes to ECV304 cells by two- to threefold. These findings suggest that the PPARgamma signaling pathway might contribute to the atherogenicity of oxLDL in vascular endothelial cells.

Differential regulation of c-fos expression in estrogen-induced hamster renal tumors compared with kidney not due to creation of an estrogen-response element by point mutation in the gene's flanking sequence.

The conversion of a palindromic sequence, GGTCTnnnAGACC, in the 5'-flanking region of the murine c-fos proto-oncogene into a functional estrogen-response element by a single base change into GGTC(A/G)nnnAGACC has previously been postulated [Nawaz et al., 1993] as a possible mechanism of the induction of tumors by estrogens. This attractive hypothesis has been investigated in estradiol-induced Syrian hamster kidneytumors, in H-301 kidney tumor cells (a cell line derived from the Syrian hamster tumor), and in normal kidney tissue. The c-fos gene is differentially regulated by a classical estrogen receptor-mediated process in tumors, whereas in the acutely treated kidney, estradiol induces c-fos expression independent of estrogen-receptor function. In this study, we identified in the 5'-flanking region of the hamster kidney c-fos gene the sequence AGTCCnnnAGACC, which closely resembled but did not appear to function as an estrogen-response element. No mutations were detected in this sequence or in the 5'-flanking region of c-fos genes from three different primary tumors and from H-301 tumor cells. To rule out the possibility of a low copy number of mutant alleles in a tumor sample, polymerase chain reaction-based single-strand conformation polymorphism analysis was performed on 372 base pairs of the 5'-flank of the c-fos gene (-367 to +5 base pairs relative to the transcription start point). Nine different kidney tumor DNA samples and five normal kidney tissue samples (controls) produced an identical pattern of DNA bands, suggesting a lack of natural polymorphisms and mutations in this region of the c-fos gene. Acute treatment of hamsters with 17beta-estradiol for 6 h significantly induced renal c-fos mRNA expression, whereas control levels of c-fos were restored by co-treatment with estradiol and either N-acetyl-L-cysteine or alpha-naphthoflavone. We concluded that the previously observed change in regulatory control of c-fos expression in kidney versus estradiol-induced tumors does not involve the creation of a functional estrogen-response element by single point mutation in the 5'-flanking region of the gene. Additionally, c-fos expression in estradiol-treated hamster kidneys appears to be mediated by free radicals generated by the catechol metabolites of estradiol and not by the activation of any estrogen receptor.

Protocolo para evaluar la eficacia de nuevos antidepresivos en depresión mayor / Protocol to evaluate the effectiveness of new antidepressants in major depression

El presente documento detalla: Justificación, objetivos, metodología, medicación, historia de enfermedades médicas y medicación concominante, descontinuación

Protocolo para evaluar la eficacia de nuevos antidepresivos en depresión mayor / Protocol to evaluate the effectiveness of new antidepressants in major depression

El presente documento detalla: Justificación, objetivos, metodología, medicación, historia de enfermedades médicas y medicación concominante, descontinuación(AU)

Characterization of cry genes in a Mexican Bacillus thuringiensis strain collection.

Mexico is located in a transition zone between the Nearctic and Neotropical biogeographical regions and contains a rich and unique biodiversity. A total of 496 Bacillus thuringiensis strains were isolated from 503 soil samples collected from the five macroregions of the country. The characterization of the strain collection provided useful information on the ecological patterns of distribution of B. thuringiensis and opportunities for the selection of strains to develop novel bioinsecticidal products. The analysis of the strains was based on multiplex PCR with novel general and specific primers that could detect the cry1, cry3, cry5, cry7, cry8, cry9, cry11, cry12, cry13, cry14, cry21, and cyt genes. The proteins belonging to the Cry1 and Cry9 groups are toxic for lepidopteran insects. The Cry3, Cry7, and Cry8 proteins are active against coleopteran insects. The Cry5, Cry12, Cry13, and Cry14 proteins are nematocidal. The Cry11, Cry21, and Cyt proteins are toxic for dipteran insects. Six pairs of general primers are used in this method. Strains for which unique PCR product profiles were obtained with the general primers were further characterized by additional PCRs with specific primers. Strains containing cry1 genes were the most abundant in our collection (49.5%). Thirty-three different cry1-type profiles were identified. B. thuringiensis strains harboring cry3 genes represented 21.5% of the strains, and 7.9% of the strains contained cry11 and cyt genes. cry7, cry8, and cry9 genes were found in 0.6, 2.4, and 2.6% of the strains, respectively. No strains carrying cry5, cry12, cry13, cry14, or cry21 genes were found. Finally, 14% of the strains did not give any PCR product and did not react with any polyclonal antisera. Our results indicate the presence of strains that may harbor potentially novel Cry proteins as well as strains with combinations of less frequently observed cry genes.

Induction of monoamine oxidase B by 17 beta-estradiol in the hamster kidney preceding carcinogenesis.

Estrogen-induced kidney tumorigenesis in the male Syrian hamster has been postulated to be mediated by free radicals generated by metabolic redox cycling of catecholestrogen intermediates. This tissue and other rodent tissues in which tumors develop in response to estrogen treatment have been shown to contain high levels of the catecholamine norepinephrine. In this study, we have thus examined the hypothesis that an additional source of free radicals may be hydrogen peroxide formed by the monoamine oxidase (MAO)-catalyzed deamination of catecholamines. We have studied the effect of 17beta-estradiol (25-mg pellet, sc) on MAO activity in the hamster kidney (a target organ) and in the hamster liver and the rat kidney and liver, organs which do not develop tumors under these conditions. 17beta-Estradiol treatment for 2 weeks significantly increased (P < 0.01) MAO activity in the hamster kidney (76.7 +/- 10.0 and 113.0 +/- 10.8% over controls for the substrates tyramine and kynuramine, respectively). MAO activity remained elevated after 4 weeks of 17beta-estradiol treatment. No significant changes were observed in the MAO activity of hamster liver or rat kidney and liver. The addition of Tamoxifen to 17beta-estradiol restored control levels of renal MAO activity. The use of selective MAO A and MAO B inhibitors (clorgyline and deprenyl, respectively) identified the B form as the major component of hamster kidney MAO activity and its hormonal regulation. In conclusion, the estrogen receptor-mediated activation of MAO in conjunction with high catecholamine concentrations in the hamster kidney as previously reported may significantly increase the production of hydrogen peroxide and hydroxyl radicals which are postulated to contribute to tumor initiation.

Mechanism of cytochrome P450-catalyzed aromatic hydroxylation of estrogens.

The mechanism of aromatic hydroxylation of estrogens by cytochrome P450 enzymes has been examined by comparing the oxidation of estrone with that of substrates carrying additional aromaticity such as equilenin and the structural analog 2-naphthol. Hamster liver microsomes preferentially catalyzed the conversion of estrone to 2-hydroxyestrone (Km = 30 and 25 microM and Vmax = 1497 and 900 pmol (mg of protein)-1 min-1 for 2- and 4-hydroxyestrone formation, respectively). In contrast, equilenin was hydroxylated exclusively at C-4 of the steroid ring system and 2-naphthol at the corresponding C-1 position (Km = 67 and 42 microM and Vmax = 2083 and 3226 pmol (mg of protein)-1 min-1 for 4-hydroxyequilenin and 1,2-dihydroxynaphthalene formation, respectively). This shift in the specificity of hydroxylation was due to the introduction of additional aromaticity at ring B of equilenin, because hamster liver microsomes are known not to contain any estrogen-4-hydroxylase, only estrogen-2-hydroxylase activity catalyzed by cytochrome P450 3A family enzymes. The exclusive 4-hydroxylation of equilenin is proposed to be due to a preferred delocalization of the naphthoxy radical an intermediate in the hydroxylation, to C-4, whereas delocalization to C-2 requires additional activation energy and is energetically not favored. Based on these electronic considerations, a mechanism of aromatic hydroxylation of estrogens is proposed which features hydrogen abstraction from the phenolic hydroxy group, electron delocalization of the phenoxy radical to a carbon-centered radical, and subsequent formation of catechol metabolites by hydroxy radical addition at C-2 or C-4 depending on steric or electronic constraints.

Metabolic deglucuronidation and demethylation of estrogen conjugates as a source of parent estrogens and catecholestrogen metabolites in Syrian hamster kidney, a target organ of estrogen-induced tumorigenesis.

Estrogen-induced tumors in kidneys of male Syrian hamsters have been postulated to arise from cells which are damaged by free radicals and other reactive species generated during metabolic redox cycling of catecholestrogens and which at the same time are exposed to excessive growth stimulation mediated by estrogen receptors. In this study, we have determined the rates of metabolic deconjugation of estrogen glucuronides and of catecholestrogen methyl ethers by cellular fractions from male hamster kidney and liver to evaluate the contribution of this process to renal pools of parent estrogens and of catecholestrogen metabolites. Lysosomes from male hamster kidney catalyzed the deconjugation of estradiol- and estrone-3 beta-D-glucuronides at rates of 51.7 and 64.6 pmol/mg protein/min, respectively, which were 65 and 34% higher than corresponding deconjugation rates by liver lysosomes. Treatment of hamsters with estradiol implants for 9 days increased lysosomal glucuronidase activities for these estrogen glucuronides by 15 to 25% in kidney and doubled the activities in liver, but it did not alter their corresponding Km values. Microsomal glucuronidase activities in kidney and liver were approximately 10 to 20% of lysosomal activities. Rates of demethylation of 2- and 4-methoxyestradiol by kidney microsomes were comparable (with Vmax values of 24 and 30 pmol/mg protein/min, respectively), whereas the rate of demethylation of 2-methoxyestradiol by liver microsomes was approximately fivefold higher than that of 4-methoxyestradiol. The rates of renal demethylation of methoxyestrogens were comparable with previously published rates of renal aromatic hydroxylation of estradiol, whereas rates of hepatic demethylation were about one-fifth of the corresponding hydroxylation rates. It is concluded that metabolic deconjugation is an important source of primary estrogens and of catecholestrogen metabolites in hamster kidney, a target of estrogen-induced tumorigenesis. The increased renal estrogen glucuronidase activity during prolonged estradiol treatment may also facilitate the development of estrogen-induced tumors in this target organ.

Is it worth using mechanical sutures in gastric surgery?

The use of stapler devices in gastrointestinal surgery has to be justified by the results. Since the cost of staplers is very high, their use should be followed by some advantage in the operating time, the morbidity or mortality rate or the postoperative stay. We have found a slight shortening in the operating time, but only statistically significant for Billroth I, and in the postoperative stay only for oesophagojejunostomies mechanically performed. We have not found any advantage with the other techniques and in the other parameters. Consequently, the use of staplers in gastric surgery should be carefully assessed by the surgeon for each patient in particular, and only used in those cases where a real benefit will be presumed.

Sulfamethazine absorption and disposition: effect of surgical procedures for gastroduodenal ulcers.

This study was designed to determine whether the surgical procedures for gastroduodenal ulcers influence sulfamethazine (SMZ) absorption and disposition. Prior to and on the average 79 days after surgery, eight patients received 10 mg kg-1 of sulfamethazine orally. Blood samples were obtained at regular intervals over 24 h and urine was collected for 48 h. Vagotomy with pyloroplasty or with gastrojejunostomy had no effect on SMZ kinetics. Vagotomy with partial gastrectomy decreased the SMZ plasma peak concentrations from 43.9 +/- 7.1 (mean +/- SEM) to 17.2 +/- 5.2 micrograms ml-1 (p less than 0.05) and increased the time required to reach this peak from 2.6 +/- 0.8 to 9.8 +/- 2.8 h (p less than 0.05). SMZ rate constant of absorption decreased only slightly (1.22 +/- 0.45 to 0.24 +/- 0.07 h-1) and SMZ bioavailability was not affected at all. In two (out of four) patients, SMZ volume of distribution and total body clearance increased, as reflected in the 41 per cent decrease in the mean area under the SMZ plasma concentration-time curve. No changes were detected in SMZ protein binding. Computer simulations indicated that in some subjects SMZ plasma concentrations at steady state could be 76 per cent lower following vagotomy with partial gastrectomy than before surgery. It was concluded that vagotomy and antrectomy with a gastroduodenostomy or Billroth I reconstruction decreased the rate of SMZ absorption and only in some subjects increased the SMZ volume of distribution and rate of elimination. The possible mechanisms involved in these reported kinetic changes are discussed.