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1.
BJS Open ; 3(4): 521-531, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31388645

RESUMEN

Background: There are concerns that non-anatomical resection (NAR) worsens perioperative and oncological outcomes compared with those following anatomical resection (AR) for colorectal liver metastases (CRLM). Most previous studies have been biased by the effect of tumour size. The aim of this study was to compare oncological outcomes after NAR versus AR. Methods: This was a retrospective study of consecutive patients who underwent CRLM resection with curative intent from 1999 to 2016. Data were retrieved from a prospectively developed database. Survival and perioperative outcomes for NAR and AR were compared using propensity score analyses. Results: Some 358 patients were included in the study. Median follow-up was 34 (i.q.r. 16-68) months. NAR was associated with significantly less morbidity compared with AR (31·1 versus 44·4 per cent respectively; P = 0·037). Larger (hazard ratio (HR) for lesions 5 cm or greater 1·81, 95 per cent c.i. 1·13 to 2·90; P = 0·035) or multiple (HR 1·48, 1·03 to 2·12; P = 0·035) metastases were associated with poor overall survival (OS). Synchronous (HR 1·33, 1·01 to 1·77; P = 0·045) and multiple (HR 1·51, 1·14 to 2·00; P = 0·004) liver metastases, major complications after liver resection (HR 1·49, 1·05 to 2·11; P = 0·026) or complications after resection of the primary colorectal tumour (HR 1·51, 1·01 to 2·26; P = 0·045) were associated with poor disease-free survival (DFS). AR was prognostic for poor OS only in tumours smaller than 30 mm, and R1 margin status was not prognostic for either OS or DFS. NAR was associated with a higher rate of salvage resection than AR following intrahepatic recurrence. Conclusions: NAR has at least equivalent oncological outcomes to AR while proving to be safer. NAR should therefore be the primary surgical approach to CRLM, especially for lesions smaller than 30 mm.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Hepáticas , Anciano , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos
2.
Hernia ; 21(4): 649-651, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-27511377

RESUMEN

PURPOSE: Whilst situs inversus is associated with intestinal malrotation and volvulus particularly in infants, this is the first known report of acute intestinal obstruction in an adult patient with a situs anomaly specifically due to a congenital transmesenteric hernia. CASE: A 54-year-old woman presented with a 12-h history of progressive abdominal pain. Contrast-enhanced computed tomography scan of the abdomen revealed an incidental finding of situs inversus abdominus, ischemic small bowel obstruction and a potential occlusive thrombus of the superior mesenteric artery. At operation, the cause of intestinal obstruction was found to be secondary to herniation of the intestine through a congenital mesenteric defect. The hernia was reduced and a strong pulse was subsequently felt in the distal superior mesenteric artery. The patient required resection of a segment of compromised small bowel, and was later anastomosed at a planned second laparotomy. Her laparostomy was closed using an absorbable BioA mesh. CONCLUSION: A high index of suspicion and low threshold for exploratory surgery should be maintained in patients with major congenital abdominal anomalies presenting with an acute abdomen.


Asunto(s)
Hernia/congénito , Obstrucción Intestinal/etiología , Situs Inversus/diagnóstico por imagen , Abdomen , Abdomen Agudo , Dolor Abdominal/etiología , Medios de Contraste , Femenino , Hernia/complicaciones , Humanos , Obstrucción Intestinal/cirugía , Intestino Delgado , Intestinos , Isquemia , Laparotomía , Mesenterio/anomalías , Persona de Mediana Edad , Situs Inversus/complicaciones , Tomografía Computarizada por Rayos X
3.
Health Educ Res ; 30(6): 811-39, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26491072

RESUMEN

The environments in which population health interventions occur shape both their implementation and outcomes. Hence, when evaluating these interventions, we must explore both intervention content and context. Mixed methods (integrating quantitative and qualitative methods) provide this opportunity. However, although criteria exist for establishing rigour in quantitative and qualitative research, there is poor consensus regarding rigour in mixed methods. Using the empirical example of school-based obesity interventions, this methodological review examined how mixed methods have been used and reported, and how rigour has been addressed. Twenty-three peer-reviewed mixed methods studies were identified through a systematic search of five databases and appraised using the guidelines for Good Reporting of a Mixed Methods Study. In general, more detailed description of data collection and analysis, integration, inferences and justifying the use of mixed methods is needed. Additionally, improved reporting of methodological rigour is required. This review calls for increased discussion of practical techniques for establishing rigour in mixed methods research, beyond those for quantitative and qualitative criteria individually. A guide for reporting mixed methods research in population health should be developed to improve the reporting quality of mixed methods studies. Through improved reporting, mixed methods can provide strong evidence to inform policy and practice.


Asunto(s)
Obesidad Infantil/terapia , Práctica de Salud Pública , Proyectos de Investigación/normas , Servicios de Salud Escolar/organización & administración , Pesos y Medidas Corporales , Recolección de Datos , Interpretación Estadística de Datos , Humanos , Conducta Sedentaria
4.
Clin Genet ; 88(3): 267-72, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25225168

RESUMEN

We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.


Asunto(s)
Carcinoma Basocelular/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Carcinoma Basocelular/metabolismo , Análisis Mutacional de ADN , Femenino , Haplotipos , Heterocigoto , Humanos , Pérdida de Heterocigocidad , Masculino , Linaje , Polimorfismo de Nucleótido Simple , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo
5.
Ann Bot ; 112(6): 973-82, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23925972

RESUMEN

BACKGROUND AND AIMS: Root architectural phenes enhancing topsoil foraging are important for phosphorus acquisition. In this study, the utility of a novel phene is described, basal root whorl number (BRWN), that has significant effects on topsoil foraging in common bean (Phaseolus vulgaris). METHODS: Whorls are defined as distinct tiers of basal roots that emerge in a tetrarch fashion along the base of the hypocotyl. Wild and domesticated bean taxa as well as two recombinant inbred line (RIL) populations were screened for BRWN and basal root number (BRN). A set of six RILs contrasting for BRWN was evaluated for performance under low phosphorus availability in the greenhouse and in the field. In the greenhouse, plants were grown in a sand-soil media with low or high phosphorus availability. In the field, plants were grown in an Oxisol in Mozambique under low and moderate phosphorus availability. KEY RESULTS: Wild bean accessions tended to have a BRWN of one or two, whereas cultivated accessions had BRWN reaching four and sometimes five. BRWN and BRN did not vary with phosphorus availability, i.e. BRWN was not a plastic trait in these genotypes. Greater BRWN was beneficial for phosphorus acquisition in low phosphorus soil. Genotypes with three whorls had almost twice the shoot biomass, greater root length and greater leaf area than related genotypes with two whorls. In low phosphorus soil, shoot phosphorus content was strongly correlated with BRWN (R(2) = 0.64 in the greenhouse and R(2) = 0.88 in the field). Genotypes with three whorls had shallower root systems with a greater range of basal root growth angles (from 10 to 45 ° from horizontal) than genotypes with two whorls (angles ranged from 60 to 85 ° from horizontal). CONCLUSIONS: The results indicate that BRWN is associated with increased phosphorus acquisition and that this trait may have value for selection of genotypes with better performance in low phosphorus soils.


Asunto(s)
Phaseolus/metabolismo , Fósforo/metabolismo , Raíces de Plantas/metabolismo , Transporte Biológico , Biomasa , Genotipo , Hipocótilo/anatomía & histología , Hipocótilo/efectos de los fármacos , Hipocótilo/crecimiento & desarrollo , Hipocótilo/metabolismo , Modelos Lineales , Phaseolus/anatomía & histología , Phaseolus/efectos de los fármacos , Phaseolus/crecimiento & desarrollo , Fenotipo , Raíces de Plantas/anatomía & histología , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/anatomía & histología , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo , Brotes de la Planta/metabolismo , Suelo
6.
Leukemia ; 27(5): 1146-54, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23160449

RESUMEN

BCR-ABL induces chronic myeloid leukemia (CML) through the aberrant regulation of multiple signaling substrates. Previous research has shown that BCR-ABL mediates down-modulation of CBL-B protein levels. A murine bone marrow transplantation (BMT) study was performed to assess the contribution of Cbl-b to BCR-ABL-induced disease. The predominant phenotype in the Cbl-b(-/-) recipients was a CML-like myeloproliferative disease (MPD) similar to that observed in the wild-type animals, but with a longer latency, diminished circulating leukocyte numbers and reduced spleen weights. Despite the decreased leukemic burden in comparison to their wild-type counterparts, the Cbl-b(-/-) animals displayed enhanced numbers of Gr-1(+)/Mac-1(+) spleen cells and neutrophilia. On the basis of prior evidence of CBL-B-dependent motility toward SDF-1α, we hypothesized that Cbl-b deficiency might impair bone marrow localization during transplantation. Homing experiments showed reduced migration of Cbl-b(-/-) cells to the bone marrow. Intrafemoral transplantation of BCR-ABL-transduced Cbl-b(-/-) cells revealed equivalent latency of disease development to the wild-type transplants, supporting the conclusion that Cbl-b deficiency diminishes homing of leukemic cells to the bone marrow, and perturbs the proliferation of BCR-ABL-expressing malignant clones during CML development.


Asunto(s)
Células de la Médula Ósea/fisiología , Proteínas de Fusión bcr-abl/fisiología , Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Proteínas Proto-Oncogénicas c-cbl/fisiología , Animales , Trasplante de Médula Ósea , Movimiento Celular , Células Cultivadas , Ratones , Ratones Endogámicos BALB C , Receptores de Quimiocina/análisis
7.
J Dairy Sci ; 95(12): 6871-81, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23040026

RESUMEN

Milk gels were made by renneting and acidifying skim milk containing 5 different starches, and then compressed by centrifugation to express whey and simulate curd syneresis during the manufacture of low-fat cheese. A series of 17 starches were examined, with 5 starches being selected for in-depth analysis: a modified waxy corn starch (WC), a waxy rice starch (WR), an instant tapioca starch (IT), a modified tapioca starch (MT), and dextrin (DX). Milks containing WC, WR, and DX were given a 72°C heat treatment, whereas those containing IT and MT had a 30-min treatment at 66°C that matched their optimum gelatinization treatments. Curd yields were calculated by weight, estimated starch content in whey was measured gravimetrically by alcohol precipitation, and starch retention in curd was calculated. Curd yields were 13.1% for the control milk (no added starch) and 18.4, 20.7, 21.5, 23.5, and 13.2% for the gels containing starches WC, WR, IT, MT, and DX, respectively. Estimated starch retentions in the curd were, respectively, 71, 90, 90, 21, and 1%. Laser scanning confocal microscopy was used to determine the location of the starches in the curd and their interaction with the protein matrix. Waxy corn, WR, and IT starches have potential to improve texture of low-fat cheese because they had high retention in the curd and they generated interruptions in the protein matrix network that may have helped limit extensive protein-protein interactions. Modified tapioca starch interfered with formation of the protein structure of the curd and produced a soft noncohesive gel, even though most (79%) of the MT starch was lost in the whey. Few distinct starch particles were present in the MT curd network. Dextrin was not retained in the curd and did not disrupt the protein network, making it unsuitable for use in low-fat cheese.


Asunto(s)
Proteínas de la Leche/química , Leche/química , Almidón/farmacología , Animales , Bovinos , Queso , Quimosina/química , Quimosina/efectos de los fármacos , Tecnología de Alimentos/métodos , Geles/química , Microscopía Confocal , Leche/efectos de los fármacos , Proteínas de la Leche/efectos de los fármacos , Proteínas de la Leche/ultraestructura , Proteína de Suero de Leche
8.
Sci Total Environ ; 408(23): 5631-8, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-19464728

RESUMEN

Diffuse pollution from agriculture remains a significant challenge to many countries seeking to improve and protect their water environments. This paper reviews literature relating to the provision of information and advice as a mechanism to encourage farmers to mitigate diffuse pollution. The paper presents findings from a literature review on influencing farmer behaviour and synthesizes three main areas of literature: psychological and institutional theories of behaviour; shifts in the approach to delivery of advice (from knowledge transfer to knowledge exchange); and the increased interest in heterogeneous farming cultures. These three areas interconnect in helping to understand how best to influence farmer behaviour in order to mitigate diffuse pollution. They are, however, literatures that are rarely cited in the water management arena. The paper highlights the contribution of the 'cultural turn' taken by rural social scientists in helping to understand collective and individual voluntary behaviour. The paper explores how these literatures can contribute to the existing understanding of water management in the agricultural context, particularly: when farmers question the scientific evidence; when there are increased calls for collaborative planning and management; and when there is increased value placed on information as a business commodity. The paper also highlights where there are still gaps in knowledge that need to be filled by future research - possibly in partnership with farmers themselves. Whilst information and advice has long been seen as an important part of diffuse pollution control, increasing climate variability that will require farmers to practice adaptive management is likely to make these mechanisms even more important.


Asunto(s)
Agricultura/métodos , Control de la Conducta , Contaminación del Agua/prevención & control , Conservación de los Recursos Naturales , Política Ambiental , Formulación de Políticas
9.
Am J Surg ; 193(3): 319-24; discussion 324-5, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17320527

RESUMEN

BACKGROUND: Long-term survival for duodenal adenocarcinoma is inconsistent in the literature, and the biology of duodenal adenocarcinoma is poorly understood. METHODS: One institution's experience with duodenal adenocarcinoma from 1984 to 2005 is reviewed. Clinicopathologic data were analyzed, and overall survival was estimated using Kaplan-Meier curves with log-rank test. RESULTS: Of the 52 patients, 35 (67%) underwent potentially curative surgery; 31 survived the postoperative period and were included in the analysis. Of these, the median survival was 34 months (range 6 to 186 months) compared with 13 months (range 1 to 24 months) for those not undergoing curative surgery (P < or = .001). Clinicopathologic factors favoring long-term survival were tumor size >3.5 cm (P < or = .001) and T-stage < or =4 (P = .014). CONCLUSIONS: Clinicopathologic factors important to survival in duodenal cancer are T4 tumor status and tumor size. Interestingly, larger tumors were less likely to be invasive, and patients with these tumors had improved survival. The biology of this cancer is poorly understood; therefore, aggressive resection for all duodenal adenocarcinomas is recommended for all patients medically fit to undergo resection.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Duodenales/cirugía , Selección de Paciente , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Illinois/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
10.
Heredity (Edinb) ; 94(6): 606-15, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15829986

RESUMEN

Comparative analyses of nuclear and organelle genetic markers may help delineate evolutionarily significant units or management units, although population differentiation estimates from multiple genomes can also conflict. Striped bass (Morone saxatilis) are long-lived, highly migratory anadromous fish recently recovered from a severe decline in population size. Previous studies with protein, nuclear DNA and mitochondrial DNA (mtDNA) markers produced discordant results, and it remains uncertain if the multiple tributaries within Chesapeake Bay constitute distinct management units. Here, 196 young-of-the-year (YOY) striped bass were sampled from Maryland's Choptank, Potomac and Nanticoke Rivers and the north end of Chesapeake Bay in 1999 and from Virginia's Mataponi and Rappahannock Rivers in 2001. A total of 10 microsatellite loci exhibited between two and 27 alleles per locus with observed heterozygosities between 0.255 and 0.893. The 10-locus estimate of R(ST) among the six tributaries was -0.0065 (95% confidence interval -0.0198 to 0.0018). All R(ST) and all but one theta estimates for pairs of populations were not significantly different from zero. Reanalysis of Chesapeake Bay striped bass mtDNA data from two previous studies estimated population differentiation between theta=-0.002 and 0.160, values generally similar to mtDNA population differentiation predicted from microsatellite R(ST) after adjusting for reduced effective population size and uniparental inheritance in organelle genomes. Based on mtDNA differentiation, breeding sex ratios or gene flow may have been slightly male biased in some years. The results reconcile conflicting past studies based on different types of genetic markers, supporting a single Chesapeake Bay management unit encompassing a panmictic striped bass breeding population.


Asunto(s)
Lubina/genética , Núcleo Celular/genética , ADN Mitocondrial/genética , Marcadores Genéticos , Repeticiones de Microsatélite , Alelos , Animales , Cruzamiento , Genética de Población , Heterocigoto , Maryland , Virginia
11.
Eur Respir J ; 24(4): 601-8, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15459139

RESUMEN

To determine relationships among social predictors and sarcoidosis severity at presentation, demographic characteristics, socioeconomic status, and barriers to care, A Case-Control Etiologic Study of Sarcoidosis (ACCESS) was set up. Patients self-reported themselves to be Black or White and were tissue-confirmed incident cases aged > or =l8-yrs-old (n=696) who had received uniform assessment procedures within one of 10 medical centres and were studied using standardised questionnaires and physical, radiographical, and pulmonary function tests. Severity was measured by objective disease indicators, subjective measures of dyspnoea and short form-36 subindices. The results of the study showed that lower income, the absence of private or Medicare health insurance, and other barriers to care were associated with sarcoidosis severity at presentation, as were race, sex, and age. Blacks were more likely to have severe disease by objective measures, while women were more likely than males to report subjective measures of severity. Older individuals were more likely to have severe disease by both measures. In conclusion, it was found that low income and other financial barriers to care are significantly associated with sarcoidosis severity at presentation even after adjusting for demographic characteristics of race, sex, and age.


Asunto(s)
Sarcoidosis/epidemiología , Adulto , Estudios de Casos y Controles , Demografía , District of Columbia/epidemiología , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Grupos Raciales , Sarcoidosis/etiología , Índice de Severidad de la Enfermedad , Factores Socioeconómicos
12.
J Burn Care Rehabil ; 25(1): 81-8, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-14726744

RESUMEN

Experimental evidence implicates Fas ligand-mediated keratinocyte apoptosis as an underlying mechanism of toxic epidermal necrolysis syndrome (TEN). In vitro studies indicate a potential role for immunoglobulin (Ig) therapy in blocking Fas ligand signaling, thus reducing the severity of TEN. Anecdotal reports have described successful treatment of TEN patients with Ig; however, no study to date has analyzed outcome data in a large series of patients treated with Ig using institutional controls. The SCORTEN severity-of-illness score ranks severity and predicts prognosis in TEN patients using age, heart rate, TBSA slough, history of malignancy, and admission blood urea nitrogen, serum bicarbonate, and glucose levels. A retrospective chart review was performed that included all patients treated for TEN at our burn center since 1997. Ig therapy was instituted for all patients with biopsy-proven TEN beginning in January 2000. Twenty-one TEN patients were treated before Ig (no-Ig group), and 24 patients have been treated with Ig. SCORTEN data were collected, as well as length of stay (LOS) and status upon discharge. Each patient was given a SCORTEN of 0 to 6, with 1 point each for age greater than 40, TBSA slough greater than 10%, history of malignancy, admission BUN greater than 28 mg/dl, HCO3 less than 20 mg/dl, and glucose greater then 252 mg/dl. Outcome was compared between patients treated with Ig and without Ig. Overall mortality for patients treated before Ig was 28.6% (6/21), and with Ig, mortality was 41.7%% (10/24). There was no significant difference in age or TBSA slough. The average SCORTEN between the groups was equivalent (2.2 in no-Ig group vs 2.7 in Ig group, P = 0.3), and no group of patients with any SCORTEN score showed a significant benefit from Ig therapy. Overall LOS as well as LOS for survivors was longer in the Ig group. This series represents the largest single-institution analysis of TEN patient outcome after institution of Ig therapy. Our data do not show a significant improvement in mortality for TEN patients treated with Ig at any level of severity and may indicate a potential detriment in using Ig. Ig should not be given to TEN patients outside of a clinical trial. A multicenter, prospective, double-blinded randomized trial is necessary and urgently indicated to determine whether Ig therapy is beneficial or harmful in the care of TEN patients.


Asunto(s)
Inmunización Pasiva , Síndrome de Stevens-Johnson/terapia , Adulto , Superficie Corporal , Unidades de Quemados , Estudios de Casos y Controles , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/mortalidad
13.
Emerg Med J ; 20(4): 383-4, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12835367

RESUMEN

Needle aspiration is a recognised emergency treatment of spontaneous pneumothorax and in the case of suspected tension is usually performed before chest radiography. Three cases are described of apparent life threatening haemorrhage after anterior aspiration in the second intercostal space, mid-clavicular line (2ICS MCL) requiring resuscitation, and transfer to a cardiothoracic unit. In these patients there was no evidence of haemothorax on initial presentation. Lateral needle aspiration, in the site recommended for chest drain insertion, the 5th intercostal space, anterior axillary line (5ICS ALL) is technically easy and may be a potentially safer option for decompressing pneumothoraces.


Asunto(s)
Biopsia con Aguja , Hemotórax/etiología , Neumotórax/terapia , Adulto , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/métodos , Urgencias Médicas , Humanos , Masculino , Succión/efectos adversos
15.
Mol Psychiatry ; 7(4): 419-23, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11986987

RESUMEN

Recently, a Leu309Met mutation in WKL1 (MLC1, KIAA0027), a gene mapped to chromosome 22q13.33, was reported to co-segregate with periodic catatonia, a clinical sub-type of schizophrenia, in seven members of an extended pedigree.(1) WKL1 encodes a putative membrane protein expressed exclusively in the brain, particularly in the amygdala, nucleus caudatus, thalamus, and hippocampus.(1) We screened WKL1 for etiologic mutations in 28 probands from the United States who were given a consensus diagnosis of schizophrenia and met at least one of these criteria: (1) were from multiplex schizophrenia families where at least two schizophrenic subjects were reported to display catatonic behavior at sometime during the course of their illness; or (2) were from multiplex schizophrenia families where, in a genome scan for schizophrenia susceptibility loci, evidence for excess allele sharing among affected family members for markers in the 22q13 region was seen. In addition, 15 affected subjects from 15 German pedigrees were similarly screened for causative mutations. This German cohort exhibited the catatonia phenotype but had ambiguous linkage to 22q13 and included the mutation-positive proband as a positive control. The 43 probands were screened for base changes in WKL1: 15 SNPs in the non-coding regions of the gene, three SNPs in the 3'UTR, four synonymous coding SNPs and two non-synonymous (amino acid changing) SNPs were identified. We were able to rapidly confirm the Leu309Met nucleotide change in the positive control. No missense mutations were detected in any of the other 42 probands studied. These data exclude the role of WKL1 in schizophrenia susceptibility in the subjects studied.


Asunto(s)
Canales Iónicos/genética , Mutación Missense , Esquizofrenia Catatónica/genética , Adolescente , Adulto , Niño , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Estados Unidos
16.
Mol Psychiatry ; 7(1): 86-9, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11803451

RESUMEN

There is significant evidence for genetic factors in the susceptibility to anorexia nervosa (AN). Previously genetic variation in the estrogen receptor 2 gene (ESR2) has been studied, however no strong evidence of association with AN has been found. In the present study variation in the estrogen receptor 1 (ESR1) and ESR2 genes was examined. Estrogen receptors have been localised to areas of the brain involved in behaviour and regulation of food intake. The anorexic effects of estrogen are accentuated by stress and thus it is postulated that variation in the estrogen receptors may contribute to the genetic susceptibility to AN in females. A cohort of 170 female, Caucasian AN sufferers and 152 female controls were typed for dinucleotide repeat polymorphisms in both ESR1 and ESR2 and two further SNPs at each locus. Variation at ESR1 was not associated with AN. However an association was found at the ESR2 locus with the heterozygous genotype of the G1082A polymorphism and AN but not with any of the other ESR2 polymorphisms analysed. Analysis of haplotypes at ESR1 and ESR2 showed no significant evidence of association with AN suggesting that the variability in ESR2 alone may contribute to the genetic susceptibility to AN.


Asunto(s)
Anorexia Nerviosa/genética , Repeticiones de Dinucleótido , Conducta Alimentaria/fisiología , Polimorfismo de Nucleótido Simple , Receptores de Estrógenos/genética , Adolescente , Anorexia Nerviosa/epidemiología , Estudios de Cohortes , Inglaterra/epidemiología , Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Exones/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo Genético , Receptores de Estrógenos/fisiología , Población Blanca/genética
17.
Plant Soil ; 232(1-2): 69-79, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11729851

RESUMEN

Root gravitropism may be an important element of plant response to phosphorus availability because it determines root foraging in fertile topsoil horizons, and thereby phosphorus acquisition. In this study we seek to test this hypothesis in both two dimensional paper growth pouch and three-dimensional solid media of sand and soil cultures. Five common bean ( Phaseolus vulgaris L.) genotypes with contrasting adaptation to low phosphorus availability were evaluated in growth pouches over 6 days of growth, and in sand culture and soil culture over 4 weeks of growth. In all three media, phosphorus availability regulated the gravitropic response of basal roots in a genotype-dependent manner. In pouches, sand, and soil, the phosphorus-inefficient genotype DOR 364 had deeper roots with phosphorus stress, whereas the phosphorus-efficient genotype G19833 responded to phosphorus stress by producing shallower roots. Genotypes were most responsive to phosphorus stress in sand culture, where relative root allocation to the 0-3- and 3-6-cm horizons increased 50% with phosphorus stress, and varied 300% (3-6 cm) to 500% (0-3 cm) among genotypes. Our results indicate that (1) phosphorus availability regulates root gravitropic growth in both paper and solid media, (2) responses observed in young seedlings continue throughout vegetative growth, (3) the response of root gravitropism to phosphorus availability varies among genotypes, and (4) genotypic adaptation to low phosphorus availability is correlated with the ability to allocate roots to shallow soil horizons under phosphorus stress.


Asunto(s)
Fabaceae/crecimiento & desarrollo , Fabaceae/genética , Gravitropismo/fisiología , Fósforo/metabolismo , Raíces de Plantas/metabolismo , Biomasa , Medios de Cultivo , Fabaceae/metabolismo , Genotipo , Papel , Fósforo/análisis , Fósforo/deficiencia , Fósforo/farmacocinética , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/genética , Brotes de la Planta/crecimiento & desarrollo , Brotes de la Planta/metabolismo , Dióxido de Silicio/análisis , Suelo/análisis
18.
Muscle Nerve ; 24(11): 1542-7, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11745958

RESUMEN

Rippling muscle disease (RMD) has previously been reported as a skeletal myopathy that was attributed to a defect in the sarcomere. Here we report a new form of RMD that is more severe, characterized by fatal arrhythmic cardiomyopathy and delayed bone age. Mortality has previously not been associated with RMD. With this report we hope to raise awareness that a subset of patients with this clinical entity are predisposed to severe cardiac disease.


Asunto(s)
Arritmias Cardíacas/genética , Músculo Esquelético/patología , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Adolescente , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidad , Electrocardiografía , Salud de la Familia , Resultado Fatal , Femenino , Genes Recesivos , Humanos , Masculino , Linaje , Fenotipo
19.
Public Health Nutr ; 4(2B): 593-9, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11683552

RESUMEN

Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.


Asunto(s)
Hígado/enzimología , Selenio/metabolismo , Glutatión Peroxidasa/metabolismo , Salud , Humanos , Inmunidad , Yoduro Peroxidasa/metabolismo , Hígado/metabolismo , Necesidades Nutricionales , Proteínas , Selenio/administración & dosificación , Selenio/sangre , Selenoproteína P , Selenoproteína W , Selenoproteínas , Reductasa de Tiorredoxina-Disulfuro/metabolismo
20.
Ann Thorac Surg ; 72(4): 1409-10, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11603487

RESUMEN

The vacuum-assisted closure (VAC; KCI International, San Antonio, TX) device is a negative pressure dressing, which we have used in the treatment of wounds with devitalized or infected tissues. Although introduced in plastic and reconstructive surgery, its use has extended to orthopedic and cardiothoracic surgical practice in the treatment of infected joint replacement and sternal wound infections, respectively. Although the VAC is becoming more widely used in surgical practice, only a small number of case reports exist in addition to the original case series by Argenta and Morykwas in 1997. Previously, the device was described in treating single wounds in adult patients. We report a case where it was successfully used to treat multiple dog bite injuries in a 9-year-old child.


Asunto(s)
Mordeduras y Picaduras/cirugía , Traumatismo Múltiple/cirugía , Apósitos Oclusivos , Infecciones por Pseudomonas/cirugía , Traumatismos Torácicos/cirugía , Infección de Heridas/cirugía , Animales , Niño , Desbridamiento , Perros , Femenino , Humanos , Succión/instrumentación , Vacio
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