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1.
Br J Anaesth ; 132(5): 1041-1048, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38448274

RESUMEN

BACKGROUND: Regional anaesthesia use is growing worldwide, and there is an increasing emphasis on research in regional anaesthesia to improve patient outcomes. However, priorities for future study remain unclear. We therefore conducted an international research prioritisation exercise, setting the agenda for future investigators and funding bodies. METHODS: We invited members of specialist regional anaesthesia societies from six continents to propose research questions that they felt were unanswered. These were consolidated into representative indicative questions, and a literature review was undertaken to determine if any indicative questions were already answered by published work. Unanswered indicative questions entered a three-round modified Delphi process, whereby 29 experts in regional anaesthesia (representing all participating specialist societies) rated each indicative question for inclusion on a final high priority shortlist. If ≥75% of participants rated an indicative question as 'definitely' include in any round, it was accepted. Indicative questions rated as 'definitely' or 'probably' by <50% of participants in any round were excluded. Retained indicative questions were further ranked based on the rating score in the final Delphi round. The final research priorities were ratified by the Delphi expert group. RESULTS: There were 1318 responses from 516 people in the initial survey, from which 71 indicative questions were formed, of which 68 entered the modified Delphi process. Eleven 'highest priority' research questions were short listed, covering themes of pain management; training and assessment; clinical practice and efficacy; technology and equipment. CONCLUSIONS: We prioritised unanswered research questions in regional anaesthesia. These will inform a coordinated global research strategy for regional anaesthesia and direct investigators to address high-priority areas.


Asunto(s)
Anestesia de Conducción , Investigación Biomédica , Humanos , Técnica Delphi , Encuestas y Cuestionarios , Proyectos de Investigación
3.
J Appl Microbiol ; 131(5): 2294-2307, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33900669

RESUMEN

AIMS: Calcium carbonate is a biomineral whose precipitation could be mediated by ureolytic bacteria and contributes in strengthening of sandy soils. The type of bacteria and grade of reagents have significant influence on microbially induced calcite precipitation (MICP). In the present study, factorial experiments based on these two factors were designed to determine their potential on MICP process, taking into consideration the economic advantages while giving quality results as well. METHODS AND RESULTS: For the first time, Alkalibacterium iburiense strain EE1 (GenBank accession no. MF355369.1) is reported for its biogrouting activity. Optimum growth conditions for MICP treatments were pH (9·56 ± 0·021), EC (44·7 ± 0·057 mS cm-1 ), OD600 (2·04 ± 0·015), NH4 + concentration (487·06 ± 1·021 mmol l-1 ), and urease activity (20·0 ± 0·75 mmol l-1 urea hydrolysed min-1 ) after 72-h incubation. Statistical analysis comparing the growth in technical-grade medium prepared in tap water and analytical-grade medium prepared in deionized water showed no significant differences (P = 1·0) in biomass and urease activity. In contrast to previous studies, the current approach could reduce the bacterial culture and cementation solution ratio by about 50%, using a simple surface percolation method with staged injection instead of parallel injection to treat different sand columns. Using fixation solution could immobilize the bacteria over the full length of columns for better strength improvement. The unconfined compressive strength ranged between 0·64 to 2·11 kg cm-2 , and the corresponding CaCO3 contents 5·7-38·5%. The scanning electron microscope images indicated that the precipitated CaCO3 by bacteria was stable calcite. CONCLUSIONS: Alkalibacterium iburiense and technical-grade reagents under nonsterile conditions are satisfactory consolidating agents for sandy soils. SIGNIFICANCE AND IMPACT OF THE STUDY: This approach is considered eco-friendly and cost-effective for future scale-up applications in various geotechnical engineering.


Asunto(s)
Carnobacteriaceae , Ureasa , Bacterias , Carbonato de Calcio , Suelo
4.
Curr Oncol ; 26(5): 338-344, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31708652

RESUMEN

Background: Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important. Methods: We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc. Results: A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for RET mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism. Summary: Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.


Asunto(s)
Carcinoma Neuroendocrino/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Calcitonina/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma Neuroendocrino/sangre , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Mutación de Línea Germinal , Humanos , Guías de Práctica Clínica como Asunto , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología
5.
Curr Oncol ; 26(6): 389-394, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31896937

RESUMEN

Medullary thyroid cancer is a rare type of neuroendocrine tumour that arises from the parafollicular cells (C cells) of the thyroid gland. It accounts for 3%-5% of thyroid cancer cases. Close to 25% of cases are familial, and 75% are considered sporadic. Familial cases are associated with a germline RET mutation; 43%-65% of sporadic cases harbour a somatic event in the gene. Germline RET mutations are associated with the autosomal-dominant inherited multiple endocrine neoplasia (men) 2a and 2b syndromes and the isolated familial medullary thyroid cancer syndrome. More than 100 RET codon mutations have been reported to date, with genotype-phenotype correlations that include the extent and aggressiveness of the medullary thyroid cancer and the presence of other features of the men2 syndromes. The latter include pheochromocytoma-paraganglioma, hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung disease. In this narrative review, we focus on RET proto-oncogene physiology and pathogenesis induced by germline and somatic RET mutations, the genotype-phenotype correlation, and the management and follow-up of patients with germline-mutated medullary thyroid cancer.


Asunto(s)
Carcinoma Neuroendocrino/genética , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genética , Estudios de Asociación Genética , Pruebas Genéticas , Humanos , Mutación , Proto-Oncogenes Mas
6.
Endocr Relat Cancer ; 24(4): C5-C8, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28264912

RESUMEN

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.


Asunto(s)
Adenoma/clasificación , Tumores Neuroendocrinos/clasificación , Neoplasias Hipofisarias/clasificación , Humanos
7.
Prog Mol Biol Transl Sci ; 143: 187-210, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27697203

RESUMEN

Gonadotrope tumors arise from the gonadotropes of the adenohypophysis. These cells rarely give rise to hyperplasia, usually only in the setting of long-standing premature gonadal failure. In contrast, gonadotrope tumors represent one of the most frequent types of pituitary tumors. Despite their relatively common occurrence, the pathogenesis of gonadotrope tumors remains unknown. Effective nonsurgical therapies remain out of reach. We review the pituitary gonadotrope from the morphologic and functional perspectives to better understand its involvement as the cell of origin of a frequent type of pituitary tumor.


Asunto(s)
Gonadotrofos/patología , Neoplasias/patología , Animales , Biomarcadores de Tumor/metabolismo , Humanos , Hiperplasia , Neoplasias/diagnóstico por imagen , Neoplasias/epidemiología , Pronóstico
8.
J Pharm Biomed Anal ; 125: 292-302, 2016 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-27061877

RESUMEN

Ocimum (sweet basil) is a plant of considerable commercial importance in traditional medicine worldwide as well as for the flavor and food industry. The goal of this study was to examine Ocimum extracts anti-acetylcholinesterase activity and to correlate the activity with their secondary metabolites profiles via a metabolome based ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) approach coupled to chemometrics. The metabolomic differences in phenolics from leaves derived from 4 Ocimum species: Ocimum basilicum, Ocimum africanum, Ocimum americanum and Ocimum minimum were assessed. Under optimized conditions, 81 metabolites were identified including 21 hydroxy cinnamic acids, 4 benzoic acid conjugates, 14C/O flavonoid conjugates, 2 alcohols, 5 acyl sugars, 4 triterpenes and 12 fatty acids. Several salviolanic acid derivatives including salviolanic acid A, B, C & I found in Salvia, were found in Ocimum herein for the first time. Unsupervised principal component analysis (PCA) and supervised orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were further used for comparing and classification of samples. A clear separation among the four investigated Ocimum species was revealed, with O. africanum samples found most enriched in hydroxy cinnamates conjugates (HC) and flavonoids. To the best of our knowledge, this is the first report for compositional differences among Ocimum leaves via a metabolomic approach revealing that among examined species O. africanum leaves present a better source of Ocimum bioactive metabolites. The anticholinesrase activity of examined species was further assessed with a potent IC50 values for O. americanum, O. africanum, O. basilicum ranging from 2.5 to 6.6mg/ml, whereas O. minimum was least active with IC50 of 31.4mg/ml. Furthermore, major HC i.e., caftaric, chlorogenic and rosmarinic acids identified in extracts via UPLC-MS analysis exhibited IC50 values of 24, 0.5 and 7.9mg/ml respectively, suggesting that HCs are likely to mediate for the anticholinesterase effect in Ocimum extracts.


Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Metabolómica , Ocimum/metabolismo
9.
Oncogene ; 2015 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-25639874

RESUMEN

Fibroblast growth factor receptor 2 (FGFR2) has been shown reproducibly in genome-wide association studies to be associated with increased breast cancer risk. Here we show that mouse mammary tumor virus-neu mice develop breast carcinomas with FGFR2 immunoreactivity that parallels HER2 expression. FGFR2 signaling promotes HER2 shedding through the metalloprotease ADAM10 leading to intracellular accumulation of the truncated p95HER2 protein. This is accompanied by enhanced HER2 signaling and diminished sensitivity to trastuzumab. Functionally, FGFR2 facilitates HER2-mediated cell proliferation, acinar growth in three-dimensional morphogenesis assays and promotes tumor progression in mouse xenografts. These data implicate FGFR2 in a novel mechanism of ErbB activation and demonstrate an important interaction between FGFR2 and HER2 in promoting breast cancer progression.Oncogene advance online publication, 2 February 2015; doi:10.1038/onc.2014.440.

10.
Springerplus ; 2: 490, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24156088

RESUMEN

OBJECTIVES: Evaluation of Fluorescent in situ hybridization (FISH) as a tool for rapid aneuploidy screening (RAS) of high risk pregnancies, before its approval in the national antenatal screening and genetic diagnosis program in Egypt. METHODS: The cytogenetic data of prenatal specimens, and results of FISH of 100 patients performed between, January 2009 and December 2009, at the Medical Genetics Center (MGC) laboratory were retrieved and reviewed. AneuVysion Assay kit was used for detection of 13, 21, X, Y, 18 aneuploidies. RESULTS: Maternal age varied from 21 to 44 years (mean was 35.6 year). Ninety percent of pregnancies had normal chromosomes and 10% of the cases had numerical chromosomal abnormalities. Trisomy 21 was the most frequent chromosomal disorder across all indications (5%), followed by Turner syndrome (2%), trisomy 18 (2%), and trisomy 13 (1%). When comparing the FISH data with karyotype results for chromosomes 13, 18, 21, X, and Y in the 83 individual tested, no false positive or negative results were detected by the FISH assay. The result obtained by FISH and the banding cytogenetic were in complete accordance. CONCLUSION: This study supports the integration of amniotic fluid (AF) FISH as a RAS test, in to routine antenatal practice for identification of chromosome aneuploidies. There are trends towards delayed childbearing and most cases of Down Syndrome (DS) are currently detected post-nataly in the Egyptian population. Consequently, the live birth prevalence of DS has increased, which might lead to a serious negative public health effects.

11.
Artículo en Inglés | MEDLINE | ID: mdl-22376138

RESUMEN

Mycotoxins such as the aflatoxins and deoxynivalenol (DON) are frequent contaminants of food. Aflatoxin B1 (AFB1) and DON affect the immune system and restrict growth; additionally AFB1 is carcinogenic. To date there are limited descriptive biomarker data concerning maternal exposures during pregnancy, and none on co-exposures to these mycotoxins. This survey was a cross-sectional assessment providing descriptive data on the concentrations of serum aflatoxin-albumin (AF-alb), urinary aflatoxin M1 (AFM1), and urinary DON for 98 pregnant women from Egypt, in relation to diet and socioeconomic status, during the third trimester. AF-alb was detected in 34 of 98 (35%) samples, geometric mean (GM) of positives = 4.9 pg AF-lys mg(-1) albumin (95% confidence interval (CI) = 4.1-5.8 pg mg(-1)), and AFM1 in 44 of 93 (48%) samples, GM of positives = 19.7 pg mg(-1) creatinine (95%CI = 14.8-26.3 pg mg(-1)). AF-alb and AFM1 levels were positively correlated (R = 0.276, p = 0.007). DON was detected in 63 of 93 (68%), GM of positives = 2.8 ng mg(-1) (95%CI = 2.1-3.6 ng mg(-1)). Aflatoxin and DON biomarkers were observed in 41% of the subjects concurrently. The frequency and level of these biomarkers in Egyptian women were modest compared with known high-risk countries. However, this study represents the first biomarker survey to report on the occurrence of DON biomarkers in an African population, in addition to the co-occurrence of these two potent mycotoxins. This combined exposure may be of particular concern during pregnancy given the potential of toxin transfer to the foetus.


Asunto(s)
Aflatoxina B1/orina , Exposición a Riesgos Ambientales , Exposición Materna , Tricotecenos/orina , Adolescente , Adulto , Biomarcadores/orina , Estudios Transversales , Egipto , Femenino , Contaminación de Alimentos , Humanos , Embarazo , Adulto Joven
12.
Oncol Rev ; 6(1): e3, 2012 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-25992205

RESUMEN

Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission. The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24-60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P<0.01).

13.
Support Care Cancer ; 20(3): 641-5, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22072050

RESUMEN

PURPOSE: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. METHODS: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. RESULTS: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). CONCLUSION: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.


Asunto(s)
Radioisótopos de Yodo/uso terapéutico , Participación del Paciente , Satisfacción del Paciente , Neoplasias de la Tiroides/radioterapia , Adolescente , Adulto , Toma de Decisiones , Emociones , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Encuestas y Cuestionarios , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto Joven
14.
Oncogene ; 31(36): 4012-21, 2012 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-22158039

RESUMEN

The growth factor receptor-bound protein (Grb) 14 is an adaptor molecule of the Grb7/10/14 family with characteristic Between Plekstrin and SH2 (BPS) domains serving to avidly bind tyrosine kinases. Grb14 inhibits insulin receptor (IR) catalytic activity through interaction with the BPS domain and impedes peptide substrate binding. Members of this Grb family have also been shown to interact with other kinases through their SH2 domain. Here we examined the functional role of Grb14 in thyroid cancer using loss- and gain-of-function approaches. Stable knockdown of Grb14 in thyroid cancer cells facilitated IR signaling. In contrast, RET phosphorylation was diminished in concert with reduced activation of Akt and signal transducer and activator of transcription 3 (STAT3). Loss of Grb14 also resulted in diminished cell proliferation and invasion both in vitro and in mouse flank xenografts. In complementary studies, forced expression of Grb14 interrupted IR signaling but facilitated RET activation, STAT3 and Akt phosphorylation. Consistent with these findings Grb14 overexpression enhanced cell invasion and resulted in striking metastases in an orthotopic thyroid cancer mouse xenograft model. Primary human thyroid cancer microarrays revealed a positive correlation between Grb14 expression and invasive behavior. Our findings uncover a new role for Grb14 in finely tuning receptor signaling and modulating thyroid cancer progression.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma/metabolismo , Proteínas Proto-Oncogénicas c-ret/metabolismo , Neoplasias de la Tiroides/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Carcinoma/patología , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Activación Enzimática , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Ratones SCID , Invasividad Neoplásica , Trasplante de Neoplasias , Interferencia de ARN , Receptor de Insulina/metabolismo , Transducción de Señal , Neoplasias de la Tiroides/patología , Análisis de Matrices Tisulares
15.
Phytomedicine ; 19(1): 38-41, 2011 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-21890334

RESUMEN

The antidiabetic activities of the aqueous (AqEx) and ethanolic (AlEx) extracts of Cleome droserifolia (Forssk.) Del., were tested in cultured C2C12 skeletal muscle cells and 3T3-L1 adipocytes. An 18-h treatment with the AqEx increased basal glucose uptake by 33% [insulin equivalent (IE)=1.3±0.04] in muscle cells comparable to a 25.5% increase caused by 100 nM insulin (IE=1±0.03). Fractionation of the tested AqEx yielded hexane (HxFr), chloroform (ClFr) and ethyl acetate (EtFr) fractions which exerted 38, 52 and 35% increase in the glucose uptake corresponding to an IE of 1.5±0.06, 2.0±0.04 and 1.4±0.04, respectively. Only the ClFr and EtFr accelerated the triglyceride accumulation [rosiglitazone equivalent (RE) was 0.9±0.13 and 0.63±0.12, respectively] in pre-adipocytes undergoing differentiation comparably with 10 µM rosiglitazone. Six terpenoids (C1-C6) and three flavonol glycosides (F1-F3) were isolated from the active ClFr and EtFr, respectively, and identified. C5, C2 and C4 had an IE of 0.86±0.05, 1.01±0.04 and 0.9±0.08, while F1, F2 and F3 gave an IE of 1.3±0.05, 2.3±0.05 and 2.0±0.04, respectively. We could conclude that the reported antihyperglycemic activity of Cleome droserifolia is attributed to significant insulin-like effects in peripheral tissues, and that compounds F2 and F3, being highly active, could be used as bioactive markers to standardize the C. droserifolia herbal extract.


Asunto(s)
Cleome/química , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Animales , Biomarcadores/análisis , Línea Celular , Cromatografía Líquida de Alta Presión , Diabetes Mellitus/metabolismo , Egipto , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Glucosa/metabolismo , Insulina/biosíntesis , Medicinas Tradicionales Africanas , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Fitoterapia , Componentes Aéreos de las Plantas/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales/química , Terpenos/aislamiento & purificación , Terpenos/farmacología
16.
BMC Pediatr ; 11: 56, 2011 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-21682854

RESUMEN

BACKGROUND: In Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. The aim of this study is to highlight the clinical, laboratory and genetic characteristics of this disease in our pediatric population as well as to report our experience with both treatment options and outcome. METHODS: The study included 77 patients from 50 unrelated families (62 were followed up for a mean period of 58.9 ± 6.4 months and 27 were asymptomatic siblings). Data were collected retrospectively by record analysis and patient interviews. Diagnosis was confirmed by sequencing of the ATP7B gene in 64 patients. RESULTS: Our patients had unique characteristics compared to other populations. They had a younger age of onset (median: 10 years), higher prevalence of Kayser-Fleischer rings (97.6% in the symptomatic patients), low ceruloplasmin (93.5%), high rate of parental consanguinity (78.9%) as well as a more severe course. 71.42% of those on long term D-penicillamine improved or were stable during the follow up with severe side effects occurring in only 11.5%. Preemptive treatment with zinc monotherapy was an effective non-toxic alternative to D-penicillamine. Homozygous mutations were found in 85.7%, yet limited by the large number of mutations detected, it was difficult to find genotype-phenotype correlations. Missense mutations were the most common while protein-truncating mutations resulted in a more severe course with higher incidence of acute liver failure and neurological symptoms. CONCLUSIONS: Egyptian children with Wilson disease present with early Kayser-Fleischer rings and early onset of liver and neurological disease. The mutational spectrum identified differs from that observed in other countries. The high rate of homozygous mutations (reflecting the high rate of consanguinity) may potentially offer further insights on genotype-phenotype correlation.


Asunto(s)
Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/fisiopatología , Adolescente , Adulto , Edad de Inicio , Niño , ATPasas Transportadoras de Cobre , Enfermedades de la Córnea/genética , Egipto , Femenino , Estudios de Seguimiento , Estudios de Asociación Genética , Humanos , Hepatopatías/genética , Masculino , Mutación Missense , Enfermedades del Sistema Nervioso/genética , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
17.
Orphanet J Rare Dis ; 6: 13, 2011 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-21477313

RESUMEN

BACKGROUND: Cockayne syndrome is a rare autosomal recessive neurodegenerative disease characterized by low-to-normal birth weight; growth failure; brain dysmyelination with calcium deposits, cutaneous photosensitivity; pigmentary retinopathy, cataract, and sensorineural hearing loss. To the best of our knowledge, cholestatic liver disease was not previously reported in these patients. AIM: To highlight the presence of cholestasis and liver dysfunction in this group of patients and to suggest modified criteria for clinical diagnosis. METHODS: The study included nine patients with Cockayne from four different families (five males and four females) in which Cockayne was suspected clinically. In all patients chromosomal breakage studies revealed mild (45%) to moderate (60%) increase in frequency of chromatid and chromosome gaps and breaks versus 25% in normal controls. Diagnosis was confirmed by DNA repair assay. RESULTS: During routine follow up of these patients, seven of them had evident liver affection ranging from mild elevation in liver enzymes to cholestatic liver disease and liver cell failure. The attacks were recurrent in two patients and were sometimes preceded by infection. The attack may lead to deterioration of neurological and/or liver condition. It may end in liver cell failure that either recovers completely or may lead to death. CONCLUSIONS: liver disease could be considered common in Egyptian patients with Cockayne with the cholestatic form being the most evident. The syndrome should be included in the list of causes of cholestatic liver disease. Chromosomal breakage study and positive family history should be included as major criteria for clinical diagnosis of Cockayne especially in a population like ours where consanguineous marriage is very high and molecular testing and UV sensitivity tests are considered unaffordable.


Asunto(s)
Colestasis/genética , Rotura Cromosómica , Síndrome de Cockayne/genética , Hígado/fisiopatología , Adolescente , Niño , Preescolar , Colestasis/diagnóstico , Colestasis/etiología , Cromátides/genética , Síndrome de Cockayne/complicaciones , Síndrome de Cockayne/diagnóstico , Reparación del ADN , Resultado Fatal , Femenino , Humanos , Lactante , Cariotipificación , Masculino , Vitaminas/uso terapéutico
18.
Clin Endocrinol (Oxf) ; 74(4): 419-23, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21198742

RESUMEN

In patients with early stage papillary thyroid carcinoma (PTC) who have had a thyroidectomy, the decision must be made to accept or reject radioactive iodine remnant ablation (RRA). Counselling patients about this decision can be challenging, given the medical evidence uncertainties and the complexity of related information. Although physicians are the primary source of medical information for patients considering RRA, some patients have a desire for supplemental information from sources such as the internet. Yet, thyroid cancer resources on the internet are of variable quality, and some may not be applicable to the individual case. We have developed a computerized educational tool [called a decision aid (DA)], directed to patients with early stage papillary thyroid cancer, and intended as an adjunct to physician counselling, to relay evidence-based medical information on disease prognosis and the choice to accept or reject RRA. DAs are tools used to inform patients about available treatment options and have been utilized in oncologic decision-making. We tested our web-based DA in fifty patients with early stage PTC and found that it improved medical knowledge. Furthermore, participants found the technical usability of the tool acceptable. We are currently conducting a randomized controlled trial comparing the use of the DA plus usual care to usual care alone to confirm the educational benefit of the website and examine its impact on the decision-making process. In the future, DAs may play an expanded role as an adjunct to physician counselling in the care of patients with thyroid cancer.


Asunto(s)
Toma de Decisiones , Radioisótopos de Yodo/uso terapéutico , Educación del Paciente como Asunto/métodos , Adolescente , Adulto , Carcinoma , Carcinoma Papilar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programas Informáticos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/terapia , Tiroidectomía , Adulto Joven
19.
Turk J Haematol ; 28(4): 299-305, 2011 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-27264587

RESUMEN

OBJECTIVE: Budd-Chiari syndrome is a multifactorial disease in which several prothrombotic disorders may predispose patients to the development of thrombosis at this uncommon location (hepatic veins). The aim of this study was to determine the prevalence and characteristics of inherited thrombophilia in Egyptian Budd-Chiari syndrome patients. METHODS: The study included 47 Budd-Chiari syndrome patients (20 children and 27 adults). Genotyping of Factor V G1691A (Leiden), prothrombin G20210A (PT), and methylenetetrahydrofolate reductase C677T were performed using real-time PCR and fluorescence melting curve detection analysis. RESULTS: Factor V Leiden was observed in 29 patients (61.7%). It is the only factor that caused Budd-Chiari syndrome in 18 of the patients and in 5 of the patients with inferior vena cava involvement. Myeloproliferative disease was noted in 12 (25.5%) patients, antiphospholipid syndrome in 5 (10.6%), and Behcet's disease in 3 (6.4%). Interestingly, 3 of the children with Budd-Chiari syndrome had lipid storage disease. CONCLUSION: Factor V Leiden was a major etiological factor in Egyptian Budd-Chiari syndrome patients, which may have been related to the high frequency of this mutation in the study region. Factor V Leiden was also a strong thrombophilic factor and the leading cause of inferior vena cava thrombosis in these patients. Lipid storage disease should be included as a risk factor for Budd-Chiari syndrome.

20.
Clin Oncol (R Coll Radiol) ; 22(10): 850-61, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20832265

RESUMEN

AIM: To compare the accuracy of radiotherapy set-up using an electronic portal imaging device (EPID) versus megavoltage cone beam computed tomography (MV-CBCT) in paediatric patients. MATERIALS AND METHODS: In total, 204 pairs of EPID and MV-CBCT were carried out for 72 patients in the first 3 treatment days and weekly thereafter. RESULTS: For the whole group, the mean systematic EPID set-up errors were 1.8 (±1.7), 1.6 (±1.3), 1.4 (±1.5) mm and 2.3 (±1.7), 1.6 (±1.3), 2.4 (±1.6) mm for MV-CBCT in the longitudinal, lateral and vertical directions, respectively, whereas the mean EPID random errors were 2.0 (±1.7), 1.4 (±1.5), 1.2 (±1.6) and 1.9 (±1.5), 1.5 (±1.3), 2.1 (±1.7) mm for MV-CBCT in the longitudinal, lateral and vertical directions, respectively. For systematic errors of head and neck patients, there was a statistically significant difference in the lateral and vertical directions (P=0.027, 0.003), whereas in the non-head and neck patients there was a statistically significant difference in the lateral direction only (P=0.031). In head and neck patients, the mean random errors were significantly different in the vertical and lateral directions, whereas in non-head and neck patients, they were significantly different in the vertical direction only. The larger values alternate between the two modalities. The systematic and random errors (detected by EPID and MV-CBCT) were significantly correlated in almost all direction in all tumour sites. CONCLUSIONS: The comparison between set-up error in EPID and MV-CBCT was not in favour of any of the two modalities. However, the two modalities were strongly correlated but fairly agreed and the differences between the shifts reported were small and hardly influenced the recommended planning target volume margin.


Asunto(s)
Neoplasias/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Niño , Tomografía Computarizada de Haz Cónico/métodos , Femenino , Humanos , Masculino , Planificación de la Radioterapia Asistida por Computador/instrumentación , Radioterapia Conformacional/instrumentación , Radioterapia Conformacional/métodos
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