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1.
Hum Reprod ; 34(8): 1450-1461, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31348827

RESUMO

STUDY QUESTION: What is the composition and stability during storage and culture of fifteen commercially available human preimplantation embryo culture media? SUMMARY ANSWER: No two culture media had the same composition, and both storage and culture had an effect on the concentrations of multiple components. WHAT IS KNOWN ALREADY: The choice of embryo culture medium not only affects the success rate of an IVF treatment, but also affects the health of the future child. Exact formulations of embryo culture media are often not disclosed by manufacturers. It is unknown whether the composition of these media changes during storage or culture in the IVF laboratory. Without details on the exact concentrations, it is not possible to determine which components might be responsible for the differences in IVF success rates and health of the resulting children. STUDY DESIGN, SIZE, DURATION: Between October 2014 and October 2015, all complete human preimplantation embryo culture media, i.e. ready to use for IVF, that were commercially available at that time, were included (n = 15). Osmolality and the concentration of thirty seven components including basic elements, metabolites, immunoglobulins, albumin, proteins and 21 amino acids were tested immediately upon arrival into the IVF laboratory, after three days of culture without embryos (sham culture) starting from the day of arrival, just before the expiry date, and after three days of sham culture just before the expiry date. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ions, glucose, immunoglobulins, albumin and the total amount of proteins were quantified using a combination of ion selective electrodes and photometric analysis modules, and lactate, pyruvate and 21 amino acids were analysed by ultra performance liquid chromatography mass spectrometry. Osmolality was analysed by an advanced micro-osmometer. Statistical analysis was done using multivariate general linear models. MAIN RESULTS AND THE ROLE OF CHANCE: The composition varied between media, no two media had the same concentration of components. Storage led to significant changes in 17 of the 37 analyzed components (magnesium, chloride, phosphate, albumin, total amount of proteins, tyrosine, tryptophan, alanine, methionine, glycine, leucine, glutamine, asparagine, arginine, serine, proline, and threonine). Storage affected the osmolality in 3 of the 15 media, but for all media combined this effect was not significant (p = 0.08). Sham culture of the analyzed media had a significant effect on the concentrations of 13 of the 37 analyzed components (calcium, phosphate, albumin, total amount of proteins, tyrosine, alanine, methionine, glycine, leucine, asparagine, arginine, proline, and histidine). Sham culture significantly affected the osmolality of the analysed culture media. Two media contained 50% D-lactate, which a toxic dead-end metabolite. In a secondary analysis we detected human liver enzymes in more than half of the complete culture media. LIMITATIONS, REASONS FOR CAUTION: The analyzed culture media could contain components that are not among the 37 components that were analyzed in this study. The clinical relevance of the varying concentrations is yet to be determined. WIDER IMPLICATIONS OF THE FINDINGS: The presence of D-lactate could be avoided and the finding of human liver enzymes was surprising. The wide variation between culture media shows that the optimal composition is still unknown. This warrants further research as the importance of embryo culture media on the efficacy and safety in IVF is evident. Companies are urged to fully disclose the composition of their culture media, and provide clinical evidence supporting the composition or future changes thereof. STUDY FUNDING/COMPETING INTEREST(S): None.


Assuntos
Blastocisto , Meios de Cultura/química , Técnicas de Cultura Embrionária/métodos , Fertilização in vitro/métodos , Humanos
2.
Mol Genet Metab ; 123(2): 76-84, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29290526

RESUMO

BACKGROUND: In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. MATERIAL AND METHODS: A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n=74). In addition, the oxysterols cholestane-3ß,5α,6ß-triol and 7-ketocholesterol were measured in a subset of these patients (n=36) as well as chitotriosidase activity (n=43). A systematic review of the literature was performed to assess the usefulness of these biochemical markers. RESULTS: Specific elevations of metabolites, i.e. without overlap between controls and other lipid storage disorders, were found for several lysosomal storage diseases: increased LysoSM levels in acid sphingomyelinase deficiency (Niemann-Pick disease type A/B), LysoGb3 levels in males with classical phenotype Fabry disease and LysoHexCer (i.e. lysoglucosylceramide/lysogalactosylceramide) in Gaucher and Krabbe diseases. While elevated levels of LysoSM-509 and cholestane-3ß,5α,6ß-triol did not discriminate between Niemann Pick disease type C and acid sphingomyelinase deficiency, LysoSM-509/LysoSM ratio was specifically elevated in Niemann-Pick disease type C. In Gaucher disease type I, mild increases in several lysosphingolipids were found including LysoGb3 with levels in the range of non-classical Fabry males and females. Chitotriosidase showed specific elevations in symptomatic Gaucher disease, and was mildly elevated in all other lipid storage disorders. Review of the literature identified 44 publications. Most findings were in line with our cohort. Several moderate elevations of biochemical markers were found across a wide range of other, mainly inherited metabolic, diseases. CONCLUSION: Measurement in plasma of LysoSLs and oxysterols by UPLC-MS/MS in combination with activity of chitotriosidase provides a useful first tier screening of patients suspected of lipid storage disease. The LysoSM-509/LysoSM ratio is a promising parameter in Niemann-Pick disease type C. Further studies in larger groups of untreated patients and controls are needed to improve the specificity of the findings.


Assuntos
Biomarcadores/metabolismo , Doença de Fabry/diagnóstico , Doença de Gaucher/diagnóstico , Doenças de Niemann-Pick/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Doença de Fabry/metabolismo , Feminino , Doença de Gaucher/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Doenças de Niemann-Pick/metabolismo , Prognóstico , Adulto Jovem
3.
Mol Genet Metab ; 124(3): 204-209, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29789193

RESUMO

Patients with primary serine biosynthetic defects manifest with intellectual disability, microcephaly, ichthyosis, seizures and peripheral neuropathy. The underlying pathogenesis of peripheral neuropathy in these patients has not been elucidated, but could be related to a decrease in the availability of certain classical sphingolipids, or to an increase in atypical sphingolipids. Here, we show that patients with primary serine deficiency have a statistically significant elevation in specific atypical sphingolipids, namely deoxydihydroceramides of 18-22 carbons in acyl length. We also show that patients with aberrant plasma serine and alanine levels secondary to mitochondrial disorders also display peripheral neuropathy along with similar elevations of atypical sphingolipids. We hypothesize that the etiology of peripheral neuropathy in patients with primary mitochondrial disorders is related to this elevation of deoxysphingolipids, in turn caused by increased availability of alanine and decreased availability of serine. These findings could have important therapeutic implications for the management of these patients.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia , Doenças Mitocondriais/fisiopatologia , Serina/deficiência , Esfingolipídeos/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
4.
Clin Genet ; 93(3): 613-621, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28857144

RESUMO

The lack of a validated severity scoring system for individuals with Zellweger spectrum disorders (ZSD) hampers optimal patient care and reliable research. Here, we describe the development of such severity score and its validation in a large, well-characterized cohort of ZSD individuals. We developed a severity scoring system based on the 14 organs that typically can be affected in ZSD. A standardized and validated method was used to classify additional care needs in individuals with neurodevelopmental disabilities (Capacity Profile [CAP]). Thirty ZSD patients of varying ages were scored by the severity score and the CAP. The median score was 9 (range 6-19) with a median scoring age of 16.0 years (range 2-36 years). The ZSD severity score was significantly correlated with all 5 domains of the CAP, most significantly with the sensory domain (r = 0.8971, P = <.0001). No correlation was found between age and severity score. Multiple peroxisomal biochemical parameters were significantly correlated with the severity score. The presently reported severity score for ZSD is a suitable tool to assess phenotypic severity in a ZSD patient at any age. This severity score can be used for objective phenotype descriptions, genotype-phenotype correlation studies, the identification of prognostic features in ZSD patients and for classification and stratification of patients in clinical trials.


Assuntos
Síndrome de Zellweger/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Estudos de Associação Genética , Humanos , Masculino , Mutação , Fenótipo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem , Síndrome de Zellweger/genética
5.
Mol Psychiatry ; 21(8): 1125-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26416544

RESUMO

The genetic basis of intellectual disability (ID) is extremely heterogeneous and relatively little is known about the role of autosomal recessive traits. In a field study performed in a highly inbred area of Northeastern Brazil, we identified and investigated a large consanguineous family with nine adult members affected by severe ID associated with disruptive behavior. The Genome-Wide Human SNP Array 6.0 microarray was used to determine regions of homozygosity by descent from three affected and one normal family member. Whole-exome sequencing (WES) was performed in one affected patient using the Nextera Rapid-Capture Exome kit and Illumina HiSeq2500 system to identify the causative mutation. Potentially deleterious variants detected in regions of homozygosity by descent and not present in either 59 723 unrelated individuals from the Exome Aggregation Consortium (Browser) or 1484 Brazilians were subject to further scrutiny and segregation analysis by Sanger sequencing. Homozygosity-by-descent analysis disclosed a 20.7-Mb candidate region at 8q12.3-q21.2 (lod score: 3.11). WES identified a homozygous deleterious variant in inositol monophosphatase 1 (IMPA1) (NM_005536), consisting of a 5-bp duplication (c.489_493dupGGGCT; chr8: 82,583,247; GRCh37/hg19) leading to a frameshift and a premature stop codon (p.Ser165Trpfs*10) that cosegregated with the disease in 26 genotyped family members. The IMPA1 gene product is responsible for the final step of biotransformation of inositol triphosphate and diacylglycerol, two second messengers. Despite its many physiological functions, no clinical phenotype has been assigned to this gene dysfunction to date. Additionally, IMPA1 is the main target of lithium, a drug that is at the forefront of treatment for bipolar disorder.


Assuntos
Deficiência Intelectual/genética , Monoéster Fosfórico Hidrolases/genética , Adulto , Brasil , Consanguinidade , Exoma/genética , Família , Feminino , Genoma Humano/genética , Genótipo , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Monoéster Fosfórico Hidrolases/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA/métodos
6.
Clin Otolaryngol ; 42(2): 354-365, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27542561

RESUMO

OBJECTIVES: Thyroid conditions are common, and their incidence is increasing. Surgery is the mainstay treatment for many thyroid conditions, and understanding its utilisation trends and morbidity is central to improving patient care. DESIGN: An N = near-all analysis of the English administrative dataset to identify trends in thyroid surgery specialisation, volume-outcome relationships, and the incidence and risk factors for short- and long-term morbidity. MAIN OUTCOME MEASURES: Between 2004 and 2012, 72 594 patients underwent elective thyroidectomy in England. Information about age, sex, morbidities, nature of thyroid disease and surgery, adjuvant treatments and complications including hypocalcaemia and vocal palsy was recorded. RESULTS: Mean age at surgery was 49 ± 30, and a female predominance (82%) was observed. Most patients underwent hemithyroidectomy (51%) or total thyroidectomy (32%). Patients underwent surgery for benign (52.5%), benign inflammatory (21%) and malignant (17%) thyroid diseases. Thyroid surgery grew by 2.9% a year and increased in specialisation. Increased surgeon volume significantly reduced lengths of stay: the proportion of length of stay outliers fell from 11.8% for patients of occasional thyroidectomists (<5 per year) to 2.8% for patients of high-volume surgeons (>50 thyroidectomies a year). Post-discharge vocal palsy and hypocalcaemia occurred in 1.87% and 1.58% of cases, respectively. High-volume surgeons had a reduced incidence of vocal palsy, and volumes >30 were consistently protective. CONCLUSIONS: Thyroid surgery is increasingly specialised. High-volume surgeons, that is patients who perform 50 or more thyroidectomies per year, achieve lower complications and shorter lengths of stay.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Padrões de Prática Médica/tendências , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/tendências , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Fatores Sexuais , Especialização , Doenças da Glândula Tireoide/epidemiologia
7.
Clin Otolaryngol ; 42(1): 11-28, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26990866

RESUMO

OBJECTIVES: To perform a national analysis of the perioperative outcome of major head and neck cancer surgery to develop a stratification strategy and outcomes assessment framework using hospital administrative data. DESIGN: A Hospital Episode Statistics N = near-all analysis. SETTINGS: The English National Health Service. MAIN OUTCOME MEASURES: Local audit data were used to assess and triangulate the quality of the administrative dataset. Within the national dataset, cancer sites, morbidities, social deprivation, treatment, complications, and in-hospital mortality were recorded. RESULTS: Within local audit datasets, the accuracy of assigning newly-derived Cancer Site Strata and Resection Strata were 92.3% and 94.2%, respectively. Accuracy of morbidities assignment was 97%. Within the national dataset, we identified 17 623 major head and neck cancer resections between 2002 and 2012. There were 12 413 males and mean age at surgery was 63 ± 12 years. The commonest cancer site strata were oral cavity (42%) and larynx-hypopharynx (32%). The commonest resection site was the larynx (n = 4217), and 13 211 and 11 841 patients had neck dissection and flap-based reconstruction, respectively. There were prognostically significant baseline differences between patients with oromandibular and pharyngolaryngeal malignancy. Patients with pharyngolaryngeal malignancies had a greater burden of morbidities, lower socio-economic status, fewer primary resections, and a sixfold increased risk of undergoing their major resection during an emergency hospital admission. Mean length of stay was 25 days and each complication linearly increased it by 9.6 days. There were 609 (3.5%) in-hospital deaths and a basket of seven medical and three surgical complications significantly increased the risk of in-hospital death. At least one potentially lethal complication occurred in 26% of patients. The risk of in-hospital death in a patient with no potentially lethal complication was 1.1% and this increased to 6% with one potentially lethal complication, and to 15.1% if two potentially lethal complications occurred in one patient. Complex oral-pharyngeal resections and pharyngolaryngectomies had the highest risks of complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows variation across different resection strata. We propose an Informatics-based Framework for Outcomes Surveillance (IFOS) in Head and Neck Surgery for perpetual quality assurance, using the local hospital coding data or its collated destination, the national administrative dataset.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Inglaterra/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/mortalidade , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Informática Médica , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Procedimentos de Cirurgia Plástica , Fatores de Tempo , Adulto Jovem
8.
Clin Genet ; 90(5): 461-465, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26853223

RESUMO

Barth syndrome (BTHS) is an X-linked inborn error of metabolism which affects males. The main manifestations are cardiomyopathy, myopathy, hypotonia, growth delay, intermittent neutropenia and 3-methylglutaconic aciduria. Diagnosis is confirmed by mutational analysis of the TAZ gene and biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin (MLCL:L4-CL) ratio. We report a 6-year-old boy who presented with severe hypoglycemia, lactic acidosis and severe dilated cardiomyopathy soon after birth. The MLCL:L4-CL ratio confirmed BTHS (3.90 on patient's fibroblast, normal: 0-0.3). Subsequent sequencing of the TAZ gene revealed only the new synonymous variant NM_000116.3 (TAZ):c.348C>T p.(Gly116Gly), which did not appear to affect the protein sequence. In silico prediction analysis suggested the new c.348C>T nucleotide change could alter the TAZ mRNA splicing processing. We analyzed TAZ mRNAs in the patient's fibroblasts and found an abnormal skipping of 24 bases (NM_000116.3:c.346_371), with the consequent ablation of 8 amino acid residues in the tafazzin protein (NP_000107.1:p.Lys117_Gly124del). Molecular analysis of at risk female family members identified the patient's sister and mother as heterozygous carriers. Apparently harmless synonymous variants in the TAZ gene can damage gene expression. Such findings widen our knowledge of molecular heterogeneity in BTHS.


Assuntos
Síndrome de Barth/genética , Cardiomiopatia Dilatada/genética , Fatores de Transcrição/genética , Transcrição Gênica , Acidose Láctica/genética , Acidose Láctica/fisiopatologia , Aciltransferases , Síndrome de Barth/sangue , Síndrome de Barth/fisiopatologia , Cardiolipinas/sangue , Cardiomiopatia Dilatada/fisiopatologia , Criança , Éxons/genética , Feminino , Heterozigoto , Humanos , Hipoglicemia/genética , Hipoglicemia/fisiopatologia , Lisofosfolipídeos/sangue , Masculino , Mutação
9.
Cytopathology ; 27(2): 91-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25656853

RESUMO

OBJECTIVE: To highlight the importance of salivary gland fine needle aspiration (FNA) cytology as a triage tool for surgery and to determine its sensitivity and specificity. To discuss the diagnostic pitfalls and potential role of ancillary techniques in diagnosis and prognosis. METHODS: The study included a total of 920 cases of salivary gland FNAs received in the cytopathology department of University College London Hospital during December 2004 to December 2012. The cases with known histological outcomes were analysed to determine the sensitivity and specificity. RESULTS: Surgery was carried out on 180 (19.6%) of 920 patients. Excluding nine with inadequate/non-diagnostic cytology, the sensitivity of FNA cytology for a malignant outcome was 89% (33/37) and the specificity was 97% (130/134). Diagnostic pitfalls are discussed with respect to eight FNAs with discrepant histology. Histological outcome was not available for 740 cases (80.4%): excluding 88 non-diagnostic FNAs, 324 (49.7%) had non-neoplastic diagnoses (not indicating surgery) and 328 (50.3%) had neoplastic diagnoses, which included recurrences/metastases of known tumours. Patients with other neoplasms on FNA were lost to follow-up and may have had surgery elsewhere. Cases with clinical concerns were discussed at weekly multidisciplinary meetings. CONCLUSION: Salivary gland FNA is crucial in the distinction of non-neoplastic from neoplastic lesions, emphasizing the fact that FNA is an excellent triage tool for surgery. Salivary gland FNA has a high sensitivity and specificity. However, it is important to interpret the cytological diagnoses in the light of clinical findings and imaging. Diagnostic pitfalls are seen in a minority of cases and could potentially be overcome with the help of recently described diagnostic and prognostic markers.


Assuntos
Biópsia por Agulha Fina/métodos , Citodiagnóstico , Neoplasias/diagnóstico , Glândulas Salivares/cirurgia , Detecção Precoce de Câncer , Humanos , Neoplasias/classificação , Neoplasias/patologia , Prognóstico , Glândulas Salivares/patologia , Triagem
10.
Brain Topogr ; 28(5): 647-656, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25998854

RESUMO

Current usage of electroencephalography (EEG) is limited to laboratory environments. Self-application of a multichannel wet EEG caps is practically impossible, since the application of state-of-the-art wet EEG sensors requires trained laboratory staff. We propose a novel EEG cap system with multipin dry electrodes overcoming this problem. We describe the design of a novel 24-pin dry electrode made from polyurethane and coated with Ag/AgCl. A textile cap system holds 97 of these dry electrodes. An EEG study with 20 volunteers compares the 97-channel dry EEG cap with a conventional 128-channel wet EEG cap for resting state EEG, alpha activity, eye blink artifacts and checkerboard pattern reversal visual evoked potentials. All volunteers report a good cap fit and good wearing comfort. Average impedances are below 150 kΩ for 92 out of 97 dry electrodes, enabling recording with standard EEG amplifiers. No significant differences are observed between wet and dry power spectral densities for all EEG bands. No significant differences are observed between the wet and dry global field power time courses of visual evoked potentials. The 2D interpolated topographic maps show significant differences of 3.52 and 0.44% of the map areas for the N75 and N145 VEP components, respectively. For the P100 component, no significant differences are observed. Dry multipin electrodes integrated in a textile EEG cap overcome the principle limitations of wet electrodes, allow rapid application of EEG multichannel caps by non-trained persons, and thus enable new fields of application for multichannel EEG acquisition.


Assuntos
Eletroencefalografia/instrumentação , Desenho de Equipamento/instrumentação , Adulto , Impedância Elétrica , Eletrodos , Eletroencefalografia/métodos , Potenciais Evocados , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
11.
J Mater Sci Mater Med ; 25(9): 2069-81, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24934877

RESUMO

DC reactive magnetron sputtered Ag:TiO2 nanocomposite thin films were developed to be used as protective coatings in pressure sensor devices. The coatings, with Ag content varying from 0 to about 30 at.%, were prepared and characterized in order to study their biological response. The as-deposited samples were annealed in vacuum at 500 °C in order to evaluate the influence of their morphological and structural differences over the response elicited upon contact with simulated bodily fluids and cultured human cells, as well as selected microorganisms. The results showed that the annealing treatment produced less porous films with an enhanced structure, with a significant reduction in structural defects and improved crystallinity. Additionally, samples with higher Ag contents (≥12.8 at.%) exhibited Ag agglomerates/clusters at the surface, a result anticipated from the XRD data. The crystallization of the TiO2 matrix was also observed by XRD analysis, albeit delayed by the dispersion of Ag into the matrix. Biological characterization showed that the antimicrobial activity and cytotoxicity of the coatings were directly related with their composition, closely followed by the particular structural and morphological features, namely those resulting from annealing process.


Assuntos
Materiais Revestidos Biocompatíveis , Prata/química , Titânio/química , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Pressão
12.
Front Pediatr ; 12: 1418963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005507

RESUMO

Background: 3ß-hydroxy-Δ5-C27-steroid-oxidoreductase (3ß-HSD) deficiency is a bile acid synthesis disorder that leads to the absence of normal primary bile acids and the accumulation of abnormal bile acids. This results in cholestatic jaundice, fat-soluble vitamin deficiency, acholic or fatty stools and failure to thrive. Bile acid supplementation is used to treat 3ß-HSD-deficiency and its symptoms. Methods: This report details the case of a 28-year-old woman diagnosed with 3ß-HSD-deficiency, who was treated with glycine-conjugated deoxycholic acid (gDCA). Results: gDCA treatment successfully restored normal bile acid levels, improved body weight by reducing fat malabsorption, and was well-tolerated with no observed liver problems or side effects. Conclusions: As a potent FXR ligand, gDCA might exert its action through FXR activation leading to bile acid synthesis regulation.

13.
J Laryngol Otol ; 137(6): 704-708, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36815299

RESUMO

OBJECTIVES: UK guidelines advocate 'one-stop' neck lump assessment for cancer referrals. This paper reports the pilot of a novel pre-clinic ultrasound pathway, presents outcomes, and discusses strengths and limitations in the context of the coronavirus disease 2019 pandemic. METHODS: Two-week-wait cancer referral patients with a neck lump were allocated a pre-clinic ultrasound scan followed by a clinic appointment. Demographic, patient journey and outcome data were collected and analysed. RESULTS: Ninety-nine patients underwent ultrasound assessment with or without biopsy on average 8 days following referral. Patients were followed up on average 14.1 days (range, 2-26 days) after initial referral. At the first clinic appointment, 45 patients were discharged, 10 were scheduled for surgery, 12 were diagnosed with cancer, 6 were referred to another specialty and cancer was excluded in 19 patients. Retrospectively, four ultrasounds were performed unnecessarily. CONCLUSION: Pre-clinic ultrasound scanning is an alternative to the one-stop neck lump pathway. This study demonstrates fewer clinic visits, faster diagnosis and a low proportion of unnecessary scans, whilst minimising face-to-face consultations and aerosol-generating procedures.


Assuntos
COVID-19 , Neoplasias de Cabeça e Pescoço , Humanos , Estudos Retrospectivos , Aerossóis e Gotículas Respiratórios , Instituições de Assistência Ambulatorial , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Encaminhamento e Consulta
14.
Mol Genet Metab Rep ; 30: 100829, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34926160

RESUMO

We describe the case of a Greek female patient with the Classic form of the ultra- rare and fatal autosomal recessive disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and the impact of allogeneic hematopoietic stem cell transplantation on the biochemical and clinical aspects of the disease. The patient presented at the age of 15 years with severe gastrointestinal symptoms, cachexia, peripheral neuropathy and diffuse leukoencephalopathy. The diagnosis of MNGIE disease was established by the increased levels of thymidine and deoxyuridine in plasma and the complete deficiency of thymidine phosphorylase activity. The novel c.[978dup] (p.Ala327Argfs*?) variant and the previously described variant c.[417 + 1G > A] were identified in TYMP. The donor for the allogeneic hematopoietic stem cell transplantation was her fully compatible sister, a carrier of the disease. The patient had a completely uneventful post- transplant period and satisfactory PB chimerism levels. A marked and rapid decrease in thymidine and deoxyuridine plasma levels and an increase of the thymidine phosphorylase activity to the levels measured in her donor sister was observed and is still present sixteen months post-transplant. Disease symptoms stabilized and some improvement was also observed both in her neurological and gastrointestinal symptoms. Follow up studies will be essential for determining the long term impact of allogeneic hematopoietic stem cell transplantation in our patient.

15.
Natl Med J India ; 24(1): 16-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21608352

RESUMO

BACKGROUND: We aimed to estimate the prevalence of diabetes mellitus and study the associated factors in a rural population in Goa, India. METHODS: A cross-sectional study was done in the rural area of Mandur, Goa. Participants>20 years of age were selected by systematic random sampling. They were interviewed with the help of a structured, pretested questionnaire. This was followed by clinical examination, anthropometry and relevant laboratory investigations. Diabetes mellitus was defined as per the American Diabetes Association (ADA) criteria. Statistical analysis was done using the SPSS software package (version 14.0). RESULTS: The prevalence of diabetes mellitus in the study population was 10.3% (130/1266) with a prevalence of 8.4% among men and 12% among women. On bivariate analysis, the prevalence of diabetes mellitus was found to be significantly associated with age, occupation, family income, family history of diabetes, smoking, obesity, hypertension, and high serum cholesterol and triglycerides levels. Multiple logistic regression analysis identified age, family history, hypertension, smoking, total cholesterol and triglyceride as the Independently associated variables for diabetes mellitus. CONCLUSION: Innovative community outreach programmes are required to create awareness, and for screening and treatment of diabetes mellitus to curb the growing epidemic of diabetes in the population.


Assuntos
Diabetes Mellitus/epidemiologia , População Rural/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
16.
J Nanosci Nanotechnol ; 10(4): 2926-32, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20355526

RESUMO

Ti-Si-C thin films were deposited onto silicon, stainless steel and high-speed steel substrates by magnetron sputtering, using different chamber configurations. The composition of the produced films was obtained by Electron Probe Micro-Analysis (EPMA) and the structure by X-ray diffraction (XRD). The hardness and residual stresses were obtained by depth-sensing indentation and substrate deflection measurements (using Stoney's equation), respectively. The tribological behavior of the produced films was studied by pin-on-disc. The increase of the concentration of non-metallic elements (carbon and silicon) caused significant changes in their properties. Structural analysis revealed the possibility of the coexistence of different phases in the prepared films, namely Ti metallic phase (alpha-Ti or beta-Ti) in the films with higher Ti content. The coatings with highest carbon contents, exhibited mainly a sub-stoichiometric fcc NaCI TiC-type structure. These structural changes were also confirmed by resistivity measurements, whose values ranged from 10(3) omega/sq for low non-metal concentration, up to 10(6) omega/sq for the highest metalloid concentration. A strong increase of hardness and residual stresses was observed with the increase of the non-metal concentration in the films. The hardness (H) values ranged between 11 and 27 GPa, with a clear dependence on both crystalline structure and composition features. Following the mechanical behavior, the tribological results showed similar trends, with both friction coefficients and wear revealing also a straight correlation with the composition and crystalline structure of the coatings.


Assuntos
Compostos Inorgânicos de Carbono/química , Galvanoplastia/métodos , Membranas Artificiais , Nanoestruturas/química , Nanotecnologia/métodos , Silicatos/química , Compostos de Silício/química , Titânio/química , Cristalização/métodos , Impedância Elétrica , Fricção , Magnetismo , Teste de Materiais , Estatística como Assunto , Estresse Mecânico
17.
Anaesthesia ; 65(1): 78-81, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19849679

RESUMO

A 29-year-old patient presented with dysphonia, dysphagia and a progressive history of stridor over 6 weeks. His past medical history included childhood nasolabial rhabdomyosarcoma treated by surgery, chemotherapy and radiotherapy. This had resulted in marked abnormalities of the facial skeleton, limited neck extension and restricted mouth opening of 1 cm, in part due to dental implants. After careful discussion and planning within a multidisciplinary team, the airway was optimised by temporary removal of the dental implants. This enabled a suspension laryngoscope to be passed, permitting carbon dioxide laser treatment to an obstruction at the laryngeal inlet and eliminating the need for a tracheostomy.


Assuntos
Obstrução das Vias Respiratórias/cirurgia , Implantes Dentários , Laringoscopia/métodos , Terapia a Laser/métodos , Adulto , Obstrução das Vias Respiratórias/etiologia , Terapia Combinada , Remoção de Dispositivo , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Equipe de Assistência ao Paciente , Rabdomiossarcoma/terapia
18.
Indian J Public Health ; 54(1): 18-20, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20859044

RESUMO

A cross-sectional study was conducted among health care workers at a tertiary care hospital in Goa to study the problem of needle stick injuries. A structured questionnaire was used to interview the study participants at their work place. Participants were asked to recall needle stick injuries in the preceding 12 months. Factors such as work experience, type of procedure, action taken following injury etc were also studied. Statistical analysis was done with SPSS software. Around 34.8% (200/575) of the Health care workers had experienced a needle stick injury in the last one year. Needle stick injuries were equally distributed across different work experience periods. Hollow bore needles were responsible for 77.5% of needle stick injuries followed by suturing needles (19.2%). As far as use of personal protection was concerned only 58% of the health care workers were wearing gloves at the time of the injury. There is therefore an urgent need at the hospital level to have a uniform needle stick injuries policy covering safe work practices, safe disposal of sharps, procedures in event of needle stick injury, training including pre-employment training, monitoring and evaluation of needle stick injuries and procedures for reporting needle stick injuries.


Assuntos
Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Recursos Humanos em Hospital , Profilaxia Pós-Exposição/estatística & dados numéricos , Estudos Transversais , Feminino , Luvas Cirúrgicas/estatística & dados numéricos , Humanos , Incidência , Índia , Masculino , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Serviços de Saúde do Trabalhador/estatística & dados numéricos , Gestão da Segurança/estatística & dados numéricos
19.
J Laryngol Otol ; 134(7): 623-625, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32741379

RESUMO

BACKGROUND: Pharyngocutaneous fistula is a troublesome complication. Recently, synthetic materials such as fibrin sealant have been used as a secondary measure to treat fistula. This work assessed whether the primary use of fibrin sealant can reduce the rate of fistula. METHOD: A retrospective review of 50 cases from 2 centres was completed. Tisseel was an adjunct to primary closure in all cases. RESULTS: In the first centre, 3 out of 34 cases developed pharyngocutaneous fistula (fistula rate of 9 per cent). All three were salvage cases. In the second centre, 0 out of 16 cases developed a fistula. CONCLUSION: The incidence of pharyngocutaneous fistula post-radiation and post-chemoradiotherapy in laryngectomy cases has been quoted as 23 per cent and 34 per cent respectively. This study represents the first patient series on the use of fibrin sealant as an adjunct in primary closure following laryngectomy. The results are promising, encouraging the use of Tisseel as an adjunct to meticulous closure.


Assuntos
Fístula Cutânea/cirurgia , Adesivo Tecidual de Fibrina/uso terapêutico , Doenças Faríngeas/cirurgia , Fístula Cutânea/etiologia , Humanos , Laringectomia/efeitos adversos , Laringectomia/métodos , Doenças Faríngeas/etiologia , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do Tratamento
20.
Neth J Med ; 77(1): 25-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30774101

RESUMO

This case report presents an adult patient with decreased levels of consciousness and bizarre behavior. A silent delirium was first suspected however, symptoms did not improve and further examination revealed elevated ammonia levels. A hepatic cause and portosystemic shunting were excluded and eventually a diagnosis of ornithine transcarbamylase deficiency was made. After treatment with high carbohydrate intake, a low protein diet and supplementation with arginine and sodium benzoate, the patient recovered.


Assuntos
Transtornos da Consciência/etiologia , Carboidratos da Dieta/administração & dosagem , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Transtornos da Consciência/diagnóstico , Carboidratos da Dieta/metabolismo , Feminino , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/etiologia , Pessoa de Meia-Idade , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações
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