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1.
Nutrients ; 16(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38794732

RESUMEN

Iron deficiency in infants can impact development, and there are concerns that the use of baby food pouches and baby-led weaning may impair iron status. First Foods New Zealand (FFNZ) was an observational study of 625 New Zealand infants aged 6.9 to 10.1 months. Feeding methods were defined based on parental reports of infant feeding at "around 6 months of age": "frequent" baby food pouch use (five+ times per week) and "full baby-led weaning" (the infant primarily self-feeds). Iron status was assessed using a venepuncture blood sample. The estimated prevalence of suboptimal iron status was 23%, but neither feeding method significantly predicted body iron concentrations nor the odds of iron sufficiency after controlling for potential confounding factors including infant formula intake. Adjusted ORs for iron sufficiency were 1.50 (95% CI: 0.67-3.39) for frequent pouch users compared to non-pouch users and 0.91 (95% CI: 0.45-1.87) for baby-led weaning compared to traditional spoon-feeding. Contrary to concerns, there was no evidence that baby food pouch use or baby-led weaning, as currently practiced in New Zealand, were associated with poorer iron status in this age group. However, notable levels of suboptimal iron status, regardless of the feeding method, emphasise the ongoing need for paying attention to infant iron nutrition.


Asunto(s)
Hierro , Estado Nutricional , Destete , Humanos , Nueva Zelanda/epidemiología , Lactante , Femenino , Masculino , Hierro/sangre , Fenómenos Fisiológicos Nutricionales del Lactante , Alimentos Infantiles/análisis , Anemia Ferropénica/epidemiología , Anemia Ferropénica/sangre , Deficiencias de Hierro
2.
Elife ; 122023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38127070

RESUMEN

Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, intracellular bacteria, and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed tumor suppressor miRNA family important for cell proliferation and survival. miR-15/16 play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and memory. Comparative Argonaute-2 high-throughput sequencing of crosslinking immunoprecipitation (AHC) combined with gene expression profiling in normal and miR-15/16-deficient mouse T cells revealed a large network of hundreds of direct miR-15/16 target mRNAs, many with functional relevance for T cell activation, survival and memory formation. Among these targets, Malat1 contained the largest absolute magnitude miR-15/16-dependent AHC peak. This binding site was among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16-binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of other miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of interleukin 2 (IL-2) and a broader CD28-responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence in mice following LCMV Armstrong and Listeria monocytogenes infection. This study marks a significant advance in the study of long non-coding RNAs in the immune system by ascribing cell-intrinsic, sequence-specific in vivo function to Malat1. These findings have implications for T cell-mediated autoimmune diseases, antiviral and anti-tumor immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed.


Asunto(s)
Células T de Memoria , MicroARNs , ARN Largo no Codificante , Linfocitos T Citotóxicos , Animales , Ratones , Antígenos CD28 , MicroARNs/genética , ARN Largo no Codificante/genética
3.
bioRxiv ; 2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37547023

RESUMEN

Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, many intracellular bacteria and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed tumor suppressor miRNA family important for cell proliferation and survival. miR-15/16 also play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and T cell memory. Comparative Argonaute-2 high throughput sequencing of crosslinking immunoprecipitation (Ago2 HITS-CLIP, or AHC) combined with gene expression profiling in normal and miR-15/16-deficient T cells revealed a large network of several hundred direct miR-15/16 target mRNAs, many with functional relevance for T cell activation, survival and memory formation. Among these targets, the long non-coding RNA Malat1 contained the largest absolute magnitude miR-15/16-dependent AHC peak in T cells. This binding site was also among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16 binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of other miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of IL-2 and a broader CD28-responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence following LCMV Armstrong and Listeria monocytogenes infection. This study marks a significant advance in the study of long noncoding RNAs in the immune system by ascribing cell-intrinsic, sequence-specific in vivo function to Malat1. These findings have implications for T cell-mediated autoimmune diseases, antiviral and anti-tumor immunity, as well as lung adenocarcinoma and other malignancies where Malat1 is overexpressed.

4.
Bone ; 173: 116791, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37263386

RESUMEN

BACKGROUND: X-linked hypophosphataemia (XLH) is the most common heritable form of rickets. Prevalence data varies across the literature between 1 in 20,000 and 1 in 200,000 per population. METHODS: Australian and New Zealand Paediatric Surveillance Units collected cross-sectional data from paediatricians on existing cases to estimate prevalence and characteristics of paediatric XLH in Australia and New Zealand. RESULTS: Seventy-five cases in Australia and 18 cases in New Zealand were identified. Estimated minimum prevalence based on these cases was 1.33 (1.04-1.66) per 100,000 and 1.60 per 100,000 (95%CI 0.97-2.58) in Australia and New Zealand respectively, with actual prevalence likely higher due to incomplete ascertainment. Despite a family history in most cases, delayed diagnosis was common, with 49 % diagnosed after 2 years of age. Delayed diagnosis was more common in sporadic versus familial cases. Most common clinical characteristics included leg bowing (89 %), bone and joint pain (68 %), abnormal gait (57 %) and short stature (49 %). There was a significant burden of orthopaedic disease and surgeries and a high rate of complications of nephrocalcinosis and hyperparathyroidism (32 % and 20 % respectively). Additionally, while guidelines stress the importance of multidisciplinary care, many did not have access to recommended health professionals, with only 3 % seeing a psychologist and 68 % seeing a dentist. This is despite the high psychological burden of XLH and a significant proportion (41 %) of this cohort having dental issues (tooth abscess, dental capping, tooth extraction). There were two cases from NZ without data available. Of the 91 cases with data collected, 46 % were on burosumab therapy. Consistent with clinical trials, those on burosumab had a higher serum phosphate levels (p < 0.001) at most recent follow-up. Three cases reported cancellation of orthopaedic surgery due to improvement in lower limb deformity after commencement of burosumab. CONCLUSION: These data describe the multisystem burden of disease for children with XLH with care impacted by delayed diagnosis and a lack of access to many health professionals, especially psychological support.


Asunto(s)
Raquitismo Hipofosfatémico Familiar , Niño , Humanos , Australia/epidemiología , Estudios Transversales , Raquitismo Hipofosfatémico Familiar/epidemiología , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Nueva Zelanda/epidemiología , Prevalencia
5.
SLAS Discov ; 25(4): 361-371, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31585521

RESUMEN

A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA processing, stability, and translation. Methylation of adenosine at the N6 position (m6A) in messenger RNA (mRNA) is currently the most well-studied RNA modification and is catalyzed by the RNA methyltransferase complex METTL3/METTL14. Once generated, m6A can modulate mRNA splicing, export, localization, degradation, and translation. Although potent and selective inhibitors exist for several members of the Type I S-adenosylmethionine (SAM)-dependent methyltransferase family, no inhibitors have been reported for METTL3/METTL14 to date. To facilitate drug discovery efforts, a sensitive and robust mass spectrometry-based assay for METTL3/METTL14 using self-assembled monolayer desorption/ionization (SAMDI) technology has been developed. The assay uses an 11-nucleotide single-stranded RNA compared to a previously reported 27-nucleotide substrate. IC50 values of mechanism-based inhibitors S-adenosylhomocysteine (SAH) and sinefungin (SFG) are comparable between the SAMDI and radiometric assays that use the same substrate. This work demonstrates that SAMDI technology is amenable to RNA substrates and can be used for high-throughput screening and compound characterization for RNA-modifying enzymes.


Asunto(s)
Espectrometría de Masas/métodos , Metiltransferasas/genética , Procesamiento Postranscripcional del ARN/efectos de los fármacos , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/farmacología , Descubrimiento de Drogas/tendencias , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Metilación/efectos de los fármacos , Complejos Multiproteicos/antagonistas & inhibidores , Complejos Multiproteicos/genética , Procesamiento Postranscripcional del ARN/genética , Estabilidad del ARN/efectos de los fármacos , Estabilidad del ARN/genética , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , S-Adenosilhomocisteína/farmacología
6.
Artículo en Inglés | MEDLINE | ID: mdl-31798536

RESUMEN

Since first described almost a century ago, vitamin D preparations have been successfully used as a public health intervention to prevent nutritional rickets. In this manuscript, we document the periods in history when nutritional rickets was described, examine early efforts to understand its etiology and the steps taken to treat and prevent it. We will also highlight that despite the wealth of historical data and multiple preventative strategies, nutritional rickets remains a significant public health disorder. Nutritional rickets has both skeletal and extraskeletal manifestations. While the skeletal manifestations are the most recognized features, it is the extraskeletal complications, hypocalcaemic seizure and cardiomyopathy that are the most devastating features and result in reported fatalities. Reviewing this history provides an opportunity to further promote recent global consensus recommendations for the prevention and management of nutritional rickets, as well as gain a greater understanding of the well-known public health measures that can be used to manage this entirely preventable disease.

7.
Immunol Rev ; 291(1): 134-153, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31402496

RESUMEN

T cells play important roles in autoimmune diseases and cancer. Following the cloning of the T cell receptor (TCR), the race was on to map signaling proteins that contributed to T cell activation downstream of the TCR as well as co-stimulatory molecules such as CD28. We term this "canonical TCR signaling" here. More recently, it has been appreciated that T cells need to accommodate increased metabolic needs that stem from T cell activation in order to function properly. A central role herein has emerged for mechanistic/mammalian target of rapamycin (mTOR). In this review we briefly cover canonical TCR signaling to set the stage for discussion on mTOR signaling, mRNA translation, and metabolic adaptation in T cells. We also discuss the role of mTOR in follicular helper T cells, regulatory T cells, and other T cell subsets. Our lab recently uncovered that "tonic signals", which pass through proximal TCR signaling components, are robustly and selectively transduced to mTOR to promote baseline translation of various mRNA targets. We discuss insights on (tonic) mTOR signaling in the context of T cell function in autoimmune diseases such as lupus as well as in cancer immunotherapy through CAR-T cell or checkpoint blockade approaches.


Asunto(s)
Activación de Linfocitos/inmunología , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Señalización del Calcio , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Factores de Intercambio de Guanina Nucleótido/metabolismo , Humanos , Activación de Linfocitos/genética , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Unión Proteica , Receptores de Antígenos de Linfocitos T/metabolismo , Sistemas de Mensajero Secundario
8.
Hosp Pediatr ; 9(1): 55-60, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30593456

RESUMEN

Since its initial discovery almost a century ago, vitamin K has been labeled as both lifesaving and malignancy causing. This has led to debate of not only its use in general but also regarding its appropriate dose and route. In this article, we review through a historical lens the past 90 years of newborn vitamin K from its discovery through to its modern use of preventing vitamin K deficiency bleeding (VKDB). Although researchers in surveillance studies have shown considerable reductions in VKDB following intramuscular vitamin K prophylaxis, ongoing barriers to the universal uptake of vitamin K prophylaxis remain. Reviewing the history of newborn vitamin K provides an opportunity for a greater understanding of the current barriers to uptake that we face. Although at times difficult, improving this understanding may allow us to address contentious issues related to parental and health professional beliefs and values as well as improve overall communication. The ultimate goal is to improve and maintain the uptake of vitamin K to prevent VKDB in newborns.


Asunto(s)
Antifibrinolíticos/administración & dosificación , Accesibilidad a los Servicios de Salud , Sangrado por Deficiencia de Vitamina K/prevención & control , Vitamina K/administración & dosificación , Humanos , Recién Nacido
9.
BMJ Open ; 8(6): e019036, 2018 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-29950456

RESUMEN

OBJECTIVE: To determine the iron intake and status of infants following a version of baby-led weaning (BLW) modified to prevent iron deficiency (Baby-Led Introduction to SolidS; BLISS) compared with those of infants following traditional spoon-feeding. DESIGN, PARTICIPANTS AND INTERVENTION: This randomised controlled trial included 206 participants assigned to control (n=101) or BLISS (n=105) groups. Both groups received standard midwifery and 'Well Child' care. BLISS participants received eight additional visits (from before birth to 9 months) providing education and support on the BLISS approach to complementary feeding (ie, BLW modified to increase iron intake). The primary outcome of the BLISS study (growth) has been previously reported. This paper reports the key prespecified secondary outcomes, iron intake and iron status. OUTCOME MEASURES: Intake of iron and key absorption modifiers were assessed using weighed 3-day diet records at 7 and 12 months. A venipuncture blood sample was collected at 12 months to determine plasma ferritin, haemoglobin, soluble transferrin receptor, C-reactive protein and α1-acid glycoprotein concentrations; and body iron was calculated. RESULTS: Differences in median dietary iron intakes between the control and BLISS groups were not significant at 7 (difference 0.6 mg/day; 95% CI -1.0 to 2.3) or 12 (-0.1 mg/day; -1.6 to 1.4) months of age. Similarly, there were no significant differences in plasma ferritin concentration (difference -2.6 µg/L; 95% CI -10.9 to 5.8), body iron (0.04 mg/kg; -1.1 to 1.2) or the prevalence of depleted iron stores, early functional iron deficiency or iron deficiency anaemia (all p≥0.65) at 12 months of age. CONCLUSIONS: A baby-led approach to complementary feeding does not appear to increase the risk of iron deficiency in infants when their parents are given advice to offer 'high-iron' foods with each meal. TRIAL REGISTRATION NUMBER: ACTRN12612001133820; Pre-results.


Asunto(s)
Anemia Ferropénica/prevención & control , Conducta Alimentaria , Conducta del Lactante , Hierro de la Dieta/administración & dosificación , Destete , Desarrollo Infantil , Femenino , Ferritinas/sangre , Hemoglobinas/análisis , Humanos , Lactante , Alimentos Infantiles , Deficiencias de Hierro , Masculino , Nueva Zelanda
10.
J Paediatr Child Health ; 54(3): 223-233, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29504223

RESUMEN

Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence-based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non-fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence-based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteogénesis Imperfecta/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Adolescente , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/efectos adversos , Parálisis Cerebral/complicaciones , Niño , Difosfonatos/efectos adversos , Humanos , Distrofia Muscular de Duchenne/complicaciones , Osteoporosis/etiología
11.
Toxicol Appl Pharmacol ; 313: 47-56, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27765658

RESUMEN

BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS2 analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed. RESULTS: 613 unique named metabolites were identified. Of these, 189 metabolites were increased in the VC exposure group while 94 metabolites were decreased. Random Forest analysis indicated that the metabolite signature could separate the groups with 94% accuracy. VC exposures were associated with increased long chain (including arachidonic acid) and essential (including linoleic acid) fatty acids. Occupational exposure increased lipid peroxidation products including monohydroxy fatty acids (including 13-HODE); fatty acid dicarboxylates; and oxidized arachidonic acid products (including 5,9, and 15-HETE). Carnitine and carnitine esters were decreased, suggesting peroxisomal/mitochondrial dysfunction and alternate modes of lipid oxidation. Differentially regulated metabolites were shown to interact with extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, AMP-activated protein kinase (AMPK), and the N-Methyl-d-aspartate (NMDA) receptor. The top canonical pathways affected by occupational exposure included tRNA charging, nucleotide degradation, amino acid synthesis/degradation and urea cycle. Methionine and homocysteine was increased with decreased cysteine, suggesting altered 1-carbon metabolism. CONCLUSIONS: Occupational exposure generated a distinct plasma metabolome with markedly altered lipid and amino acid metabolites. ERK1/2, Akt, AMPK, and NMDA were identified as protein targets for vinyl chloride toxicity.


Asunto(s)
Proteínas Sanguíneas/metabolismo , Metabolómica , Exposición Profesional , Cloruro de Polivinilo/toxicidad , Adulto , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Cloruro de Polivinilo/síntesis química
12.
Sci Rep ; 6: 21583, 2016 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-26898606

RESUMEN

Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Microambiente Celular , Glioblastoma/metabolismo , Células Madre Neoplásicas/metabolismo , Taxia , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Estimulación Eléctrica , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Glioblastoma/patología , Humanos , Iones , Miosina Tipo II/metabolismo , Células Madre Neoplásicas/patología , Péptidos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal
13.
Case Rep Med ; 2016: 6206358, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28058050

RESUMEN

Central venous access is an important aspect of neonatal intensive care management. Malpositioned central catheters have been reported to induce cardiac tachyarrhythmia in adult populations and there are case reports within the neonatal population. We present a case of a preterm neonate with a preexisting umbilical venous catheter (UVC), who then developed a supraventricular tachycardia (SVT). This was initially treated with intravenous adenosine with transient reversion. Catheter migration was subsequently detected, with the UVC tip located within the heart. Upon withdrawal of the UVC and a final dose of adenosine, the arrhythmia permanently resolved. Our literature review confirms that tachyarrhythmia is a rare but recognised neonatal complication of malpositioned central venous catheters. We recommend the immediate investigation of central catheter position when managing neonatal tachyarrhythmia, as catheter repositioning is an essential aspect of management.

14.
Artículo en Inglés | MEDLINE | ID: mdl-26113981

RESUMEN

UNLABELLED: Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion. LEARNING POINTS: Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.Serial/diurnal cortisol levels, ACTH measurement +/- low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.

15.
N Z Med J ; 127(1389): 31-9, 2014 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-24548955

RESUMEN

BACKGROUND: Pseudomyxoma peritonei is a condition characterised by dissemination of mucin-producing neoplastic cells throughout the peritoneal cavity. There are two pathological subsets, disseminated peritoneal adenomucinosis and peritoneal mucinosis carcinomatosis. Once a lethal disease, cytoreductive surgery combined with heated intraperitoneal chemotherapy (HIPEC) is challenging debulking as the standard of care. OBJECTIVE: We present the first case series detailing the postoperative morbidity, mortality and survival outcomes of patients treated for pseudomyxoma peritonei by cytoreductive surgery without heated intraperitoneal chemotherapy by a single surgeon. DESIGN: Wellington Hospital clinical databases were retrospectively searched. Inclusion criteria were a diagnosis of pseudomyxoma peritonei with a major cytoreductive operation with the intention of complete cytoreductive clearance. Exclusion criteria were palliative debulking operations and patient records not available for analysis. RESULTS: 25 patients underwent cytoreductive surgery between June 1999 and July 2011. Mean follow-up was 43.5 months (1.5-138). Histological classification was DPAM for 13/25 and PMCA for 12/25. Complete cytoreduction (CC-0 and CC-1) was achieved in 21/25 patients. There was no 30 day mortality following primary cytoreduction. Six patients underwent subsequent debulking/cytoreductive surgery; one patient died following repeat surgery. Clavien-Dindo grade 3 or 4 complications occurred in 7/25 patients. Combined 5-year survival was 64%, 92% for DPAM and 33% for PMCA. CONCLUSION: Cytoreductive surgery alone may result in comparable survival outcomes to those achieved with combined surgery and HIPEC in selected patients, especially for patients with DPAM.


Asunto(s)
Carcinoma/cirugía , Neoplasias Peritoneales/cirugía , Peritoneo/cirugía , Seudomixoma Peritoneal/cirugía , Adulto , Anciano , Carcinoma/mortalidad , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Nueva Zelanda , Tempo Operativo , Neoplasias Peritoneales/mortalidad , Complicaciones Posoperatorias , Seudomixoma Peritoneal/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento
16.
Surg Endosc ; 26(6): 1730-6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22258294

RESUMEN

BACKGROUND: Fatigue is one of the main complaints after surgery and may last longer than physical symptoms. It prevents return to normal function and activity. Relaxation interventions, performed prior to abdominal surgery, have been shown to reduce pain, wound erythema, and systemic cortisol levels. However, there is a lack of data on the impact of this intervention on patient well-being, functional recovery, activities of daily living, and fatigue after discharge from hospital. METHODS: The study was a randomised single-blinded trial. Patients who were to undergo elective laparoscopic cholecystectomy for any indication between April 2008 and May 2010 were screened for inclusion. Those in the intervention group attended a standardised 45 min relaxation session with a health psychologist and were given relaxation exercise CDs to take home. The control group did not have the intervention. Patients were followed for 30 days. Fatigue was measured using the identity-consequence fatigue scale. RESULTS: Seventy-five patients were randomised. Fifteen patients were excluded after randomization for various reasons; hence, 60 patients were followed up and analysed. Both groups had similar fatigue at baseline. There was improved fatigue and consequence of fatigue on postoperative day 30 in the intervention group. There was no difference in fatigue at any other time point postoperatively. CONCLUSION: This was the first interventional study targeting fatigue after laparoscopic cholecystectomy by using a brief psychological relaxation intervention. It has shown a reduction of fatigue and impact of fatigue at 30 days postoperatively in the intervention group.


Asunto(s)
Colecistectomía Laparoscópica/efectos adversos , Fatiga/prevención & control , Atención Perioperativa/métodos , Terapia por Relajación/métodos , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Calidad de Vida , Resultado del Tratamiento , Adulto Joven
17.
Brain Behav Immun ; 26(2): 212-7, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21741471

RESUMEN

Psychological stress has been shown to impair wound healing, but experimental research in surgical patients is lacking. This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients. This randomised controlled trial was conducted at a surgical centre. Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy; exclusion criteria were cancellation of surgery, medical complications, and refusal of consent. Seventy five patients were randomised and 15 patients were excluded; 60 patients completed the study (15 male, 45 female). Participants were randomised to receive standard care or standard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery. In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing. Change in perceived stress from before surgery to 7-day follow-up was assessed using questionnaires. Intervention group patients showed a reduction in perceived stress compared with the control group, controlling for age. Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients (difference in means 0.35, 95% CI 0.66-0.03; t(43)=2.23, p=0.03). Changes in perceived stress were not associated with hydroxyproline deposition. A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients. The intervention may have particular clinical application for those at risk of poor healing following surgery.


Asunto(s)
Terapia por Relajación/métodos , Estrés Psicológico/prevención & control , Cicatrización de Heridas , Colecistectomía Laparoscópica/psicología , Femenino , Humanos , Hidroxiprolina/análisis , Masculino , Persona de Mediana Edad , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Resultado del Tratamiento
18.
Med Teach ; 33(9): e479-84, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21854141

RESUMEN

BACKGROUND: Clerkship performance is commonly evaluated by consultant surgeons who seldom supervise medical students directly. In contrast, surgical residents and interns frequently supervise students and provide essential teaching but are not tasked with evaluating them. AIM: To prospectively investigate and compare the accuracy of general surgery clerkship performance evaluations by clinical supervisors of differing seniorities. METHOD: Between September 2008 and May 2010, clinical supervisors of varying seniorities independently evaluated 57 fourth-year medical students using a multi-dimensional performance evaluation tool. Total evaluation grades and subtotal grades for clinical ability were correlated to the results of a validated surgical objective structured clinical examination (OSCE). RESULTS: In this study, 85 clinical supervisors provided 427 student performance evaluations. Total evaluation grades awarded by consultant surgeons had weak correlation to student OSCE results (r = 0.27, p < 0.05) and associated subtotal grades for clinical ability had no correlation. In comparison, the equivalent sets of grades awarded by residents and interns had moderate correlations to OSCE results (r = 0.49 and r = 0.54, p < 0.01). CONCLUSIONS: Validity of clinical supervisor evaluations during general surgery clerkships vary according to assessor seniority. Including performance evaluation grades by surgical residents and interns may enhance the overall validity of this common clerkship evaluation tool and improve its summative and formative assessment value.


Asunto(s)
Prácticas Clínicas , Competencia Clínica , Evaluación Educacional/normas , Cirugía General/educación , Humanos , Nueva Zelanda , Estudios Prospectivos , Estudiantes de Medicina
19.
J Surg Res ; 168(1): e17-23, 2011 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-20031155

RESUMEN

BACKGROUND: Surgical clerkship teaching for medical students at the University of Auckland is undertaken across multiple clinical campuses. Concerns are that differences in clinical experience may result in variability of learning outcome achievements. Our objectives were to investigate whether differences in clinical experience existed between teaching sites, and whether these differences correlate to differences in learning outcome achievements. Influence of clinical experience on future career choice was also explored. MATERIALS AND METHODS: Prospectively collected data were retrospectively reviewed. Clinical experience from assigned hospitals was collected using student Feedback Questionnaires and case history logbooks. Results were analyzed for inter-hospital differences. The Questionnaire included a question on influence of clinical experience on future career choice. A formative Objective Structured Clinical Examination (OSCE) was administered and results were analyzed for inter-hospital differences in learning outcome achievements. RESULTS: Feedback Questionnaires and case history logbooks identified inter-hospital differences in clinical experience. Clerkship enjoyment and involvement in theater correlated with increased likelihood of choosing a future surgical career. The OSCE had acceptable internal reliability (Cronbach's α 0.69-0.74) and strong correlations with other formal assessments, indicating its external validity. No significant inter-hospital differences in OSCE results were found after one-way analysis of variance comparison (P=0.125). CONCLUSION: Heterogeneity of clinical experience from multiple teaching sites did not translate into heterogeneity in achievement of learning outcomes when teaching and assessment materials were standardized. Clinical experience during undergraduate clerkships may influence future career choices. The OSCE is a validated and reliable tool for assessing student achievement of learning outcomes.


Asunto(s)
Prácticas Clínicas/normas , Curriculum/normas , Educación Médica/normas , Selección de Profesión , Cirugía General/educación , Humanos , Nueva Zelanda , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Estudios Retrospectivos , Encuestas y Cuestionarios
20.
ANZ J Surg ; 80(12): 902-6, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21114730

RESUMEN

BACKGROUND: Surgical clerkships facilitate development of knowledge and competency, but their structure and content vary. Establishment of new medical schools and raising student numbers are new challenges to the provision of standardized surgical teaching across Australasian medical schools. A survey was conducted to investigate how Australian and New Zealand medical schools structure their general surgery clerkships. METHODS: Between April and August 2009, a 30-item web-based survey was electronically sent to academic and administrative staff members of 22 Australian and New Zealand medical schools. RESULTS: Eighteen surveys were returned by 16 medical schools, summarizing 20 clerkships. Ten schools utilize five or more different clinical teaching sites for general surgery clerkships and these include urban and rural hospitals from both public and private health sectors. Student teaching and assessment methods are similar between clerkships and standardized across clinical sites during 10 and 16 of the clerkships, respectively. Only eight of the surveyed clerkships use centralized assessments to evaluate student learning outcomes across different clinical sites. Four clerkships do not routinely use direct observational student assessments. CONCLUSIONS: Australian and New Zealand medical schools commonly assign students to multiple diverse clinical sites during general surgery clerkships and they vary in their approaches to standardizing curriculum delivery and student assessment across these sites. Differences in student learning are likely to exist and deficiencies in clinical ability may go undetected. This should be a focus for future improvement.


Asunto(s)
Prácticas Clínicas/organización & administración , Cirugía General/educación , Australia , Competencia Clínica , Estudios Transversales , Curriculum , Humanos , Evaluación de Necesidades , Nueva Zelanda
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