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1.
J Perinatol ; 40(10): 1513-1517, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32203175

RESUMEN

OBJECTIVE: Determine whether management of neonatal hyperbilirubinemia differs if one used end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) measurements instead of direct antiglobulin test (DAT) results to assess the severity of hemolysis. STUDY DESIGN: Retrospective chart review of infants with total bilirubin and ETCOc levels measured from July 2016 to August 2018. The reported treatment is the hypothetical management infants might have received had there been strict adherence to American Academy of Pediatrics guidelines, rather than the actual management they received. RESULT: Only 27.2% of 191 DAT(+) infants were hemolyzing based on ETCOc, while 29.1% of DAT (-) infants were hemolyzing based on ETCOc. Management of 18 (9.4%) infants differed depending if ETCOc or DAT were used to determine hemolysis. Eight fewer infants would have received phototherapy if ETCOc was used. CONCLUSIONS: ETCOc is a more accurate determinant of hemolysis in the newborn, and its use can lead to less phototherapy.


Asunto(s)
Monóxido de Carbono , Hiperbilirrubinemia Neonatal , Bilirrubina , Niño , Prueba de Coombs , Humanos , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/terapia , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Recién Nacido , Estudios Retrospectivos
2.
Water Res ; 148: 86-96, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30352324

RESUMEN

In situ fluorometers can be used as a real-time cyanobacteria detection tool to maintain safe drinking and recreational water standards. However, previous studies into fluorometers have established issues arising mainly from measurement inaccuracies due to green algae interference. Therefore, this study focusses on developing correction factors from a systematic study on the impact of green algae as an interference source. This study brings a novel technique where the chlorophyll-a (Chl-a) and phycocyanin measurements are used to correct the fluorometer output for interference bias; four fluorometers were tested against three key cyanobacterial species and the relationship between phycocyanin output, green algae and cyanobacteria concentrations were investigated. Good correlation (R2 > 0.9, p-value < 0.05) was found between the fluorometer phycocyanin output and increasing green algae concentration. The optimal correction method was selected for each of the fluorometer and cyanobacteria species pairs by validating against data from the investigation of green algae as an interference source. The correction factors determined in this study reduced the measurement error for almost all the fluorometers and species tested by 21%-99% depending on the species and fluorometer, compared to previous published correction factors in which the measurement error was reduced by approximately 11%-81%. Field validation of the correction factors showed reduction in fluorometer measurement error at sites in which cyanobacterial blooms were dominated by a single species.


Asunto(s)
Clorofila A , Cianobacterias , Clorofila , Monitoreo del Ambiente , Fluorescencia , Ficocianina
3.
S Afr Med J ; 107(11): 1022-1025, 2017 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-29262947

RESUMEN

BACKGROUND: Endoscopy services are central to the diagnosis and management of many gastrointestinal (GI) diseases. OBJECTIVE: To evaluate the adequacy of endoscopy services in the public sector hospitals of KwaZulu-Natal (KZN) Province, South Africa, in 2016. METHODS: A cross-sectional study was performed using a questionnaire completed by the clinical heads of endoscopy units in the public hospitals in KZN. RESULTS: The heads of 11 of the 12 endoscopy units responded. Two units were in tertiary-level hospitals and nine in regional hospitals. A total of 22 353 endoscopic procedures were performed annually, averaging 2 032 cases per annum per centre; they were performed by 89 endoscopists, of whom 72 (80.1%) were general surgeons. There were 0.06 registered gastroenterologists (GEs) per 100 000 population. Each endoscopist performed an average of 263 endoscopies per annum. There were 1.18 endoscopy rooms available per unit, and two units had on-site fluoroscopy available. The average waiting period for an upper endoscopy was 27 (range 7 - 60) days, for colonoscopy 29 (range 7 - 90) days and for duodenoscopy/endoscopic retrograde cholangiopancreatography 13 (range 4 - 20) days. This included patients with alarm symptoms for GI cancers. Equipment breakages interrupted most services, except for one hospital that had a service contract. Unit heads cited lack of equipment, trained staff and maintenance contracts as major shortcomings. CONCLUSIONS: Endoscopy units in KZN are not adequately equipped to deal with the endoscopy workload and services are plagued by frequent disruptions, which impact negatively on service delivery. There is a need to train more GEs. Patient care is compromised in these public hospitals.

4.
Ann R Coll Surg Engl ; 99(1): 63-69, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27791418

RESUMEN

INTRODUCTION The spleen remains one of the most frequently injured organs following blunt abdominal trauma. In 2012, regional trauma networks were launched across England and Wales with the aim of improving outcomes following trauma. This retrospective cohort study investigated the management and outcomes of blunt splenic injuries before and after the establishment of regional trauma networks. METHODS A dataset was drawn from the Trauma Audit Research Network database of all splenic injuries admitted to English and Welsh hospitals from 1 April 2010 to 31 March 2014. Demographic data, injury severity, treatment modalities and outcomes were collected. Management and outcomes were compared before and after the launch of regional trauma networks. RESULTS There were 1457 blunt splenic injuries: 575 between 2010 and 2012 and 882 in 2012-14. Following the introduction of the regional trauma networks, use of splenic artery embolotherapy increased from 3.5% to 7.6% (P = 0.001) and splenectomy rates decreased from 20% to 14.85% (P = 0.012). Significantly more patients with polytrauma and blunt splenic injury were treated with splenic embolotherapy following 2012 (61.2% vs. 30%, P < 0.0001). Increasing age, injury severity score, polytrauma and Charlson Comorbidity Index above 10 were predictors of increased mortality (P < 0.001). Increasing systolic blood pressure (odds ratio, OR, 0.757, 95% confidence interval, CI, 0.716-0.8) and Glasgow Coma Scale (OR 0.988, 95% CI 0.982-0.995) were protective. CONCLUSIONS This study demonstrates a reduction in splenectomy rate and an increased use of splenic artery embolotherapy since the introduction of the regional trauma networks. This may have resulted from improved access to specialist services and reduced practice variation since the establishment of these networks.


Asunto(s)
Bazo/lesiones , Heridas no Penetrantes/terapia , Adulto , Embolización Terapéutica/estadística & datos numéricos , Inglaterra/epidemiología , Humanos , Tiempo de Internación , Traumatismo Múltiple/mortalidad , Traumatismo Múltiple/terapia , Estudios Retrospectivos , Esplenectomía/mortalidad , Esplenectomía/estadística & datos numéricos , Tiempo de Tratamiento , Centros Traumatológicos/estadística & datos numéricos , Resultado del Tratamiento , Gales/epidemiología , Heridas no Penetrantes/mortalidad
5.
Cell Death Differ ; 23(9): 1565-76, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27177019

RESUMEN

Necroptosis is a caspase-independent form of cell death that is triggered by activation of the receptor interacting serine/threonine kinase 3 (RIPK3) and phosphorylation of its pseudokinase substrate mixed lineage kinase-like (MLKL), which then translocates to membranes and promotes cell lysis. Activation of RIPK3 is regulated by the kinase RIPK1. Here we analyze the contribution of RIPK1, RIPK3, or MLKL to several mouse disease models. Loss of RIPK3 had no effect on lipopolysaccharide-induced sepsis, dextran sodium sulfate-induced colitis, cerulein-induced pancreatitis, hypoxia-induced cerebral edema, or the major cerebral artery occlusion stroke model. However, kidney ischemia-reperfusion injury, myocardial infarction, and systemic inflammation associated with A20 deficiency or high-dose tumor necrosis factor (TNF) were ameliorated by RIPK3 deficiency. Catalytically inactive RIPK1 was also beneficial in the kidney ischemia-reperfusion injury model, the high-dose TNF model, and in A20(-/-) mice. Interestingly, MLKL deficiency offered less protection in the kidney ischemia-reperfusion injury model and no benefit in A20(-/-) mice, consistent with necroptosis-independent functions for RIPK1 and RIPK3. Combined loss of RIPK3 (or MLKL) and caspase-8 largely prevented the cytokine storm, hypothermia, and morbidity induced by TNF, suggesting that the triggering event in this model is a combination of apoptosis and necroptosis. Tissue-specific RIPK3 deletion identified intestinal epithelial cells as the major target organ. Together these data emphasize that MLKL deficiency rather than RIPK1 inactivation or RIPK3 deficiency must be examined to implicate a role for necroptosis in disease.


Asunto(s)
Inflamación/patología , Proteínas Quinasas/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Animales , Apoptosis/efectos de los fármacos , Ceruletida/toxicidad , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Femenino , Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Pancreatitis/patología , Proteínas Quinasas/deficiencia , Proteínas Quinasas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/antagonistas & inhibidores , Proteína Serina-Treonina Quinasas de Interacción con Receptores/deficiencia , Daño por Reperfusión/metabolismo , Daño por Reperfusión/mortalidad , Daño por Reperfusión/patología , Sepsis/etiología , Sepsis/metabolismo , Sepsis/patología , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/patología , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/deficiencia , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética
6.
Br J Surg ; 103(8): 1063-8, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27061287

RESUMEN

INTRODUCTION: Management of perianal abscesses has remained largely unchanged for over 50 years. The evidence for postoperative wound packing is limited and may expose patients to painful procedures with no clinical benefit and at considerable increased cost. METHODS: Patients were recruited in 15 UK centres between December 2013 and October 2014. Outcome measures included number of dressing (pack) changes, healing, recurrence, return to work/normal function, postoperative fistula in ano and health utility scores (EQ-5D™). Pain was measured before, during and after dressing change on a visual analogue scale. RESULTS: Some 141 patients were recruited (median age 39 (range 18-86) years). The mean number of dressing changes in the first 3 weeks was 13 (range 0-21), equating to an annual cost to the National Health Service of €6 453 360 in England alone per annum. Some 43·8 per cent of wounds were healed by 8 weeks after surgery and 86 per cent of patients had returned to normal function. Some 7·6 per cent of abscesses had recurred and 26·7 per cent of patients developed a fistula in ano by 6 months following surgery. Patients reported a twofold to threefold increase in pain scores during and after dressing changes. CONCLUSION: Recurrent abscess is rare and fistula occurs in one-quarter of the patients. Packing is painful and costly.


Asunto(s)
Absceso/terapia , Enfermedades del Ano/terapia , Drenaje , Absceso/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades del Ano/economía , Vendajes/economía , Vendajes/estadística & datos numéricos , Enfermería en Salud Comunitaria/economía , Femenino , Fisura Anal/etiología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Recurrencia , Reino Unido , Escala Visual Analógica , Cicatrización de Heridas , Adulto Joven
7.
J R Army Med Corps ; 162(1): 68-70, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25736444

RESUMEN

We report a case of traumatic cardiac arrest in a combat casualty who was resuscitated to return of spontaneous circulation despite asystole and no visible cardiac activity on initial ultrasound examination. This return of spontaneous circulation suggests that survival may be possible in traumatic cardiac arrest due to exsanguination, even when there is no demonstrable cardiac activity on ultrasound. Cardiac ultrasonography was performed for 10 s only. We suggest that cardiac ultrasonography should be performed for a minimum of 1 min during volume resuscitation. If absence of cardiac activity is confirmed once the heart is full, and there are no other signs of life (including pupillary reaction), then termination of resuscitation should be considered.


Asunto(s)
Ecocardiografía , Paro Cardíaco , Personal Militar , Resucitación/métodos , Adulto , Afganistán , Amputación Traumática , Traumatismos por Explosión , Resultado Fatal , Humanos , Masculino , Tromboelastografía , Adulto Joven
8.
Clin Endocrinol (Oxf) ; 84(5): 672-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26663024

RESUMEN

OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.


Asunto(s)
Ejercicio Físico/fisiología , Ácidos Grasos Omega-3/uso terapéutico , Sofocos/prevención & control , Hidrocortisona/análisis , Saliva/química , Adulto , Ritmo Circadiano , Estudios Transversales , Femenino , Sofocos/metabolismo , Sofocos/fisiopatología , Humanos , Modelos Lineales , Modelos Logísticos , Menopausia/fisiología , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos
9.
Artif Organs ; 40(2): 175-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26153483

RESUMEN

The flow patterns of a prosthetic heart valve in the aortic or mitral position can change according to its type and orientation. This work describes the use of 2D particle image velocimetry (PIV) applied to the in vitro flow fields characterization inside the upper part of a left ventricular model at various heart rates and as a function of two orientations of stented tricuspid mitral bioprostheses. In the ventricular model, each mitral bioprosthesis (27 and 31 mm diameter) was installed in two orientations, rotated by 180°, while the aortic bileaflet mechanical valve (27 mm diameter) remained in a fixed orientation. The results (N = 50) showed changes in the intraventricular flow fields according to the mitral bioprostheses positioning. Also, changes in the aortic upstream velocity profiles were noticed as a function of mitral orientations.


Asunto(s)
Bioprótesis , Prótesis Valvulares Cardíacas , Ventrículos Cardíacos/fisiopatología , Válvula Mitral/fisiopatología , Válvula Tricúspide/fisiopatología , Simulación por Computador , Frecuencia Cardíaca , Humanos , Hidrodinámica , Modelos Cardiovasculares , Contracción Miocárdica , Diseño de Prótesis , Reología
10.
Climacteric ; 18(6): 859-66, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26517583

RESUMEN

OBJECTIVE: To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). METHODS: Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. RESULTS: The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. CONCLUSIONS: Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research.


Asunto(s)
Trastornos del Conocimiento/terapia , Fatiga/terapia , Sofocos/terapia , Menopausia , Prioridad del Paciente , Trastornos del Sueño-Vigilia/terapia , Adulto , Área Bajo la Curva , Atención , Estudios Transversales , Ejercicio Físico/fisiología , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Curva ROC , Encuestas y Cuestionarios , Yoga
11.
Cell Death Dis ; 6: e1800, 2015 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-26111062

RESUMEN

Necroptosis is a caspase-independent regulated type of cell death that relies on receptor-interacting protein kinases RIP1 (receptor-interacting protein kinases 1) and RIP3. Tumor necrosis factor-α (TNFα)-stimulated assembly of the TNFR1 (TNF receptor 1)-associated signaling complex leads to the recruitment of RIP1, whose ubiquitination is mediated by the cellular inhibitors of apoptosis (c-IAPs). Translocation of RIP1 to the cytoplasm and association of RIP1 with the necrosome is believed to correlate with deubiquitination of RIP1. However, we found that RIP1 is ubiquitinated with K63 and linear polyubiquitin chains during TNFα, IAP antagonist BV6 and caspase inhibitor zVAD-fmk-induced necroptotic signaling. Furthermore, ubiquitinated RIP1 is associated with the necrosome, and RIP1 ubiquitination in the necrosome coincides with RIP3 phosphorylation. Both cellular IAPs and LUBAC (linear ubiquitin chain assembly complex) modulate RIP1 ubiquitination in IAP antagonist-treated necrotic cells, but they use different mechanisms. c-IAP1 regulates RIP1 recruitment to the necrosome without directly affecting RIP1 ubiquitination, whereas HOIP and HOIL1 mediate linear ubiquitination of RIP1 in the necrosome, but are not essential for necrosome formation. Knockdown of the E3 ligase c-IAP1 decreased RIP1 ubiquitination, necrosome assembly and necroptosis induced by TNFα, BV6 and zVAD-fmk. c-IAP1 deficiency likely decreases necroptotic cell death through the activation of the noncanonical NF-κB pathway and consequent c-IAP2 upregulation. The ability to upregulate c-IAP2 could determine whether c-IAP1 absence will have a positive or negative impact on TNFα-induced necroptotic cell death and necrosome formation. Collectively, these results reveal unexpected complexity of the roles of IAP proteins, IAP antagonists and LUBAC in the regulation of necrosome assembly.


Asunto(s)
Proteínas Inhibidoras de la Apoptosis/genética , Necrosis/patología , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ubiquitina-Proteína Ligasas/genética , Clorometilcetonas de Aminoácidos/farmacología , Animales , Apoptosis/fisiología , Proteína 3 que Contiene Repeticiones IAP de Baculovirus , Inhibidores de Caspasas/farmacología , Línea Celular Tumoral , Células HT29 , Humanos , Proteínas Inhibidoras de la Apoptosis/biosíntesis , Proteínas Inhibidoras de la Apoptosis/metabolismo , Células L , Ratones , FN-kappa B/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factores de Transcripción , Factor de Necrosis Tumoral alfa/metabolismo , Ubiquitina/química , Ubiquitina-Proteína Ligasas/biosíntesis , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
12.
Chemosphere ; 120: 206-10, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25062026

RESUMEN

Titanium dioxide nanoparticles (TiO2 NP) are one of the most abundantly utilized nanoparticles in the world. Studies have demonstrated the ability of the anatase crystal of TiO2 NP to produce reactive oxygen species (ROS) in the presence of ultraviolet radiation (UVR), a co-exposure likely to occur in aquatic ecosystems. The goal of this study was to examine the photo-induced toxicity of anatase TiO2 NP under natural sunlight to Daphnia magna. D. magna were exposed to a range of UVR intensities and anatase TiO2 concentrations in an outdoor exposure system using the sun as the source of UVR. Different UVR intensities were achieved using UVR opaque and transparent plastics. AnataseTiO2-NP demonstrated the reciprocal relationship seen in other phototoxic compounds such as polycyclic aromatic hydrocarbons (PAHs) at higher UVR treatments. The calculated 8h LC50 of anatase TiO2 NP was 139 ppb under full intensity ambient natural sunlight, 778 ppb under 50% natural sunlight, and >500 ppm under 10% natural sunlight. Mortality was also compared between animals allowed to accumulate a body burden of anatase TiO2 for 1h and organisms whose first exposure to anatase TiO2 aqueous suspensions occurred under UVR. A significantly greater toxic effect was observed in aqueous, low body burden suspensions than that of TiO2 1h body burdens, which is dissimilar from the model presented in PAHs. Anatase TiO2 presents a unique photo-induced toxic model that is different than that of established phototoxic compounds.


Asunto(s)
Daphnia/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Luz Solar , Titanio/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales
13.
Colorectal Dis ; 17(1): 38-46, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25213040

RESUMEN

AIM: Colonic surveillance reduces the lifetime risk of colorectal cancer in patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer) from 60 to 80% to 10% and confers a 7-year survival advantage. The British Society of Gastroenterologists recommends colonoscopy at least every 2 years from the age of 25. Currently in the UK, genetic diagnosis is made by a regional genetics service, and screening recommendations are made to the referring clinician. The aim of this study was to investigate compliance with and the effectiveness of large bowel surveillance in Lynch syndrome. METHOD: A retrospective longitudinal study of Lynch syndrome mutation carriers on the Regional Familial Colorectal Cancer Registry under and not under screening was conducted. To investigate screening compliance, patients were included if they were alive at the start of the study. Data were gathered on timeliness, quality and outcome of screening. To examine the effectiveness of screening, the cumulative incidence of colorectal cancer was estimated using Kaplan-Meier curves and the screened population compared with patients not being screened. RESULTS: A total of 227 Lynch syndrome mutation carriers were under screening at 26 hospitals. We assessed 439 colonoscopies for timeliness, of which 68% were compliant (interval < 27 months). Compliance on the 1 November 2011 was 87%. The cumulative incidence of colorectal cancer to the age of 70 was 25% (95% CI 17-32%) in the surveillance population and 81% (95% CI 78-84%) in 689 mutation-positive patients not being screened (P < 0.0001). CONCLUSION: Overall, 68% of colonoscopies were on time. The incidence of colorectal cancer was greatly reduced by screening but remained significant. Patients with Lynch syndrome need proactive surveillance management.


Asunto(s)
Colonoscopía , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales/epidemiología , Detección Precoz del Cáncer/métodos , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Detección Precoz del Cáncer/normas , Humanos , Incidencia , Estudios Longitudinales , Persona de Mediana Edad , Cooperación del Paciente , Vigilancia de la Población , Estudios Retrospectivos , Reino Unido/epidemiología , Adulto Joven
14.
J Med Genet ; 51(12): 789-96, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25280751

RESUMEN

BACKGROUND AND AIMS: Lynch syndrome (LS) patients have DNA mismatch repair deficiency and up to 80% lifetime risk of colorectal cancer (CRC). Screening of mutation carriers reduces CRC incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour-derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from LS (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations. METHODS: Tumour DNA was extracted (formalin fixed, paraffin embedded, FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared. FINDINGSS: Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2% to 98.4%), specificity 87.7% (95% CI 77.9% to 94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7% to 76.5%), specificity 98.6% (95% CI 92.4% to 100.0%) for the identification of those with pathogenic MLH1 mutations. CONCLUSIONS: Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Metilación de ADN , Pruebas Genéticas , Neoplasias/genética , Proteínas Nucleares/genética , Regiones Promotoras Genéticas , Adulto , Alelos , Neoplasias Encefálicas/genética , Neoplasias Colorrectales/genética , Islas de CpG , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Heterocigoto , Humanos , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Mutación , Síndromes Neoplásicos Hereditarios/genética , Proteínas Proto-Oncogénicas B-raf/genética , Sensibilidad y Especificidad
15.
J Appl Microbiol ; 117(6): 1663-73, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25179003

RESUMEN

AIMS: The aim of this study was to isolate novel antibiofilm compounds produced by environmental bacteria. METHODS AND RESULTS: Cell-free extracts were prepared from lawns of bacteria cultured on agar. A total of 126 bacteria isolated from soil, cave and river habitats were employed. Extracts were tested for their ability to inhibit Staphylococcus aureus biofilm in a 96-well microtitre plate assay. A total of 55/126 extracts (44%) significantly inhibited Staph. aureus biofilm. Seven extracts were selected for further analysis. The antibiofilm activities in all seven extracts exhibited unique patterns of molecular mass, chemical polarity, heat stability and spectrum of activity against Staph. aureus, Staphylococcus epidermidis and Pseudomonas fluorescens, suggesting that these seven antibiofilm activities were mediated by unique chemical compounds with different mechanisms of action. CONCLUSIONS: Environmental bacteria produce abundant and diverse antibiofilm compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: Screening cell-free extracts is a useful method for identifying secreted compounds that regulate biofilm formation. Such compounds may represent a novel source of antibiofilm agents for technological development.


Asunto(s)
Antibacterianos/farmacología , Bacterias/química , Biopelículas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/metabolismo , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Biopelículas/crecimiento & desarrollo , Microbiología Ambiental , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología
17.
Acta Orthop ; 85(3): 259-65, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24758321

RESUMEN

BACKGROUND AND PURPOSE: In patients with metal-on-metal (MoM) hip prostheses, pain and joint effusions may be associated with elevated blood levels of cobalt and chromium ions. Since little is known about the kinetics of metal ion clearance from the body and the rate of resolution of elevated blood ion levels, we examined the time course of cobalt and chromium ion levels after revision of MoM hip replacements. PATIENTS AND METHODS: We included 16 patients (13 female) who underwent revision of a painful MoM hip (large diameter, modern bearing) without fracture or infection, and who had a minimum of 4 blood metal ion measurements over an average period of 6.1 (0-12) months after revision. RESULTS: Average blood ion concentrations at the time of revision were 22 ppb for chromium and 43 ppb for cobalt. The change in ion levels after revision surgery varied extensively between patients. In many cases, over the second and third months after revision surgery ion levels decreased to 50% of the values measured at revision. Decay of chromium levels occurred more slowly than decay of cobalt levels, with a 9% lag in return to normal levels. The rate of decay of both metals followed second-order (exponential) kinetics more closely than first-order (linear) kinetics. INTERPRETATION: The elimination of cobalt and chromium from the blood of patients who have undergone revision of painful MoM hip arthroplasties follows an exponential decay curve with a half-life of approximately 50 days. Elevated blood levels of cobalt and chromium ions can persist for at least 1 year after revision, especially in patients with high levels of exposure.


Asunto(s)
Artroplastia de Reemplazo de Cadera/instrumentación , Cromo/sangre , Cobalto/sangre , Remoción de Dispositivos , Prótesis de Cadera , Metales , Anciano , Artralgia/cirugía , Femenino , Articulación de la Cadera/cirugía , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Falla de Prótesis , Análisis de Regresión , Reoperación , Estudios Retrospectivos
18.
Aliment Pharmacol Ther ; 38(10): 1267-77, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24117728

RESUMEN

BACKGROUND: Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. AIM: To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. METHODS: Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. RESULTS: Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. CONCLUSIONS: Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner.


Asunto(s)
Hígado Graso/diagnóstico , Hepatopatías/diagnóstico , Obesidad/complicaciones , Sobrepeso/complicaciones , Adolescente , Alanina Transaminasa/metabolismo , Niño , Femenino , Estudios de Seguimiento , Gastroenterología/métodos , Humanos , Hepatopatías/fisiopatología , Masculino , Tamizaje Masivo/métodos , Enfermedad del Hígado Graso no Alcohólico , Atención Primaria de Salud , Estudios Prospectivos , Derivación y Consulta , Sensibilidad y Especificidad
19.
S Afr Med J ; 103(5 Pt 2): 337-49, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23967497

RESUMEN

Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.


Asunto(s)
Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica/terapia , Adulto , Antivirales/administración & dosificación , Niño , Monitoreo de Drogas/métodos , Anticuerpos contra la Hepatitis B/análisis , Antígenos de la Hepatitis B/análisis , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/etiología , Hepatitis B Crónica/fisiopatología , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/prevención & control , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Administración del Tratamiento Farmacológico , Sudáfrica
20.
Maturitas ; 75(2): 152-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23562010

RESUMEN

OBJECTIVES: Evaluate the association of self-reported vasomotor symptom (VMS) frequency with race/ethnicity among a diverse midlife US population and explore menopause symptom differences by dietary soy isoflavone (genistein+daidzein) consumption. STUDY DESIGN: Cross-sectional population-based study of peri- and postmenopausal women, ages 45-58. OUTCOMES: Recent VMS frequency, VMS ever; recent symptom bother (hot flashes, night sweats, headache and joint-ache). RESULTS: Of 18,500 potentially eligible women, 9325 returned questionnaires (50.4% response); 3691 were excluded (premenopausal, missing data, taking hormones). Of 5634 remaining women, 82.1% reported hot flashes ever, 73.1% reported night sweats ever; 48.8% and 38.6% reported recent hot flashes or night sweats, respectively. Compared with White women, Chinese, Japanese, Vietnamese, other Asian (each p<0.001) and Filipino (p<0.01) women less commonly reported ever having hot flashes; Asian women less commonly reported recent VMS bother (p<0.001). Black women more commonly reported hot flashes ever (p<0.05) and recent VMS bother (p<0.05). Compared with non-Hispanic White women, Hispanic women were less likely to report hot flashes (p<0.05) or night sweats (p<0.001) ever. Women were classified by isoflavone consumption: (1) none (n=1819), (2) 0.01-4.30 mg/day (n=1931), (3) 4.31-24.99 mg/day (n=1347) and (4) ≥ 25 mg/day (n=537). There were no group differences in recent VMS number/day: (1) 7.0 (95% CI 6.5, 7.5); (2) 6.4 (95% CI 6.0, 7.1); (3) 7.0 (95% CI 6.3, 8.2); and (4) 6.8 (95% CI 6.1, 7.7). CONCLUSIONS: Menopausal symptoms, independent of isoflavone intake, varied considerably by race/ethnicity and were least common among Asian races.


Asunto(s)
Dieta , Sofocos/etnología , Isoflavonas/uso terapéutico , Menopausia/etnología , Fitoterapia , Grupos Raciales , Alimentos de Soja , Pueblo Asiatico , Población Negra , Femenino , Hispánicos o Latinos , Sofocos/prevención & control , Humanos , Isoflavonas/farmacología , Persona de Mediana Edad , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Autoinforme , Sudoración/efectos de los fármacos , Estados Unidos/epidemiología , Población Blanca
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