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1.
Eur J Radiol ; 157: 110561, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36308849

RESUMEN

BACKGROUND: Achieving pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) improves survival outcomes for breast cancer patients. Currently, conventional histopathological biomarkers predicting such responses are inconsistent. Studies investigating radiomic texture analysis from breast magnetic resonance imaging (MRI) to predict pCR have varied radiomic protocols introducing heterogeneity between results. Thus, the efficacy of radiomic profiles compared to conventional strategies to predict pCR are inconclusive. PURPOSE: Comparing the predictive accuracy of different breast MRI radiomic protocols to identify the optimal strategy in predicting pCR to NAC. MATERIAL AND METHODS: A systematic review and network meta-analysis was performed according to PRISMA guidelines. Four databases were searched up to October 4th, 2021. Nine predictive strategies were compared, including conventional biomarker parameters, MRI radiomic analysis conducted before, during, or after NAC, combination strategies and nomographic methodology. RESULTS: 14 studies included radiomic data from 2,722 breast cancers, of which 994 were used in validation cohorts. All MRI derived radiomic features improved predictive accuracy when compared to biomarkers, except for pre-NAC MRI radiomics (odds ratio [OR]: 0.00; 95 % CI: -0.07-0.08). During-NAC and post-NAC MRI improved predictive accuracy compared to Pre-NAC MRI (OR: 0.14, 95 % CI: 0.02-0.26) and (OR: 0.26, 95 % CI: 0.07-0.45) respectively. Combining multiple MRIs did not improve predictive performance compared to Mid- or Post-NAC MRIs individually. CONCLUSION: Radiomic analysis of breast MRIs improve identification of patients likely to achieve a pCR to NAC. Post-NAC MRI are the most accurate imaging method to extrapolate radiomic data to predict pCR.


Asunto(s)
Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Femenino , Terapia Neoadyuvante/métodos , Metaanálisis en Red , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mama/diagnóstico por imagen , Mama/patología , Imagen por Resonancia Magnética/métodos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Estudios Retrospectivos
2.
Diabetes Res Clin Pract ; 163: 108144, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32298706

RESUMEN

AIMS: Screening for Gestational Diabetes Mellitus (GDM) is controversial. This prospectivestudy compared different sets of diagnostic cut-off points for plasma glucose measurements following a 75 g Oral Glucose Tolerance Test (OGTT). METHODS: Women who had maternal risk factors for GDM were recruited at their convenience attheir first prenatal visit and consented to a one-step OGTT at 26-28 weeks gestation.All women fulfilling the World Health Organization (WHO) 2013 diagnostic criteriareceived standard care for GDM. RESULTS: Of the 202 women, 139 (69%) had one risk factor for GDM and 63 (31%) had > 1.Using the WHO criteria, 53% (n = 108) had GDM compared with 35% (n = 71) usingCanadian criteria and 18% (n=36) using National Institute for Health Care Excellencecriteria (NICE) criteria (both p<0.001). Of the 108 women, 50% (n = 54) requiredpharmacological treatment to control hyperglycaemia. If the Canadian criteria wereapplied, 11/54 (20.4%) women would not have received hypoglycaemics. If the NICEcriteria were applied, 36/54 (66.7%) women would not have received hypoglycaemics.Maternal insulin, HOMA-IR and C-peptide measured at the time of the OGTT showed evidence of increased insulin resistance in women who had GDM based on the WHOcriteria but who had a normal OGTT based on the Canadian or NICE criteria. CONCLUSIONS: Under stringent research conditions, our study suggeststhat the Canadian and, in particular, the NICE criteria are not identifying women who may benefit fromimproved glycaemic control. These findings support the need for the planned review of the NICE guidelines on GDM in 2020.


Asunto(s)
Diabetes Gestacional/diagnóstico , Prueba de Tolerancia a la Glucosa/métodos , Adulto , Femenino , Humanos , Embarazo , Estudios Prospectivos , Factores de Riesgo
3.
J Public Health (Oxf) ; 42(1): e18-e25, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-30608605

RESUMEN

BACKGROUND: This longitudinal study examined the profile and pregnancy-related behaviours of women who reported smoking in two successive pregnancies when they presented for prenatal care in a large maternity hospital. METHODS: Using the hospital electronic medical records, women who delivered two successive singleton pregnancies during the years 2011-15 were analyzed. Standardized data were computerized by a midwife at the first prenatal visit, following delivery and before discharge. RESULTS: Over the 5 years, 6647 women delivered twice. Overall 5754 (86.6%) were persistent non-smokers in both pregnancies, 609 (9.2%) were persistent smokers in both pregnancies and between pregnancies 202 (3.0%) quit and 82 (1.2%) started smoking. Compared with persistent non-smokers, persistent smokers had higher rates of reported illicit drug use, alcohol consumption and psychological problems and lower rates of planned pregnancy, folic acid supplementation and breastfeeding in both pregnancies (all P < 0.001). In persistent smokers, folic acid supplementation practices deteriorated and illicit drug use increased in the subsequent pregnancy. CONCLUSIONS: We found that approximately one in 10 women smoked in two consecutive pregnancies. Furthermore, compared with non-smokers, persistent smokers were more likely to report other health behaviours associated with adverse pregnancy outcomes and may require additional multidisciplinary support.


Asunto(s)
Cese del Hábito de Fumar , Fumar , Femenino , Humanos , Estudios Longitudinales , Embarazo , Resultado del Embarazo , Atención Prenatal , Fumar/epidemiología
5.
J Public Health (Oxf) ; 41(2): 371-378, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30010835

RESUMEN

BACKGROUND: Maternal nutrition is a determinant of pregnancy outcomes. Few studies have evaluated the potential of online nutrition resources to modify behaviour. This randomized controlled trial aimed to determine whether access to a customized evidence-based nutrition website in pregnancy improved neonatal outcomes. METHODS: Women <18 weeks gestation were recruited at their convenience. The control group received standard care. In addition to standard care, the intervention group received access to an evidence-based nutrition website, customized to the preferences of pregnant women. RESULTS: Of the 250 women, there were no differences in characteristics between the two groups. Of the women, 91.0% reported they make a conscious effort currently to eat a healthy diet. However, only 19.6% met dietary requirements for calcium, 13.2% for iron, 2.7% for folate and 2.3% for iodine. The most popular website section was pregnancy nutrition advice but engagement was not sustained. Access to the website was not associated with any improvement in clinical outcomes (P > 0.05). CONCLUSIONS: We found that provision of a customized website providing nutrition information, did not improve neonatal outcomes. Future studies should explore whether redesign with website interactivity or embedding information on popular digital platforms sustains women's engagement and modifies dietary behaviour.


Asunto(s)
Dieta Saludable , Educación en Salud/métodos , Fenómenos Fisiologicos Nutricionales Maternos , Resultado del Embarazo , Adulto , Femenino , Humanos , Internet , Embarazo
6.
Ir Med J ; 111(6): 771, 2018 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-30519173

RESUMEN

Aims Screening for gestational diabetes mellitus (GDM) may be universal or selective based on risk factors. We audited selective screening with an Oral Glucose Tolerance Test (OGTT). Methods Clinical and laboratory details of the first 200 women who delivered a baby in 2017 were analysed. Results Based on national recommendations, 46.5% (n=93) had maternal risk factors (RF) and an additional 6.5% (n=13) had fetal RF. Nine women with RF, for unexplained reasons did not have their OGTT. Of the 95 who had their OGTT, the diagnosis of GDM was made in 27.4% (n=26). The diagnosis of GDM was made in an additional 8 women outside selective screening giving an overall incidence of 17.0%. Discussion More than half of the women needed to be screened selectively for GDM. Compliance with the national recommendations was incomplete and thus the diagnosis of GDM may be missed even in an academic setting.

7.
J Public Health (Oxf) ; 40(3): e296-e302, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29394368

RESUMEN

Background: The World Health Organization recommends that women take 400 µg of folate supplementation daily throughout pregnancy. We examined the relationship between total folate intake from the diet and supplements at the first prenatal visit and haematological indices at this visit and subsequently. Methods: Women were recruited at their convenience and in addition to clinical and sociodemographic details, detailed questionnaires on dietary intakes and supplementation consumption were completed under supervision. A full blood count and serum and red blood cell (RBC) folate levels were taken. Results: Of the 502 women studied, 97.5% had inadequate total dietary folate intake at the first visit, but, 98.2% were taking folic acid (FA) supplementation. Only 1.8% (n = 9) had anaemia at their first visit (with no case of macrocytosis). Subsequently, 212 women had a further Hb sample in the third trimester and 8.5% (n = 18) were anaemic and 43.4% (89/205) were anaemic postnatally. There was a relationship between the development of anaemia postnatally and lower RBC folate levels at the first visit (P = 0.02). Conclusions: In a country where FA food fortification remains voluntary, these findings support the recommendation that women should start FA supplementation before pregnancy and continue FA after the first trimester.


Asunto(s)
Anemia/complicaciones , Suplementos Dietéticos , Ácido Fólico/uso terapéutico , Complicaciones del Embarazo/epidemiología , Adulto , Anemia/epidemiología , Dieta/estadística & datos numéricos , Femenino , Ácido Fólico/administración & dosificación , Humanos , Incidencia , Embarazo
8.
Br J Pharmacol ; 174(20): 3482-3495, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28257140

RESUMEN

Perivascular adipose tissue (PVAT) is now recognized as an active player in vascular homeostasis. The expansion of PVAT in obesity and its possible role in vascular dysfunction have attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediators, for instance, angiotensin peptides, reactive oxygen species, chemokines and cytokines. The secretory profile of PVAT is altered by obesity, hypertension and other cardiovascular diseases, leading to an imbalance between its pro-contractile and anti-contractile effects. PVAT adipocytes represent an important source of the mediators, but infiltrating immune cells may become more important under conditions of hypoxia and inflammation. This review describes recent advances in the effects of PVAT on the regulation of vascular tone, highlighting the evidence for a pro-contractile action in health and disease. The role of the endothelium, vascular smooth muscle, immune cells and probably perivascular nerves in PVAT function is also discussed. LINKED ARTICLES: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.


Asunto(s)
Tejido Adiposo/fisiología , Vasos Sanguíneos/fisiología , Adipocitos/fisiología , Animales , Humanos , Sistema Inmunológico/fisiología , Vasoconstricción , Vasodilatación
9.
QJM ; 108(3): 183-7, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25086107

RESUMEN

BACKGROUND: People with severe obesity (body mass index [BMI] > 40 kg/m(2)) have an 85% higher mortality than people with a healthy BMI. Poor physical function may contribute to this excess mortality. Lymphoedema-like swelling can affect the legs of severely obese people with normal lymphoscintigraphy. AIM: We sought to determine the relationship between the presence of lymphoedema-like swelling and physical function in the severely obese. DESIGN AND METHODS: In people with severe obesity, we ascertained whether lower leg lymphoedema-like swelling was present and determined the circumference of the lower leg, time taken to ascend and descend a 17-cm step 50 times and time taken to walk 500 m. RESULTS: The 330 participants, 33% of whom were male, were aged 43.4 ± 12.7 years (mean ± standard deviation) and had a BMI of 51.7 ± 8.4 kg/m(2). Lymphoedema-like swelling was present in approximately one-third (n = 108) in whom a prior history of cellulitis and venous thromboembolism was more common (relative risks 6.16 and 3.86, respectively) than in those without lymphoedema-like swelling. Participants with lymphoedema-like swelling, compared with non-affected counterparts, had a higher lower leg circumference (35.0 ± 7.1 vs. 32.4 ± 4.8 cm), a slower step speed (0.40 ± 0.12 vs. 0.43 ± 0.10 steps/s) and a slower walking speed (0.97 ± 0.37 vs. 1.08 ± 0.30 m/s, P < 0.05 for all comparisons). CONCLUSIONS: In this cross-sectional study, 33% of our severely obese participants had lymphoedema-like swelling. Participants with lymphoedema-like swelling had worse physical function than those without. This association was independent of BMI. The presence of obesity-related chronic lymphoedema-like swelling should lead to interventions that improve physical function.


Asunto(s)
Linfedema/etiología , Obesidad Mórbida/complicaciones , Caminata/fisiología , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Enfermedad Crónica , Estudios Transversales , Tolerancia al Ejercicio/fisiología , Femenino , Humanos , Pierna , Linfedema/fisiopatología , Masculino , Anamnesis/métodos , Persona de Mediana Edad , Obesidad Mórbida/fisiopatología , Examen Físico/métodos , Adulto Joven
10.
J Clin Endocrinol Metab ; 99(7): E1327-31, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24735426

RESUMEN

CONTEXT: Mortality is 85% higher in severely obese subjects (body mass index [BMI] > 40 kg/m(2)) than in subjects with a healthy BMI; poor physical function may be contributory. Hypovitaminosis D is common in obese subjects and is associated with physical dysfunction in the elderly. OBJECTIVE: We determined the relationship between vitamin D status and physical function in severely obese subjects. DESIGN, SETTING, AND PATIENTS: We conducted a clinic-based, cross-sectional study of severely obese subjects. Participants were stratified into three groups according to the Institute of Medicine (IOM) vitamin D status categorization. MAIN OUTCOME MEASURES: We compared levels of self-reported activity and times taken to walk 500 m and to ascend and descend a 17-cm step 50 times. RESULTS: We recruited 252 subjects (age, 43.7 ± 11.2 y; BMI, 50.7 ± 9.7 kg/m(2)); 25-hydroxyvitamin D (25OHD) concentrations were less than 30 nmol/L in 109 participants. Participants with a 25OHD > 50 nmol/L, compared to those with a 25OHD < 30 nmol/L, had the highest activity levels (3.1 ± 3.4 h/wk versus 1.5 ± 2.5 h/wk; P = .015) and the shortest 500-m walk times (6.2 ± 1.1 min versus 7.4 ± 1.5 min; P = .003). Serum 25OHD concentrations had a weakly positive association with activity level (r = 0.19; P = .008) and a moderately negative association with 500-m walk time (r = -0.343; P < .001). CONCLUSIONS: Vitamin D status had a significant relationship with physical activity and physical function in this cohort of severely obese subjects. Low activity levels are likely to perpetuate the problem of hypovitaminosis D due to less time spent outdoors. Studies exploring the effects of vitamin D supplementation in this population are warranted.


Asunto(s)
Actividad Motora , Obesidad Mórbida/sangre , Obesidad Mórbida/fisiopatología , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/fisiopatología , Adulto Joven
11.
Sleep ; 22(6): 728-34, 1999 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-10505818

RESUMEN

STUDY OBJECTIVES: We addressed the issue of how commuting affects sleep habits, and its association with general health and potential sleep disorders in individuals on a large, U.S. commuter rail system. DESIGN: Postage-paid mail back questionnaires were distributed to commuters over 6 consecutive weekdays. The questionnaire incorporated previously validated questions regarding sleep habits. SETTING: Questionnaires were dispensed at 15 different rail stations. PARTICIPANTS: 21,000 commuters accepted the questionnaire. MEASUREMENTS AND RESULTS: Data was analyzed by total group and length of commute. A total of 4715 (22%) questionnaires were returned. Over 50% of the sample reported difficulty with sleep and wakefulness while only 3% sought professional help. Sleep apnea was suspected in 4.2% of male and 1% of female respondents and was associated with increased reports of excessive daytime sleepiness, and history of hypertension, diabetes and obesity. Total nocturnal sleep time was significantly less in those subjects with long commutes. Seventy percent of respondents reported napping during the commute. Length of commute was associated with hypertension. CONCLUSION: Commuting long distances negatively impacts one's ability to capture adequate sleep. Data suggests that there may be significant numbers of respondents with unrecognized sleep disorders which further impact on general health.


Asunto(s)
Hábitos , Vías Férreas , Trastornos del Sueño-Vigilia/epidemiología , Viaje , Adulto , Áreas de Influencia de Salud , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , New York , Obesidad/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Encuestas y Cuestionarios
12.
Electroencephalogr Clin Neurophysiol ; 103(5): 554-62, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9402886

RESUMEN

The maintenance of wakefulness test (MWT) is a daytime polysomnographic procedure which quantifies wake tendency by measuring the ability to remain awake during soporific circumstances. We present normative data based on 64 healthy subjects (27 males and 37 females) who adhered to uniform MWT procedural conditions including polysomnographic montage, illuminance level, seating position, room temperature, meal timing, and subject instructions. When allowed a maximum trial duration of 40 min, subjects' mean sleep latency to the first epoch of sustained sleep was 35.2 +/- 7.9 min. The lower normal limit, defined as two standard deviations below the mean, was 19.4 min. Calculation of data on the basis of a maximum trial duration of 20 min and sleep latency to the first appearance of brief sleep (a microsleep episode or one epoch of any stage of sleep) yielded a mean sleep latency of 18.1 +/- 3.6 min and a lower normal limit of 10.9 min. Sleep latency scores were significantly higher than those previously reported in patients with disorders of excessive somnolence. Therefore, the MWT appears to be a useful procedure in differentiating groups with normal daytime wake tendency from those with impaired wake tendency and in identifying individuals with pathologic inability to remain awake under soporific circumstances.


Asunto(s)
Polisomnografía , Fases del Sueño/fisiología , Vigilia/fisiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sueño/fisiología
13.
Biochemistry ; 36(31): 9340-8, 1997 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-9235976

RESUMEN

Infection by hepatitis C viruses (HCVs) is a serious medical problem with no broadly effective treatment available for the progression of chronic hepatitis. The catalytic activity of a viral serine protease located in the N-terminal one-third of nonstructural protein 3 (NS3) is required for polyprotein processing at four site-specific junctions. The three-dimensional crystal structure of the NS3-NS4A co-complex [Kim, J. L., Morgenstern, K. A., Lin, C., Fox, T., Dwyer, M. D., Landro, J. A., Chambers, S. P., Markland, W., Lepre, C. A., O'Malley, E. T., Harbeson, S. L., Rice, C. M., Murcko, M. A., Caron, P. R., & Thomson, J. A. (1996) Cell 87, 343-355] delineates a small hydrophobic region within the 54-residue NS4A protein that intercalates with and makes extensive contacts to the core of the protease. The current investigation addresses the mechanism of NS3 protease catalytic activation by NS4A utilizing a small synthetic NS4A peptide (residues 1678-1691 of the virus polyprotein sequence) and the recombinantly expressed protease domain of NS3. The addition of NS4A dramatically increased NS3 kcat and kcat/Km catalytic parameters when measured against small peptide substrates representing the different site-specific junctions of the polyprotein. The catalytic effect of natural and non-natural amino acid substitutions at the P1 position in a 5A/5B peptide substrate was investigated. NS3-NS4A demonstrated a marked catalytic preference for the cysteine residue commonly found in authentic substrates. The pH dependence of the NS3 hydrolysis reaction is not affected by the presence of NS4A. This result suggests that NS4A does not change the pKa values of the active site residues of NS3 protease. A steady state kinetic analysis was performed and indicated that the binding of NS4A and the peptide substrate occurs in an ordered fashion during the catalytic cycle, with NS4A binding first. Two distinct kinetic classes of peptidyl inhibitors based upon the 5A/5B cleavage site were identified. An NS4A-independent class is devoid of prime residues. A second class of inhibitors is NS4A-dependent and contains a natural or non-natural cyclic amino acid substituted for the commonly found P1' residue serine. These inhibitors display an up to 80-fold increase in affinity for NS3 protease in the presence of NS4A. Sequential truncation of prime and P residues from this inhibitor class demonstrated the fact that the P4' and P1' residues are crucial for potent inhibition. The selectivity of this NS4A effect is interpreted using a model of the 5A/5B decapeptide substrate bound to the active site of the NS3-NS4A structure.


Asunto(s)
Serina Endopeptidasas/metabolismo , Proteínas no Estructurales Virales/metabolismo , Secuencia de Aminoácidos , Cinética , Datos de Secuencia Molecular , Péptidos/química , Péptidos/metabolismo , Serina Endopeptidasas/química , Relación Estructura-Actividad , Especificidad por Sustrato , Proteínas no Estructurales Virales/química
14.
Cell ; 87(2): 343-55, 1996 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-8861917

RESUMEN

An estimated 1% of the global human population is infected by hepatitis C viruses (HCVs), and there are no broadly effective treatments for the debilitating progression of chronic hepatitis C. A serine protease located within the HCV NS3 protein processes the viral polyprotein at four specific sites and is considered essential for replication. Thus, it emerges as an attractive target for drug design. We report here the 2.5 angstrom resolution X-ray crystal structure of the NS3 protease domain complexed with a synthetic NS4A activator peptide. The protease has a chymotrypsin-like fold and features a tetrahedrally coordinated metal ion distal to the active site. The NS4A peptide intercalates within a beta sheet of the enzyme core.


Asunto(s)
Hepacivirus/enzimología , Proteínas no Estructurales Virales/ultraestructura , Secuencia de Aminoácidos , Sitios de Unión , Cristalografía por Rayos X , Activación Enzimática , Sustancias Macromoleculares , Modelos Moleculares , Datos de Secuencia Molecular , Unión Proteica , Conformación Proteica , Alineación de Secuencia , Especificidad por Sustrato , Proteínas no Estructurales Virales/metabolismo , Zinc
15.
Am J Ophthalmol ; 120(4): 456-61, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7573303

RESUMEN

PURPOSE: We studied a two-generation family with an inherited syndrome of prominent corneal nerves and lesions of the tongue resembling neuromas without the characteristic neoplasms of the multiple endocrine neoplasia type 2B syndrome. Several different point mutations in the RET proto-oncogene on chromosome 10 have been associated with the multiple endocrine neoplasia type 2 syndromes. Molecular genetic studies of families with partial phenotypic expression of these syndromes may aid in further understanding the origin of the variety of clinical manifestations observed in multiple endocrine neoplasia type 2. METHODS: A family consisting of an 8-year-old male proband, his 10-year-old sister, and 40-year-old mother was identified as having prominent corneal nerves and lesions of the tongue resembling neuromas. Pentagastrin-stimulated serum calcitonin levels were measured in the mother and sister. Molecular genetic studies were performed on all three affected members, to look for the specific point mutation seen in over 95% of patients with multiple endocrine neoplasia type 2B. RESULTS: Serum calcitonin levels were normal, indicating no C-cell hyperplasia or medullary thyroid carcinoma. Molecular genetic studies on these individuals did not disclose the specific point mutation seen in multiple endocrine neoplasia type 2B. CONCLUSIONS: This family demonstrates some of the phenotypic features of the multiple endocrine neoplasia type 2B syndrome without the characteristic neoplasms or the mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B. Their physical findings may be caused by genetic alterations within the RET proto-oncogene on chromosome 10 at yet undetermined sites.


Asunto(s)
Córnea/inervación , Enfermedades de la Córnea/genética , Proteínas de Drosophila , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neuroma/genética , Neoplasias de la Lengua/genética , Adulto , Secuencia de Bases , Calcitonina/sangre , Niño , Cromosomas Humanos Par 10 , Córnea/patología , Enfermedades de la Córnea/sangre , Enfermedades de la Córnea/patología , ADN/análisis , Cartilla de ADN/química , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Neoplasia Endocrina Múltiple Tipo 2b/sangre , Neoplasia Endocrina Múltiple Tipo 2b/patología , Neuroma/sangre , Neuroma/patología , Fenotipo , Mutación Puntual/genética , Reacción en Cadena de la Polimerasa , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Proto-Oncogenes , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de la Lengua/sangre , Neoplasias de la Lengua/patología
16.
J Med Ethics ; 21(1): 49-54, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7776349

RESUMEN

Attitudes towards active voluntary euthanasia (AVE) and physician-assisted suicide (PAS) among 1,238 doctors on the medical register of New South Wales varied significantly with self-identified religious affiliation. More doctors without formal religious affiliation ('non-theists') were sympathetic to AVE, and acknowledged that they had practised AVE, than were doctors who gave any religious affiliation ('theists'). Of those identifying with a religion, those who reported a Protestant affiliation were intermediate in their attitudes and practices between the agnostic/atheist and the Catholic groups. Catholics recorded attitudes most opposed to AVE, but even so, 18 per cent of Catholic medical respondents who had been so requested, recorded that they had taken active steps to bring about the death of patients.


Asunto(s)
Eutanasia Activa Voluntaria , Eutanasia Activa , Eutanasia/psicología , Religión y Psicología , Actitud del Personal de Salud , Actitud Frente a la Muerte , Eutanasia/estadística & datos numéricos , Humanos , Modelos Logísticos , Nueva Gales del Sur , Médicos/psicología , Protestantismo , Suicidio Asistido/psicología , Suicidio Asistido/estadística & datos numéricos , Encuestas y Cuestionarios
17.
Med J Aust ; 161(2): 137, 140, 142-4, 1994 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-8028538

RESUMEN

OBJECTIVE: To record doctors' attitudes towards, and practice of, active voluntary euthanasia (AVE) and physician-assisted suicide (PAS) in New South Wales and the Australian Capital Territory. METHODS: A postal survey was sent to a random sample of 2000 practitioners on the Medical Register of NSW (which includes medical practitioners in the ACT). RESULTS: Almost half the practitioners had been asked to perform euthanasia, of whom 28% had complied. Of practitioners asked to assist with suicide, 7% had complied. There was majority support for changes to the law concerning euthanasia. CONCLUSIONS: There are relatively high levels of support for, and practice of, AVE and PAS by medical practitioners in New South Wales and the ACT, suggesting that the current legislation should be reviewed.


Asunto(s)
Actitud del Personal de Salud , Eutanasia Activa Voluntaria , Eutanasia , Médicos , Suicidio Asistido , Adulto , Factores de Edad , Toma de Decisiones , Eutanasia/legislación & jurisprudencia , Eutanasia Activa , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Defensa del Paciente , Relaciones Médico-Paciente , Médicos de Familia , Suicidio Asistido/legislación & jurisprudencia , Cuidado Terminal
18.
Brain Res ; 647(1): 83-90, 1994 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-8069707

RESUMEN

Our studies have been directed to the identification of local, naturally-occurring molecules that support substantia nigra (SN) dopaminergic (DA) neuron survival. We have previously demonstrated that local Type I astrocytes selectively increase the dopaminergic population [30,31]. However, the mechanism of action remains to be defined. To determine whether survival is elicited through diffusible agents, Type I astrocyte conditioned medium (CM) was tested on SN dissociates. After 7 days of exposure to CM, DA neuronal integrity was monitored immunocytochemically with antibody to tyrosine hydroxylase (TH), the DA biosynthetic enzyme, or by TH catalytic assay. CM increased TH+ cell number greater than 2-fold, suggesting that a soluble factor(s) promoted neuron survival. Neurons cultured in serum free medium (SFM) are known to contain few, but detectable numbers of glia [34]. To examine whether CM affected neurons directly, or indirectly through glia, glial populations were stained with antibody against the glial marker, glial fibrillary acidic protein (GFAP). We employed several approaches to define the potential role of glia. Initially, CM was compared to basic fibroblast growth factor (bFGF), a glial mitogen that reportedly enhances nigral DA neuron survival. bFGF enhanced TH activity in our system, as well, but the effect was blocked by the mitotic inhibitor 5-fluorodeoxyuridine (FDUR), which kills dividing glia. In parallel studies CM increased enzyme activity and TH cell number in cultures exhibiting GFAP+ cells. To define the role of these glial cells in the CM effect, we completely eliminated astrocytes in CM-treated cultures employing alpha-aminoadipic acid (AA; 10-30 microM), a specific gliotoxin. At a concentration of AA that eliminated detectable GFAP+ cells, CM continued to elicit a significant increase in TH cell number. These data suggest that, in contrast to effects of bFGF, the DA neurotrophic activity in CM acts directly on nigral neurons to enhance survival.


Asunto(s)
Astrocitos/metabolismo , Dopamina/fisiología , Neuronas/fisiología , Sustancia Negra/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo/farmacología , Relación Dosis-Respuesta a Droga , Factor 2 de Crecimiento de Fibroblastos/farmacología , Neuroglía/fisiología , Ratas , Ratas Sprague-Dawley , Solubilidad , Sustancia Negra/citología
19.
Sleep ; 16(8 Suppl): S76-8, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8178035

RESUMEN

A study was undertaken to determine whether topographic brain mapping of standard EEG and cognitive evoked potentials would provide additional information for the detection of subtle brain abnormalities associated with obstructive sleep apnea. During nocturnal sleep, significant brain activity was detected in frontal regions not usually monitored with standard sleep recordings. Moreover, preliminary results suggest that total brain activity decreased in association with apneic events and depth of O2 desaturation. Also, component asymmetry in the P300 waveform observed in brain areas not typically recorded improved with treatment. We conclude that the use of topographic mapping adds important information to the study of brain function during sleep and sleep apnea.


Asunto(s)
Mapeo Encefálico , Encéfalo/fisiopatología , Electroencefalografía , Síndromes de la Apnea del Sueño/complicaciones , Estimulación Eléctrica , Potenciales Evocados , Humanos , Hipoxia/etiología , Oxígeno/sangre , Respiración con Presión Positiva/métodos , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/terapia , Resultado del Tratamiento
20.
Brain Res ; 582(1): 65-70, 1992 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-1379874

RESUMEN

We previously demonstrated that substantia nigra (SN) support cells selectively increase SN dopamine (DA) neuron survival in dissociated primary culture. Increased survival was elicited specifically by nigral support cells; glia from other brain regions exerted lesser effects. We now report that Type I astrocytes, the principal component of SN support cell monolayers, mediate the enhanced DA cell survival. Initially, the predominant glial subtypes in SN support cell cultures were identified. Postnatal day 1 rat SN was dissociated and cells were grown to confluence (7-9 days in vitro; DIV). Monolayers were immunostained with antibodies against glial fibrillary acidic protein (GFAP; an astrocyte-specific marker), myelin basic protein (MBP; an oligodendrocyte marker), or A2B5 (recognizes 0-2A progenitors and Type II astrocytes). The number of GFAP+ cells far exceeded MBP+ and A2B5+ cells, suggesting that astrocytes constituted the predominant subpopulation. Further, direct comparison of GFAP+ (Type I and Type II astrocytes) and A2B5+ (Type II astrocytes) cells indicated that the vast majority were Type I astrocytes. Greater than 98% of cells reacted with glial antibodies. To definitively characterize the cellular subtype that augments survival of DA neurons, glial subcultures were established. At 2 DIV, enriched populations of Type I or Type II astrocytes, or oligodendrocytes, were tested for the ability to elicit DA neuron survival. Embryonic day 16 rat SN dissociates were added and DA cell number was assessed with antibody against tyrosine hydroxylase (TH), the DA biosynthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Astrocitos/fisiología , Comunicación Celular , Supervivencia Celular , Dopamina/fisiología , Mesencéfalo/fisiología , Neuronas/citología , Sustancia Negra/citología , Tirosina 3-Monooxigenasa/análisis , Análisis de Varianza , Animales , Animales Recién Nacidos , Astrocitos/citología , Recuento de Células , Células Cultivadas , Proteína Ácida Fibrilar de la Glía/análisis , Inmunohistoquímica , Mesencéfalo/citología , Proteína Básica de Mielina/análisis , Neuronas/fisiología , Ratas , Ratas Endogámicas , Sustancia Negra/fisiología
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