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1.
Osteoporos Int ; 31(9): 1769-1777, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32377809

RESUMEN

Osteoporosis is more common than most feared non-communicable diseases in the Middle East. This justifies the need to place osteoporosis as a health priority in the region. INTRODUCTION: Osteoporosis is a common disease associated with severe debilitating consequences. The objective of this study is To evaluate and compare disease burden from osteoporosis and other non-communicable diseases (NCDs) in Lebanon. METHODS: We assessed the prevalence of osteoporosis and other NCDs, such as obesity, diabetes, hypertension, dyslipidemia, and cardiovascular diseases, based on a published population-based study of Lebanese ≥ 65 years. We compared incidence rates of hip fractures and major osteoporotic fractures (MOF) (spine, hip, humerus, and forearm) to the five commonest cancers in women ≥ 50 years. Rates were based on the national hip fracture and cancer registry data, provided by the Lebanese Ministry of Public Health. MOF incidence rates were derived from national hip fracture incidence rates and MOF/hip fractures incidence rate ratios from the literature. RESULTS: Over 70% of elderly Lebanese had osteoporosis defined by densitometric criteria or prevalent morphometric vertebral fractures. This by far exceeded the prevalence of other NCDs, such as hypertension (53%), diabetes (21%), dyslipidemia (31%), and cardiovascular diseases (30%). Morphometric vertebral fractures (grades 2 and 3) were present in 19% of women and 12% of men. The incidence rates for MOF were 1.6 times greater than those for breast cancer, and 7.4-9.9 folds higher than those for the next commonest cancers of the lungs, colon, and ovaries. Hip fracture incidence rates were lower than those of breast cancer but were 2.1-2.8 folds higher than those of the above-mentioned cancers. CONCLUSION: This first of its kind study in the Middle East demonstrates that osteoporosis is a common disease, more common than most feared NCDs. Our findings are comparable to those in western populations and justify placing osteoporosis on the top of NCDs' priority list in our country and possibly the region.


Asunto(s)
Fracturas de Cadera , Enfermedades no Transmisibles , Osteoporosis , Fracturas Osteoporóticas , Anciano , Costo de Enfermedad , Femenino , Fracturas de Cadera/epidemiología , Humanos , Incidencia , Líbano/epidemiología , Masculino , Enfermedades no Transmisibles/epidemiología , Osteoporosis/epidemiología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología
2.
BJOG ; 127(6): 757-767, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32003141

RESUMEN

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.


Asunto(s)
Aborto Espontáneo/economía , Aborto Espontáneo/prevención & control , Progesterona/economía , Progestinas/economía , Hemorragia Uterina/tratamiento farmacológico , Aborto Espontáneo/etiología , Adolescente , Adulto , Análisis Costo-Beneficio , Método Doble Ciego , Femenino , Humanos , Nacimiento Vivo/economía , Embarazo , Progesterona/uso terapéutico , Progestinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina Estatal , Resultado del Tratamiento , Reino Unido , Hemorragia Uterina/complicaciones , Hemorragia Uterina/economía , Adulto Joven
3.
BJOG ; 125(13): 1663-1670, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29697890

RESUMEN

OBJECTIVE: To estimate the incidence of caesarean scar pregnancy (CSP) and to describe the management outcomes associated with this condition. DESIGN: A national cohort study using the UK Early Pregnancy Surveillance Service (UKEPSS). SETTING: 86 participating Early Pregnancy Units. POPULATION: All women diagnosed in the participating units with CSP between November 2013 and January 2015. METHODS: Cohort study of women identified through the UKEPSS monthly mailing system. MAIN OUTCOME MEASURES: Incidence, clinical outcomes and complications. RESULTS: 102 cases of CSP were reported, with an estimated incidence of 1.5 per 10 000 (95% CI 1.1-1.9) maternities. Full outcome data were available for 92 women. Management was expectant in 21/92 (23%), medical in 15/92 (16%) and surgical in 56/92 (61%). The success rates of expectant, medical and surgical management were 43% (9/21), 46% (7/15) and 96% (54/56), respectively. The complication rates were 15/21 (71%) with expectant, 9/15 (60%) with medical and 20/56 (36%) with surgical management. Discharge from care (median number of days) was 82 (range 37-174) with expectant, 21 (range 10-31) with medical and 11 (range 4-49) with surgical management. CONCLUSIONS: Surgical management appears to be associated with a high success rate, low complication rate and short post-treatment follow up. TWEETABLE ABSTRACT: Surgery for CSP appears to be successful, with low complication rates and short post-treatment follow up.


Asunto(s)
Cesárea/efectos adversos , Cicatriz/complicaciones , Embarazo Ectópico/epidemiología , Embarazo Ectópico/terapia , Abortivos no Esteroideos/uso terapéutico , Estudios de Cohortes , Dilatación y Legrado Uterino/efectos adversos , Femenino , Humanos , Incidencia , Nacimiento Vivo , Metotrexato/uso terapéutico , Embarazo , Embarazo Ectópico/diagnóstico , Embarazo Ectópico/etiología , Resultado del Tratamiento , Reino Unido/epidemiología , Espera Vigilante
4.
Hum Reprod ; 30(8): 1882-95, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26082479

RESUMEN

STUDY QUESTION: What is the chance of natural conception when salpingostomy is used to treat hydrosalpinx?. SUMMARY ANSWER: The natural clinical pregnancy rate following salpingostomy is 27%, in the hands of experienced surgeons who publish their results. WHAT IS KNOWN ALREADY: Tubal surgery is not commonly offered for women with hydrosalpinges since the advent of assisted conception treatment. This is the first systematic review to investigate natural conception rates following salpingostomy in the treatment of hydrosalpinx. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of 22 observational studies encompasses 2810 patients undergoing salpingostomy and attempting natural conception. PARTICIPANTS/MATERIALS, SETTING, METHODS: Literature searches were conducted to retrieve observational studies which reported salpingostomy for hydrosalpinx. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL, with no language restriction. Only studies that focused on salpingostomy (rather than other tubal conserving surgeries) for the treatment of hydrosalpinx were included. A total of 22 studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The pooled natural clinical pregnancy rate from the 22 observational studies (including 2810 patients) was 27% (95% confidence interval (CI): 25-29%) after salpingostomy was performed for hydrosalpinx. The cumulative clinical pregnancy rates were 8.7% (95% CI: 6.6-11.5%) at 6 months, 13.3% (95% CI: 10.6-16.7%) at 9 months, 20.0% (95% CI: 17.5-22.8%) at 12 months, 21.2% (95% CI: 18.6-24.1%) at 18 months and 25.5% (95% CI: 22.2-29.4%) at 24 months after salpingostomy. The pooled live birth rate (10 studies, 1469 patients) was 25% (95% CI: 22-28%) after salpingostomy was performed for hydrosalpinx. The pooled ectopic pregnancy rate (19 studies, 2662 patients) was 10% (95% CI: 9-11%). The pooled miscarriage rate (seven studies, 924 patients) was 7% (95% CI: 6-9%). The included studies scored well on the Newcastle Ottawa quality assessment scale. LIMITATIONS, REASONS FOR CAUTION: Strict inclusion criteria were used in the conduct of the systematic review. However, the studies included are clinically heterogeneous in many aspects including patient characteristics, surgical technique and duration of follow-up after salpingostomy. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this systematic review suggest that salpingostomy is an alternative treatment strategy to tubal clipping or salpingectomy in patients presenting to fertility services with hydrosalpinx. Further prospective, large and high quality studies are needed to identify the subpopulation that would most benefit from tube conserving surgery. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Índice de Embarazo , Salpingitis/cirugía , Salpingostomía , Adulto , Femenino , Fertilización In Vitro , Humanos , Embarazo
5.
BJOG ; 122(2): 190-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25546040

RESUMEN

BACKGROUND: Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. OBJECTIVES: To provide an overview of active women's health trials in LMICs. SEARCH STRATEGY: The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. SELECTION CRITERIA: Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. MAIN RESULTS: Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. AUTHORS' CONCLUSIONS: Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international prioritisation of maternal health.


Asunto(s)
Países en Desarrollo , Enfermedades de los Genitales Femeninos , Servicios de Salud Materna , Complicaciones del Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Salud de la Mujer , Femenino , Salud Global , Humanos , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Salud Reproductiva
6.
East Mediterr Health J ; 21(6): 381-8, 2015 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-26369996

RESUMEN

This study aimed to examine the association between the payer mix and the financial performance of public and private hospitals in Lebanon. The sample comprised 24 hospitals, representing the variety of hospital characteristics in Lebanon. The distribution of the payer mix revealed that the main sources of revenue were public sources (61.1%), out-of-pocket (18.4%) and private insurance (18.2%). Increases in the percentage of revenue from public sources were associated with lower total costs and revenues, but not profit margins. An inverse association was noted between increased revenue from private insurance and profitability, attributed to increased costs. Increased percentage of out of- pocket payments was associated with lower costs and higher profitability. The study provides evidence that payer mix is associated with hospital costs, revenues and profitability. This should initiate/inform discussions between public and private payers and hospitals about the level of payment and its association with hospital sector financial viability.


Asunto(s)
Economía Hospitalaria/estadística & datos numéricos , Administración Financiera de Hospitales/estadística & datos numéricos , Costos de Hospital , Seguro de Salud/economía , Estudios Transversales , Humanos , Renta/estadística & datos numéricos , Seguro de Salud/estadística & datos numéricos , Líbano , Pacientes no Asegurados/estadística & datos numéricos , Modelos Económicos
7.
Clin Exp Allergy ; 43(3): 353-64, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23414544

RESUMEN

BACKGROUND: Oral supplementation with probiotic bacteria can protect against the development of allergic and inflammatory diseases. OBJECTIVE: The aim of this study was to investigate potential immunomodulatory and allergy-protective effects of processed Lactobacillus rhamnosus GG (LGG)-derived supernatants early in life in neonatal mice. METHODS: In vitro, RAW264.7 mouse macrophages were stimulated with viable LGG, LGG-derived supernatants, prepared from different growth phases, and different size fractions thereof, and pro- and anti-inflammatory cytokine production was analysed. Supernatant fractions were also treated with protease, DNAse or carbohydrate-digesting enzymes to define the nature of immunomodulatory components. In vivo, neonatal Balb/c mice were orally supplemented with differentially processed LGG supernatants. Starting at 4 weeks of age, a protocol of ovalbumin-induced acute allergic airway inflammation was applied and protective effects of processed LGG supernatants were assessed. RESULTS: Incubation of RAW264.7 cells with LGG-derived supernatants significantly increased TNFα and IL-10 production. These effects were not restricted to a particular molecular size fraction. Treatment with protease, but not with DNAse or carbohydrate-digesting enzymes, completely abolished the immunomodulatory activities. Incubation of TLR/NOD-transfected cells with LGG-derived supernatants revealed that recognition and signalling of bioactive components is mediated by TLR2 and NOD2. In vivo supplementation of newborn mice with processed LGG-derived supernatants resulted in pronounced protective effects on the allergic inflammatory response as reflected by reduced eosinophil numbers, modified T helper cell cytokine production, significantly less lung inflammation and reduced goblet cell numbers in comparison with sham-treated controls. CONCLUSION: LGG-derived supernatants exert immunomodulatory activities, and neonatal administration of specifically processed supernatants may provide an alternative to viable probiotics in reducing allergic inflammatory responses.


Asunto(s)
Medios de Cultivo Condicionados/farmacología , Hipersensibilidad/inmunología , Factores Inmunológicos/farmacología , Inflamación/inmunología , Lacticaseibacillus rhamnosus/inmunología , Probióticos , Animales , Línea Celular , Femenino , Humanos , Hipersensibilidad/metabolismo , Hipersensibilidad/terapia , Inflamación/metabolismo , Inflamación/terapia , Lacticaseibacillus rhamnosus/química , Lacticaseibacillus rhamnosus/crecimiento & desarrollo , Ratones , Proteína Adaptadora de Señalización NOD2/metabolismo , Receptor Toll-Like 2/metabolismo
8.
Allergy ; 68(3): 322-9, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23369007

RESUMEN

BACKGROUND: Farm-derived dust samples have been screened for bacteria with potential allergo-protective properties. Among those was Staphylococcus sciuri W620 (S. sciuri W620), which we tested with regard to its protective capacities in murine models of allergic airway inflammation. METHODS: We employed two protocols of acute airway inflammation in mice administering either ovalbumin (OVA) or house dust mite extract (HDM) for sensitization. Mechanistic studies on the activation of innate immune responses to S. sciuri W620 were carried out using human primary monocytic dendritic cells (moDC) and co-culture with autologous T cells. RESULTS: The allergo-protective properties of S. sciuri W620 were proven in a T(H)2-driven OVA model as well as in a mixed T(H)1/T(H)2 phenotype HDM model as demonstrated by abrogation of eosinophils and neutrophils in the airways after intranasal treatment. In the HDM model, lymph node cell T(H)1/T(H)2 signature cytokines were decreased in parallel. Studies on human moDC revealed an activation of TLR2 and NOD2 receptors and initiation of DC maturation following incubation with S. sciuri W620. Cytokine expression analyses after exposure to S. sciuri W620 showed a lack of IL-12 production in moDC due to missing transcription of the IL-12p35 mRNA. However, such DC selectively supported T(H)1 cytokine release by co-cultured T cells. CONCLUSION AND CLINICAL RELEVANCE: Our proof-of-concept experiments verify the screening system of farm-derived dust samples as suitable to elucidate new candidates for allergo-protection. S. sciuri W620 was shown to possess preventive properties on airway inflammation providing the basis for further mechanistic studies and potential clinical implication.


Asunto(s)
Asma/inmunología , Asma/prevención & control , Fenotipo , Staphylococcus/inmunología , Animales , Asma/metabolismo , Línea Celular , Niño , Técnicas de Cocultivo , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunización , Ratones , Mucosa Nasal/inmunología , Mucosa Nasal/microbiología , Proteína Adaptadora de Señalización NOD2/metabolismo , Ovalbúmina/inmunología , Pyroglyphidae/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Células Th2/inmunología , Receptor Toll-Like 2/metabolismo
9.
BJOG ; 120(11): 1308-20, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23834505

RESUMEN

BACKGROUND: Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. OBJECTIVES: To explore the association between endometriosis and IVF outcome. SEARCH STRATEGY: Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. SELECTION CRITERIA: Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. DATA COLLECTION AND ANALYSIS: Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. MAIN RESULTS: Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. CONCLUSION: The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment.


Asunto(s)
Endometriosis/complicaciones , Fertilización In Vitro , Enfermedades Uterinas/complicaciones , Implantación del Embrión , Endometriosis/clasificación , Femenino , Humanos , Infertilidad Femenina/etiología , Infertilidad Femenina/terapia , Nacimiento Vivo , Embarazo , Índice de Embarazo , Índice de Severidad de la Enfermedad , Enfermedades Uterinas/clasificación
10.
J Prev Med Hyg ; 54(3): 159-62, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24783894

RESUMEN

OBJECTIVES: To determine the frequency and profile of induced abortions among hospitalized cases of abortions in three tertiary hospitals in Egypt. METHODS: A total of 517 consecutive cases of abortions with complete records were enrolled from three tertiary hospitals in Egypt: two hospitals in Cairo and one hospital in Alexandria. A data extraction sheet was designed to extract the required information from the records. It included: File No., Age, marital status, occupation, parity, number of children, previous abortion, history of contraception, trial of induction for this abortion and management of abortion in the hospital. The World Health Organization (WHO) criteria of categorizing the abortion as possible, probable or certainly induced abortion was used for classification of abortion cases. RESULTS: The proportion of classified induced abortions (certainly, probably and possibly induced abortions) was 30.6% in the total sample, being higher in Alexandria hospital (60.9%) compared to 14 and 19% in the other two hospitals respectively. Using the multiple logistic regression, the following factors were found independently related to induced abortions: Alexandria hospital (as proxy for residence), age > or = 30 years and having more than 2 children. CONCLUSION: The current study revealed that about one third of hospitalized cases of abortion can be suspected of being induced. Induced abortion may be linked to elder age, higher number of children in the family and probably have geographical variation in Egypt.


Asunto(s)
Aborto Inducido/estadística & datos numéricos , Adulto , Egipto , Femenino , Hospitalización , Humanos , Modelos Logísticos , Edad Materna , Paridad , Embarazo , Características de la Residencia
11.
Osteoporos Int ; 22(9): 2499-506, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21069293

RESUMEN

UNLABELLED: Crude incidence rates for hip fractures in individuals aged 50 and above in Lebanon were determined using data from the national hip fracture registry. For the years 2006-2008, crude rates varied between 164 and 188/100,000 for females and between 88 and 106 per 100,000 for males. Using the US 2000 white population as a reference, the calculated age-standardized rates were closest to rates derived for southern Europe. INTRODUCTION: Owing to the demographic explosion, it is projected that the rates of hip fractures would increase the most in the Middle East and Asia. Few are the population-based studies investigating the incidence of hip fractures in the region. METHODS: Using the Ministry of Health registry data, this population-based study evaluated the incidence of hip fractures in individuals aged 50 and above in Lebanon for the years 2006, 2007, and 2008. RESULTS: Hip fracture crude incidence rates varied across the years between 164 and 188 per 100,000 for females and between 88 and 106 per 100,000 for males, with a female/male ratio of 1.6-2.1. The overall mean age (SD) for hip fractures was 75.9 (9.2), 76.8 (9.0), and 77.0 (9.9) years in females in 2006, 2007, and 2008, respectively, and 74.4 (11.6), 76.3 (10.3), and 74.0 (12.1) years in males, respectively. Using the US 2000 white population as a reference, the age-standardized rates were 370.4, 335.1, and 329.0 for females and 109.7, 134.1, and 128.7 for males, for the years 2006, 2007, and 2008, respectively. CONCLUSIONS: The hip fracture age-standardized incidence rates in the Lebanese subjects receiving Ministry of Health coverage were lower than those found in northern Europe and the US and closest to rates derived for southern Europe.


Asunto(s)
Fracturas de Cadera/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Sistema de Registros
12.
Psychoneuroendocrinology ; 86: 134-143, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28957772

RESUMEN

To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/análisis , Estrés Fisiológico/fisiología , Acetilación , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Epigénesis Genética , Femenino , Cabello/química , Cabello/metabolismo , Hipocampo/metabolismo , Histonas/metabolismo , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Dolor Nociceptivo , Proyectos Piloto , Sistema Hipófiso-Suprarrenal/metabolismo , Regiones Promotoras Genéticas/genética
13.
Mucosal Immunol ; 8(2): 307-15, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25100292

RESUMEN

Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of gut homeostasis and intestinal immunopathology. Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice. Stimulation of dendritic cells (DCs) with anti-CD40 or CD40L led to translocation of c-Rel into the nucleus resulting in induction of expression of interleukin-12 (IL-12) and IL-23, key regulators of innate cell-induced colitis. While c-Rel deficiency completely abrogated anti-CD40-induced colitis, adoptively transferred wild-type DCs were able to induce pronounced colonic inflammation in rag1(-/-)rel(-/-) mice. In summary, these results suggest that the expression of c-Rel in DCs is essential for initiating anti-CD40-mediated intestinal pathogenesis.


Asunto(s)
Antígenos CD40/inmunología , Colitis/genética , Colitis/inmunología , Inmunidad Innata , Proteínas Proto-Oncogénicas c-rel/genética , Factores de Transcripción/genética , Animales , Colitis/metabolismo , Colitis/patología , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Humanos , Mediadores de Inflamación/metabolismo , Interferón gamma/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones , Ratones Noqueados , FN-kappa B/metabolismo , Unión Proteica , Proteínas Proto-Oncogénicas c-rel/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo
14.
Br J Pharmacol ; 119(2): 423-31, 1996 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8886430

RESUMEN

1. The ability of a range of substituted imidazole compounds to inhibit mouse cerebellar neuronal nitric oxide synthase (nNOS), bovine aortic endothelial NOS (eNOS) and inducible NOS (iNOS) from lungs of endotoxin-pretreated rats was investigated. In each case the substrate (L-arginine) concentration employed was 120 nM. 2. 1-(2-Trifluoromethylphenyl) imidazole (TRIM) was a relatively potent inhibitor of nNOS and iNOS (IC50S of 28.2 microM and 27.0 microM respectively) but was a relatively weak inhibitor of eNOS (IC50, 1057.5 microM). The parent compound, imidazole, was a weak inhibitor of all three NOS isoforms (IC50S: nNOS, 290.6 microM; eNOS, 101.3 microM; iNOS, 616.0 microM). Substitution of imidazole with a phenyl group to yield I-phenylimidazole (PI) resulted in an isoform non-selective increase in inhibitory potency (IC50S: nNOS, 72.1 microM; eNOS, 86.9 microM; iNOS, 53.9 microM). Further substitution of the attached phenyl group resulted in an increase in nNOS and a decrease in eNOS inhibitory potency as in TRIM, 1-chlorophenylimidazole (CPI; IC50S: nNOS, 43.4 microM; eNOS, 392.3 microM; iNOS, 786.5 microM) and 1-(2,3,5,6-tetrafluorophenyl) imidazole (TETRA-FPI; IC50S; nNOS, 56.3 microM; eNOS, 559.6 microM; iNOS, 202.4 microM). 3. The ability of TRIM to inhibit mouse cerebellar nNOS activity in vitro was influenced by the concentration of L-arginine (0.12-10.0 microM) in the incubation medium. When mouse cerebellar nNOS was used as enzyme source a double reciprocal (Lineweaver-Burk) plot in the presence/absence of TRIM (50 microM) revealed a competitive inhibitory profile. The K(m) for L-arginine and the Ki for TRIM calculated from these data were 2.4 microM and 21.7 microM, respectively. The ability of TRIM to inhibit mouse cerebellar nNOS activity in vitro was unaffected by varying the time of exposure of the enzyme to TRIM from 0-60 min at 0 degree C. 4. TRIM exhibits potent antinociceptive activity in the mouse as evidenced by inhibition of acetic acid induced abdominal constrictions. The ED50 for TRIM following i.p. administration was 20 mg kg-1 (94.5 mumol kg-1). The antinociceptive effect of TRIM was reversed by pretreatment of animals with L-arginine (50 mg kg-1, i.p.) and was not accompanied by sedation, motor ataxia or behavioural changes (rearing, crossing, circling, dipping) as assessed by use of a box maze procedure. 5. L-NG nitro arginine methyl ester (L-NAME, 20 mg kg-1, i.v.) but not TRIM (0.5-20 mg kg-1, i.v.) increased mean arterial blood pressure (MAP) in the urethane-anaesthetized rat. 6. L-NAME (100 microM) potentiated the contractile response of the rabbit isolated aorta to phenylephrine (ED50; 0.084 +/- 0.01 microM in the presence and 0.25 +/- 0.05 microM in the absence of L-NAME; maximum response, 7.7 +/- 0.4 g in the presence and 5.6 +/- 0.5 g in the absence of L-NAME, n = 6, (P < 0.05) whilst TRIM (1-100 microM) was without effect. L-NAME (100 microM) but not TRIM (1-100 microM) also reduced carbachol-induced relaxation of the phenylephrine-precontracted rabbit aorta preparation. 7. L-NAME (50 microM) potentiated the vasoconstrictor effect of bolus-injected noradrenaline (10-1000 nmol) and reduced the vasodilator effect of carbachol (10 microM) added to the Krebs reservoir in the rat perfused mesentery preparation. L-NAME (50 microM) also reduced nitric oxide (NO) release (measured by chemiluminescence of nitrite in the Krebs perfusate) in response to noradrenaline (100 nmol; 53.8 +/- 4.0 pmol ml-1 in the presence and 84.8 +/- 8.0 pmol ml-1 in the absence of L-NAME, n = 15, P < 0.05) and carbachol (10 microM; 63.9 +/- 5.0 pmol ml-1 in the presence and 154.0 +/- 9.0 pmol ml-1 in the absence of L-NAME, n = 15, P < 0.05). TRIM (50 microM) did not affect either the vasoconstrictor response to noradrenaline or the vasodilator response to carbachol or the accompanying release of NO from the perfused rat mesentery.


Asunto(s)
Analgésicos/farmacología , Sistema Cardiovascular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Imidazoles/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nociceptores/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Aorta/enzimología , Aorta/fisiología , Conducta Animal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Bovinos , Cerebelo/efectos de los fármacos , Cerebelo/enzimología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Técnicas In Vitro , Pulmón/enzimología , Masculino , Ratones , Ratones Endogámicos , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/fisiología , Óxido Nítrico Sintasa/metabolismo , Conejos , Ratas , Ratas Wistar , Relación Estructura-Actividad , Vasodilatación/efectos de los fármacos
15.
ASAIO J ; 43(1): 60-4, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9116355

RESUMEN

Setting the occlusion of a roller pump may be facilitated using the TRansonic HT109 Ultrasonic Flowmeter (Transonic Systems, Inc. Ithaca, NY) with non-invasive transducer. The process addresses the need to set occlusion quickly and accurately before initiation of extracorporeal membrane oxygenation (ECMO). This can be performed with the circuit tubing before blood prime and does not require opening the fluid filled ECMO apparatus to air. The principle is based on the fact that fluid flow through the tubing will change with roller occlusion. Using the Transonic flowmeter, a pre determined (partially occlusive) setting can be achieved by first determining the point of total occlusion, then decreasing occlusion a small percentage from this maximum (i.e., total) occlusion. Clinical application in 35 neonatal ECMO cases has shown the practice to be safe, reliable, and efficient.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Humanos , Recién Nacido , Reología
16.
J Extra Corpor Technol ; 28(2): 79-87, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10160448

RESUMEN

A failure analysis was performed on Norton S-65-HL Tygon tubing. Fatigue testing was performed on four sizes of this tubing, and essentially showed how the tubing wears out. A dynamic "life hours to failure" test, which was performed on the 3/8" internal diameter (ID) size, quantified when the tubing ruptured. Based on results of laboratory testing and the institution's clinical extracorporeal membrane oxygenation (ECMO) experience, a reasonable life expectancy for the 3/8" S-65-HL Tygon size was determined for use in this institution's neonatal ECMO system. An understanding of the expected performance of roller pump tubing-an integral component of the ECMO system-is imperative to providing safe, effective extracorporeal life support.


Asunto(s)
Oxigenación por Membrana Extracorpórea/instrumentación , Intubación/instrumentación , Elasticidad , Falla de Equipo , Circulación Extracorporea/instrumentación , Humanos , Recién Nacido , Cuidado Intensivo Neonatal , Cuidados para Prolongación de la Vida/instrumentación , Ensayo de Materiales , Estrés Mecánico , Propiedades de Superficie , Resistencia a la Tracción , Factores de Tiempo
19.
Langenbecks Arch Chir ; 369: 441-2, 1986.
Artículo en Alemán | MEDLINE | ID: mdl-3807561

RESUMEN

UNLABELLED: 32 cases of local recurrence following curative mastectomy were operated between 1975 and 1984. The primary operation was: radical mastectomy n = 20, simple mastectomy n = 6, lumpectomy with axillary dissection n = 6. The rate of local recurrence amounted to: 4.8% (20 patients out of 416) after radical mastectomy; 6 out of 15 patients after simple mastectomy (2 were N1-cases); 6 out of 15 patients after lumpectomy (one case: N1). CONCLUSION: With regard to local recurrence radical mastectomy showed significant better results when compared with less radical operations.


Asunto(s)
Neoplasias de la Mama/cirugía , Recurrencia Local de Neoplasia/etiología , Terapia Combinada , Femenino , Humanos , Escisión del Ganglio Linfático , Mastectomía , Pronóstico , Riesgo
20.
Zentralbl Chir ; 104(1): 23-9, 1979.
Artículo en Alemán | MEDLINE | ID: mdl-419896

RESUMEN

Some years will have to pass, until there will be evidence, if the application of laser beam in surgery of breastcancer, melanomas or basaliomas will be justified and whether it will be possible or not to interrupt or reduce intraoperative tumor cellspread. As an increasing number of surgeons have started to use laser rays in these cases of illness, results of laser surgery and those of tradional methods could be compared in a couple of years. Possibly other indications for the use of laser than those we have worked out will be outlined in general surgery. Surgeons working with laser beam may discredit the method by putting the indication not rigorusly enough. Greatest care should be taken by everybody who starts working with laser rays. Collaboration with a technician is recommended.


Asunto(s)
Terapia por Láser , Enfermedades de la Mama/cirugía , Neoplasias de la Mama/cirugía , Dióxido de Carbono , Carcinoma Basocelular/cirugía , Femenino , Humanos , Masculino , Melanoma/cirugía , Neoplasias Cutáneas/cirugía , Humo
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