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1.
Orthop Traumatol Surg Res ; 102(8): 1043-1047, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27777087

RESUMEN

INTRODUCTION: Lateral femoral cutaneous nerve (LFCN) injury is a risk specific to the direct anterior approach (DAA) for total hip arthroplasty (THA). However, prevention strategies have not been established. This study aimed to identify the predisposing factors determining LFCN injury during THA via a DAA. HYPOTHESIS: Patients with LFCN injury after THA via DAA would demonstrate predisposing factors. MATERIAL AND METHODS: LFCN injury was identified using a patient questionnaire. Potential factors predisposing to LFCN injury were identified in four categories in patient records: patient factors (age, sex, BMI, diagnosis and range of hip motion), surgical factors (surgical time and surgeon's experience of the DAA), preoperative radiographic factors (neck-shaft angle, femoral offset, acetabular offset, total offset and length of muscle on computed tomography axial image) and radiographic changes (differences between each offset pre- and post-surgery). Multivariate analysis was performed to identify risk factors for LFCN injury during this surgery. RESULTS: After application of inclusion and exclusion criteria, 102 hips (28 with LFCN injury; 74 without) in 102 patients (17 males, 85 females; mean age 66.0 years [range, 26-88 years]) were included. Univariate analysis of patients with and without LFCN injury revealed that small preoperative femoral offset and short preoperative long axis of the tensor fascia lata were statistically significant risk factors for LFCN injury (P=0.004, and P=0.01, respectively). Multivariate analysis showed that small preoperative femoral offset was the only independent risk factor for LFCN injury (odds ratio, 0.895; 95% Confidence Interval, 0.817-0.981; P=0.0018). DISCUSSION: Smaller femoral offset was a significant risk factor for LFCN injury following THA via a DAA. Our recommendations are that careful attention should be paid to the skin-fascia incision and subcutaneous exposure, and that excessive retraction of the sartorius muscle and tensor fascia lata should be avoided, to reduce the risk of LFCN injury in patients with a small femoral offset. LEVEL OF EVIDENCE: IV, retrospective historical cohort study.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Fémur/diagnóstico por imagen , Fémur/patología , Traumatismos de los Nervios Periféricos/etiología , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/métodos , Estudios de Casos y Controles , Fascia Lata/diagnóstico por imagen , Fascia Lata/patología , Femenino , Fémur/inervación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Muslo/inervación , Tomografía Computarizada por Rayos X
2.
Transfus Clin Biol ; 22(3): 158-67, 2015 Aug.
Artículo en Francés | MEDLINE | ID: mdl-26119049

RESUMEN

Risk management is a fundamental component of any successful company, whether it is in economic, societal or environmental aspect. Risk management is an especially important activity for companies that optimal security challenge of products and services is great. This is the case especially for the health sector institutions. Risk management is therefore a decision support tool and a means to ensure the sustainability of an organization. In this context, what methods and approaches implemented to manage the risks? Through this state of the art, we are interested in the concept of risk and risk management processes. Then we focus on the different methods of risk management and the criteria for choosing among these methods. Finally we highlight the need to supplement these methods by a systemic and global approach including through risk assessment by the audits.


Asunto(s)
Técnicas de Apoyo para la Decisión , Gestión de Riesgos , Comisión sobre Actividades Profesionales y Hospitalarias , Análisis de Peligros y Puntos de Control Críticos , Análisis de Modo y Efecto de Fallas en la Atención de la Salud , Humanos , Sistemas de Información , Modelos Teóricos , Riesgo , Factores de Riesgo , Gestión de Riesgos/métodos , Gestión de Riesgos/organización & administración , Gestión de Riesgos/tendencias , Administración de la Seguridad/métodos , Administración de la Seguridad/organización & administración
3.
Transfus Clin Biol ; 20(2): 198-210, 2013 May.
Artículo en Francés | MEDLINE | ID: mdl-23602675

RESUMEN

After a reminder on the fundamental concepts of the management of risk, the author describes the overall analysis of risk (AGR), name given by the author to the up-to-date APR method which after several changes of the initial process aims to cover a perimeter of analysis and broader management both at the level of structural that business risks of any kind throughout the system development life cycle, of the study of its feasibility to dismantling.


Asunto(s)
Modelos Teóricos , Gestión de Riesgos/métodos , Administración de la Seguridad/métodos , Prevención de Accidentes , Documentación , Control de Formularios y Registros , Humanos , Medición de Riesgo
4.
J Gynecol Obstet Biol Reprod (Paris) ; 41(7): 623-30, 2012 Nov.
Artículo en Francés | MEDLINE | ID: mdl-23040672

RESUMEN

Restructuring the surgery and gynecology-obstetrics departments taking place now raise many interrogations. It appears as a mandatory necessity to some people and as a tribute to financial strategies to others to the detriment of quality and accessibility of care. Its effect is to clarify a good amount of socioeconomical and medical indicators. The plans of perinatality for the obstetrical aspect and the thresholds of activity for the surgical aspect constitute the major lines of these restructurings. A survey soliciting all the French public hospitals was used to assess the state of obstetrics and gynecology departments in the light of these recent restructurings. Medical demography, preserving and improving the quality and continuity of care, efficiency of the technical supports are discriminating criteria of the involved challenges. Such restructurings have an impact on the doctor's lives, which looks globally positive and a good omen to complete this remodeling process. The activity was safeguarded by a redistribution and a refocusing of institutions. One should not minimize the social impact of these changes, with a potential deterioration of working conditions (internal professional reclassifications, mobility obligation towards other sites). It thus appears that the deep changes which affect the small size institutions will be able to achieve well only if they are clearly done (information) and truly integrated in their medical project.


Asunto(s)
Hospitales Públicos/tendencias , Servicio de Ginecología y Obstetricia en Hospital/tendencias , Femenino , Procedimientos Quirúrgicos Ginecológicos/tendencias , Ginecología , Encuestas de Atención de la Salud , Hospitales Públicos/economía , Humanos , Obstetricia , Personal de Hospital , Médicos , Embarazo , Calidad de la Atención de Salud
5.
J Investig Allergol Clin Immunol ; 20(4): 289-94, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20815306

RESUMEN

BACKGROUND: Peanut allergy is an important public health problem in western countries. However, the risk factors associated with this allergy remain uncertain. OBJECTIVE: To determine whether the consumption of peanuts during pregnancy and breastfeeding is a risk factor for peanut allergy in infants. METHODS: We enrolled 403 infants in a case-control study. The cases were infants aged 18 months or less with a diagnosis of peanut allergy based on a history of clinical reaction after exposure to peanuts and the presence of peanut-specific immunoglobulin E. Controls were age-matched infants with no known clinical history or signs of atopic disease. The mothers of the children filled out a detailed questionnaire about maternal diet during pregnancy and breastfeeding, the infant's diet, the presence of peanut products in the infant's environment, and family history of atopy. RESULTS: The mean (SD) age of cases was 1.23 (0.03) years. The groups were comparable in terms of the rate and duration of breastfeeding. However, the reported consumption of peanuts during pregnancy and breastfeeding was higher in the case group and associated with an increased risk of peanut allergy in offspring (odds ratio [OR], 4.22 [95% confidence interval [CI], 1.57-11.30 and OR, 2.28 [95% CI, 1.31-3.97] for pregnancy and breastfeeding, respectively). Overall, the infants with peanut allergy did not seem to be more exposed to peanut products in their environment than the controls. CONCLUSION: Early exposure to peanut allergens, whether in utero or through human breast milk, seems to increase the risk of developing peanut allergy.


Asunto(s)
Antígenos de Plantas/metabolismo , Lactancia Materna/epidemiología , Transfusión Fetomaterna/inmunología , Hipersensibilidad al Cacahuete/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Antígenos de Plantas/inmunología , Lactancia Materna/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Inmunización , Lactante , Recién Nacido , Masculino , Exposición Materna/efectos adversos , Hipersensibilidad al Cacahuete/diagnóstico , Hipersensibilidad al Cacahuete/inmunología , Hipersensibilidad al Cacahuete/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Fenómenos Fisiologicos de la Nutrición Prenatal/inmunología , Factores de Riesgo
6.
J Gynecol Obstet Biol Reprod (Paris) ; 39(8): 667-71, 2010 Dec.
Artículo en Francés | MEDLINE | ID: mdl-20692111

RESUMEN

Risk for leukemic conditions increases in individuals with Down syndrome. We report a third trimester antenatal diagnosis of leukemia in a Down syndrome fetus. The third trimester ultrasound examination revealed a hepatosplenomegaly, which may suggest a myelopoiesis disorder. A review of the literature of eight cases described antenatally and 14 cases in the immediate neonatal period is presented.


Asunto(s)
Síndrome de Down/diagnóstico por imagen , Enfermedades Fetales/diagnóstico por imagen , Edad Gestacional , Hepatomegalia/diagnóstico por imagen , Leucemia/diagnóstico , Esplenomegalia/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Amniocentesis , Síndrome de Down/complicaciones , Síndrome de Down/embriología , Femenino , Francia , Hepatomegalia/complicaciones , Hepatomegalia/embriología , Humanos , Leucemia/complicaciones , Leucemia/embriología , Medida de Translucencia Nucal , Embarazo , Esplenomegalia/complicaciones , Esplenomegalia/embriología
7.
J Gynecol Obstet Biol Reprod (Paris) ; 39(6): 471-7, 2010 Oct.
Artículo en Francés | MEDLINE | ID: mdl-20609529

RESUMEN

OBJECTIVE: To evaluate the obstetrical management of umbilical cord prolapse and the neonatal outcomes. METHODS: Retrospective study of 57 prolapses of umbilical cord between 1998 and 2009. Arterial pH of umbilical cord, Apgar score and diagnosis delivery time (DDT) were analyzed. RESULTS: The incidence of the cord prolapse was of 1.25 for 1000 deliveries. Cord prolapse occurred with the artificial rupture of membranes in 24 cases (42%) out of 57. There were 48 caesarean births. There were three hydramnios and seven cases of twin pregnancy. The mean pH in the umbilical arteries was 7.15 ± 0.13 in 27 cases. The mean Apgar for the 57 newborns was 6 ± 3 at 1 min and 8 ± 3 at 5 min. The mean DDT was 18 ± 8 min (range: 3-44). In 17 cases out of 27, the mean arterial umbilical pH was 7.07 ± 0.09. Fifteen newborns (26%) had a 5-minute Apgar score less than 7 and were admitted in intensive care unit. The mean Apgar score in the nine vaginal deliveries was 8 ± 4 min. In case of cephalic presentations without associated foetal or maternal pathologies there was a tendency of a better pH when the DDT was shorter. In non-cephalic presentations (14 cases), the mean Apgar score was 8 ± 3 at 5 min. The mean pH measured in eight cases was 7.20 ± 0.13 with mean DDT of 20 minutes. CONCLUSION: The umbilical cord prolapse remains a serious event for the newborns. The reduction of the DDT in cephalic presentation seems to be correlated to a better neonatal state. The caesarean section is the preferential way of childbirth.


Asunto(s)
Parto Obstétrico/métodos , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/cirugía , Resultado del Embarazo/epidemiología , Cordón Umbilical/patología , Cordón Umbilical/cirugía , Puntaje de Apgar , Cesárea , Femenino , Humanos , Incidencia , Mortalidad Infantil , Recién Nacido , Polihidramnios/epidemiología , Polihidramnios/cirugía , Embarazo , Prolapso , Estudios Retrospectivos , Resultado del Tratamiento , Arterias Umbilicales/fisiología
8.
Transfus Clin Biol ; 16(5-6): 505-11, 2009.
Artículo en Francés | MEDLINE | ID: mdl-19932630

RESUMEN

The organisations' performance is not restricted to economic criteria, it integrates other dimensions: social, safety, quality, environmental, ethical, scientific... There are few multicriteria design and management methods for organisations. In this article, we propose an analysis and modelling method of the values creation based on systematic approach. This method enables to integrate all the stakeholders' points of view and expectations in order to have a global vision of the performance. We have applied this method to one French Blood Establishment process.


Asunto(s)
Bancos de Sangre/normas , Técnicas de Apoyo para la Decisión , Toma de Decisiones , Francia , Humanos , Gestión de Riesgos/economía , Seguridad/economía
9.
J Clin Endocrinol Metab ; 88(8): 3491-8, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12915623

RESUMEN

Inactivating mutations of the FSH receptor have been described in rare cases of premature ovarian failure. Only one mutation was associated with a complete phenotype, including delayed puberty, primary amenorrhea, and small ovaries. We describe here a new patient presenting a similar complete phenotype of premature ovarian failure, with high plasma FSH levels associated with very low estrogen and inhibin B levels. No biological response to high doses of recombinant FSH was detected. A novel homozygous Pro(519)Thr mutation was found in this patient. This mutation is located in the second extracellular loop of the FSH receptor, within a motif highly conserved in gonadotropin and TSH receptors. The mutation totally impairs adenylate cyclase stimulation in vitro. FSH binding experiments and confocal microscopy showed that this mutation alters the cell surface targeting of the mutated receptor, which remains trapped intracellularly. Histological studies of the ovaries of the patient showed an increase in the density of small follicles compared with age-matched normal women. A complete block in follicular maturation after the primary stage was also observed. Immunocytochemical studies allowed detection of the expression of c-Kit and proliferation cellular nuclear antigen, whereas no apoptosis was shown by the 3'-end-labeling method. This observation supports the concept that in humans FSH seems mandatory for the initiation of follicular growth only after the primary stage. In our patient complete FSH resistance yields infertility, which is remarkably associated with the persistence of a high number of small follicles.


Asunto(s)
Amenorrea/genética , Mutación/fisiología , Pubertad Tardía/genética , Receptores de HFE/genética , Adulto , Amenorrea/complicaciones , Amenorrea/patología , Sustitución de Aminoácidos , Animales , Células COS , Chlorocebus aethiops , ADN/química , ADN/genética , Exones/genética , Femenino , Técnica del Anticuerpo Fluorescente , Hormona Folículo Estimulante/sangre , Vectores Genéticos , Humanos , Inmunohistoquímica , Microscopía Confocal , Ovario/patología , Pubertad Tardía/complicaciones , Pubertad Tardía/patología , Transfección
10.
J Radiol ; 84(11 Pt 1): 1753-6, 2003 Nov.
Artículo en Francés | MEDLINE | ID: mdl-15022988

RESUMEN

OBJECTIVE: To describe the color-Doppler findings and the spectral forms of pulsed Doppler in tubal ectopic pregnancies. MATERIALS AND METHODS: A prospective study of one hundred patients with tubal ectopic pregnancies was carried out in the emergency ward by two operators from January 1993 to March 1999. Following transabdominal and/or endovaginal sonography of the pelvis, color Doppler of the adnexa and of any suspected latero-uterine abnormal vascularity were studied with pulsed Doppler. The diastolic index (D/S) was measured on 4 consecutive complexes. RESULTS: Sixty-six peripheral hypervascularizations, 27 irregular hypervascularizations and 7 false negatives were found with color Doppler. The pulsed Doppler spectrum revealed a low-impedance flow in 47 cases (D/S index > or = 0.35) and a high-impedance flow in 46 cases (D/S index < 0.35). The latter spectrum was found in 7 cases of tubal rupture with massive hemorrhage and 39 cases of barely evolutive ectopic pregnancies. CONCLUSION: Color Doppler facilitated the diagnosis of small ectopic pregnancies (gestational sac less than 1 cm and echogenic lesions less than 2 cm in maximum diameter). Our work with pulsed Doppler revealed the frequence of high-impedance flow which, in the absence of massive hemoperitoneum, strongly suggests a barely evolutive ectopic pregnancy.


Asunto(s)
Embarazo Ectópico/diagnóstico por imagen , Ultrasonografía Doppler en Color , Ultrasonografía Doppler de Pulso , Femenino , Humanos , Embarazo , Estudios Prospectivos
13.
J Am Vet Med Assoc ; 217(3): 376-83, 2000 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-10935044

RESUMEN

OBJECTIVE: To determine risk factors for development of sequestra in cattle and identify factors associated with a successful outcome. DESIGN: Retrospective study. ANIMALS: 110 cattle. PROCEDURE: Medical records of cattle treated at veterinary teaching hospitals in North America were reviewed. To determine risk factors for osseous sequestration, breed, age, and sex of cattle with osseous sequestration were compared with breed, age, and sex of all other cattle admitted during the study period. RESULTS: 110 cattle were included in the study. Three had 2 sequestra; thus, 113 lesions were identified. Most sequestra were associated with the bones of the extremities, most commonly the third metacarpal or third metatarsal bone. Ninety-two animals were treated surgically (i.e., sequestrectomy), 7 were treated medically, 3 were initially treated medically and were then treated surgically, and 8 were not treated. Follow-up information was available for 65 animals treated surgically and 6 animals treated medically. Fifty-one (78%) animals treated surgically and 5 animals treated medically had a successful outcome. Cattle that were 6 months to 2 years old had a significantly increased risk of developing a sequestrum, compared with cattle < 6 months old. Cattle in which sequestrectomy was performed with the aid of local anesthesia were significantly more likely to undergo 2 or more surgical procedures than were cattle in which sequestrectomy was performed with the aid of general anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sequestrectomy will result in a successful outcome for most cattle with osseous sequestration.


Asunto(s)
Enfermedades Óseas/veterinaria , Enfermedades de los Bovinos/epidemiología , Factores de Edad , Animales , Enfermedades Óseas/epidemiología , Enfermedades Óseas/cirugía , Cruzamiento , Bovinos , Enfermedades de los Bovinos/etiología , Enfermedades de los Bovinos/cirugía , Femenino , Estudios de Seguimiento , Masculino , Registros/veterinaria , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Heridas y Lesiones/complicaciones , Heridas y Lesiones/veterinaria
15.
Mol Endocrinol ; 13(11): 1844-54, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10551778

RESUMEN

Premature ovarian failure occurs in almost 1% of women under age 40. Molecular alterations of the FSH receptor (FSHR) have recently been described. A first homozygous mutation of the FSHR was identified in Finland. More recently, we described two new mutations of the FSHR in a woman presenting a partial FSH-resistance syndrome (patient 1). We now report new molecular alterations of the FSHR in another woman (patient 2) who presented at the age of 19 with primary amenorrhea contrasting with normal pubertal development. She had high plasma FSH, and numerous ovarian follicles up to 3 mm in size were evidenced by ultrasonography. Histological and immunohistochemical examination of ovarian biopsies revealed the presence of a normal follicular development up to the antral stage and disruption at further stages. DNA sequencing showed two heterozygous mutations: Asp224Val in the extracellular domain and Leu601Val in the third extracellular loop of FSHR. Cells transfected with expression vectors encoding the wild type or the mutated Leu601Val receptors bound hormone with similar affinity, whereas binding was barely detectable with the Asp224Val mutant. Confocal microscopy showed the latter to have an impaired targeting to the cell membrane. This was confirmed by its accumulation as a mannose-rich precursor. Adenylate cyclase stimulation by FSH of the Leu601Val mutant receptor showed a 12+/-3% residual activity, whereas in patient 1 a 24+/-4% residual activity was detected for the Arg573Cys mutant receptor. These results are in keeping with the fact that estradiol and inhibin B levels were higher in patient 1 and that stimulation with recombinant FSH did not increase follicular size, estradiol, or inhibin B levels in patient 2 in contrast to what was observed for patient 1. Thus, differences in the residual activity of mutated FSHR led to differences in the clinical, biological, and histological phenotypes of the patient.


Asunto(s)
Amenorrea/genética , Mutación , Ovario/fisiopatología , Receptores de HFE/genética , Adenilil Ciclasas/efectos de los fármacos , Adenilil Ciclasas/metabolismo , Adulto , Amenorrea/tratamiento farmacológico , Animales , Células COS/efectos de los fármacos , Células COS/metabolismo , Femenino , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/uso terapéutico , Silenciador del Gen , Humanos , Inmunohistoquímica , Masculino , Ovario/diagnóstico por imagen , Ovario/patología , Fenotipo , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Insuficiencia Ovárica Primaria/genética , Procesamiento Proteico-Postraduccional , Receptores de HFE/efectos de los fármacos , Receptores de HFE/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Análisis de Secuencia , Ultrasonografía
16.
J Gynecol Obstet Biol Reprod (Paris) ; 28(3): 239-44, 1999 Jun.
Artículo en Francés | MEDLINE | ID: mdl-10456306

RESUMEN

OBJECTIVES: In a population of 45 placenta previa observed at third trimester of gestation we have tried to make the prenatal diagnosis of placenta percreta and vasa previa with color and pulsed Doppler ultrasonography. MATERIALS AND METHODS: We used a transabdominal sonography with full bladder and a transvaginal sonography with empty bladder. The first images obtained showed 20 placenta previa over the internal cervical os, 3 marginal and 22 low-lying placenta previa. We tried to find evidence of placenta percreta with gray-scale ultrasonography (loss of normal hypoechoic retroplacental myometrial zone, focal disruption of the uterine serosa and surrounding tissues, presence of intra placental lacunae) and with color and pulsed Doppler (arterial vessels with a diastolic flow value less than the flow value of a spiral artery behind the placenta, arterial vessels crossing from the placenta to surrounding tissues, intraplacental lacunae with arterial flow). We tried to find evidence of vasa previa in color and pulsed Doppler (a fetal vessel in seen above the lower segment of the uterus and below the fetal head. There is no change in the location of the vessel despite positional changes in both mother and fetus). The positivity of one sign in gray-scale ultrasonography or in color and pulsed Doppler led us to believe that the patient was affected by the anomaly. The final diagnosis of abnormal adherence of the placenta and of vasa previa was made on histological examination. RESULTS: Among the 20 placenta previa over the internal cervical os, we found 1 placenta percreta, 1 placenta accreta and 3 cases of vasa previa. In spite of our limited sample of cases of abnormal adherences, our results showed that gray-scale ultrasonography was sufficient to make a prenatal diagnosis of placenta accreta/percreta. Negative predictive value is 100% on a sample of 43 patients with no abnormal placental adherence. Color and pulsed Doppler brought no further evidence. In our population, color and pulsed Doppler had 100% positive predictive value for diagnosis of vasa previa. CONCLUSION: We found the only 2 cases of abnormal adherent placental fragments and the 3 cases of vasa previa present in our population. The study of the lower segment of the uterus should be thorough as abnormal zones may be small-sized. Color Doppler is the reference technique for sighting vasa previa and gray-scale ultrasonography for abnormal adherences of the placenta.


Asunto(s)
Placenta Accreta/diagnóstico por imagen , Placenta Previa/diagnóstico por imagen , Ultrasonografía Doppler en Color , Ultrasonografía Doppler de Pulso , Ultrasonografía Prenatal , Cordón Umbilical/diagnóstico por imagen , Femenino , Humanos , Valor Predictivo de las Pruebas , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Factores de Riesgo
17.
J Biol Chem ; 274(1): 101-7, 1999 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-9867816

RESUMEN

The thyrotropin (TSH) receptor belongs to a subfamily of G protein-coupled receptors, which also includes luteinizing hormone and follicle-stimulating hormone receptors. The TSH receptor (TSHR) differs from the latter by the presence of an additional specific segment in the C-terminal part of its ectodomain. We show here that this insertion is excised in the majority of receptor molecules. Preparation of specific monoclonal antibodies to this region, microsequencing, enzyme-linked immunosorbent assay, and immunoblot studies have provided insight into the mechanisms of this excision. In the human thyroid gland, N termini of the transmembrane receptor beta subunit were found to be phenylalanine 366 and leucines 370 and 378. In transfected L cells a variety of other more proximal N termini were found, probably corresponding to incomplete excisions. The most extreme N terminus was observed to lie at Ser-314. These observations suggest that after initial cleavage at Ser-314 the inserted fragment of TSHR is progressively clipped out by a series of cleavage reactions progressing up to amino acids 366-378. The impossibility of recovering the excised fragment from purified receptor, cell membranes, or culture medium supports this interpretation. The cleavage enzyme has previously been shown to be inhibited by BB-2116, an inhibitor of matrix metalloproteases. However, we show here that it is unaffected by tissue inhibitors of metalloproteases. The cleavage enzyme is very similar to TACE (tumor necrosis factor alpha-converting enzyme) in both these characteristics. However, incubation of the TSH receptor with the purified recombinant catalytic domain of TACE, co-transfection of cells with TACE and TSHR expression vectors, and the use of mutated Chinese hamster ovary cells in which TACE is inactive suggested that the TSHR cleavage enzyme is different from TACE. TACE and TSHR cleavage enzyme may thus possibly be related but different members of the adamalysin family of metzincin metalloproteases.


Asunto(s)
Receptores de Tirotropina/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Células CHO , Membrana Celular/metabolismo , Cricetinae , Medios de Cultivo , Hidrólisis , Receptores de Tirotropina/antagonistas & inhibidores , Receptores de Tirotropina/inmunología , Inhibidores Tisulares de Metaloproteinasas/farmacología
18.
J Allergy Clin Immunol ; 102(4 Pt 1): 571-8, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9802364

RESUMEN

BACKGROUND: Cells producing a T(H2)-cytokine profile play an important role in the onset and maintenance of atopic diseases, and therefore specific immunotherapy is aimed to induce a switch to cells producing a T(H1)- or T(H0)-cytokine profile. Recently, a novel form of immunotherapy making use of synthetic peptides from the major cat allergen Fel d 1 has been developed, but its mechanisms of action are unknown. OBJECTIVES: We examined the effects of immunotherapy with Fel d 1 peptides on the response to bronchial provocation tests (PD20FEV1) with a standardized Fel d 1 cat extract on Fel d 1-specific serum IgE and IgG levels and in vitro IL-4 and IFN-gamma production. METHODS: Patients allergic to cats received 6 weekly injections of 7.5 micro(g) (low dose), 75 micro(g) (medium dose), or 750 micro(g) (high dose) of Fel d 1 peptides (25 patients) or a placebo (6 patients). RESULTS: Six weeks after ending immunotherapy, posttreatment PD20FEV1 was not significantly different between the treated and placebo groups. However, in the medium- and high-dose groups there was a significant improvement between baseline and posttreatment days. IL-4 release was significantly reduced in the high dose-treated group (P <.005, Wilcoxon W test), whereas it was unchanged in the low or medium dose- and in the placebo-treated groups. In all groups, IFN-gamma, IgE, and IgG levels remained unchanged. CONCLUSION: There was no correlation between the improvement of PD20FEV1 and the decrease in IL-4 production. These data suggest that peptide immunotherapy may act by shifting the Fel d 1-induced response of PBMCs in vitro from the T(H2)-like to the T(H0)-like phenotype.


Asunto(s)
Alérgenos/uso terapéutico , Desensibilización Inmunológica , Glicoproteínas/uso terapéutico , Interleucina-4/sangre , Linfocitos T/metabolismo , Adulto , Animales , Basófilos/metabolismo , Pruebas de Provocación Bronquial , Gatos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Glicoproteínas/administración & dosificación , Humanos , Inmunoglobulina E/biosíntesis , Inmunoglobulina G/biosíntesis , Interferón gamma/sangre
19.
J Clin Invest ; 102(7): 1352-9, 1998 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-9769327

RESUMEN

A single natural loss of function mutation of the follicle stimulating hormone receptor (FSHR) has been described to date. Present in the Finnish population it markedly impairs receptor function, blocking follicle development at the primary stage and presenting as primary amenorrhea with atrophic ovaries. When Western European women with this phenotype were examined for FSHR mutations the result was negative, suggesting that other etiologies corresponding to this clinical pattern are markedly more frequent. We now describe a novel phenotype related to mutations provoking a partial loss of function of the FSHR. A woman with secondary amenorrhea had very high plasma gonadotropin concentrations (especially FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at ultrasonography. Histological and immunohistochemical examination of the ovaries showed normal follicular development up to the small antral stage and a disruption at further stages. The patient was found to carry compound heterozygotic mutations of the FSHR gene: Ile160Thr and Arg573Cys substitutions located, respectively, in the extracellular domain and in the third intracellular loop of the receptor. The mutated receptors, when expressed in COS-7 cells, showed partial functional impairment, consistent with the clinical and histological observations: the first mutation impaired cell surface expression and the second altered signal transduction of the receptor. This observation suggests that a limited FSH effect is sufficient to promote follicular growth up to the small antral stage. Further development necessitates strong FSH stimulation. The contrast between very high FSH levels and normal sized ovaries with antral follicles may thus be characteristic of such patients.


Asunto(s)
Amenorrea/genética , Infertilidad Femenina/genética , Mutación Puntual , Receptores de HFE/genética , Adulto , Amenorrea/sangre , Amenorrea/diagnóstico por imagen , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Secuencia de Bases , Células COS , Bovinos , Membrana Celular/fisiología , Europa (Continente) , Femenino , Finlandia , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/metabolismo , Heterocigoto , Humanos , Infertilidad Femenina/sangre , Cinética , Masculino , Ratones , Modelos Moleculares , Ovario/diagnóstico por imagen , Ovario/patología , Linaje , Fenotipo , Conformación Proteica , Ratas , Receptores de HFE/biosíntesis , Receptores de HFE/fisiología , Proteínas Recombinantes/biosíntesis , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Ovinos , Transducción de Señal , Porcinos , Transfección , Ultrasonografía
20.
Prenat Diagn ; 18(12): 1294-9, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9885022

RESUMEN

We present an antenatal ultrasonographic diagnosis of the cerebro-costo-mandibular syndrome. This rare dysmorphic disorder (only 51 cases have been reported to date) mainly associates defective costal development with features of the Pierre-Robin syndrome. The diagnosis is very often made at birth and the prognosis is very poor. Antenatal ultrasound examination may show a combination of orofacial and chest maldevelopment. In our case the diagnosis was made at 20 weeks' gestation during a routine ultrasound examination and the patient chose to terminate the pregnancy at 24 weeks.


Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Encéfalo/anomalías , Mandíbula/anomalías , Costillas/anomalías , Ultrasonografía Prenatal , Anomalías Múltiples/patología , Adulto , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Edad Gestacional , Humanos , Mandíbula/diagnóstico por imagen , Embarazo , Segundo Trimestre del Embarazo , Costillas/diagnóstico por imagen , Síndrome
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