Aplicación de la clasificación de Robson como método útil para estandarizar el manejo del parto. Un ejercicio que reduce la tasa de cesáreas / Application of Robson's Ten Group Classification System to standardize patient management. A useful way to reduce cesarean rates

Introducción: La tasa de cesárea es un motivo de controversia y la clasificación de Robson es un método de estandarización que evalúa las causas de esta. En nuestro trabajo analizamos si las medidas de mejora de manejo prenatal e intraparto implementadas tras la revisión de Robson suponen un descenso de índice de cesáreas sin incrementar los de morbimortalidad neonatal y materna. Material y método: Estudio cuasi experimental antes-después, entre 2019 y 2020, con un total de 2.181 pacientes con parto en el Hospital Universitario de Valme (1.027 en el grupo 2019 y 1.154 en el de 2020). Resultados: Observamos que se produjo una disminución estadísticamente significativa de la tasa de cesárea entre 2019 y 2020 (21 vs. 15,8%; p = 0,001) sin ser relevante la reducción en ningún subgrupo de estudio. Hubo un menor índice de parto inducido (29,3 vs. 24,6%; p = 0.01), un aumento en la tasa de parto vaginal (79 vs. 84,2%; p = 0,001) tanto de eutócicos como instrumentales (57,9 vs. 60,3%; 21 vs. 23,9%; p = 0.005) y una baja estadísticamente significativa de la de cesáreas por fallo de inducción o no progresión del parto (NPP) (34,7 vs. 20,9%; p = 0,008). En las inducciones mediante balón de Cook observamos una disminución del índice de cesárea (45,3 vs. 22,2% p = 0,001). Hallamos que redujo el porcentaje de ingreso en la Unidad de Cuidados Intensivos Neonatales (UCIN) (10,5 vs. 7.6%; p = 0,016) y la morbilidad neonatal global (11,4 vs. 8,2%; p = 0,013) sin encontrar diferencia en los resultados maternos. Conclusiones: La aplicación de la clasificación de Robson puede ser un método útil para identificar grupos que requieran de medidas específicas destinadas a estandarizar el manejo de las pacientes, con lo que se permite reducir la tasa de cesáreas.(AU)

Background: Cesarean section rate is controversial and the Robson classification is a method for standardizing the evaluation of the causes of cesarean section. The aim of this study was to evaluate whether the measures to improve prenatal and intrapartum management implemented after the Robson classification evaluation lead to a decrease in the rate of cesarean sections without increasing the rates of neonatal and maternal morbidity and mortality. Material and method: Quasi-experimental study before-after,between-2019 and 2020, including a total of 2181 patients with delivery at Hospital-Universitario-Valme(1027 patients in Group-2019, and 1154 patients in group-2020).Results: We observed that there was a statistically significant decrease in the cesarean section rate between 2019 and 2020 (21.0% vs 15.8%; p = 0.001) without the decrease being significant in any study subgroup. There was a lower rate of induced labor(29.3% vs 24.6%; p = 0.01), an increased rate of vaginal delivery (79.0% vs 84.2%; p = 0.001), both eutocic and instrumental deliveries (57.9% vs 60.3%; 21% vs 23.9%; p = 0.005) and a statistically significant decrease in the rate of cesarean sections due to failure of induction or non-progression of labor(34.7% vs 20.9%;p = 0.008). In inductions using the balloon-Cook we observed a decrease in the rate of cesarean section (45.3% versus 22.2% p = 0.001). We found a decrease in the percentage of admission to the Neonatal ICU (10.5% vs 7.6%; p = 0.016) and global neonatal morbidity(11.4% vs 8.2%; p = 0.013) without observing a difference in maternal outcomes. Conclusions: The application of the Robson classification can be a useful method to identify groups that require the application of specific measures aimed at standardizing the management of these patients, thus allowing to reduce the rate of cesarean sections.(AU)

Biopsia guiada por ecografía para el diagnóstico de masas ováricas. Revisión sistemática / Ecography guided biopsy for the diagnosis of ovarian masses. Systematic review

El diagnóstico definitivo del cáncer de ovario precisa de confirmación histológica. En determinadas situaciones, para evitar la morbilidad de la resección quirúrgica, es posible hacer una biopsia guiada por ecografía para obtener el diagnóstico anatomopatológico. El objetivo de esta revisión sistemática fue evaluar la adecuación, fiabilidad, precisión y perfil de seguridad de la biopsia guiada por ecografía de masas ováricas. Siguiendo el modelo PRISMA 2020, se hizo una búsqueda bibliográfica en PubMed, Embase y Scopus y se recopilaron un total de 10.245 artículos, de los cuales 24 fueron finalmente incluidos. Los trabajos incluían de forma mayoritaria pacientes con tumores inoperables avanzados, pobre performance status y otros factores de mal pronóstico, con masas de contenido sólido y márgenes irregulares, generalmente accesibles por vía transvaginal. En la mayoría de los artículos las pacientes presentaban historia previa de malignidad o tumores inoperables en estadios avanzados. Las masas ováricas biopsiables se definían en la ecografía como malignas o potencialmente malignas, con la presencia destacada de un componente sólido o mixto con márgenes irregulares o heterogéneos. La técnica más utilizada en los estudios incluidos fue la biopsia con aguja gruesa o tru-cut, con altos valores de adecuación, fiabilidad, precisión y rendimiento, así como un buen perfil de seguridad y bajas tasas de complicaciones. En conclusión, la biopsia con aguja gruesa de las masas anexiales guiada por ecografía, en pacientes subsidiarios de tratamiento neoadyuvante, es una técnica con altas tasas de adecuación, fiabilidad, precisión y buen perfil de seguridad.(AU)

The definitive diagnosis of ovarian cancer requires histological confirmation. In certain situations, to avoid the morbidity of surgical resection, it is possible to perform an ultrasound-guided biopsy to obtain the pathological diagnosis. The aim of this systematic review was to assess the adequacy, reliability, accuracy, and safety profile of ultrasound-guided biopsy of ovarian masses. Following the PRISMA 2020 model, a bibliographic search was carried out in PubMed, Embase and Scopus, collecting a total of 10,245 articles, of which 24 were finally included. The studies mainly included patients with advanced inoperable tumors, poor performance status and other poor prognostic factors, with masses of solid content and irregular margins, generally accessible through the transvaginal route. In most of the articles, the patients had a previous history of malignancy or had inoperable tumors in advanced stages. Biopsiable ovarian masses were defined ultrasonographically as malignant or potentially malignant, mainly highlighting the presence of a solid or mixed component and irregular or heterogeneous margins. The most widely used technique in the included studies was core needle or tru-cut biopsy, presenting high values of adequacy, reliability, precision and performance, as well as a good safety profile with low complication rates. In conclusion, ultrasound-guided core needle biopsy of adnexal masses in patients eligible for neoadjuvant treatment is a technique with high adequacy, reliability, and precision rates, as well as a good safety profile.(AU)

Descripción de un caso de hernia diafragmática de Morgagni con derrame pericárdico masivo resuelto mediante pericardiocentesis intrauterina / Description of a case of Morgagni's diaphragmatic hernia with massive pericardial effusion resolved by intrauterine pericardiocentesis

Introducción: Las hernias diafragmáticas de Morgagni diagnosticadas prenatalmente son una rara entidad, con menor riesgo asociado de hipoplasia pulmonar y problemas respiratorios que las hernias diafragmáticas posteriores. Nuestro caso pone de manifiesto cómo en los casos de hernia diafragmática de Morgagni los pulmones tienden a desarrollarse completamente, a pesar del significativo derrame pericárdico o cuán disminuidos pueden aparentar. Principales síntomas y/o hallazgos clínicos: Hernia diafragmática de Morgagni diagnosticada a las 14 semanas de gestación, con derrame pericárdico masivo y herniación torácica anterior del hígado. Diagnósticos principales, intervenciones terapéuticas y resultados: No se identificaron otras malformaciones asociadas, se descartaron otras causas de derrame pericárdico y el cariotipo fetal analizado fue normal. A las 25 semanas, se realizó una pericardiocentesis fetal intrauterina, consiguiendo una significativa distensión pulmonar, con una adecuada vascularización. Tras el nacimiento, la recién nacida precisó soporte ventilatorio debido a una hipoxemia severa causada por la hipertensión pulmonar, corrigiéndose el defecto quirúrgicamente a los 6 días de vida. La evolución posterior fue favorable, sin presentar problemas respiratorios significativos. Conclusión: La detección ecográfica de esta rara anomalía resulta útil para el manejo óptimo, y el drenaje pericárdico puede favorecer una resolución prenatal del derrame pericárdico, permitiéndonos evaluar de forma adecuada el riesgo de hipoplasia pulmonar.(AU)

Introduction: Morgagni diaphragmatic hernia with prenatal diagnosis is a rare entity, with lower risk of pulmonary hypoplasia and respiratory problems than posterior diaphragmatic hernia. Our case highlights how in Morgagni diaphragmatic hernia cases lungs tend to develop properly, despite significant pericardial effusion or how greatly diminished they may seem. Main symptoms and/or clinical findings: Morgagni diaphragmatic hernia diagnosed at 14 weeks, with massive pericardial effusion and anterior thoracic herniation of the liver. Main diagnosis, therapeutic interventions, and results: No other malformations were identified, other causes of pericardial effusion were ruled out and foetal karyotype was normal. At 25 weeks, in-utero pericardiocentesis was performed, observing significant pulmonary distension and adequate vascularization. After delivery, the newborn required respiratory support due to severe hypoxaemia related to pulmonary hypertension. Six days later surgical diaphragm closure was performed. The newborn had no significant respiratory problems and progressed positively after surgery. Conclusion: Ultrasonographic detection of this rare anomaly is useful for optimal management, and pericardial drainage can provide prenatal resolution of pericardial effusion, enabling us to evaluate pulmonary hypoplasia risk.(AU)

Tumor miofibroblástico inflamatorio tras cáncer de mama. Un reto en el diagnóstico diferencial. Revisión de la literatura / Myofibroblastic tumour after breast cancer. A challenge in differential diagnosis. Literature review

Introducción El tumor miofibroblástico inflamatorio (TMI) es un tumor mesenquimal benigno, con potencial de transformación maligna. Puede aparecer en múltiples órganos (pulmón, intestino…), siendo la mama una ubicación excepcional. Hallazgos clínicos: Se presenta el caso de una paciente de 53 años que tiene como antecedente un carcinoma de mama derecha, tipo ductal infiltrante G2, luminal A. Fue tratada con cirugía, radioterapia y quimioterapia, consiguiéndose curación. Transcurridos nueve años, reinició estudio por aparición de una tumoración sospechosa de 3 cm en la misma mama. Diagnósticos principales, intervenciones terapéuticas y resultados: Se realizó una biopsia con aguja gruesa. El estudio anatomopatológico no fue concluyente, por lo que se decidió realizar una exéresis de la lesión. Los resultados del análisis anatomopatológico fueron: tumor miofibroblástico inflamatorio. La paciente no precisó tratamiento adyuvante posterior y se encuentra libre de enfermedad actualmente. Conclusión: El TMI es una entidad poco frecuente, con pocos casos publicados hasta la fecha. Representa un reto diagnóstico, tanto a nivel radiológico como anatomopatológico. A pesar de ser una neoplasia con comportamiento benigno, está indicado realizar una exéresis amplia y completa de la lesión, ya que en algunos casos se ha descrito su recurrencia, y de forma excepcional se han descrito casos de metastatización. El conocimiento de su existencia y comportamiento es clave a la hora orientar el diagnóstico y tratamiento.(AU)

Introduction: Inflammatory myofibroblastic tumour (IMT) is a benign mesenchymal tumour, with potential for malignant transformation. It can appear in multiple organs (lung, intestine…), the breast being an exceptional location. Clinical findings: We present the case of a 53-year-old female patient with a history of right breast ductal infiltrating carcinoma, G2, Luminal A. She was treated with surgery, radiotherapy, and chemotherapy, achieving complete response. Nine years later, she was re-examined due to the appearance of a new suspicious tumour in the same breast, which measured three centimetres. Main diagnosis, therapeutic intervention, and outcomes: A core needle biopsy was performed. The anatomopathological study was inconclusive, so it was decided to perform total excision of the lesion. The results of the anatomopathological analysis were: Inflammatory Myofibroblastic Tumour. The patient did not require further adjuvant treatment and is disease free at present. Conclusions: IMT is a rare entity, with few cases published to date. It represents a diagnostic challenge, both radiologically and anatomopathologically. Although it is a tumour with benign behaviour, wide and complete excision of the lesion is indicated, as its recurrence has been described in some cases, as well as some exceptional cases of metastatisation. Knowledge of its existence and behaviour is a key factor in guiding diagnosis and treatment.(AU)

Metodología para el estudio ecográfico transperineal del suelo pélvico / Methodology for the transperineal ultrasound imaging of the pelvic floor

Las técnicas de imagen cada vez son más utilizadas dentro de la medicina en general y de la ginecología en particular. La ecografía de suelo pélvico, a diferencia de la aplicación ecográfica en las otras subespecialidades ginecológicas, se encuentra bastante estandarizada y con planos de estudios definidos. Dependiendo del transductor utilizado y del modo de aplicación, se han descrito diferentes métodos ecográficos de valoración del suelo pélvico. De todos estos, el estudio transperineal es el más documentado para el diagnóstico de las disfunciones del suelo pélvico. Por ello, el objetivo de esta revisión es describir el método aplicado para realizar un estudio transperineal 2 D y 3-4D del suelo pélvico, describiendo los planos ecográficos necesarios.(AU)

Imaging techniques are increasingly used within medicine in general, and in gynaecology in particular. Pelvic floor ultrasound, unlike ultrasound application in the other gynaecological subspecialties, is fairly standardised and with defined study plans. Depending on the transducer used, and the mode of application, different ultrasound methods for evaluating the pelvic floor have been described. Of all these methods, the transperineal study is the most documented for the diagnosis of pelvic floor dysfunctions. Therefore, the objective of this review is to describe the method applied to perform a 2 D and 3-4D transperineal study of the pelvic floor, describing the necessary ultrasound planes.(AU)

Malmström vacuum or Kielland forceps: which causes more damage to pelvic floor?

OBJECTIVE: To determine whether differences exist in the rate of levator ani muscle (LAM) avulsion between women who had undergone either Malmström vacuum delivery (MVD) or Kielland forceps delivery (KFD), allowing for potential confounding factors. METHODS: This was a prospective observational study of nulliparous women undergoing instrumental delivery using Malmström vacuum extractor or Kielland forceps, at two hospital centers in Spain. Fetal head position (anterior, posterior or transverse) and fetal head station (low or mid) were assessed by ultrasound and digital examination, respectively. Avulsion was defined on tomographic ultrasound imaging as an abnormal insertion of the LAM in the three central slices from the plane of minimal hiatal dimensions. RESULTS: In total, 414 patients were included in the study (212 MVD and 202 KFD). We observed a higher rate of LAM avulsion in the KFD group (KFD 49.5% vs MVD 32.5%; P = 0.001). When the results were evaluated according to fetal head position and station, we observed no differences in LAM avulsion. The crude odds ratio (OR) for the difference in avulsion between women in the KFD and MVD groups was 2.03 (95% CI, 1.36-3.03). However, when adjusted for duration of second stage of labor, fetal head circumference and fetal head station, the OR was no longer statistically significant (OR, 2.14 (95% CI, 0.95-4.85); P = 0.068). CONCLUSION: When potential confounding factors are taken into account, the rate of LAM avulsion does not differ between women according to whether they have undergone KFD or MVD. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Online learning for 3D/4D transperineal ultrasound of the pelvic floor.

Introduction. To evaluate the feasibility of an online learning process for performing and analyzing 3D/4D transperineal ultrasound imaging of the pelvic floor.Materials and methods: A prospective study was conducted with 20 patients. The learning process of three inexperienced examiners (IEs) performing and analyzing 3D/4D transperineal ultrasound volumes was evaluated. The learning process for the IEs was conducted online by an expert examiner (EE); no face-to-face tutoring was provided. The IEs' competency and analysis of the volumes were estimated using the intraclass correlation coefficient (ICC).Results: The interobserver analysis of the levator hiatus dimensions provided by the EE and those from each IE (for the 20 studied cases) had ICCs ranging from 0.81 to 0.96. The dimensions of the levator hiatus performed by the IEs for the first 10 patients showed ICCs ranging from 0.55 to 0.9. However, when the IEs proceeded with the next 10 patients, they obtained ICCs ranging from 0.81 to 0.96.Conclusions: Conducting 3D/4D transperineal ultrasound of the pelvic floor is a technique that can be learned online in a short period of time. A learning programme designed specifically for this purpose provides excellent reliability.Key Message: Conducting 3D/4D transperineal ultrasound of the pelvic floor is a technique that can be learned online in a short period of time.

Resolution of hydrops fetalis caused by atrioventricular block: good postnatal evolution with terbutaline treatment.

INTRODUCTION: Complete atrioventricular block (CAVB) is rarely seen, as it occurs in only 1:11 000 to 1:20 000 newborns. There is a serious risk of mortality in CAVB, mainly in those cases associated with hydrops, fetal cardiac frequency ≤ 55 beats/minute, and premature delivery. CASE REPORT: Case of complete atrioventricular block with a poor prognosis (hydrops fetalis and foetal cardiac frequency < 5 beats/minute) caused by anti-La and anti-Ro antibodies. Intrauterine symptoms improved after treatment with terbutaline, permit- ting foetal viability and successful postnatal treatment with a cardiac pacemaker. DISCUSSION: In case of complete atrioventricular block of cause autoimmune with poor prognosis should be treated with positive inotropic drugs, anticholinergics or b-mimetic in the attempt to maintain adequate ventricular frequency, and thus prevent hydrops fetalis from occurring.

Levator ani muscle injuries associated with vaginal vacuum assisted delivery determined by 3/4D transperineal ultrasound.

OBJECTIVES: To determine the rate of pelvic floor trauma, levator ani muscle (LAM) avulsion as well as the mean difference in levator hiatus area, after normal vaginal deliveries (NVD) and vacuum assisted deliveries (VD), assessed with three-dimensional transperineal ultrasound (3D-TpUS). MATERIALS AND METHODS: Prospective observational study with 151 nulliparous women with NVD or VD at ≥37 weeks between 9-2012 and 6-2013. 3D-TpUS was performed six months after every patient's delivery, during which LAM, anteroposterior diameter, transverse diameter and levator hiatus area were assessed. RESULTS: A total of 146 nulliparous were studied, comprising 73 NVD and 73 VD. No differences in obstetric, intrapartum or neonatal characteristics were observed between study groups, with the following exceptions: maternal age (28.1 ± 5.4 versus 30.4 ± 5.5; p = 0.008, OR = 1.1) and episiotomy rate (35.6% versus 97.3%; p = 0.011, OR = 4.3). LAM avulsion rate was 9.6% in NVD versus 34.2% in VD (p = 0.001, OR 3.99), while levator hiatus area at rest was 16.5 ± 3.2 versus 18.2 ± 3.9 (p = 0.016). CONCLUSIONS: Vacuum assisted deliveries present a higher rate of LAM avulsion, as well as a greater increase in levator hiatal area than in NVD.

Cribado prenatal de cardiopatías congénitas en población de bajo riesgo de defectos congénitos. Una realidad en la actualidad / Prenatal screening of congenital heart defects in population at low risk of congenital defects. A reality today

INTRODUCCIÓN: Nos proponemos demostrar que es posible la implantación de un cribado prenatal de cardiopatías congénitas de garantía (sensibilidad diagnóstica para malformaciones cardíacas mayores del 90%) y universal (aplicado a más del 90% de las gestantes). MATERIAL Y MÉTODO: Estudio prospectivo. Hemos valorado a 12.478 gestantes (enero del 2008-diciembre del 2010). Realizamos un cribado de cardiopatías congénitas aplicando una ecocardiografía fetal básica ampliada. RESULTADOS: La prevalencia de los defectos congénitos en general y de las cardiopatías congénitas es del 2,5% (2,2-2,7%) y el 0,9% (0,7-1%), respectivamente. Las cardiopatías congénitas presentan una tasa de asociación a otras malformaciones estructurales del 11,5% (5,6-17,4%), 21% en caso de cardiopatía congénita mayor (9,9-32%) y a cromosomopatías del 15,9% (9,1- 22,7%), 32,6% en caso de cardiopatía congénita mayor (19,8-45,3%). Hemos logrado realizar una valoración ecográfica cardiaca fetal al 99,2% de las gestantes. La ecocardiografía fetal presenta, para el diagnóstico de las cardiopatías congénitas en general y de las cardiopatías congénitas mayores, una sensibilidad 42,8% (33,5-52,5%) y el 90,4% (78,9-96,8%), respectivamente, y una especificidad para ambas del 99,9% (99,8-99,9%). CONCLUSIONES: Es posible realizar un cribado prenatal de garantías y universal de las cardiopatías congénitas mayores

INTRODUCTION: We propose to demonstrate that it is possible to implement a valid (diagnostic sensitivity for major cardiac malformations 90%), and universal (applied to over 90% of pregnant women), prenatal screening method for congenital heart defects. MATERIALS AND METHODS: Prospective study. A total of 12478 pregnant women were evaluated between January 2008 and December 2010. Congenital heart diseases were screened using fetal extended basic echocardiography (cardiac ultrasound). RESULTS: The prevalence of birth defects in general and congenital heart disease was 2.5% (2.2- 2.7%) and 0.9% (0.7-1%) respectively. Congenital heart disease had a higher rate of association with other structural abnormalities with 11.5% (5.6-17.4%), 21% for major congenital heart disease (9.9-32%), and chromosomal abnormalities of 15.9% (9.1-22.7%), with 32.6% for major congenital heart disease (19.8-45.3%). A fetal cardiac ultrasound assessment was performed on 99.2% of pregnant women. The fetal echocardiography is useful for the diagnosis of congenital heart disease in general, and major congenital heart disease, with a sensitivity of 42.8% (33.5- 52.5%) and 90.4% (78.9-96.8%), respectively, and a specificity for both of 99.9% (99.8-99.9%). CONCLUSIONS: It is possible to perform a valid prenatal and universal screening of major congenital heart disease

[Prenatal screening of congenital heart defects in population at low risk of congenital defects. A reality today]. / Cribado prenatal de cardiopatías congénitas en población de bajo riesgo de defectos congénitos. Una realidad en la actualidad.

INTRODUCTION: We propose to demonstrate that it is possible to implement a valid (diagnostic sensitivity for major cardiac malformations 90%), and universal (applied to over 90% of pregnant women), prenatal screening method for congenital heart defects. MATERIALS AND METHODS: Prospective study. A total of 12478 pregnant women were evaluated between January 2008 and December 2010. Congenital heart diseases were screened using fetal extended basic echocardiography (cardiac ultrasound). RESULTS: The prevalence of birth defects in general and congenital heart disease was 2.5% (2.2-2.7%) and 0.9% (0.7-1%) respectively. Congenital heart disease had a higher rate of association with other structural abnormalities with 11.5% (5.6-17.4%), 21% for major congenital heart disease (9.9-32%), and chromosomal abnormalities of 15.9% (9.1-22.7%), with 32.6% for major congenital heart disease (19.8-45.3%). A fetal cardiac ultrasound assessment was performed on 99.2% of pregnant women. The fetal echocardiography is useful for the diagnosis of congenital heart disease in general, and major congenital heart disease, with a sensitivity of 42.8% (33.5-52.5%) and 90.4% (78.9-96.8%), respectively, and a specificity for both of 99.9% (99.8-99.9%). CONCLUSIONS: It is possible to perform a valid prenatal and universal screening of major congenital heart disease.

Identification of alpha interferon-induced genes associated with antiviral activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene.

A novel assay was developed for Daudi cells in which the antiviral (AV) and antiproliferative (AP) activities of interferon (IFN) can be measured simultaneously. Using this novel assay, conditions allowing IFN AV protection but no growth inhibition were identified and selected. Daudi cells were treated under these conditions, and gene expression microarray analyses were performed. The results of the analysis identified 25 genes associated with IFN-α AV activity. Upregulation of 23 IFN-induced genes was confirmed by using reverse transcription-PCR. Of 25 gene products, 17 were detected by Western blotting at 24 h. Of the 25 genes, 10 have not been previously linked to AV activity of IFN-α. The most upregulated gene was IFIT3 (for IFN-induced protein with tetratricopeptide repeats 3). The results from antibody neutralizing experiments suggested an association of the identified genes with IFN-α AV activity. This association was strengthened by results from IFIT3-small interfering RNA transfection experiments showing decreased expression of IFIT3 and a reduction in the AV activity induced by IFN-α. Overexpression of IFIT3 resulted in a decrease of virus titer. Transcription of AV genes after the treatment of cells with higher concentrations of IFN having an AP effect on Daudi cells suggested pleiotropic functions of identified gene products.